Dose Escalation Study Investigating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics of ASP2215 in Patients With Relapsed or Refractory Acute Myeloid Leukemia

• ClinicalTrials.gov Identifier: NCT02014558
• Recruitment Status: Completed
• First Posted: December 18, 2013
• Results First Posted: February 20, 2019
• Last Update Posted: May 23, 2019
• Sponsor: Astellas Pharma Global Development, Inc.
• Information provided by (Responsible Party): Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Acute Myeloid Leukemia
• Interventions: Drug: Gilteritinib; Drug: Voriconazole; Drug: Midazolam; Drug: Cephalexin
• Enrollment: 265

Participant Flow

Recruitment Details	This dose-escalation/dose-expansion study was conducted in sites in the United States, France, Germany and Italy. The study had 7 dose-escalation cohorts with ≥3 participants enrolled at each dose level. Following escalation to the next dose cohort, additional participants were enrolled to the dose-expansion cohorts per protocol-specified criteria.
Pre-assignment Details	Participants with acute myeloid leukemia (AML) who relapsed after or were refractory to induction or salvage treatment were selected for this study. Five participants were re-enrolled into the dose-expansion cohorts as they discontinued treatment for reasons other than toxicity or disease progression, as long as they met the eligibility criteria.

Arm/Group Title	Gilteritinib 20 mg in Escalation Phase	Gilteritinib 40 mg in Escalation Phase	Gilteritinib 80 mg in Escalation Phase	Gilteritinib 120 mg in Escalation Phase	Gilteritinib 200 mg in Escalation Phase	Gilteritinib 300 mg in Escalation Phase	Gilteritinib 450 mg in Escalation Phase	Gilteritinib 20 mg in Expansion Phase	Gilteritinib 40 mg in Expansion Phase	Gilteritinib 80 mg in Expansion Phase	Gilteritinib 120 mg in Expansion Phase	Gilteritinib 200 mg in Expansion Phase	Gilteritinib 300 mg in Expansion Phase
Arm/Group Description	Participants received a single dose of 20 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.	Participants received a single dose of 40 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.	Participants received a single dose of 80 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.	Participants received a single dose of 120 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.	Participants received a single dose of 200 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.	Participants received a single dose of 300 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.	Participants received a single dose of 450 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.	Participants received 20 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. Starting on day 16 of cycle 1, participants also received 200 mg voriconazole orally every 12 hours through day 1 of cycle 2.	Participants received 40 mg gilteritinib orally once daily starting on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study.	Participants received 80 mg gilteritinib orally once daily starting on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study.	Participants received 120 mg gilteritinib orally once daily starting on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study.	Participants received 200 mg gilteritinib orally once daily starting on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. On day -1 and day 15 of cycle 1, certain participants also received 500 mg cephalexin as a single oral dose.	Participants received 300 mg gilteritinib orally once daily starting on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. On day -1 and day 15 of cycle 1, participants also received 2 mg midazolam as a single oral dose.
Period Title: Overall Study
Started [1]	5	3	3	3	4	3	4	11	15	21	69	102	17
Treated	5	3	3	3	3	3	3	12 [2]	13	21	66 [2]	100	17
Completed	0	0	0	0	0	0	0	0	0	0	0	0	0
Not Completed	5	3	3	3	4	3	4	11	15	21	69	102	17
Reason Not Completed
Never Received Study Drug	0	0	0	0	1	0	1	0	2	0	2	2	0
Adverse Event	0	0	0	0	1	0	0	0	2	2	5	21	3
Death	1	0	0	0	0	0	1	1	2	5	5	19	2
Lack of Efficacy	1	2	1	1	0	0	1	3	3	3	16	8	5
Lost to Follow-up	0	0	0	0	0	0	0	0	0	0	1	0	0
Progressive Disease	1	0	1	1	1	2	1	6	5	6	22	31	6
Withdrawal by Subject	0	0	0	0	1	0	0	0	0	2	6	10	0
Miscellaneous	2	1	1	1	0	1	0	1	1	3	12	11	1
[1] Re-enrolled participants (assigned to the 120 mg [1] & 200 mg [4] expansion groups) were excluded.; [2] A participant randomized to the 120 mg was treated with an initial dose of 20 mg by mistake.

Baseline Characteristics

Arm/Group Title		Gilteritinib 20 mg in Escalation Phase	Gilteritinib 40 mg in Escalation Phase	Gilteritinib 80 mg in Escalation Phase	Gilteritinib 120 mg in Escalation Phase	Gilteritinib 200 mg in Escalation Phase	Gilteritinib 300 mg in Escalation Phase	Gilteritinib 450 mg in Escalation Phase	Gilteritinib 20 mg in Expansion Phase	Gilteritinib 40 mg in Expansion Phase	Gilteritinib 80 mg in Expansion Phase	Gilteritinib 120 mg in Expansion Phase	Gilteritinib 200 mg in Expansion Phase	Gilteritinib 300 mg in Expansion Phase	Total
Arm/Group Description		Participants received a single dose of 20 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.	Participants received a single dose of 40 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.	Participants received a single dose of 80 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.	Participants received a single dose of 120 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.	Participants received a single dose of 200 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.	Participants received a single dose of 300 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.	Participants received a single dose of 450 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.	Participants received 20 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. Starting on day 16 of cycle 1, participants also received 200 mg voriconazole orally every 12 hours through day 1 of cycle 2.	Participants received 40 mg gilteritinib orally once daily starting on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study.	Participants received 80 mg gilteritinib orally once daily starting on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study.	Participants received 120 mg gilteritinib orally once daily starting on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study.	Participants received 200 mg gilteritinib orally once daily starting on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. On day -1 and day 15 of cycle 1, certain participants also received 500 mg cephalexin as a single oral dose.	Participants received 300 mg gilteritinib orally once daily starting on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. On day -1 and day 15 of cycle 1, participants also received 2 mg midazolam as a single oral dose.	Total of all reporting groups
Overall Number of Baseline Participants		5	3	3	3	3	3	3	12	13	21	66	100	17	252
Baseline Analysis Population Description		The analysis population was the safety analysis set (SAF), which consisted of all participants who received at least 1 dose of study drug and excluded re-enrolled participants.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	5 participants	3 participants	3 participants	3 participants	3 participants	3 participants	3 participants	12 participants	13 participants	21 participants	66 participants	100 participants	17 participants	252 participants
		65.8 (6.8)	56.7 (6.7)	61 (8.7)	61.7 (6)	64 (1)	55.3 (25)	61.7 (10.7)	59.3 (15.6)	59.6 (14)	56.3 (18.1)	58.3 (16.7)	59.8 (14.6)	57.7 (15.9)	59 (15.1)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	5 participants	3 participants	3 participants	3 participants	3 participants	3 participants	3 participants	12 participants	13 participants	21 participants	66 participants	100 participants	17 participants	252 participants
	Female	2 40.0%	1 33.3%	1 33.3%	1 33.3%	2 66.7%	1 33.3%	0 0.0%	8 66.7%	4 30.8%	12 57.1%	37 56.1%	49 49.0%	5 29.4%	123 48.8%
	Male	3 60.0%	2 66.7%	2 66.7%	2 66.7%	1 33.3%	2 66.7%	3 100.0%	4 33.3%	9 69.2%	9 42.9%	29 43.9%	51 51.0%	12 70.6%	129 51.2%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	5 participants	3 participants	3 participants	3 participants	3 participants	3 participants	3 participants	12 participants	13 participants	21 participants	66 participants	100 participants	17 participants	252 participants
	Black or African American	0 0.0%	0 0.0%	0 0.0%	1 33.3%	1 33.3%	0 0.0%	0 0.0%	1 8.3%	0 0.0%	4 19.0%	2 3.0%	4 4.0%	3 17.6%	16 6.3%
	White	5 100.0%	2 66.7%	3 100.0%	2 66.7%	1 33.3%	3 100.0%	3 100.0%	10 83.3%	9 69.2%	14 66.7%	57 86.4%	91 91.0%	13 76.5%	213 84.5%
	Asian	0 0.0%	1 33.3%	0 0.0%	0 0.0%	1 33.3%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 1.5%	4 4.0%	0 0.0%	7 2.8%
	Other	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 8.3%	4 30.8%	3 14.3%	6 9.1%	1 1.0%	1 5.9%	16 6.3%
Ethnicity; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	5 participants	3 participants	3 participants	3 participants	3 participants	3 participants	3 participants	12 participants	13 participants	21 participants	66 participants	100 participants	17 participants	252 participants
	Not Hispanic or Latino	5 100.0%	3 100.0%	2 66.7%	3 100.0%	3 100.0%	3 100.0%	3 100.0%	11 91.7%	12 92.3%	20 95.2%	62 93.9%	97 97.0%	17 100.0%	241 95.6%
	Hispanic or Latino	0 0.0%	0 0.0%	1 33.3%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 8.3%	1 7.7%	1 4.8%	4 6.1%	3 3.0%	0 0.0%	11 4.4%
Duration of Disease (AML) [1]; Mean (Standard Deviation); Unit of measure: Months
	Number Analyzed	4 participants	3 participants	2 participants	3 participants	2 participants	1 participants	3 participants	10 participants	11 participants	17 participants	46 participants	77 participants	15 participants	194 participants
		19.70 (24.62)	10.81 (8.58)	62.46 (6.97)	49.53 (72.17)	9.46 (2.23)	19.75 [2] (NA)	7.21 (4.27)	11.3 (6.61)	10.53 (11.22)	16.3 (9.85)	12.65 (11.33)	10.9 (9.94)	12.09 (17.76)	13.16 (14.97)
		[1] Measure Analysis Population Description: The analysis population was the SAF, with participants with data available.; [2] Data could not be calculated as there is only one participant in this arm who had available data.
Local FLT3 Mutation Status; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	5 participants	3 participants	3 participants	3 participants	3 participants	3 participants	3 participants	12 participants	13 participants	21 participants	66 participants	100 participants	17 participants	252 participants
	Negative	1 20.0%	0 0.0%	0 0.0%	1 33.3%	1 33.3%	1 33.3%	1 33.3%	1 8.3%	8 61.5%	12 57.1%	13 19.7%	10 10.0%	9 52.9%	58 23.0%
	Positive	4 80.0%	3 100.0%	3 100.0%	2 66.7%	2 66.7%	2 66.7%	2 66.7%	11 91.7%	5 38.5%	9 42.9%	53 80.3%	90 90.0%	8 47.1%	194 77.0%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Dose Limiting Toxicities (DLTs)
Description	To determine the maximum tolerated dose, safety was assessed by DLTs, defined as any grade ≥ 3 non-hematologic or extramedullary toxicity that occurred within 30 days starting with the first dose taken on day -2, and included the first treatment cycle in the dose escalation phase and in the first treatment cycle (28 days) in the dose expansion phase, that was considered to be possibly or probably related to study drug. Exceptions to this were the following: (1) Alopecia, anorexia or fatigue, (2) Grade 3 nausea and/or vomiting if not required tube feeding or total parenteral nutrition, or diarrhea if not required or prolonged hospitalization that was managed to grade ≤ 2 with standard antiemetic or antidiarrheal medications used at prescribed dose within 7 days of onset, (3) Grade 3 fever with neutropenia, with or without infection, (4) Grade 3 infection.
Time Frame	From first dose up to end of cycle 1 (30 days)

Outcome Measure Data

Analysis Population Description

The analysis population was the SAF. Only evaluable participants (defined as participants who received at least 80% of the intended dose during cycle 1 [received at least 23 daily doses in escalation phase or 22 daily doses in expansion phase during cycle 1] or participants who developed DLT within cycle 1) were included.

Arm/Group Title	Gilteritinib 20 mg in Escalation Phase	Gilteritinib 40 mg in Escalation Phase	Gilteritinib 80 mg in Escalation Phase	Gilteritinib 120 mg in Escalation Phase	Gilteritinib 200 mg in Escalation Phase	Gilteritinib 300 mg in Escalation Phase	Gilteritinib 450 mg in Escalation Phase	Gilteritinib 20 mg in Expansion Phase	Gilteritinib 40 mg in Expansion Phase	Gilteritinib 80 mg in Expansion Phase	Gilteritinib 120 mg in Expansion Phase	Gilteritinib 200 mg in Expansion Phase	Gilteritinib 300 mg in Expansion Phase
Arm/Group Description:	Participants received a single dose of 20 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.	Participants received a single dose of 40 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.	Participants received a single dose of 80 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.	Participants received a single dose of 120 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received a single dose of 200 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.	Participants received a single dose of 300 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.	Participants received a single dose of 450 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.	Participants received 20 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. Starting on day 16 of cycle 1, participants also received 200 mg voriconazole orally every 12 hours through day 1 of cycle 2.	Participants received 40 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study.	Participants received 80 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study.	Participants received 120 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study.	Participants received 200 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. On day -1 and day 15 of cycle 1, certain participants also received 500 mg cephalexin as a single oral dose.	Participants received 300 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. On day -1 and day 15 of cycle 1, participants also received 2 mg midazolam as a single oral dose.
Overall Number of Participants Analyzed	3	3	3	3	3	3	3	9	11	18	62	87	13
Measure Type: Count of Participants; Unit of Measure: Participants
Any DLT	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	2 66.7%	1 11.1%	1 9.1%	2 11.1%	7 11.3%	15 17.2%	3 23.1%
Blood and lymphatic system disorders	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 7.7%
Cardiac disorders	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 1.6%	0 0.0%	0 0.0%
Eye disorders	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 5.6%	0 0.0%	0 0.0%	0 0.0%
Gastrointestinal disorders	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 33.3%	0 0.0%	0 0.0%	0 0.0%	1 1.6%	4 4.6%	1 7.7%
General disorders & administration site conditions	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 1.1%	0 0.0%
Hepatobiliary disorders	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 1.6%	0 0.0%	0 0.0%
Infections and infestations	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 9.1%	1 5.6%	0 0.0%	0 0.0%	0 0.0%
Investigations	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 33.3%	0 0.0%	0 0.0%	0 0.0%	2 3.2%	6 6.9%	2 15.4%
Metabolism and nutrition disorders	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	2 2.3%	0 0.0%
Musculoskeletal and connective tissue disorders	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 1.1%	1 7.7%
Nervous system disorders	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 11.1%	0 0.0%	0 0.0%	0 0.0%	3 3.4%	0 0.0%
Renal and urinary disorders	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 1.6%	0 0.0%	0 0.0%
Reproductive system and breast disorders	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 1.1%	0 0.0%
Respiratory, thoracic and mediastinal disorders	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 1.6%	2 2.3%	1 7.7%
Vascular disorders	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	2 2.3%	1 7.7%

2. Primary Outcome

Title	Number of Participants With Adverse Events (AEs)
Description	Safety was assessed by AEs, which included abnormalities identified during a medical test (e.g. laboratory tests, vital signs, electrocardiogram, etc.) if the abnormality induced clinical signs or symptoms, needed active intervention, interruption or discontinuation of study medication or was clinically significant. A treatment-emergent AE (TEAE) was defined as an AE observed after starting administration of the study drug up to 30 days after last dose of study drug (for participants who underwent hematopoietic stem cell transplantation [HSCT]: defined as AEs observed after starting study drug until the last dose before on study HSCT plus 30 days, and AEs that began after resumption of gilteritinib and within 30 days after the last dose of gilteritinib). AEs were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (1-Mild, 2-Moderate, 3-Severe, 4-LifeThreatening, 5-Death).
Time Frame	From first dose of study drug up to 30 days after last dose of study drug (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

Outcome Measure Data

Analysis Population Description

The analysis population was the SAF.

Arm/Group Title	Gilteritinib 20 mg in Escalation Phase	Gilteritinib 40 mg in Escalation Phase	Gilteritinib 80 mg in Escalation Phase	Gilteritinib 120 mg in Escalation Phase	Gilteritinib 200 mg in Escalation Phase	Gilteritinib 300 mg in Escalation Phase	Gilteritinib 450 mg in Escalation Phase	Gilteritinib 20 mg in Expansion Phase	Gilteritinib 40 mg in Expansion Phase	Gilteritinib 80 mg in Expansion Phase	Gilteritinib 120 mg in Expansion Phase	Gilteritinib 200 mg in Expansion Phase	Gilteritinib 300 mg in Expansion Phase
Arm/Group Description:	Participants received a single dose of 20 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.	Participants received a single dose of 40 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.	Participants received a single dose of 80 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.	Participants received a single dose of 120 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.	Participants received a single dose of 200 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.	Participants received a single dose of 300 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.	Participants received a single dose of 450 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.	Participants received 20 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. Starting on day 16 of cycle 1, participants also received 200 mg voriconazole orally every 12 hours through day 1 of cycle 2.	Participants received 40 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study.	Participants received 80 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study.	Participants received 120 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study.	Participants received 200 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. On day -1 and day 15 of cycle 1, certain participants also received 500 mg cephalexin as a single oral dose.	Participants received 300 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. On day -1 and day 15 of cycle 1, participants also received 2 mg midazolam as a single oral dose.
Overall Number of Participants Analyzed	5	3	3	3	3	3	3	12	13	21	66	100	17
Measure Type: Count of Participants; Unit of Measure: Participants
AEs	5 100.0%	3 100.0%	3 100.0%	3 100.0%	3 100.0%	3 100.0%	3 100.0%	12 100.0%	13 100.0%	20 95.2%	64 97.0%	100 100.0%	17 100.0%
Drug-Related AEs	3 60.0%	2 66.7%	1 33.3%	3 100.0%	3 100.0%	2 66.7%	3 100.0%	7 58.3%	6 46.2%	17 81.0%	52 78.8%	77 77.0%	13 76.5%
Deaths	2 40.0%	2 66.7%	0 0.0%	1 33.3%	1 33.3%	1 33.3%	1 33.3%	3 25.0%	4 30.8%	11 52.4%	23 34.8%	49 49.0%	7 41.2%
Serious AEs	2 40.0%	2 66.7%	2 66.7%	1 33.3%	2 66.7%	2 66.7%	2 66.7%	8 66.7%	12 92.3%	19 90.5%	52 78.8%	92 92.0%	14 82.4%
Drug-Related Serious AEs	0 0.0%	0 0.0%	0 0.0%	1 33.3%	1 33.3%	0 0.0%	2 66.7%	2 16.7%	1 7.7%	10 47.6%	19 28.8%	36 36.0%	4 23.5%
AEs Leading to Discontinuation of Study Drug	2 40.0%	0 0.0%	1 33.3%	0 0.0%	1 33.3%	0 0.0%	1 33.3%	2 16.7%	5 38.5%	11 52.4%	12 18.2%	46 46.0%	6 35.3%
Drug-Related AEs Leading to Discont. of Study Drug	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 8.3%	1 7.7%	4 19.0%	5 7.6%	10 10.0%	3 17.6%
Grade 3 or Higher TEAEs	3 60.0%	2 66.7%	2 66.7%	1 33.3%	2 66.7%	2 66.7%	3 100.0%	9 75.0%	13 100.0%	20 95.2%	59 89.4%	99 99.0%	14 82.4%
AEs During On-Study HSCT Period	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	3 4.5%	7 7.0%	0 0.0%
Serious AEs During On-Study HSCT	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	3 3.0%	0 0.0%

3. Primary Outcome

Title	Area Under the Concentration-time Curve Over the 24-Hour Dosing Interval (AUC24) After Single and Multiple Doses of Gilteritinib
Description	Plasma samples were used for pharmacokinetic assessments.
Time Frame	Day -2 and cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose

Outcome Measure Data

Analysis Population Description

Pharmacokinetics analysis set (PKAS) - consisted of the subset of the SAF for which sufficient plasma concentration data were available to facilitate derivation of at least 1 pharmacokinetic parameter and for whom the time of dosing on the day of sampling was known. Participants with available data were included in the analysis.

Arm/Group Title		Gilteritinib 20 mg in Escalation Phase	Gilteritinib 40 mg in Escalation Phase	Gilteritinib 80 mg in Escalation Phase	Gilteritinib 120 mg in Escalation Phase	Gilteritinib 200 mg in Escalation Phase	Gilteritinib 300 mg in Escalation Phase	Gilteritinib 450 mg in Escalation Phase
Arm/Group Description:		Participants received a single dose of 20 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.	Participants received a single dose of 40 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.	Participants received a single dose of 80 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.	Participants received a single dose of 120 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.	Participants received a single dose of 200 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.	Participants received a single dose of 300 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.	Participants received a single dose of 450 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.
Overall Number of Participants Analyzed		5	3	3	3	3	3	3
Mean (Standard Deviation); Unit of Measure: ng*h/mL
Day -2	Number Analyzed	5 participants	3 participants	3 participants	3 participants	3 participants	3 participants	2 participants
		302.1 (207.0)	360.0 (223.5)	1216 (472.6)	2480 (1972)	3022 (843.6)	4163 (3178)	3324 (221.1)
Cycle 1 Day 15	Number Analyzed	3 participants	2 participants	3 participants	3 participants	2 participants	3 participants	1 participants
		1299 (1006)	2482 (33.28)	6958 (3273)	6943 (3221)	31428 (21412)	31005 (10068)	34768 [1] (NA)

[1]

This cannot be calculated due to insufficient data (only 1 participant had available data).

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gilteritinib 20 mg in Escalation Phase, Gilteritinib 40 mg in Escalation Phase, Gilteritinib 80 mg in Escalation Phase, Gilteritinib 120 mg in Escalation Phase, Gilteritinib 200 mg in Escalation Phase, Gilteritinib 300 mg in Escalation Phase, Gilteritinib 450 mg in Escalation Phase
	Comments	Dose Proportionality (Single Dose / Day -2) was evaluated using the power model.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Slope
	Estimated Value	0.990
	Confidence Interval	(2-Sided) 90%; 0.788 to 1.19
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Gilteritinib 20 mg in Escalation Phase, Gilteritinib 40 mg in Escalation Phase, Gilteritinib 80 mg in Escalation Phase, Gilteritinib 120 mg in Escalation Phase, Gilteritinib 200 mg in Escalation Phase, Gilteritinib 300 mg in Escalation Phase, Gilteritinib 450 mg in Escalation Phase
	Comments	Dose Proportionality (Multiple Dose / Cycle 1 Day 15) was evaluated using the power model.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Slope
	Estimated Value	1.22
	Confidence Interval	(2-Sided) 90%; 1.00 to 1.43
	Estimation Comments	[Not Specified]

4. Primary Outcome

Title	Maximum Concentration (Cmax) After Single and Multiple Doses of Gilteritinib
Description	Plasma samples were used for pharmacokinetic assessments.
Time Frame	Day -2 and cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose

Outcome Measure Data

Analysis Population Description

The analysis population was the PKAS with available data.

Arm/Group Title		Gilteritinib 20 mg in Escalation Phase	Gilteritinib 40 mg in Escalation Phase	Gilteritinib 80 mg in Escalation Phase	Gilteritinib 120 mg in Escalation Phase	Gilteritinib 200 mg in Escalation Phase	Gilteritinib 300 mg in Escalation Phase	Gilteritinib 450 mg in Escalation Phase
Arm/Group Description:		Participants received a single dose of 20 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study..	Participants received a single dose of 40 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study..	Participants received a single dose of 80 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.	Participants received a single dose of 120 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.	Participants received a single dose of 200 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.	Participants received a single dose of 300 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.	Participants received a single dose of 450 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.
Overall Number of Participants Analyzed		5	3	3	3	3	3	3
Mean (Standard Deviation); Unit of Measure: ng/mL
Day -2	Number Analyzed	5 participants	3 participants	3 participants	3 participants	3 participants	3 participants	3 participants
		28.13 (21.49)	24.98 (14.58)	75.29 (25.22)	136.7 (94.37)	168.2 (45.34)	204.3 (136.4)	207.6 (51.81)
Cycle 1 day 15	Number Analyzed	4 participants	3 participants	3 participants	3 participants	2 participants	3 participants	1 participants
		64.64 (48.77)	107.6 (31.92)	376.4 (150.5)	374.2 (190.1)	1462 (815.1)	1525 (664.6)	1528 [1] (NA)

[1]

This cannot be calculated due to insufficient data (only 1 participant had available data).

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gilteritinib 20 mg in Escalation Phase, Gilteritinib 40 mg in Escalation Phase, Gilteritinib 80 mg in Escalation Phase, Gilteritinib 120 mg in Escalation Phase, Gilteritinib 200 mg in Escalation Phase, Gilteritinib 300 mg in Escalation Phase, Gilteritinib 450 mg in Escalation Phase
	Comments	Dose Proportionality (Single Dose / Day -2) was evaluated using the power model.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Slope
	Estimated Value	0.808
	Confidence Interval	(2-Sided) 90%; 0.629 to 0.988
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Gilteritinib 20 mg in Escalation Phase, Gilteritinib 40 mg in Escalation Phase, Gilteritinib 80 mg in Escalation Phase, Gilteritinib 120 mg in Escalation Phase, Gilteritinib 200 mg in Escalation Phase, Gilteritinib 300 mg in Escalation Phase, Gilteritinib 450 mg in Escalation Phase
	Comments	Dose Proportionality (Multiple Dose / Cycle 1 Day 15) was evaluated using the power model.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Slope
	Estimated Value	1.21
	Confidence Interval	(2-Sided) 90%; 1.02 to 1.41
	Estimation Comments	[Not Specified]

5. Primary Outcome

Title	Area Under the Concentration-time Curve From the Time of Dosing to the Last Measurable Concentration (AUClast) After Single and Multiple Doses of Gilteritinib
Description	Plasma samples were used for pharmacokinetic assessments.
Time Frame	Day -2 and cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose

Outcome Measure Data

Analysis Population Description

The analysis population was the PKAS with available data.

Arm/Group Title		Gilteritinib 20 mg in Escalation Phase	Gilteritinib 40 mg in Escalation Phase	Gilteritinib 80 mg in Escalation Phase	Gilteritinib 120 mg in Escalation Phase	Gilteritinib 200 mg in Escalation Phase	Gilteritinib 300 mg in Escalation Phase	Gilteritinib 450 mg in Escalation Phase
Arm/Group Description:		Participants received a single dose of 20 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.	Participants received a single dose of 40 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.	Participants received a single dose of 80 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.	Participants received a single dose of 120 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.	Participants received a single dose of 200 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.	Participants received a single dose of 300 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.	Participants received a single dose of 450 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.
Overall Number of Participants Analyzed		5	3	3	3	3	3	3
Mean (Standard Deviation); Unit of Measure: ng*h/mL
Day -2	Number Analyzed	5 participants	3 participants	3 participants	3 participants	3 participants	3 participants	3 participants
		303.0 (207.1)	360.4 (224.1)	1216 (472.6)	2480 (1972)	3024 (846.2)	4181 (3189)	2544 (1427)
Cycle 1 day -15	Number Analyzed	4 participants	3 participants	3 participants	3 participants	2 participants	3 participants	1 participants
		1030 (984.2)	1990 (1422)	7111 (3525)	6943 (3221)	32248 (22571)	31749 (10090)	35506 [1] (NA)

[1]

This cannot be calculated due to insufficient data (only 1 participant had available data).

6. Primary Outcome

Title	Time to Observed Cmax (Tmax) After Single and Multiple Doses of Gilteritinib
Description	Plasma samples were used for pharmacokinetic assessments.
Time Frame	Day -2 and cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose

Outcome Measure Data

Analysis Population Description

The analysis population was the PKAS with available data.

Arm/Group Title		Gilteritinib 20 mg in Escalation Phase	Gilteritinib 40 mg in Escalation Phase	Gilteritinib 80 mg in Escalation Phase	Gilteritinib 120 mg in Escalation Phase	Gilteritinib 200 mg in Escalation Phase	Gilteritinib 300 mg in Escalation Phase	Gilteritinib 450 mg in Escalation Phase
Arm/Group Description:		Participants received a single dose of 20 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.	Participants received a single dose of 40 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.	Participants received a single dose of 80 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.	Participants received a single dose of 120 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.	Participants received a single dose of 200 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.	Participants received a single dose of 300 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.	Participants received a single dose of 450 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.
Overall Number of Participants Analyzed		5	3	3	3	3	3	3
Median (Full Range); Unit of Measure: hours
Day -2	Number Analyzed	5 participants	3 participants	3 participants	3 participants	3 participants	3 participants	3 participants
		2.00; (0.500 to 4.03)	5.983; (3.97 to 24.0)	4.000; (4.00 to 4.08)	2.083; (2.00 to 3.83)	5.233; (4.00 to 5.97)	6.067; (4.08 to 24.1)	5.783; (4.08 to 5.92)
Cycle 1 day 15	Number Analyzed	4 participants	3 participants	3 participants	3 participants	2 participants	3 participants	1 participants
		4.008; (4.00 to 6.00)	3.867; (0.50 to 6.00)	4.333; (4.00 to 4.42)	2.167; (1.95 to 5.75)	6.033; (6.00 to 6.07)	6.050; (4.08 to 6.07)	5.933 [1]; (NA to NA)

[1]

This cannot be calculated due to insufficient data (only 1 participant had available data).

7. Primary Outcome

Title	Terminal Elimination Half-life (t1/2) After Multiple Doses of Gilteritinib
Description	Plasma samples were used for pharmacokinetic assessments.
Time Frame	Cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose

Outcome Measure Data

Analysis Population Description

The analysis population was the PKAS with available data.

Arm/Group Title	Gilteritinib 20 mg in Escalation Phase	Gilteritinib 40 mg in Escalation Phase	Gilteritinib 80 mg in Escalation Phase	Gilteritinib 120 mg in Escalation Phase	Gilteritinib 200 mg in Escalation Phase	Gilteritinib 300 mg in Escalation Phase	Gilteritinib 450 mg in Escalation Phase
Arm/Group Description:	Participants received a single dose of 20 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.	Participants received a single dose of 40 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.	Participants received a single dose of 80 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.	Participants received a single dose of 120 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.	Participants received a single dose of 200 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.	Participants received a single dose of 300 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.	Participants received a single dose of 450 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.
Overall Number of Participants Analyzed	3	2	3	3	2	3	0
Mean (Standard Deviation); Unit of Measure: hours
	62.14 (17.88)	151.8 (129.2)	86.11 (24.08)	45.85 (18.83)	141.9 (61.51)	142.2 (55.04)

8. Primary Outcome

Title	Accumulation Ratio After Multiple Doses of Gilteritinib
Description	Plasma samples were used for pharmacokinetic assessments.
Time Frame	Cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose

Outcome Measure Data

Analysis Population Description

The analysis population was the PKAS with available data.

Arm/Group Title	Gilteritinib 20 mg in Escalation Phase	Gilteritinib 40 mg in Escalation Phase	Gilteritinib 80 mg in Escalation Phase	Gilteritinib 120 mg in Escalation Phase	Gilteritinib 200 mg in Escalation Phase	Gilteritinib 300 mg in Escalation Phase	Gilteritinib 450 mg in Escalation Phase
Arm/Group Description:	Participants received a single dose of 20 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.	Participants received a single dose of 40 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.	Participants received a single dose of 80 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.	Participants received a single dose of 120 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.	Participants received a single dose of 200 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.	Participants received a single dose of 300 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.	Participants received a single dose of 450 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in in the escalation phase of the study.28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.
Overall Number of Participants Analyzed	3	2	3	3	2	3	0
Mean (Standard Deviation); Unit of Measure: ratio
	4.259 (1.069)	9.640 (7.754)	5.693 (1.442)	3.290 (1.118)	9.041 (3.693)	9.057 (3.303)

9. Secondary Outcome

Title	Percentage of Participants With Complete Remission (CR) During the First 2 Cycles
Description	CR was defined according to modified Cheson criteria (2003), using centrally evaluated myeloblast counts from bone marrow aspirate/biopsy assessments and centrally evaluated hematology results; if neither central bone marrow aspirate nor biopsy was available, myeloblast was imputed with locally evaluated bone marrow aspirate/biopsy assessments (derived response). Participants were classified as being in CR when they had bone marrow regenerating normal hematopoietic cells, achieved a morphologic leukemia-free state, had an absolute neutrophil count (ANC) > 1 x 10^9/L, platelet count ≥ 100 x 10^9/L, normal marrow differential with < 5% blasts, had been red blood cell (RBC) and platelet transfusion independent (defined as 1 week without RBC transfusion and 1 week without platelet transfusion), had no presence of Auer rods and no evidence of extramedullary leukemia, and blast counts in peripheral blood had been ≤ 2%. Exact 95% confidence interval was estimated using binomial distribution.
Time Frame	During the first 2 cycles (56 days)

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) - consisted of all participants who were enrolled, took at least 1 dose of study drug and who had at least 1 posttreatment data point. Re-enrolled participants and participants from one site due to concerns with this site's GCP compliance were excluded. Participants were summarized under planned reporting groups in the FAS.

Arm/Group Title		Gilteritinib 20 mg	Gilteritinib 40 mg	Gilteritinib 80 mg	Gilteritinib 120 mg	Gilteritinib 200 mg	Gilteritinib 300 mg	Gilteritinib 450 mg
Arm/Group Description:		Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Overall Number of Participants Analyzed		16	16	24	70	100	20	3
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
FLT3 Mutation Positive	Number Analyzed	14 participants	8 participants	12 participants	56 participants	89 participants	10 participants	2 participants
		0 [1]; (NA to NA)	0 [1]; (NA to NA)	8.3; (0.2 to 38.5)	3.6; (0.4 to 12.3)	3.4; (0.7 to 9.5)	10; (0.3 to 44.5)	0 [1]; (NA to NA)
FLT3 Mutation Negative	Number Analyzed	2 participants	8 participants	12 participants	14 participants	11 participants	10 participants	1 participants
		50.0; (1.3 to 98.7)	0 [1]; (NA to NA)	0 [1]; (NA to NA)	0 [1]; (NA to NA)	0 [1]; (NA to NA)	0 [1]; (NA to NA)	0 [1]; (NA to NA)
All Participants	Number Analyzed	16 participants	16 participants	24 participants	70 participants	100 participants	20 participants	3 participants
		6.3; (0.2 to 30.2)	0 [1]; (NA to NA)	4.2; (0.1 to 21.1)	2.9; (0.3 to 9.9)	3.0; (0.6 to 8.5)	5.0; (0.1 to 24.9)	0 [1]; (NA to NA)

[1]

Data could not be calculated due to the low number of events.

10. Secondary Outcome

Title	Percentage of Participants With CR During Treatment
Description	CR was defined according to modified Cheson criteria (2003), using centrally evaluated myeloblast counts from bone marrow aspirate/biopsy assessments and centrally evaluated hematology results; if neither central bone marrow aspirate nor biopsy was available, myeloblast was imputed with locally evaluated bone marrow aspirate/biopsy assessments (derived response). Participants were classified as being in CR when they had bone marrow regenerating normal hematopoietic cells, achieved a morphologic leukemia-free state, had an absolute neutrophil count (ANC) > 1 x 10^9/L, platelet count ≥ 100 x 10^9/L, normal marrow differential with < 5% blasts, had been red blood cell (RBC) and platelet transfusion independent (defined as 1 week without RBC transfusion and 1 week without platelet transfusion), had no presence of Auer rods and no evidence of extramedullary leukemia, and blast counts in peripheral blood had been ≤ 2%. Exact 95% confidence interval was estimated using binomial distribution.
Time Frame	Up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

Outcome Measure Data

Analysis Population Description

The analysis population was the FAS.

Arm/Group Title		Gilteritinib 20 mg	Gilteritinib 40 mg	Gilteritinib 80 mg	Gilteritinib 120 mg	Gilteritinib 200 mg	Gilteritinib 300 mg	Gilteritinib 450 mg
Arm/Group Description:		Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Overall Number of Participants Analyzed		16	16	24	70	100	20	3
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
FLT3 Mutation Positive	Number Analyzed	14 participants	8 participants	12 participants	56 participants	89 participants	10 participants	2 participants
		0 [1]; (NA to NA)	0 [1]; (NA to NA)	16.7; (2.1 to 48.4)	12.5; (5.2 to 24.1)	11.2; (5.5 to 19.7)	10.0; (0.3 to 44.5)	0 [1]; (NA to NA)
FLT3 Mutation Negative	Number Analyzed	2 participants	8 participants	12 participants	14 participants	11 participants	10 participants	1 participants
		50.0; (1.3 to 98.7)	0 [1]; (NA to NA)	0 [1]; (NA to NA)	0 [1]; (NA to NA)	0 [1]; (NA to NA)	0 [1]; (NA to NA)	0 [1]; (NA to NA)
All Participants	Number Analyzed	16 participants	16 participants	24 participants	70 participants	100 participants	20 participants	3 participants
		6.3; (0.2 to 30.2)	0 [1]; (NA to NA)	8.3; (1.0 to 27.0)	10.0; (4.1 to 19.5)	10.0; (4.9 to 17.6)	5.0; (0.1 to 54.9)	0 [1]; (NA to NA)

[1]

Data could not be calculated due to the low number of events.

11. Secondary Outcome

Title	Percentage of Participants With CR With Incomplete Platelet Recovery (CRp)
Description	CRp was defined according to modified Cheson criteria (2003), using centrally evaluated myeloblast counts from bone marrow aspirate/biopsy assessments and centrally evaluated hematology results; if neither central bone marrow aspirate nor biopsy was available, myeloblast was imputed with locally evaluated bone marrow aspirate/biopsy assessments (derived response). Participants were classified as being in CRp when they achieved CR except for incomplete platelet recovery (< 100 x 10^9/L). Exact 95% confidence interval was estimated using the binomial distribution.
Time Frame	Up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

Outcome Measure Data

Analysis Population Description

The analysis population was the FAS.

Arm/Group Title		Gilteritinib 20 mg	Gilteritinib 40 mg	Gilteritinib 80 mg	Gilteritinib 120 mg	Gilteritinib 200 mg	Gilteritinib 300 mg	Gilteritinib 450 mg
Arm/Group Description:		Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Overall Number of Participants Analyzed		16	16	24	70	100	20	3
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
FLT3 Mutation Positive	Number Analyzed	14 participants	8 participants	12 participants	56 participants	89 participants	10 participants	2 participants
		0 [1]; (NA to NA)	0 [1]; (NA to NA)	0 [1]; (NA to NA)	3.6; (0.4 to 12.3)	9.0; (4.0 to 16.9)	10.0; (0.3 to 44.5)	0 [1]; (NA to NA)
FLT3 Mutation Negative	Number Analyzed	2 participants	8 participants	12 participants	14 participants	11 participants	10 participants	1 participants
		0 [1]; (NA to NA)	0 [1]; (NA to NA)	0 [1]; (NA to NA)	0 [1]; (NA to NA)	0 [1]; (NA to NA)	0 [1]; (NA to NA)	0 [1]; (NA to NA)
All Participants	Number Analyzed	16 participants	16 participants	24 participants	70 participants	100 participants	20 participants	3 participants
		0 [1]; (NA to NA)	0 [1]; (NA to NA)	0 [1]; (NA to NA)	2.9; (0.3 to 9.9)	8.0; (3.5 to 15.2)	5.0; (0.1 to 24.9)	0 [1]; (NA to NA)

[1]

Data could not be calculated due to the low number of events.

12. Secondary Outcome

Title	Percentage of Participants With CR With Incomplete Hematological Recovery (CRi)
Description	CRi was defined according to modified Cheson criteria (2003), using centrally evaluated myeloblast counts from bone marrow aspirate/biopsy assessments and centrally evaluated hematology results; if neither central bone marrow aspirate nor biopsy was available, myeloblast was imputed with locally evaluated bone marrow aspirate/biopsy assessments (derived response). Participants were classified as being in CRi when they fulfilled all the criteria for CR except for incomplete hematological recovery with residual neutropenia < 1 x 10^9/L with or without complete platelet recovery. RBC and platelet transfusion independence were not required. Exact 95% confidence interval was estimated using the binomial distribution.
Time Frame	Up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

Outcome Measure Data

Analysis Population Description

The analysis population was the FAS.

Arm/Group Title		Gilteritinib 20 mg	Gilteritinib 40 mg	Gilteritinib 80 mg	Gilteritinib 120 mg	Gilteritinib 200 mg	Gilteritinib 300 mg	Gilteritinib 450 mg
Arm/Group Description:		Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Overall Number of Participants Analyzed		16	16	24	70	100	20	3
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
FLT3 Mutation Positive	Number Analyzed	14 participants	8 participants	12 participants	56 participants	89 participants	10 participants	2 participants
		7.1; (0.2 to 33.9)	0 [1]; (NA to NA)	25.0; (5.5 to 57.2)	30.4; (18.8 to 44.1)	20.2; (12.4 to 30.1)	10.0; (0.3 to 44.5)	0 [1]; (NA to NA)
FLT3 Mutation Negative	Number Analyzed	2 participants	8 participants	12 participants	14 participants	11 participants	10 participants	1 participants
		0 [1]; (NA to NA)	0 [1]; (NA to NA)	16.7; (2.1 to 48.4)	7.1; (0.2 to 33.9)	9.1; (0.2 to 41.3)	0 [1]; (NA to NA)	0 [1]; (NA to NA)
All Participants	Number Analyzed	16 participants	16 participants	24 participants	70 participants	100 participants	20 participants	3 participants
		6.3; (0.2 to 30.2)	0 [1]; (NA to NA)	20.8; (7.1 to 42.2)	25.7; (16.0 to 37.6)	19.0; (11.8 to 28.1)	5.0; (0.1 to 24.9)	0 [1]; (NA to NA)

[1]

Data could not be calculated due to the low number of events.

13. Secondary Outcome

Title	Percentage of Participants With Complete Remission With Partial Hematologic Recovery (CRh)
Description	CRh was defined according to modified Cheson criteria (2003), using centrally evaluated myeloblast counts from bone marrow aspirate/biopsy assessments and centrally evaluated hematology results; if neither central bone marrow aspirate nor biopsy was available, myeloblast was imputed with locally evaluated bone marrow aspirate/biopsy assessments (derived response). Participants were classified as being in CRh when they could not be classified as being in CR and had bone marrow blasts < 5% and partial hematologic recovery ANC >= 0.5 x 10^9/L and platelets >= 50 x 10^9/L. There should not be evidence of extramedullary leukemia. Exact 95% confidence interval was estimated using the binomial distribution. CRh was calculated only for participants who were FLT3 mutation positive.
Time Frame	Up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

Outcome Measure Data

Analysis Population Description

The analysis population was the FAS, with participants who were FLT3 mutation positive.

Arm/Group Title	Gilteritinib 20 mg	Gilteritinib 40 mg	Gilteritinib 80 mg	Gilteritinib 120 mg	Gilteritinib 200 mg	Gilteritinib 300 mg	Gilteritinib 450 mg
Arm/Group Description:	Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Overall Number of Participants Analyzed	14	8	12	56	89	10	2
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	7.1; (0.2 to 33.9)	0; (0 to 0)	8.3; (0.2 to 38.5)	10.7; (4.0 to 21.9)	7.9; (3.2 to 15.5)	20.0; (2.5 to 55.6)	0; (0 to 0)

14. Secondary Outcome

Title	Percentage of Participants With Composite CR (CRc)
Description	CRc was defined according to modified Cheson criteria (2003), using centrally evaluated myeloblast counts from bone marrow aspirate/biopsy assessments and centrally evaluated hematology results; if neither central bone marrow aspirate nor biopsy was available, myeloblast was imputed with locally evaluated bone marrow aspirate/biopsy assessments (derived response). Participants were classified as being in CRc when they had achieved either CR, complete remission with incomplete platelet recovery (CRp, defined as had achieved CR except for incomplete platelet recovery (< 100 x 10^9/L) or complete remission with incomplete hematologic recovery (CRi, defined as had fulfilled all the criteria for CR except for incomplete hematological recovery with residual neutropenia < 1 x 10^9/L with or without complete platelet recovery; RBC platelet transfusion independence not required). Exact 95% confidence interval was estimated using the binomial distribution.
Time Frame	Up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

Outcome Measure Data

Analysis Population Description

The analysis population was the FAS.

Arm/Group Title		Gilteritinib 20 mg	Gilteritinib 40 mg	Gilteritinib 80 mg	Gilteritinib 120 mg	Gilteritinib 200 mg	Gilteritinib 300 mg	Gilteritinib 450 mg
Arm/Group Description:		Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Overall Number of Participants Analyzed		16	16	24	70	100	20	3
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
FLT3 Mutation Positive	Number Analyzed	14 participants	8 participants	12 participants	56 participants	89 participants	10 participants	2 participants
		7.1; (0.2 to 33.9)	0 [1]; (NA to NA)	41.7; (15.2 to 72.3)	46.4; (33.0 to 60.3)	40.4; (30.2 to 51.4)	30.0; (6.7 to 65.2)	0 [1]; (NA to NA)
FLT3 Mutation Negative	Number Analyzed	2 participants	8 participants	12 participants	14 participants	11 participants	10 participants	1 participants
		50.0; (1.3 to 98.7)	0 [1]; (NA to NA)	16.7; (2.1 to 48.4)	7.1; (0.2 to 33.9)	9.1; (0.2 to 41.3)	0 [1]; (NA to NA)	0 [1]; (NA to NA)
All Participants	Number Analyzed	16 participants	16 participants	24 participants	70 participants	100 participants	20 participants	3 participants
		12.5; (1.6 to 38.3)	0 [1]; (NA to NA)	29.2; (12.6 to 51.1)	38.6; (27.2 to 51.0)	37.0; (27.6 to 47.2)	15.0; (3.2 to 37.9)	0 [1]; (NA to NA)

[1]

Data could not be calculated due to the low number of events.

15. Secondary Outcome

Title	Percentage of Participants With Partial Remission (PR)
Description	PR was defined according to modified Cheson criteria (2003), using centrally evaluated myeloblast counts from bone marrow aspirate/biopsy assessments and centrally evaluated hematology results; if neither central bone marrow aspirate nor biopsy was available, myeloblast was imputed with locally evaluated bone marrow aspirate/biopsy assessments (derived response). Participants were classified as being in PR when they had bone marrow regenerating normal hematopoietic cells with evidence of peripheral recovery with no (or only a few regenerating) circulating blasts and with a decrease of at least 50% in the percentage of blasts in the bone marrow aspirate with the total marrow blasts between 5% and 25%. A value of less or equal than 5% blasts was also considered a PR if Auer rods were present. There should be no evidence of extramedullary leukemia. Exact 95% confidence interval was estimated using the binomial distribution.
Time Frame	Up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

Outcome Measure Data

Analysis Population Description

The analysis population was the FAS.

Arm/Group Title		Gilteritinib 20 mg	Gilteritinib 40 mg	Gilteritinib 80 mg	Gilteritinib 120 mg	Gilteritinib 200 mg	Gilteritinib 300 mg	Gilteritinib 450 mg
Arm/Group Description:		Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Overall Number of Participants Analyzed		16	16	24	70	100	20	3
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
FLT3 Mutation Positive	Number Analyzed	14 participants	8 participants	12 participants	56 participants	89 participants	10 participants	2 participants
		7.1; (0.2 to 33.9)	37.5; (8.5 to 75.5)	25.0; (5.5 to 57.2)	7.1; (2.0 to 17.3)	7.9; (3.2 to 15.5)	30.0; (6.7 to 65.2)	50.0; (1.3 to 98.7)
FLT3 Mutation Negative	Number Analyzed	2 participants	8 participants	12 participants	14 participants	11 participants	10 participants	1 participants
		0 [1]; (NA to NA)	0 [1]; (NA to NA)	0 [1]; (NA to NA)	7.1; (0.2 to 33.9)	9.1; (0.2 to 41.3)	0 [1]; (NA to NA)	0 [1]; (NA to NA)
All Participants	Number Analyzed	16 participants	16 participants	24 participants	70 participants	100 participants	20 participants	3 participants
		6.3; (0.2 to 30.2)	18.8; (4.0 to 45.6)	12.5; (2.7 to 32.4)	7.1; (2.4 to 15.9)	8.0; (3.5 to 15.2)	15.0; (3.2 to 37.9)	33.3; (0.8 to 90.6)

[1]

Data could not be calculated due to the low number of events.

16. Secondary Outcome

Title	Percentage of Participants With Best Response
Description	Best response was defined according to modified Cheson criteria (2003), using centrally evaluated myeloblast counts from bone marrow aspirate/biopsy assessments and centrally evaluated hematology results; if neither central bone marrow aspirate nor biopsy was available, myeloblast was imputed with locally evaluated bone marrow aspirate/biopsy assessments (derived response). BR was defined as the best measured response for all visits (in the order of CR, CRp, CRi, and PR) post-treatment. Participants who achieved the best response of CR, CRp, CRi or PR were classified as responders. Participants who did not achieve at least PR were considered as non-responders. Exact 95% confidence interval was estimated using the binomial distribution.
Time Frame	Up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

Outcome Measure Data

Analysis Population Description

The analysis population was the FAS.

Arm/Group Title		Gilteritinib 20 mg	Gilteritinib 40 mg	Gilteritinib 80 mg	Gilteritinib 120 mg	Gilteritinib 200 mg	Gilteritinib 300 mg	Gilteritinib 450 mg
Arm/Group Description:		Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Overall Number of Participants Analyzed		16	16	24	70	100	20	3
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
FLT3 Mutation Positive	Number Analyzed	14 participants	8 participants	12 participants	56 participants	89 participants	10 participants	2 participants
		14.3; (1.8 to 42.8)	37.5; (8.5 to 75.5)	66.7; (34.9 to 90.1)	53.6; (39.7 to 67.0)	48.3; (37.6 to 59.2)	60.0; (26.2 to 87.8)	50.0; (1.3 to 98.7)
FLT3 Mutation Negative	Number Analyzed	2 participants	8 participants	12 participants	14 participants	11 participants	10 participants	1 participants
		50.0; (1.3 to 98.7)	0 [1]; (NA to NA)	16.7; (2.1 to 48.4)	14.3; (1.8 to 42.8)	18.2; (2.3 to 51.8)	0 [1]; (NA to NA)	0 [1]; (NA to NA)
All Participants	Number Analyzed	16 participants	16 participants	24 participants	70 participants	100 participants	20 participants	3 participants
		18.8; (4.0 to 45.6)	18.8; (4.0 to 45.6)	41.7; (22.1 to 63.4)	45.7; (33.7 to 58.1)	45.0; (35.0 to 55.3)	30.0; (11.9 to 54.3)	33.3; (0.8 to 90.6)

[1]

Data could not be calculated due to the low number of events.

17. Secondary Outcome

Title	Percentage of Participants With Complete Remission and Complete Remission With Partial Hematologic Recovery (CR/CRh)
Description	Participants with CR/CRh were defined as participants who achieved either CR or CRh. Participants with CR had bone marrow regenerating normal hematopoietic cells, achieved a morphologic leukemia-free state, had an ANC > 1 x 10^9/L, platelet count ≥ 100 x 10^9/L, and normal marrow differential with < 5% blasts, had been RBC and platelet transfusion independent (defined as 1 week without RBC transfusion and 1 week without platelet transfusion). Also, there had been no presence of Auer rods, no evidence of extramedullary leukemia, and blast counts in peripheral blood had been ≤ 2%. Participants with CRh could not be classified as being in CR and had bone marrow blasts < 5%, partial hematologic recovery ANC >= 0.5 x 10^9/L and platelets >= 50 x 10^9/L. There should not be evidence of extramedullary leukemia. Exact 95% confidence interval was estimated using the binomial distribution. CR/CRh was calculated only for participants who were FLT3 mutation positive.
Time Frame	Up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

Outcome Measure Data

Analysis Population Description

The analysis population was the FAS, with participants who were FLT3 mutation positive.

Arm/Group Title	Gilteritinib 20 mg	Gilteritinib 40 mg	Gilteritinib 80 mg	Gilteritinib 120 mg	Gilteritinib 200 mg	Gilteritinib 300 mg	Gilteritinib 450 mg
Arm/Group Description:	Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Overall Number of Participants Analyzed	14	8	12	56	89	10	2
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	7.1; (0.2 to 33.9)	0 [1]; (NA to NA)	25.0; (5.5 to 57.2)	23.2; (13.0 to 36.4)	19.1; (11.5 to 28.8)	30.0; (6.7 to 65.2)	0 [1]; (NA to NA)

[1]

Data could not be calculated due to the low number of events.

18. Secondary Outcome

Title	Duration of CR (DCR)
Description	DCR was defined as the time from the date of first CR until the date of documented relapse for participants who achieved CR. Participants who died without report of relapse were considered non-events and censored at their last relapse-free disease assessment date. Other participants who did not relapse on study were considered non-events and censored at the last relapse-free disease assessment date. DCR was calculated using Kaplan-Meier method and therefore data are estimated.
Time Frame	From date of remission until end of study (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

Outcome Measure Data

Analysis Population Description

The analysis population was the FAS. Only participants who achieved CR were included in the analysis.

Arm/Group Title		Gilteritinib 20 mg	Gilteritinib 40 mg	Gilteritinib 80 mg	Gilteritinib 120 mg	Gilteritinib 200 mg	Gilteritinib 300 mg	Gilteritinib 450 mg
Arm/Group Description:		Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Overall Number of Participants Analyzed		1	0	2	7	10	1	0
Median (95% Confidence Interval); Unit of Measure: days
FLT3 Mutation Positive	Number Analyzed	0 participants	0 participants	2 participants	7 participants	10 participants	1 participants	0 participants
				NA [1]; (NA to NA)	NA [1]; (86.0 to NA)	419.0 [1]; (64.0 to NA)	NA [1]; (NA to NA)
FLT3 Mutation Negative	Number Analyzed	1 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants
		NA [1]; (NA to NA)
All Participants	Number Analyzed	1 participants	0 participants	2 participants	7 participants	10 participants	1 participants	0 participants
		NA [1]; (NA to NA)		NA [1]; (NA to NA)	NA [1]; (86.0 to NA)	419.0 [1]; (64.0 to NA)	NA [1]; (NA to NA)

[1]

Data could not be calculated due to the low number of events.

19. Secondary Outcome

Title	Duration of CRp (DCRp)
Description	DCRp was defined as the time from the date of first CRp until the date of documented relapse for participants who achieved CRp. Participants who died without report of relapse were considered non-events and censored at their last relapse-free disease assessment date. Other participants who did not relapse on study were considered non-events and censored at the last relapse-free disease assessment date. DCRp was calculated using Kaplan-Meier method and therefore data are estimated.
Time Frame	From date of remission until end of study (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

Outcome Measure Data

Analysis Population Description

The analysis population was the FAS. Only participants who achieved CRp were included in the analysis.

Arm/Group Title		Gilteritinib 20 mg	Gilteritinib 40 mg	Gilteritinib 80 mg	Gilteritinib 120 mg	Gilteritinib 200 mg	Gilteritinib 300 mg	Gilteritinib 450 mg
Arm/Group Description:		Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Overall Number of Participants Analyzed		0	0	1	6	12	2	0
Median (95% Confidence Interval); Unit of Measure: days
FLT3 Mutation Positive	Number Analyzed	0 participants	0 participants	1 participants	6 participants	12 participants	2 participants	0 participants
				NA [1]; (NA to NA)	NA [1]; (57.0 to NA)	450.0 [1]; (43.0 to NA)	NA [1]; (NA to NA)
FLT3 Mutation Negative	Number Analyzed	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants
All Participants	Number Analyzed	0 participants	0 participants	1 participants	6 participants	12 participants	2 participants	0 participants
				NA [1]; (NA to NA)	NA [1]; (57.0 to NA)	450.0 [1]; (43.0 to NA)	NA [1]; (NA to NA)

[1]

Data could not be calculated due to the low number of events.

20. Secondary Outcome

Title	Duration of CRi (DCRi)
Description	DCRi was defined as the time from the date of first CRi until the date of documented relapse for participants who achieved CRi. Participants who died without report of relapse and participants who did not relapse were considered non-events and censored at the last relapse-free disease assessment date. DCRi was calculated using Kaplan-Meier method and therefore data are estimated.
Time Frame	From date of remission until end of study (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

Outcome Measure Data

Analysis Population Description

The analysis population was the FAS. Only participants who achieved CRi were included in the analysis.

Arm/Group Title		Gilteritinib 20 mg	Gilteritinib 40 mg	Gilteritinib 80 mg	Gilteritinib 120 mg	Gilteritinib 200 mg	Gilteritinib 300 mg	Gilteritinib 450 mg
Arm/Group Description:		Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Overall Number of Participants Analyzed		1	0	7	24	31	1	0
Median (95% Confidence Interval); Unit of Measure: days
FLT3 Mutation Positive	Number Analyzed	1 participants	0 participants	5 participants	23 participants	30 participants	1 participants	0 participants
		NA [1]; (NA to NA)		NA [1]; (79.0 to NA)	120.0; (56.0 to 383.0)	191.0; (57.0 to 420.0)	NA [1]; (NA to NA)
FLT3 Mutation Negative	Number Analyzed	0 participants	0 participants	2 participants	1 participants	0 participants	0 participants	0 participants
				41.0; (22.0 to 60.0)	99.0 [1]; (NA to NA)
All Participants	Number Analyzed	1 participants	0 participants	7 participants	24 participants	31 participants	1 participants	0 participants
		NA [1]; (NA to NA)		79.0 [1]; (22.0 to NA)	120.0; (58.0 to 383.0)	191.0; (57.0 to 420.0)	NA [1]; (NA to NA)

[1]

Data could not be calculated due to the low number of events.

21. Secondary Outcome

Title	Duration of CRh (DCRh)
Description	DCRh was defined as the time from the date of first CRh until the date of documented relapse for participants who achieved CRh but did not have a best response of CR. Participants who died without report of relapse and participants who did not relapse were considered non-events and censored at the last relapse-free disease assessment date. DCRh was calculated using Kaplan-Meier method and therefore data are estimated. DCRh was calculated only for participants who were FLT3 mutation positive.
Time Frame	From date of remission until end of study (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

Outcome Measure Data

Analysis Population Description

The analysis population was the FAS. Only participants who achieved CRh were included in the analysis.

Arm/Group Title	Gilteritinib 20 mg	Gilteritinib 40 mg	Gilteritinib 80 mg	Gilteritinib 120 mg	Gilteritinib 200 mg	Gilteritinib 300 mg	Gilteritinib 450 mg
Arm/Group Description:	Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Overall Number of Participants Analyzed	1	0	1	6	7	2	0
Median (95% Confidence Interval); Unit of Measure: days
	NA [1]; (NA to NA)		NA [1]; (NA to NA)	64.0; (18.0 to 85.0)	101.0 [1]; (29.0 to NA)	NA [1]; (NA to NA)

[1]

Data could not be calculated due to the low number of events.

22. Secondary Outcome

Title	Duration of CRc (DCRc)
Description	DCRc was defined as the time from the date of first CRc until the date of documented relapse for participants who achieved CRc. Participants who died without report of relapse and participants who did not relapse were considered non-events and censored at the last relapse-free disease assessment date. DCRc was calculated using Kaplan-Meier method and therefore data are estimated.
Time Frame	From date of remission until end of study (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

Outcome Measure Data

Analysis Population Description

The analysis population was the FAS. Only participants who achieved CRc were included in the analysis.

Arm/Group Title		Gilteritinib 20 mg	Gilteritinib 40 mg	Gilteritinib 80 mg	Gilteritinib 120 mg	Gilteritinib 200 mg	Gilteritinib 300 mg	Gilteritinib 450 mg
Arm/Group Description:		Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Overall Number of Participants Analyzed		2	0	7	27	37	3	0
Median (95% Confidence Interval); Unit of Measure: days
FLT3 Mutation Positive	Number Analyzed	1 participants	0 participants	5 participants	26 participants	36 participants	3 participants	0 participants
		NA [1]; (NA to NA)		NA [1]; (79.0 to NA)	98.0; (57.0 to 307.0)	191.0; (101.0 to 465.0)	NA [1]; (NA to NA)
FLT3 Mutation Negative	Number Analyzed	1 participants	0 participants	2 participants	1 participants	1 participants	0 participants	0 participants
		NA [1]; (NA to NA)		41.0; (22.0 to 60.0)	99.0 [1]; (NA to NA)	NA [1]; (NA to NA)
All Participants	Number Analyzed	2 participants	0 participants	7 participants	27 participants	37 participants	3 participants	0 participants
		NA [1]; (NA to NA)		79.0 [1]; (22.0 to NA)	99.0; (58.0 to 307.0)	191.0; (101.0 to 465.0)	NA [1]; (NA to NA)

[1]

Data could not be calculated due to the low number of events.

23. Secondary Outcome

Title	Duration of CR/CRh (DCRCRh)
Description	DCRCRh was defined as the time from the date of first DCRCRh until the date of documented relapse for participants who achieved CR or CRh. For participants who achieved both CR and CRh, the first CR date or CRh date, whichever occurred first, was used. Participants who died without report of relapse and participants who did not relapse were considered non-events and censored at the last relapse-free disease assessment date. DCRCRh was calculated using Kaplan-Meier method and therefore data are estimated. DCRCRh was calculated only for participants who were FLT3 mutation positive.
Time Frame	From date of remission until end of study (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

Outcome Measure Data

Analysis Population Description

The analysis population was the FAS. Only participants who achieved CR or CRh were included in the analysis.

Arm/Group Title	Gilteritinib 20 mg	Gilteritinib 40 mg	Gilteritinib 80 mg	Gilteritinib 120 mg	Gilteritinib 200 mg	Gilteritinib 300 mg	Gilteritinib 450 mg
Arm/Group Description:	Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Overall Number of Participants Analyzed	1	0	3	13	17	3	0
Median (95% Confidence Interval); Unit of Measure: days
	NA [1]; (NA to NA)		NA [1]; (NA to NA)	307.0 [1]; (56.0 to NA)	308.0 [1]; (101.0 to NA)	NA [1]; (NA to NA)

[1]

Data could not be calculated due to the low number of events.

24. Secondary Outcome

Title	Duration of Response
Description	Duration of response was defined as the time from the date of either first CRc or PR until the date of documented relapse of any type for participants who achieved CRc or PR. Participants who died without report of relapse were considered non-events and censored at their last relapse-free disease assessment date. Other participants who did not relapse on study are considered non-events and censored at the last relapse-free assessment date. Duration of response was calculated using Kaplan-Meier method and therefore data are estimated.
Time Frame	From date of remission until end of study (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

Outcome Measure Data

Analysis Population Description

The analysis population was the FAS. Only participants who achieved CRc or PR were included in the analysis.

Arm/Group Title		Gilteritinib 20 mg	Gilteritinib 40 mg	Gilteritinib 80 mg	Gilteritinib 120 mg	Gilteritinib 200 mg	Gilteritinib 300 mg	Gilteritinib 450 mg
Arm/Group Description:		Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Overall Number of Participants Analyzed		3	3	10	32	45	6	1
Median (95% Confidence Interval); Unit of Measure: days
FLT3 Mutation Positive	Number Analyzed	2 participants	3 participants	8 participants	30 participants	43 participants	6 participants	1 participants
		NA [1]; (NA to NA)	NA [1]; (NA to NA)	88.0 [1]; (9.0 to NA)	141.0; (58.0 to 383.0)	220.0; (111.0 to 482.0)	59.0; (15.0 to 59.0)	NA [1]; (NA to NA)
FLT3 Mutation Negative	Number Analyzed	1 participants	0 participants	2 participants	2 participants	2 participants	0 participants	0 participants
		NA [1]; (NA to NA)		41.0; (22.0 to 60.0)	109.5; (99.0 to 120.0)	85.0 [1]; (NA to NA)
All Participants	Number Analyzed	3 participants	3 participants	10 participants	32 participants	45 participants	6 participants	1 participants
		NA [1]; (NA to NA)	NA [1]; (NA to NA)	79.0 [1]; (9.0 to NA)	126.0; (58.0 to 307.0)	220.0; (85.0 to 482.0)	59.0; (15.0 to 59.0)	NA [1]; (NA to NA)

[1]

Data could not be calculated due to the low number of events.

25. Secondary Outcome

Title	Time to CR (TTCR)
Description	TTCR was defined as the time from the first dose of study drug until the date of first CR.
Time Frame	From first dose of study drug up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

Outcome Measure Data

Analysis Population Description

The analysis population was the FAS. Only participants who achieved CR were included in the analysis.

Arm/Group Title		Gilteritinib 20 mg	Gilteritinib 40 mg	Gilteritinib 80 mg	Gilteritinib 120 mg	Gilteritinib 200 mg	Gilteritinib 300 mg	Gilteritinib 450 mg
Arm/Group Description:		Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Overall Number of Participants Analyzed		1	0	2	7	10	1	0
Median (Full Range); Unit of Measure: days
FLT3 Mutation Positive	Number Analyzed	0 participants	0 participants	2 participants	7 participants	10 participants	1 participants	0 participants
				171.5; (28 to 315)	141.0; (29 to 364)	93.0; (27 to 225)	56.0; (56 to 56)
FLT3 Mutation Negative	Number Analyzed	1 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants
		30.0; (30 to 30)
All Participants	Number Analyzed	1 participants	0 participants	2 participants	7 participants	10 participants	1 participants	0 participants
		30.0; (30 to 30)		171.5; (28 to 315)	141.0; (29 to 364)	93.0; (27 to 225)	56.0; (56 to 56)

26. Secondary Outcome

Title	Time to CRp (TTCRp)
Description	TTCRp was defined as the time from the first dose of study drug until the date of first CRp. TTCRp was evaluated for participants who achieved CRp.
Time Frame	From first dose of study drug up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

Outcome Measure Data

Analysis Population Description

The analysis population was the FAS. Only participants who achieved CRp were included in the analysis.

Arm/Group Title		Gilteritinib 20 mg	Gilteritinib 40 mg	Gilteritinib 80 mg	Gilteritinib 120 mg	Gilteritinib 200 mg	Gilteritinib 300 mg	Gilteritinib 450 mg
Arm/Group Description:		Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Overall Number of Participants Analyzed		0	0	1	6	12	2	0
Median (Full Range); Unit of Measure: days
FLT3 Mutation Positive	Number Analyzed	0 participants	0 participants	1 participants	6 participants	12 participants	2 participants	0 participants
				140.0; (140 to 140)	195.0; (30 to 418)	84.5; (28 to 392)	29.0; (28 to 30)
FLT3 Mutation Negative	Number Analyzed	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants
All Participants	Number Analyzed	0 participants	0 participants	1 participants	6 participants	12 participants	2 participants	0 participants
				140.0; (140 to 140)	195.0; (30 to 418)	84.5; (28 to 392)	29.0; (28 to 30)

27. Secondary Outcome

Title	Time to CRi (TTCRi)
Description	TTCRi was defined as the time from the first dose of study drug until the date of first CRi. TTCRi was evaluated for participants who achieved CRi.
Time Frame	From first dose of study drug up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

Outcome Measure Data

Analysis Population Description

The analysis population was the FAS. Only participants who achieved CRi were included in the analysis.

Arm/Group Title		Gilteritinib 20 mg	Gilteritinib 40 mg	Gilteritinib 80 mg	Gilteritinib 120 mg	Gilteritinib 200 mg	Gilteritinib 300 mg	Gilteritinib 450 mg
Arm/Group Description:		Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Overall Number of Participants Analyzed		1	0	7	24	31	1	0
Median (Full Range); Unit of Measure: days
FLT3 Mutation Positive	Number Analyzed	1 participants	0 participants	5 participants	23 participants	30 participants	1 participants	0 participants
		57.0; (57 to 57)		57.0; (31 to 70)	57.0; (26 to 170)	39.5; (26 to 133)	28.0; (28 to 28)
FLT3 Mutation Negative	Number Analyzed	0 participants	0 participants	2 participants	1 participants	1 participants	0 participants	0 participants
				71.5; (71 to 72)	30.0; (30 to 30)	30.0; (30 to 30)
All Participants	Number Analyzed	1 participants	0 participants	7 participants	24 participants	31 participants	1 participants	0 participants
		57.0; (57 to 57)		64.0; (31 to 72)	43.5; (26 to 170)	35.0; (26 to 133)	28.0; (28 to 28)

28. Secondary Outcome

Title	Time to First CR/CRh (TTFCRCRh)
Description	TTFCRCRh was defined as the time from the first dose of study drug until the date of first either CR or CRh. TTFCRCRh was evaluated for participants who achieved CR or CRh. For participants who achieve both CR and CRh, the first CR date or CRh date, whichever occurs first was used. TTFCRCRh was calculated only for participants who were FLT3 mutation positive.
Time Frame	From first dose of study drug up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

Outcome Measure Data

Analysis Population Description

The analysis population was the FAS. Only participants who achieved CR or CRh were included in the analysis.

Arm/Group Title	Gilteritinib 20 mg	Gilteritinib 40 mg	Gilteritinib 80 mg	Gilteritinib 120 mg	Gilteritinib 200 mg	Gilteritinib 300 mg	Gilteritinib 450 mg
Arm/Group Description:	Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Overall Number of Participants Analyzed	1	0	3	13	17	3	0
Median (Full Range); Unit of Measure: days
	57.0; (57 to 57)		57.0; (28 to 140)	59.0; (29 to 280)	57.0; (27 to 245)	28.0; (28 to 30)

29. Secondary Outcome

Title	Time to Best CR/CRh (TTBCRCRh)
Description	TTBCRCRh was defined as the time from the first dose of study drug until the first date that the best response of CR or CRh was achieved. TTBCRCRh was evaluated for participants who achieved CR or CRh. For participants who achieve both CR and CRh, the first CR date was used. TTBCRCRh was calculated only for participants who were FLT3 mutation positive.
Time Frame	From first dose of study drug up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

Outcome Measure Data

Analysis Population Description

The analysis population was the FAS. Participants who achieved CR or CRh were included in the analysis.

Arm/Group Title	Gilteritinib 20 mg	Gilteritinib 40 mg	Gilteritinib 80 mg	Gilteritinib 120 mg	Gilteritinib 200 mg	Gilteritinib 300 mg	Gilteritinib 450 mg
Arm/Group Description:	Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Overall Number of Participants Analyzed	1	0	3	13	17	3	0
Median (Full Range); Unit of Measure: days
	57.0; (57 to 57)		57.0; (28 to 315)	63.0; (29 to 364)	88.0; (27 to 245)	30.0; (28 to 56)

30. Secondary Outcome

Title	Time to CRc (TTCRc)
Description	TTCRc was defined as the time from the first dose of study drug until the date of first CRc. TTCRc was evaluated for participants who achieved CRc.
Time Frame	From first dose of study drug up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

Outcome Measure Data

Analysis Population Description

The analysis population was the FAS. Only participants who achieved CRc were included in the analysis.

Arm/Group Title		Gilteritinib 20 mg	Gilteritinib 40 mg	Gilteritinib 80 mg	Gilteritinib 120 mg	Gilteritinib 200 mg	Gilteritinib 300 mg	Gilteritinib 450 mg
Arm/Group Description:		Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Overall Number of Participants Analyzed		2	0	7	27	37	3	0
Median (Full Range); Unit of Measure: days
FLT3 Mutation Positive	Number Analyzed	1 participants	0 participants	5 participants	26 participants	36 participants	3 participants	0 participants
		57.0; (57 to 57)		56.0; (28 to 64)	30.0; (26 to 211)	31.5; (26 to 197)	28.0; (28 to 30)
FLT3 Mutation Negative	Number Analyzed	1 participants	0 participants	2 participants	1 participants	1 participants	0 participants	0 participants
		30.0; (30 to 30)		71.5; (71 to 72)	30.0; (30 to 30)	30.0; (30 to 30)
All Participants	Number Analyzed	2 participants	0 participants	7 participants	27 participants	37 participants	3 participants	0 participants
		43.5; (30 to 57)		57.0; (28 to 72)	30.0; (26 to 211)	31.0; (26 to 197)	28.0; (28 to 30)

31. Secondary Outcome

Title	Time to Response (TTR)
Description	TTR was defined as the time from the first dose of study drug until the date of either first CRc or PR. TTR was evaluated for participants who achieved CRc or PR.
Time Frame	From first dose of study drug up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

Outcome Measure Data

Analysis Population Description

The analysis population was the FAS. Only participants who achieved CRc or PR were included in the analysis.

Arm/Group Title		Gilteritinib 20 mg	Gilteritinib 40 mg	Gilteritinib 80 mg	Gilteritinib 120 mg	Gilteritinib 200 mg	Gilteritinib 300 mg	Gilteritinib 450 mg
Arm/Group Description:		Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Overall Number of Participants Analyzed		3	3	10	32	45	6	1
Median (Full Range); Unit of Measure: days
FLT3 Mutation Positive	Number Analyzed	2 participants	3 participants	8 participants	30 participants	43 participants	6 participants	1 participants
		61.5; (29 to 94)	57.0; (31 to 64)	31.0; (28 to 59)	29.0; (26 to 211)	29.0; (26 to 197)	28.0; (26 to 61)	31.0; (31 to 31)
FLT3 Mutation Negative	Number Analyzed	1 participants	0 participants	2 participants	2 participants	2 participants	0 participants	0 participants
		30.0; (30 to 30)		71.5; (71 to 72)	29.5; (29 to 30)	29.5; (29 to 30)
All Participants	Number Analyzed	3 participants	3 participants	10 participants	32 participants	45 participants	6 participants	1 participants
		30.0; (29 to 94)	57.0; (31 to 64)	43.5; (28 to 72)	29.0; (26 to 211)	29.0; (26 to 197)	28.0; (26 to 61)	31.0; (31 to 31)

32. Secondary Outcome

Title	Time to Best Response (TTBR)
Description	TTBR was defined as the time from the first dose of study drug until the first disease assessment date when participant achieved best response. TTBR was evaluated in participants who achieved best response of CR, CRp, CRi, or PR.
Time Frame	From first dose of study drug up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

Outcome Measure Data

Analysis Population Description

The analysis population was the FAS. Only participants who achieved CR, CRp, CRi, or PR were included in the analysis.

Arm/Group Title		Gilteritinib 20 mg	Gilteritinib 40 mg	Gilteritinib 80 mg	Gilteritinib 120 mg	Gilteritinib 200 mg	Gilteritinib 300 mg	Gilteritinib 450 mg
Arm/Group Description:		Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Overall Number of Participants Analyzed		3	3	10	32	45	6	1
Median (Full Range); Unit of Measure: days
FLT3 Mutation Positive	Number Analyzed	2 participants	3 participants	8 participants	30 participants	43 participants	6 participants	1 participants
		75.5; (57 to 94)	57.0; (31 to 64)	44.0; (28 to 315)	43.5; (26 to 364)	57.0; (26 to 245)	29.0; (26 to 61)	31.0; (31 to 31)
FLT3 Mutation Negative	Number Analyzed	1 participants	0 participants	2 participants	2 participants	2 participants	0 participants	0 participants
		30.0; (30 to 30)		71.5; (71 to 72)	29.5; (29 to 30)	29.5; (29 to 30)
All Participants	Number Analyzed	3 participants	3 participants	10 participants	32 participants	45 participants	6 participants	1 participants
		57.0; (30 to 94)	57.0; (31 to 64)	58.0; (28 to 315)	30.0; (26 to 364)	56.0; (26 to 245)	29.0; (26 to 61)	31.0; (31 to 31)

33. Secondary Outcome

Title	Overall Survival (OS)
Description	The time from the date of first dose of study drug until the date of death from any cause. For a participant who was not known to have died by the end of study follow-up, OS was censored at the date of last contact. OS was calculated using Kaplan-Meier method and therefore data are estimated.
Time Frame	From first dose of study drug up to end of study (median time on study was 157.0 days, minimum of 5 days and maximum of 1320 days)

Outcome Measure Data

Analysis Population Description

The analysis population was the FAS.

Arm/Group Title		Gilteritinib 20 mg	Gilteritinib 40 mg	Gilteritinib 80 mg	Gilteritinib 120 mg	Gilteritinib 200 mg	Gilteritinib 300 mg	Gilteritinib 450 mg
Arm/Group Description:		Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Overall Number of Participants Analyzed		16	16	24	70	100	20	3
Median (95% Confidence Interval); Unit of Measure: days
FLT3 Mutation Positive	Number Analyzed	14 participants	8 participants	12 participants	56 participants	89 participants	10 participants	2 participants
		123.0; (17.0 to 267.0)	199.5; (56.0 to 905.0)	197.5; (61.0 to 329.0)	246.0; (190.0 to 309.0)	214.0; (126.0 to 264.0)	157.0; (20.0 to 218.0)	204.0; (51.0 to 357.0)
FLT3 Mutation Negative	Number Analyzed	2 participants	8 participants	12 participants	14 participants	11 participants	10 participants	1 participants
		NA [1]; (227.0 to NA)	71.5; (5.0 to 180.0)	136.0; (14.0 to 314.0)	144.0; (83.0 to 195.0)	67.0; (21.0 to 336.0)	68.0; (8.0 to 249.0)	89.0 [1]; (NA to NA)
All Participants	Number Analyzed	16 participants	16 participants	24 participants	70 participants	100 participants	20 participants	3 participants
		149.5; (31.0 to 267.0)	95.0; (55.0 to 195.0)	154.0; (74.0 to 299.0)	216.0; (161.0 to 285.0)	176.0; (124.0 to 253.0)	128.5; (36.0 to 199.0)	89.0; (51.0 to 357.0)

[1]

Data could not be calculated due to the low number of events.

34. Secondary Outcome

Title	Event Free Survival (EFS)
Description	EFS was defined as the time from the date of first dose of study drug until the date of documented relapse, treatment failure or death from any cause, whichever occurred first. For a participant with none of these events, EFS was censored at the date of last relapse-free disease assessment. A participant without post-treatment disease assessment was censored at randomization date. Treatment failure included those participants who discontinued the treatment due to "progressive disease" or "lack of efficacy" without a previous response of CR, CRp, CRi or PR. Treatment failure date referred to the start of new anti-leukemia therapy or the last treatment evaluation date when new anti-leukemia therapy date was not available. For participants who were censored, last relapse-free disease assessment date referred to the participant's last disease assessment date. EFS was calculated using Kaplan-Meier method and therefore data are estimated.
Time Frame	From first dose of study drug up to end of study (median time on study was 157.0 days, minimum of 5 days and maximum of 1320 days)

Outcome Measure Data

Analysis Population Description

The analysis population was the FAS.

Arm/Group Title		Gilteritinib 20 mg	Gilteritinib 40 mg	Gilteritinib 80 mg	Gilteritinib 120 mg	Gilteritinib 200 mg	Gilteritinib 300 mg	Gilteritinib 450 mg
Arm/Group Description:		Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Overall Number of Participants Analyzed		16	16	24	70	100	20	3
Median (95% Confidence Interval); Unit of Measure: days
FLT3 Mutation Positive	Number Analyzed	14 participants	8 participants	12 participants	56 participants	89 participants	10 participants	2 participants
		52.0; (14.0 to 88.0)	109.0; (29.0 to 357.0)	93.5; (61.0 to 127.0)	112.0; (92.0 to 143.0)	121.0; (92.0 to 155.0)	85.0; (11.0 to 157.0)	86.0; (51.0 to 121.0)
FLT3 Mutation Negative	Number Analyzed	2 participants	8 participants	12 participants	14 participants	11 participants	10 participants	1 participants
		58.0 [1]; (NA to NA)	39.0; (5.0 to 67.0)	74.0; (12.0 to 131.0)	85.5; (37.0 to 126.0)	45.0; (21.0 to 113.0)	43.0; (8.0 to 83.0)	71.0 [1]; (NA to NA)
All Participants	Number Analyzed	16 participants	16 participants	24 participants	70 participants	100 participants	20 participants	3 participants
		58.0; (19.0 to 88.0)	55.5; (38.0 to 92.0)	76.0; (61.0 to 119.0)	108.0; (90.0 to 126.0)	118.0; (88.0 to 140.0)	65.0; (20.0 to 100.0)	71.0; (51.0 to 121.0)

[1]

Data could not be calculated due to the low number of events.

35. Secondary Outcome

Title	Leukemia Free Survival (LFS)
Description	LFS was defined as the time from the date of first CRc until the date of documented relapse or death for participants who achieved CRc. For a participant who was not known to have relapsed or died, LFS was censored on the date of last relapse-free disease assessment date. LFS was calculated using Kaplan-Meier method and therefore data are estimated.
Time Frame	From first dose of study drug up to end of study (median time on study was 157.0 days, minimum of 5 days and maximum of 1320 days)

Outcome Measure Data

Analysis Population Description

The analysis population was the FAS. Only participants who achieved CRc were included in the analysis.

Arm/Group Title		Gilteritinib 20 mg	Gilteritinib 40 mg	Gilteritinib 80 mg	Gilteritinib 120 mg	Gilteritinib 200 mg	Gilteritinib 300 mg	Gilteritinib 450 mg
Arm/Group Description:		Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Overall Number of Participants Analyzed		2	0	7	27	37	3	0
Median (95% Confidence Interval); Unit of Measure: days
FLT3 Mutation Positive	Number Analyzed	1 participants	0 participants	5 participants	26 participants	36 participants	3 participants	0 participants
		242.0 [1]; (NA to NA)		98.0; (56.0 to 1126.0)	98.0; (58.0 to 187.0)	146.0; (47.0 to 247.0)	296.0; (130.0 to 462.0)
FLT3 Mutation Negative	Number Analyzed	1 participants	0 participants	2 participants	1 participants	1 participants	0 participants	0 participants
		NA [1]; (NA to NA)		41.0; (22.0 to 60.0)	99.0 [1]; (NA to NA)	38.0 [1]; (NA to NA)
All Participants	Number Analyzed	2 participants	0 participants	7 participants	27 participants	37 participants	3 participants	0 participants
		242.0 [1]; (NA to NA)		79.0; (22.0 to 1126.0)	98.0; (58.0 to 187.0)	146.0; (45.0 to 247.0)	296.0; (130.0 to 462.0)

[1]

Data could not be calculated due to the low number of events.

36. Secondary Outcome

Title	Percentage of Participants Who Achieved Transfusion Conversion
Description	Participants who achieved transfusion conversion were defined as the number of participants who were transfusion dependent at baseline period but became transfusion independent at post-baseline period divided by the total number of participants who were transfusion dependent at baseline period. Participants were considered baseline transfusion dependent if there were RBC or platelet transfusions within the baseline period. Participants were considered post-baseline transfusion independent if they were on treatment >=84 days, and if there was one consecutive 56 days without any RBC or platelet transfusion within post-baseline period. If participants were on treatment >28 days but <84 days, and there was no RBC or platelet transfusion within post-baseline period, or on treatment <=28 days, post-baseline transfusion status was not evaluable. Exact 95% confidence interval was estimated using the binomial distribution.
Time Frame	Baseline (28 days prior to first dose until 28 days after the first dose) and postbaseline (from 29 days after first dose date until last dose date); median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days

Outcome Measure Data

Analysis Population Description

The analysis population was the FAS. Participants who were transfusion dependent at baseline and had evaluable post-baseline transfusion status were included in the analysis.

Arm/Group Title		Gilteritinib 20 mg	Gilteritinib 40 mg	Gilteritinib 80 mg	Gilteritinib 120 mg	Gilteritinib 200 mg	Gilteritinib 300 mg	Gilteritinib 450 mg
Arm/Group Description:		Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Overall Number of Participants Analyzed		7	8	16	49	63	8	2
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
FLT3 Mutation Positive	Number Analyzed	6 participants	5 participants	8 participants	40 participants	57 participants	4 participants	1 participants
		0 [1]; (NA to NA)	0 [1]; (NA to NA)	37.5; (8.5 to 75.5)	27.5; (14.6 to 43.9)	40.4; (27.6 to 54.2)	NA [1]; (NA to NA)	NA [1]; (NA to NA)
FLT3 Mutation Negative	Number Analyzed	1 participants	3 participants	8 participants	9 participants	6 participants	4 participants	1 participants
		NA [1]; (NA to NA)	NA [1]; (NA to NA)	12.5; (0.3 to 52.7)	22.2; (2.8 to 60.0)	33.3; (4.3 to 77.7)	NA [1]; (NA to NA)	NA [1]; (NA to NA)
All Participants	Number Analyzed	7 participants	8 participants	16 participants	49 participants	63 participants	8 participants	2 participants
		NA [1]; (NA to NA)	NA [1]; (NA to NA)	25.0; (7.3 to 52.4)	26.5; (14.9 to 41.1)	39.7; (27.6 to 52.8)	NA [1]; (NA to NA)	NA [1]; (NA to NA)

[1]

No data could be calculated due to the low number of participants who had evaluable transfusion status postbaseline.

37. Secondary Outcome

Title	Percentage of Participants Who Achieved Transfusion Maintenance
Description	Participants who achieved transfusion maintenance were defined as the number of participants who were transfusion independent at baseline period and still maintained transfusion independent at post-baseline period divided by the total number of participants who were transfusion independent at baseline period.
Time Frame	Baseline (28 days prior to first dose until 28 days after the first dose) and postbaseline (from 29 days after first dose date until last dose date); median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days

Outcome Measure Data

Analysis Population Description

The analysis population was the FAS. Participants who were transfusion independent at baseline and had evaluable post-baseline transfusion status were included in the analysis.

Arm/Group Title		Gilteritinib 20 mg	Gilteritinib 40 mg	Gilteritinib 80 mg	Gilteritinib 120 mg	Gilteritinib 200 mg	Gilteritinib 300 mg	Gilteritinib 450 mg
Arm/Group Description:		Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.	Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation.
Overall Number of Participants Analyzed		0	0	1	7	10	0	1
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
FLT3 Mutation Positive	Number Analyzed	0 participants	0 participants	1 participants	4 participants	10 participants	0 participants	1 participants
				100.0; (2.5 to 100)	75.0; (19.4 to 99.4)	80.0; (44.4 to 97.5)		100.0; (2.5 to 100.0)
FLT3 Mutation Negative	Number Analyzed	0 participants	0 participants	0 participants	3 participants	0 participants	0 participants	0 participants
					33.3; (0.8 to 90.6)
All Participants	Number Analyzed	0 participants	0 participants	1 participants	7 participants	10 participants	0 participants	1 participants
				100.0; (2.5 to 100.0)	57.1; (18.4 to 90.1)	80.0; (44.4 to 97.5)		100.0; (2.5 to 100.0)

38. Secondary Outcome

Title	AUC24 of Gilteritinib in Co-administration With Voriconazole
Description	Plasma samples were used for pharmacokinetic assessments.
Time Frame	Cycle 1 Day 15 and Cycle 2 Day 1: predose, 0.5, 1, 2, 4, 6, 24 hours postdose (gilteritinib)

Outcome Measure Data

Analysis Population Description

The analysis population was the PKAS, with participants administered 20 mg gilteritinib and voriconazole.

Arm/Group Title	Gilteritinib 20 mg in Expansion Phase
Arm/Group Description:	Participants received 20 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. Starting on day 16 of cycle 1, participants also received 200 mg voriconazole orally every 12 hours through day 1 of cycle 2.
Overall Number of Participants Analyzed	1
Mean (Standard Deviation); Unit of Measure: ng*h/mL
	919.3 [1] (NA)

[1]

SD could not be calculated due to a sample size of 1.

39. Secondary Outcome

Title	Cmax of Gilteritinib in Co-administration With Voriconazole
Description	Plasma samples were used for pharmacokinetic assessments.
Time Frame	Cycle 1 Day 15 and Cycle 2 Day 1: predose, 0.5, 1, 2, 4, 6, 24 hours postdose (gilteritinib)

Outcome Measure Data

Analysis Population Description

The analysis population was the PKAS, with participants administered 20 mg gilteritinib and voriconazole.

Arm/Group Title	Gilteritinib 20 mg in Expansion Phase
Arm/Group Description:	Participants received 20 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. Starting on day 16 of cycle 1, participants also received 200 mg voriconazole orally every 12 hours through day 1 of cycle 2.
Overall Number of Participants Analyzed	1
Mean (Standard Deviation); Unit of Measure: ng/mL
	63.79 [1] (NA)

[1]

SD could not be calculated due to a sample size of 1.

40. Secondary Outcome

Title	AUClast of Gilteritinib in Co-administration With Voriconazole
Description	Plasma samples were used for pharmacokinetic assessments.
Time Frame	Cycle 1 Day 15 and Cycle 2 Day 1: predose, 0.5, 1, 2, 4, 6, 24 hours postdose (gilteritinib)

Outcome Measure Data

Analysis Population Description

The analysis population was the PKAS, with participants administered 20 mg gilteritinib and voriconazole.

Arm/Group Title	Gilteritinib 20 mg in Expansion Phase
Arm/Group Description:	Participants received 20 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. Starting on day 16 of cycle 1, participants also received 200 mg voriconazole orally every 12 hours through day 1 of cycle 2.
Overall Number of Participants Analyzed	1
Mean (Standard Deviation); Unit of Measure: ng*h/mL
	919.3 [1] (NA)

[1]

SD could not be calculated due to a sample size of 1.

41. Secondary Outcome

Title	Tmax of Gilteritinib in Co-administration With Voriconazole
Description	Plasma samples were used for pharmacokinetic assessments.
Time Frame	Cycle 1 Day 15 and Cycle 2 Day 1: predose, 0.5, 1, 2, 4, 6, 24 hours postdose (gilteritinib)

Outcome Measure Data

Analysis Population Description

The analysis population was the PKAS, with participants administered 20 mg gilteritinib and voriconazole.

Arm/Group Title	Gilteritinib 20 mg in Expansion Phase
Arm/Group Description:	Participants received 20 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. Starting on day 16 of cycle 1, participants also received 200 mg voriconazole orally every 12 hours through day 1 of cycle 2.
Overall Number of Participants Analyzed	1
Median (Full Range); Unit of Measure: hours
	2.08; (2.08 to 2.08)

42. Secondary Outcome

Title	AUC24 of Midazolam Administered With and Without Gilteritinib
Description	Plasma samples were used for pharmacokinetic assessments.
Time Frame	Day -1 and cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose (midazolam)

Outcome Measure Data

Analysis Population Description

The analysis population was the PKAS, with participants administered 300 mg gilteritinib and midazolam.

Arm/Group Title		Gilteritinib 300 mg in Expansion Phase
Arm/Group Description:		Participants received 300 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. On day -1 and day 15 of cycle 1, participants also received 2 mg midazolam as a single oral dose.
Overall Number of Participants Analyzed		17
Mean (Standard Deviation); Unit of Measure: ng*h/mL
Midazolam Alone (Day -1)	Number Analyzed	15 participants
		66.55 (57.70)
Midazolam + Gilteritinib (Cycle 1 Day 15)	Number Analyzed	8 participants
		81.56 (65.84)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gilteritinib 300 mg in Expansion Phase
	Comments	Statistical Comparison of Midazolam Exposure after Administration of Midazolam Alone or Coadministered with Gilteritinib: The difference of least squares (LS) means of log-transformed pharmacokinetic parameters between midazolam alone and midazolam + gilteritinib and its 90% CI are backtransformed to the raw scale and are expressed as percent.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Geometric LS Mean Ratio
	Estimated Value	109.46
	Confidence Interval	(2-Sided) 90%; 49.82 to 240.48
	Estimation Comments	[Not Specified]

43. Secondary Outcome

Title	AUC24 of Metabolite 1-Hydroxymidazolam After Administration of Midazolam With and Without Gilteritinib
Description	Plasma samples were used for pharmacokinetic assessments.
Time Frame	Day -1 and cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose (midazolam)

Outcome Measure Data

Analysis Population Description

The analysis population was the PKAS, with participants administered 300 mg gilteritinib and midazolam.

Arm/Group Title		Gilteritinib 300 mg in Expansion Phase
Arm/Group Description:		Participants received 300 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. On day -1 and day 15 of cycle 1, participants also received 2 mg midazolam as a single oral dose.
Overall Number of Participants Analyzed		17
Mean (Standard Deviation); Unit of Measure: ng*h/mL
Midazolam Alone (Day -1)	Number Analyzed	15 participants
		20.44 (24.80)
Midazolam + Gilteritinib (Cycle 1 Day 15)	Number Analyzed	8 participants
		23.10 (21.64)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gilteritinib 300 mg in Expansion Phase
	Comments	Statistical Comparison of Midazolam Exposure after Administration of Midazolam Alone or Coadministered with Gilteritinib: The difference of LS means of log-transformed pharmacokinetic parameters between 1-hydroxymidazolam alone and 1-hydroxymidazolam + gilteritinib and its 90% CI are backtransformed to the raw scale and are expressed as percent.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Geometric LS Mean Ratio
	Estimated Value	149.90
	Confidence Interval	90%; 74.88 to 300.06
	Estimation Comments	[Not Specified]

44. Secondary Outcome

Title	Cmax of Midazolam Administered With and Without Gilteritinib
Description	Plasma samples were used for pharmacokinetic assessments.
Time Frame	Day -1 and cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose (midazolam)

Outcome Measure Data

Analysis Population Description

The analysis population was the PKAS, with participants administered 300 mg gilteritinib and midazolam.

Arm/Group Title		Gilteritinib 300 mg in Expansion Phase
Arm/Group Description:		Participants received 300 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. On day -1 and day 15 of cycle 1, participants also received 2 mg midazolam as a single oral dose.
Overall Number of Participants Analyzed		17
Mean (Standard Deviation); Unit of Measure: ng/mL
Midazolam Alone (Day -1)	Number Analyzed	16 participants
		14.68 (8.923)
Midazolam + Gilteritinib (Cycle 1 Day 15)	Number Analyzed	9 participants
		18.45 (9.452)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gilteritinib 300 mg in Expansion Phase
	Comments	Statistical Comparison of Midazolam Exposure after Administration of Midazolam Alone or Coadministered with Gilteritinib: The difference of LS means of log-transformed pharmacokinetic parameters between midazolam alone and midazolam + gilteritinib and its 90% CI are backtransformed to the raw scale and are expressed as percent.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Geometric LS Mean Ratio
	Estimated Value	111.64
	Confidence Interval	(2-Sided) 90%; 69.54 to 179.25
	Estimation Comments	[Not Specified]

45. Secondary Outcome

Title	Cmax of 1-Hydroxymidazolam After Administration of Midazolam With and Without Gilteritinib
Description	Plasma samples were used for pharmacokinetic assessments.
Time Frame	Day -1 and cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose (midazolam)

Outcome Measure Data

Analysis Population Description

The analysis population was the PKAS, with participants administered 300 mg gilteritinib and midazolam.

Arm/Group Title		Gilteritinib 300 mg in Expansion Phase
Arm/Group Description:		Participants received 300 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. On day -1 and day 15 of cycle 1, participants also received 2 mg midazolam as a single oral dose.
Overall Number of Participants Analyzed		17
Mean (Standard Deviation); Unit of Measure: ng/mL
Midazolam Alone (Day -1)	Number Analyzed	16 participants
		4.562 (2.858)
Midazolam + Gilteritinib (Cycle 1 Day 15)	Number Analyzed	9 participants
		5.053 (3.158)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gilteritinib 300 mg in Expansion Phase
	Comments	Statistical Comparison of Midazolam Exposure after Administration of Midazolam Alone or Coadministered with Gilteritinib: The difference of LS means of log-transformed pharmacokinetic parameters between 1-hydroxymidazolam/midazolam alone and 1-hydroxymidazolam/midazolam + gilteritinib and its 90% CI are backtransformed to the raw scale and are expressed as percent.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Geometric LS Mean Ratio
	Estimated Value	123.47
	Confidence Interval	(2-Sided) 90%; 72.41 to 210.52
	Estimation Comments	[Not Specified]

46. Secondary Outcome

Title	AUClast of Midazolam Administered With and Without Gilteritinib
Description	Plasma samples were used for pharmacokinetic assessments.
Time Frame	Day -1 and cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose (midazolam)

Outcome Measure Data

Analysis Population Description

The analysis population was the PKAS, with participants administered 300 mg gilteritinib and midazolam.

Arm/Group Title		Gilteritinib 300 mg in Expansion Phase
Arm/Group Description:		Participants received 300 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. On day -1 and day 15 of cycle 1, participants also received 2 mg midazolam as a single oral dose.
Overall Number of Participants Analyzed		17
Mean (Standard Deviation); Unit of Measure: ng*h/mL
Midazolam Alone (Day -1)	Number Analyzed	16 participants
		59.48 (59.49)
Midazolam + Gilteritinib (Cycle 1 Day 15)	Number Analyzed	9 participants
		82.44 (64.25)

47. Secondary Outcome

Title	AUClast of 1-Hydroxymidazolam After Administration of Midazolam With and Without Gilteritinib
Description	Plasma samples were used for pharmacokinetic assessments.
Time Frame	Day -1 and cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose (midazolam)

Outcome Measure Data

Analysis Population Description

The analysis population was the PKAS, with participants administered 300 mg gilteritinib and midazolam.

Arm/Group Title		Gilteritinib 300 mg in Expansion Phase
Arm/Group Description:		Participants received 300 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. On day -1 and day 15 of cycle 1, participants also received 2 mg midazolam as a single oral dose.
Overall Number of Participants Analyzed		17
Mean (Standard Deviation); Unit of Measure: ng*h/mL
Midazolam Alone (Day -1)	Number Analyzed	16 participants
		17.05 (24.70)
Midazolam + Gilteritinib (Cycle 1 Day 15)	Number Analyzed	9 participants
		23.58 (22.07)

48. Secondary Outcome

Title	Tmax of Midazolam Administered With and Without Gilteritinib
Description	Plasma samples were used for pharmacokinetic assessments.
Time Frame	Day -1 and cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose (midazolam)

Outcome Measure Data

Analysis Population Description

The analysis population was the PKAS, with participants administered 300 mg gilteritinib and midazolam.

Arm/Group Title		Gilteritinib 300 mg in Expansion Phase
Arm/Group Description:		Participants received 300 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. On day -1 and day 15 of cycle 1, participants also received 2 mg midazolam as a single oral dose.
Overall Number of Participants Analyzed		17
Median (Full Range); Unit of Measure: hours
Midazolam Alone (Day -1)	Number Analyzed	16 participants
		0.5000; (0.367 to 2.00)
Midazolam + Gilteritinib (Cycle 1 Day 15)	Number Analyzed	9 participants
		1.00; (0.317 to 4.13)

49. Secondary Outcome

Title	Tmax of 1-Hydroxymidazolam After Administration of Midazolam With and Without Gilteritinib
Description	Plasma samples were used for pharmacokinetic assessments.
Time Frame	Day -1 and cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose (midazolam)

Outcome Measure Data

Analysis Population Description

The analysis population was the PKAS, with participants administered 300 mg gilteritinib and midazolam.

Arm/Group Title		Gilteritinib 300 mg in Expansion Phase
Arm/Group Description:		Participants received 300 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. On day -1 and day 15 of cycle 1, participants also received 2 mg midazolam as a single oral dose.
Overall Number of Participants Analyzed		17
Median (Full Range); Unit of Measure: hours
Midazolam Alone (Day -1)	Number Analyzed	16 participants
		0.5583; (0.483 to 2.00)
Midazolam + Gilteritinib (Cycle 1 Day 15)	Number Analyzed	9 participants
		1.00; (0.317 to 4.13)

50. Secondary Outcome

Title	Area Under the Concentration-time Curve From the Time of Dosing Extrapolated to Time Infinity (AUCinf) of Cephalexin Administered With and Without Gilteritinib
Description	Plasma samples were used for pharmacokinetic assessments.
Time Frame	Day -1 and cycle 1 day 15: predose, 0.5, 1, 1.5, 2, 3, 4, 6, 24 hours postdose (cephalexin)

Outcome Measure Data

Analysis Population Description

The analysis population was the PKAS, with participants administered 200 mg gilteritinib and cephalexin.

Arm/Group Title		Gilteritinib 200 mg in Expansion Phase
Arm/Group Description:		Participants received 200 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. On day -1 and day 15 of cycle 1, certain participants also received 500 mg cephalexin as a single oral dose.
Overall Number of Participants Analyzed		100
Mean (Standard Deviation); Unit of Measure: ng*h/mL
Cephalexin Alone (Day -1)	Number Analyzed	18 participants
		57650 (20386)
Cephalexin + Gilteritinib (Cycle 1 Day 15)	Number Analyzed	13 participants
		51873 (18819)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gilteritinib 200 mg in Expansion Phase
	Comments	Statistical Assessment of the Effect of Gilteritinib on Cephalexin Pharmacokinetics after Administration of Cephalexin Alone or Coadministered with Gilteritinib: The difference of LS means of log-transformed pharmacokinetic parameters between cephalexin alone and cephalexin + gilteritinib and its 90% CI are backtransformed to the raw scale and are expressed as percent.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Geometric LS Mean Ratio
	Estimated Value	93.96
	Confidence Interval	(2-Sided) 90%; 75.29 to 117.26
	Estimation Comments	[Not Specified]

51. Secondary Outcome

Title	Cmax of Cephalexin Administered With and Without Gilteritinib
Description	Plasma samples were used for pharmacokinetic assessments.
Time Frame	Day -1 and cycle 1 day 15: predose, 0.5, 1, 1.5, 2, 3, 4, 6, 24 hours postdose (cephalexin)

Outcome Measure Data

Analysis Population Description

The analysis population was the PKAS, with participants administered 200 mg gilteritinib and cephalexin.

Arm/Group Title		Gilteritinib 200 mg in Expansion Phase
Arm/Group Description:		Participants received 200 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. On day -1 and day 15 of cycle 1, certain participants also received 500 mg cephalexin as a single oral dose.
Overall Number of Participants Analyzed		100
Mean (Standard Deviation); Unit of Measure: ng/mL
Cephalexin Alone (Day -1)	Number Analyzed	20 participants
		17688 (6680)
Cephalexin + Gilteritinib (Cycle 1 day 15)	Number Analyzed	16 participants
		16075 (4606)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gilteritinib 200 mg in Expansion Phase
	Comments	Statistical Assessment of the Effect of Gilteritinib on Cephalexin Pharmacokinetics after Administration of Cephalexin Alone or Coadministered with Gilteritinib: The difference of LS means of log-transformed pharmacokinetic parameters between cephalexin alone and cephalexin + gilteritinib and its 90% CI are backtransformed to the raw scale and are expressed as percent.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Geometric LS Mean Ratio
	Estimated Value	91.46
	Confidence Interval	(2-Sided) 90%; 74.60 to 112.12
	Estimation Comments	[Not Specified]

52. Secondary Outcome

Title	AUClast of Cephalexin Administered With and Without Gilteritinib
Description	Plasma samples were used for pharmacokinetic assessments.
Time Frame	Day -1 and cycle 1 day 15: predose, 0.5, 1, 1.5, 2, 3, 4, 6, 24 hours postdose (cephalexin)

Outcome Measure Data

Analysis Population Description

The analysis population was the PKAS, with participants administered 200 mg gilteritinib and cephalexin.

Arm/Group Title		Gilteritinib 200 mg in Expansion Phase
Arm/Group Description:		Participants received 200 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. On day -1 and day 15 of cycle 1, certain participants also received 500 mg cephalexin as a single oral dose.
Overall Number of Participants Analyzed		100
Mean (Standard Deviation); Unit of Measure: ng*h/mL
Cephalexin Alone (Day -1)	Number Analyzed	20 participants
		53183 (26877)
Cephalexin + Gilteritinib (Cycle 1 Day 15)	Number Analyzed	16 participants
		54963 (29531)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gilteritinib 200 mg in Expansion Phase
	Comments	Statistical Assessment of the Effect of Gilteritinib on Cephalexin Pharmacokinetics after Administration of Cephalexin Alone or Coadministered with Gilteritinib: The difference of LS means of log-transformed pharmacokinetic parameters between cephalexin alone and cephalexin + gilteritinib and its 90% CI are backtransformed to the raw scale and are expressed as percent.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Geometric LS Mean Ratio
	Estimated Value	97.71
	Confidence Interval	(2-Sided) 90%; 74.19 to 128.70
	Estimation Comments	[Not Specified]

53. Secondary Outcome

Title	Tmax of Cephalexin Administered With and Without Gilteritinib
Description	Plasma samples were used for pharmacokinetic assessments.
Time Frame	Day -1 and cycle 1 day 15: predose, 0.5, 1, 1.5, 2, 3, 4, 6, 24 hours postdose (cephalexin)

Outcome Measure Data

Analysis Population Description

The analysis population was the PKAS, with participants administered 200 mg gilteritinib and cephalexin.

Arm/Group Title		Gilteritinib 200 mg in Expansion Phase
Arm/Group Description:		Participants received 200 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. On day -1 and day 15 of cycle 1, certain participants also received 500 mg cephalexin as a single oral dose.
Overall Number of Participants Analyzed		100
Median (Full Range); Unit of Measure: hours
Cephalexin Alone (Day -1)	Number Analyzed	20 participants
		1.500; (1.00 to 4.02)
Cephalexin + Gilteritinib (Cycle 1 Day 15)	Number Analyzed	16 participants
		1.483; (1.00 to 5.88)

54. Secondary Outcome

Title	T1/2 of Cephalexin Administered With and Without Gilteritinib
Description	Plasma samples were used for pharmacokinetic assessments.
Time Frame	Day -1 and cycle 1 day 15: predose, 0.5, 1, 1.5, 2, 3, 4, 6, 24 hours postdose (cephalexin)

Outcome Measure Data

Analysis Population Description

The analysis population was the PKAS, with participants administered 200 mg gilteritinib and cephalexin.

Arm/Group Title		Gilteritinib 200 mg in Expansion Phase
Arm/Group Description:		Participants received 200 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. On day -1 and day 15 of cycle 1, certain participants also received 500 mg cephalexin as a single oral dose.
Overall Number of Participants Analyzed		100
Mean (Standard Deviation); Unit of Measure: hours
Cephalexin Alone (Day -1)	Number Analyzed	18 participants
		1.822 (0.5914)
Cephalexin + Gilteritinib (Cycle 1 Day 15)	Number Analyzed	13 participants
		1.827 (0.7175)

55. Secondary Outcome

Title	Apparent Total Systemic Clearance After Single or Multiple Extravascular Dosing (CL/F) of Cephalexin Administered With and Without Gilteritinib
Description	Plasma samples were used for pharmacokinetic assessments.
Time Frame	Day -1 and cycle 1 day 15: predose, 0.5, 1, 1.5, 2, 3, 4, 6, 24 hours postdose (cephalexin)

Outcome Measure Data

Analysis Population Description

The analysis population was the PKAS, with participants administered 200 mg gilteritinib and cephalexin.

Arm/Group Title		Gilteritinib 200 mg in Expansion Phase
Arm/Group Description:		Participants received 200 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. On day -1 and day 15 of cycle 1, certain participants also received 500 mg cephalexin as a single oral dose.
Overall Number of Participants Analyzed		100
Mean (Standard Deviation); Unit of Measure: L/h
Cephalexin Alone (Day -1)	Number Analyzed	18 participants
		9.713 (3.319)
Cephalexin + Gilteritinib (Cycle 1 Day 15)	Number Analyzed	13 participants
		10.58 (2.977)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gilteritinib 200 mg in Expansion Phase
	Comments	Statistical Assessment of the Effect of Gilteritinib on Cephalexin Pharmacokinetics after Administration of Cephalexin Alone or Coadministered with Gilteritinib: The difference of LS means of log-transformed pharmacokinetic parameters between cephalexin alone and cephalexin + gilteritinib and its 90% CI are backtransformed to the raw scale and are expressed as percent.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Geometric LS Mean Ratio
	Estimated Value	106.42
	Confidence Interval	(2-Sided) 90%; 85.28 to 132.81
	Estimation Comments	[Not Specified]

56. Secondary Outcome

Title	Apparent Volume of Distribution During the Terminal Elimination Phase After Single Extravascular Dosing (Vz/F) of Cephalexin Administered With and Without Gilteritinib
Description	Plasma samples were used for pharmacokinetic assessments.
Time Frame	Day -1 and cycle 1 day 15: predose, 0.5, 1, 1.5, 2, 3, 4, 6, 24 hours postdose (cephalexin)

Outcome Measure Data

Analysis Population Description

The analysis population was the PKAS, with participants administered 200 mg gilteritinib and cephalexin.

Arm/Group Title		Gilteritinib 200 mg in Expansion Phase
Arm/Group Description:		Participants received 200 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. On day -1 and day 15 of cycle 1, certain participants also received 500 mg cephalexin as a single oral dose.
Overall Number of Participants Analyzed		100
Mean (Standard Deviation); Unit of Measure: liters
Cephalexin Alone (Day -1)	Number Analyzed	18 participants
		24.07 (7.173)
Cephalexin + Gilteritinib (Cycle 1 Day 15)	Number Analyzed	13 participants
		25.86 (5.346)

57. Secondary Outcome

Title	Amount of Drug Excreted in Urine (Aelast) of Cephalexin Administered With and Without Gilteritinib
Description	Urine samples were used for pharmacokinetic assessments.
Time Frame	Day -1 and cycle 1 day 15: 0-3 hours, 3-6 hours, 6-24 hours postdose (cephalexin)

Outcome Measure Data

Analysis Population Description

The analysis population was the PKAS, with participants administered 200 mg gilteritinib and cephalexin.

Arm/Group Title		Gilteritinib 200 mg in Expansion Phase
Arm/Group Description:		Participants received 200 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. On day -1 and day 15 of cycle 1, certain participants also received 500 mg cephalexin as a single oral dose.
Overall Number of Participants Analyzed		100
Mean (Standard Deviation); Unit of Measure: mg
Cephalexin Alone (Day -1)	Number Analyzed	13 participants
		548.9 (523.7)
Cephalexin + Gilteritinib (Cycle 1 Day 15)	Number Analyzed	10 participants
		448.8 (306.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gilteritinib 200 mg in Expansion Phase
	Comments	Statistical Assessment of the Effect of Gilteritinib on Cephalexin Pharmacokinetics after Administration of Cephalexin Alone or Coadministered with Gilteritinib: The difference of LS means of log-transformed pharmacokinetic parameters between cephalexin alone and cephalexin + gilteritinib and its 90% CI are backtransformed to the raw scale and are expressed as percent.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Geometric LS Mean Ratio
	Estimated Value	83.93
	Confidence Interval	(2-Sided) 90%; 46.53 to 151.39
	Estimation Comments	[Not Specified]

58. Secondary Outcome

Title	Fraction of Drug Excreted Into Urine in Percentage (%Ae) of Cephalexin Administered With and Without Gilteritinib
Description	Urine samples were used for pharmacokinetic assessments.
Time Frame	Day -1 and cycle 1 day 15: 0-3 hours, 3-6 hours, 6-24 hours postdose (cephalexin)

Outcome Measure Data

Analysis Population Description

The analysis population was the PKAS, with participants administered 200 mg gilteritinib and cephalexin.

Arm/Group Title		Gilteritinib 200 mg in Expansion Phase
Arm/Group Description:		Participants received 200 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. On day -1 and day 15 of cycle 1, certain participants also received 500 mg cephalexin as a single oral dose.
Overall Number of Participants Analyzed		100
Mean (Standard Deviation); Unit of Measure: percentage
Cephalexin Alone (Day -1)	Number Analyzed	13 participants
		109.8 (104.7)
Cephalexin + Gilteritinib (Cycle 1 Day 15)	Number Analyzed	10 participants
		89.75 (61.21)

59. Secondary Outcome

Title	Renal Clearance (CLr) of Cephalexin in Administered With and Without Gilteritinib
Description	Urine samples were used for pharmacokinetic assessments.
Time Frame	Day -1 and cycle 1 day 15: 0-3 hours, 3-6 hours, 6-24 hours postdose (cephalexin)

Outcome Measure Data

Analysis Population Description

The analysis population was the PKAS, with participants administered 200 mg gilteritinib and cephalexin.

Arm/Group Title		Gilteritinib 200 mg in Expansion Phase
Arm/Group Description:		Participants received 200 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. On day -1 and day 15 of cycle 1, certain participants also received 500 mg cephalexin as a single oral dose.
Overall Number of Participants Analyzed		100
Mean (Standard Deviation); Unit of Measure: L/h
Cephalexin Alone (Day -1)	Number Analyzed	13 participants
		8.784 (8.727)
Cephalexin + Gilteritinib (Cycle 1 Day 15)	Number Analyzed	6 participants
		11.04 (8.430)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gilteritinib 200 mg in Expansion Phase
	Comments	Statistical Assessment of the Effect of Gilteritinib on Cephalexin Pharmacokinetics after Administration of Cephalexin Alone or Coadministered with Gilteritinib: The difference of LS means of log-transformed pharmacokinetic parameters between cephalexin alone and cephalexin + gilteritinib and its 90% CI are backtransformed to the raw scale and are expressed as percent.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Geometric LS Mean Ratio
	Estimated Value	82.84
	Confidence Interval	(2-Sided) 90%; 40.25 to 170.48
	Estimation Comments	[Not Specified]

Adverse Events

Time Frame	From first dose of study drug up to 30 days after last dose of study drug (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)
Adverse Event Reporting Description	The total number of deaths (all causes) includes deaths reported after the time frame above.
Arm/Group Title	Gilterinib 20 mg in Escalation Phase		Gilterinib 40 mg in Escalation Phase		Gilterinib 80 mg in Escalation Phase		Gilterinib 120 mg in Escalation Phase		Gilterinib 200 mg in Escalation Phase		Gilterinib 300 mg in Escalation Phase		Gilterinib 450 mg in Escalation Phase		Gilterinib 20 mg in Expansion Phase		Gilterinib 40 mg in Expansion Phase		Gilterinib 80 mg in Expansion Phase		Gilterinib 120 mg in Expansion Phase		Gilterinib 200 mg in Expansion Phase		Gilterinib 300 mg in Expansion Phase
Arm/Group Description	Participants received a single dose of 20 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.		Participants received a single dose of 40 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.		Participants received a single dose of 80 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.		Participants received a single dose of 120 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.		Participants received a single dose of 200 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.		Participants received a single dose of 300 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.		Participants received a single dose of 450 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.		Participants received 20 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. Starting on day 16 of cycle 1, participants also received 200 mg voriconazole orally every 12 hours through day 1 of cycle 2.		Participants received 40 mg gilteritinib orally once daily starting on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study.		Participants received 80 mg gilteritinib orally once daily starting on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study.		Participants received 120 mg gilteritinib orally once daily starting on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study.		Participants received 200 mg gilteritinib orally once daily starting on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. On day -1 and day 15 of cycle 1, certain participants also received 500 mg cephalexin as a single oral dose.		Participants received 300 mg gilteritinib orally once daily starting on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. On day -1 and day 15 of cycle 1, participants also received 2 mg midazolam as a single oral dose.
All-Cause Mortality
	Gilterinib 20 mg in Escalation Phase		Gilterinib 40 mg in Escalation Phase		Gilterinib 80 mg in Escalation Phase		Gilterinib 120 mg in Escalation Phase		Gilterinib 200 mg in Escalation Phase		Gilterinib 300 mg in Escalation Phase		Gilterinib 450 mg in Escalation Phase		Gilterinib 20 mg in Expansion Phase		Gilterinib 40 mg in Expansion Phase		Gilterinib 80 mg in Expansion Phase		Gilterinib 120 mg in Expansion Phase		Gilterinib 200 mg in Expansion Phase		Gilterinib 300 mg in Expansion Phase
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	4/5 (80.00%)		2/3 (66.67%)		3/3 (100.00%)		3/3 (100.00%)		2/3 (66.67%)		3/3 (100.00%)		3/3 (100.00%)		10/12 (83.33%)		13/13 (100.00%)		21/21 (100.00%)		53/66 (80.30%)		82/100 (82.00%)		16/17 (94.12%)
Serious Adverse Events
	Gilterinib 20 mg in Escalation Phase		Gilterinib 40 mg in Escalation Phase		Gilterinib 80 mg in Escalation Phase		Gilterinib 120 mg in Escalation Phase		Gilterinib 200 mg in Escalation Phase		Gilterinib 300 mg in Escalation Phase		Gilterinib 450 mg in Escalation Phase		Gilterinib 20 mg in Expansion Phase		Gilterinib 40 mg in Expansion Phase		Gilterinib 80 mg in Expansion Phase		Gilterinib 120 mg in Expansion Phase		Gilterinib 200 mg in Expansion Phase		Gilterinib 300 mg in Expansion Phase
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/5 (40.00%)		2/3 (66.67%)		2/3 (66.67%)		1/3 (33.33%)		2/3 (66.67%)		2/3 (66.67%)		2/3 (66.67%)		8/12 (66.67%)		12/13 (92.31%)		19/21 (90.48%)		52/66 (78.79%)		92/100 (92.00%)		14/17 (82.35%)
Blood and lymphatic system disorders
Anaemia † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/12 (0.00%)	0	0/13 (0.00%)	0	1/21 (4.76%)	1	0/66 (0.00%)	0	4/100 (4.00%)	6	0/17 (0.00%)	0
Disseminated intravascular coagulation † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	1/17 (5.88%)	1
Febrile neutropenia † 1	0/5 (0.00%)	0	1/3 (33.33%)	1	1/3 (33.33%)	1	1/3 (33.33%)	1	2/3 (66.67%)	6	2/3 (66.67%)	5	0/3 (0.00%)	0	4/12 (33.33%)	6	7/13 (53.85%)	7	5/21 (23.81%)	11	18/66 (27.27%)	28	35/100 (35.00%)	58	4/17 (23.53%)	4
Haemolytic anaemia † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	1/21 (4.76%)	1	0/66 (0.00%)	0	0/100 (0.00%)	0	0/17 (0.00%)	0
Leukocytosis † 1	1/5 (20.00%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	2/66 (3.03%)	2	3/100 (3.00%)	3	1/17 (5.88%)	1
Neutropenia † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	2	2/100 (2.00%)	2	0/17 (0.00%)	0
Pancytopenia † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	2/100 (2.00%)	2	0/17 (0.00%)	0
Thrombocytopenia † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	2/100 (2.00%)	2	0/17 (0.00%)	0
Cardiac disorders
Acute myocardial infarction † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	1/21 (4.76%)	1	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Atrial fibrillation † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	3/66 (4.55%)	3	3/100 (3.00%)	4	0/17 (0.00%)	0
Atrial thrombosis † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	1	0/100 (0.00%)	0	0/17 (0.00%)	0
Atrioventricular block second degree † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	1/21 (4.76%)	1	0/66 (0.00%)	0	0/100 (0.00%)	0	0/17 (0.00%)	0
Cardiac arrest † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/12 (0.00%)	0	0/13 (0.00%)	0	1/21 (4.76%)	1	0/66 (0.00%)	0	0/100 (0.00%)	0	0/17 (0.00%)	0
Cardiac failure † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Cardiac failure congestive † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	1/21 (4.76%)	1	0/66 (0.00%)	0	2/100 (2.00%)	4	0/17 (0.00%)	0
Myocardial infarction † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Myocarditis † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	2/100 (2.00%)	2	0/17 (0.00%)	0
Pericardial effusion † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	1	1/100 (1.00%)	1	0/17 (0.00%)	0
Pericarditis † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Supraventricular tachycardia † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	1	2/100 (2.00%)	2	0/17 (0.00%)	0
Tachycardia † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	1	0/100 (0.00%)	0	0/17 (0.00%)	0
Ventricular fibrillation † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	2	0/100 (0.00%)	0	0/17 (0.00%)	0
Ventricular tachycardia † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Endocrine disorders
Diabetes insipidus † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	1	0/100 (0.00%)	0	0/17 (0.00%)	0
Eye disorders
Conjunctival oedema † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	1/21 (4.76%)	1	0/66 (0.00%)	0	0/100 (0.00%)	0	0/17 (0.00%)	0
Papilloedema † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	1	0/100 (0.00%)	0	0/17 (0.00%)	0
Gastrointestinal disorders
Colitis † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	2	0/17 (0.00%)	0
Diarrhoea † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/12 (0.00%)	0	0/13 (0.00%)	0	1/21 (4.76%)	1	5/66 (7.58%)	5	5/100 (5.00%)	5	0/17 (0.00%)	0
Dysphagia † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	0/100 (0.00%)	0	1/17 (5.88%)	1
Enteritis † 1	0/5 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	0/100 (0.00%)	0	0/17 (0.00%)	0
Enterocolitis † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	1/13 (7.69%)	1	0/21 (0.00%)	0	0/66 (0.00%)	0	0/100 (0.00%)	0	0/17 (0.00%)	0
Gastric haemorrhage † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Gastrointestinal haemorrhage † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	1/21 (4.76%)	1	2/66 (3.03%)	4	2/100 (2.00%)	4	1/17 (5.88%)	1
Haematemesis † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Haematochezia † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Intestinal obstruction † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Intestinal perforation † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Large intestinal ulcer † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Lower gastrointestinal haemorrhage † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	2/66 (3.03%)	3	0/100 (0.00%)	0	0/17 (0.00%)	0
Malabsorption † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Nausea † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	1	3/100 (3.00%)	3	0/17 (0.00%)	0
Neutropenic colitis † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	2/66 (3.03%)	3	0/100 (0.00%)	0	0/17 (0.00%)	0
Pancreatitis † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Pancreatitis acute † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Rectal haemorrhage † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Rectal tenesmus † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Small intestinal obstruction † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	1/21 (4.76%)	1	0/66 (0.00%)	0	1/100 (1.00%)	1	1/17 (5.88%)	1
Stomatitis † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Swollen tongue † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	1	0/100 (0.00%)	0	0/17 (0.00%)	0
Upper gastrointestinal haemorrhage † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	0/100 (0.00%)	0	1/17 (5.88%)	1
Vomiting † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	1/21 (4.76%)	1	2/66 (3.03%)	2	2/100 (2.00%)	2	0/17 (0.00%)	0
General disorders
Asthenia † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	1/21 (4.76%)	1	0/66 (0.00%)	0	0/100 (0.00%)	0	0/17 (0.00%)	0
Chills † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	1/21 (4.76%)	1	0/66 (0.00%)	0	0/100 (0.00%)	0	0/17 (0.00%)	0
Death † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	2/66 (3.03%)	2	1/100 (1.00%)	1	0/17 (0.00%)	0
Fatigue † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	2/66 (3.03%)	2	1/100 (1.00%)	1	0/17 (0.00%)	0
Mucosal inflammation † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	1/17 (5.88%)	1
Multiple organ dysfunction syndrome † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	1/13 (7.69%)	1	0/21 (0.00%)	0	1/66 (1.52%)	2	4/100 (4.00%)	6	0/17 (0.00%)	0
Oedema peripheral † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Pyrexia † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	1/3 (33.33%)	1	1/3 (33.33%)	1	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	9/66 (13.64%)	10	9/100 (9.00%)	13	1/17 (5.88%)	1
Sudden death † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Systemic inflammatory response syndrome † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Hepatobiliary disorders
Cholecystitis † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	0/100 (0.00%)	0	0/17 (0.00%)	0
Hepatic failure † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Hyperbilirubinaemia † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	1	2/100 (2.00%)	2	0/17 (0.00%)	0
Immune system disorders
Acute graft versus host disease † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Acute graft versus host disease in intestine † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Acute graft versus host disease in skin † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	1	3/100 (3.00%)	4	0/17 (0.00%)	0
Anaphylactic reaction † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	1	1/100 (1.00%)	1	0/17 (0.00%)	0
Chronic graft versus host disease in skin † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Graft versus host disease in skin † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	1/21 (4.76%)	1	0/66 (0.00%)	0	0/100 (0.00%)	0	0/17 (0.00%)	0
Infections and infestations
Abscess limb † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/12 (8.33%)	2	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	0/100 (0.00%)	0	0/17 (0.00%)	0
Arthritis bacterial † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	1/21 (4.76%)	2	1/66 (1.52%)	1	0/100 (0.00%)	0	0/17 (0.00%)	0
Bacteraemia † 1	1/5 (20.00%)	1	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	5/21 (23.81%)	9	2/66 (3.03%)	2	5/100 (5.00%)	7	0/17 (0.00%)	0
Bacterial infection † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	2	0/100 (0.00%)	0	0/17 (0.00%)	0
Bronchopulmonary aspergillosis † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	2	3/100 (3.00%)	4	0/17 (0.00%)	0
Cellulitis † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	4/66 (6.06%)	4	4/100 (4.00%)	4	0/17 (0.00%)	0
Clostridial infection † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	0/100 (0.00%)	0	1/17 (5.88%)	1
Clostridium bacteraemia † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	2/100 (2.00%)	3	0/17 (0.00%)	0
Clostridium difficile colitis † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	1	6/100 (6.00%)	6	0/17 (0.00%)	0
Clostridium difficile infection † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	1	2/100 (2.00%)	2	1/17 (5.88%)	1
Corona virus infection † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	0/100 (0.00%)	0	1/17 (5.88%)	1
Device related infection † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Diverticulitis † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Encephalitis viral † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	1	0/100 (0.00%)	0	0/17 (0.00%)	0
Enterococcal bacteraemia † 1	0/5 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	2/100 (2.00%)	2	0/17 (0.00%)	0
Enterococcal infection † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	0/100 (0.00%)	0	1/17 (5.88%)	1
Enterocolitis infectious † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	1	0/100 (0.00%)	0	0/17 (0.00%)	0
Epiglottitis † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	1	0/100 (0.00%)	0	0/17 (0.00%)	0
Escherichia bacteraemia † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	1	1/100 (1.00%)	1	0/17 (0.00%)	0
Escherichia sepsis † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	1/21 (4.76%)	1	0/66 (0.00%)	0	0/100 (0.00%)	0	0/17 (0.00%)	0
Escherichia urinary tract infection † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	1	0/100 (0.00%)	0	0/17 (0.00%)	0
Fungaemia † 1	0/5 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	0/100 (0.00%)	0	0/17 (0.00%)	0
Gastroenteritis viral † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	1	0/100 (0.00%)	0	0/17 (0.00%)	0
Hepatic infection † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	2	0/100 (0.00%)	0	0/17 (0.00%)	0
Herpes zoster † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	1	0/100 (0.00%)	0	0/17 (0.00%)	0
Infection † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	2/100 (2.00%)	2	0/17 (0.00%)	0
Influenza † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	1	0/100 (0.00%)	0	1/17 (5.88%)	1
Klebsiella bacteraemia † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	2/100 (2.00%)	2	0/17 (0.00%)	0
Lung infection † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	2/66 (3.03%)	2	7/100 (7.00%)	10	0/17 (0.00%)	0
Oral infection † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	1/13 (7.69%)	1	0/21 (0.00%)	0	0/66 (0.00%)	0	0/100 (0.00%)	0	0/17 (0.00%)	0
Osteomyelitis † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Otitis externa † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Parainfluenzae virus infection † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	1	1/100 (1.00%)	1	0/17 (0.00%)	0
Periodontitis † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Periorbital infection † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	1/21 (4.76%)	1	0/66 (0.00%)	0	0/100 (0.00%)	0	0/17 (0.00%)	0
Pneumonia † 1	0/5 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	2/3 (66.67%)	2	0/3 (0.00%)	0	0/3 (0.00%)	0	1/12 (8.33%)	2	1/13 (7.69%)	1	2/21 (9.52%)	2	13/66 (19.70%)	15	12/100 (12.00%)	15	1/17 (5.88%)	1
Pneumonia fungal † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	5/66 (7.58%)	5	5/100 (5.00%)	5	0/17 (0.00%)	0
Pneumonia haemophilus † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	1	0/100 (0.00%)	0	0/17 (0.00%)	0
Pneumonia parainfluenzae viral † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	1	0/100 (0.00%)	0	0/17 (0.00%)	0
Pneumonia viral † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	1	0/100 (0.00%)	0	0/17 (0.00%)	0
Post procedural cellulitis † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Pseudomonas infection † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Pyelonephritis † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Respiratory syncytial virus infection † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	2/66 (3.03%)	2	0/100 (0.00%)	0	0/17 (0.00%)	0
Sepsis † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	2/13 (15.38%)	2	7/21 (33.33%)	8	10/66 (15.15%)	10	19/100 (19.00%)	25	0/17 (0.00%)	0
Septic shock † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	3/21 (14.29%)	4	0/66 (0.00%)	0	4/100 (4.00%)	6	0/17 (0.00%)	0
Sinusitis † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	1/21 (4.76%)	1	1/66 (1.52%)	1	0/100 (0.00%)	0	1/17 (5.88%)	1
Sinusitis fungal † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Skin bacterial infection † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Skin infection † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	1/21 (4.76%)	1	1/66 (1.52%)	1	2/100 (2.00%)	2	0/17 (0.00%)	0
Soft tissue infection † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	2/66 (3.03%)	2	0/100 (0.00%)	0	0/17 (0.00%)	0
Staphylococcal bacteraemia † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	1/21 (4.76%)	1	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Staphylococcal sepsis † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	2/100 (2.00%)	4	0/17 (0.00%)	0
Streptococcal bacteraemia † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	2/66 (3.03%)	3	1/100 (1.00%)	1	1/17 (5.88%)	1
Streptococcal sepsis † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Systemic candida † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	0/100 (0.00%)	0	1/17 (5.88%)	1
Systemic mycosis † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	1/13 (7.69%)	1	0/21 (0.00%)	0	0/66 (0.00%)	0	0/100 (0.00%)	0	0/17 (0.00%)	0
Tooth abscess † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Tooth infection † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Toxic shock syndrome † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	1/13 (7.69%)	1	0/21 (0.00%)	0	0/66 (0.00%)	0	0/100 (0.00%)	0	0/17 (0.00%)	0
Upper respiratory tract infection † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	1/21 (4.76%)	1	3/66 (4.55%)	3	0/100 (0.00%)	0	0/17 (0.00%)	0
Urinary tract infection † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	2/21 (9.52%)	2	3/66 (4.55%)	4	2/100 (2.00%)	4	0/17 (0.00%)	0
Urinary tract infection bacterial † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	2	0/100 (0.00%)	0	0/17 (0.00%)	0
Urinary tract infection enterococcal † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	1	0/100 (0.00%)	0	0/17 (0.00%)	0
Urosepsis † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	1/21 (4.76%)	1	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Injury, poisoning and procedural complications
Facial bones fracture † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Fall † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	2/66 (3.03%)	2	2/100 (2.00%)	2	0/17 (0.00%)	0
Hip fracture † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	0/100 (0.00%)	0	1/17 (5.88%)	1
Pelvic fracture † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	1/21 (4.76%)	1	0/66 (0.00%)	0	0/100 (0.00%)	0	0/17 (0.00%)	0
Post procedural haemorrhage † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	1	0/100 (0.00%)	0	0/17 (0.00%)	0
Road traffic accident † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Subdural haematoma † 1	0/5 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	1/21 (4.76%)	1	1/66 (1.52%)	1	2/100 (2.00%)	2	1/17 (5.88%)	1
Tendon rupture † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	1/21 (4.76%)	1	0/66 (0.00%)	0	0/100 (0.00%)	0	0/17 (0.00%)	0
Wound complication † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	0/100 (0.00%)	0	0/17 (0.00%)	0
Investigations
Alanine aminotransferase increased † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	2/100 (2.00%)	2	0/17 (0.00%)	0
Aspartate aminotransferase increased † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	2/100 (2.00%)	2	1/17 (5.88%)	1
Blood bilirubin increased † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	2/66 (3.03%)	3	2/100 (2.00%)	3	0/17 (0.00%)	0
Blood creatine phosphokinase increased † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	2/66 (3.03%)	2	3/100 (3.00%)	3	0/17 (0.00%)	0
Blood creatinine increased † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	1	2/100 (2.00%)	4	0/17 (0.00%)	0
Blood lactate dehydrogenase increased † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Blood uric acid increased † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Ejection fraction decreased † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/12 (8.33%)	1	1/13 (7.69%)	1	0/21 (0.00%)	0	1/66 (1.52%)	1	0/100 (0.00%)	0	0/17 (0.00%)	0
Electrocardiogram QT prolonged † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	1	0/100 (0.00%)	0	0/17 (0.00%)	0
Liver function test increased † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	1	0/100 (0.00%)	0	0/17 (0.00%)	0
Platelet count decreased † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	2/100 (2.00%)	2	0/17 (0.00%)	0
Transaminases increased † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	1/21 (4.76%)	1	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Troponin I increased † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
White blood cell count increased † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Metabolism and nutrition disorders
Dehydration † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	1	1/100 (1.00%)	1	1/17 (5.88%)	1
Diabetic ketoacidosis † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	1/21 (4.76%)	1	0/66 (0.00%)	0	0/100 (0.00%)	0	0/17 (0.00%)	0
Failure to thrive † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	1	1/100 (1.00%)	1	0/17 (0.00%)	0
Hyperkalaemia † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Hyperuricaemia † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Hypocalcaemia † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Hyponatraemia † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	1/21 (4.76%)	1	2/66 (3.03%)	4	1/100 (1.00%)	1	0/17 (0.00%)	0
Tumour lysis syndrome † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Musculoskeletal and connective tissue disorders
Arthralgia † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Back pain † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	1	1/100 (1.00%)	1	0/17 (0.00%)	0
Joint effusion † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	0/100 (0.00%)	0	1/17 (5.88%)	1
Muscular weakness † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	2/66 (3.03%)	2	0/100 (0.00%)	0	0/17 (0.00%)	0
Musculoskeletal chest pain † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	1	0/100 (0.00%)	0	0/17 (0.00%)	0
Myalgia † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Myositis † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	1	0/100 (0.00%)	0	0/17 (0.00%)	0
Neck pain † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Necrotising myositis † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	0/100 (0.00%)	0	0/17 (0.00%)	0
Osteonecrosis † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	0/100 (0.00%)	0	0/17 (0.00%)	0
Pain in extremity † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	2	1/100 (1.00%)	1	0/17 (0.00%)	0
Rhabdomyolysis † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	0/100 (0.00%)	0	1/17 (5.88%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia † 1	1/5 (20.00%)	1	2/3 (66.67%)	2	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	2/12 (16.67%)	2	3/13 (23.08%)	3	5/21 (23.81%)	8	9/66 (13.64%)	10	20/100 (20.00%)	25	4/17 (23.53%)	5
Acute myeloid leukaemia recurrent † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	1/21 (4.76%)	1	0/66 (0.00%)	0	0/100 (0.00%)	0	0/17 (0.00%)	0
Basal cell carcinoma † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	1	0/100 (0.00%)	0	0/17 (0.00%)	0
Central nervous system leukaemia † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Leukaemia † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Squamous cell carcinoma † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	2/66 (3.03%)	2	1/100 (1.00%)	1	0/17 (0.00%)	0
Squamous cell carcinoma of skin † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	2/100 (2.00%)	2	0/17 (0.00%)	0
Nervous system disorders
Aphasia † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Cerebral ischaemia † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	2	0/17 (0.00%)	0
Cerebrovascular accident † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Coordination abnormal † 1	0/5 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	0/100 (0.00%)	0	0/17 (0.00%)	0
Encephalopathy † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Haemorrhage intracranial † 1	1/5 (20.00%)	2	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	2	0/3 (0.00%)	0	0/3 (0.00%)	0	1/12 (8.33%)	1	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	1	0/100 (0.00%)	0	0/17 (0.00%)	0
Headache † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	0/100 (0.00%)	0	1/17 (5.88%)	1
Intracranial pressure increased † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	1	0/100 (0.00%)	0	0/17 (0.00%)	0
Lethargy † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	1/21 (4.76%)	1	0/66 (0.00%)	0	0/100 (0.00%)	0	0/17 (0.00%)	0
Loss of consciousness † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Neuralgia † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	1	0/100 (0.00%)	0	0/17 (0.00%)	0
Posterior reversible encephalopathy syndrome † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	1	1/100 (1.00%)	1	0/17 (0.00%)	0
Presyncope † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	2	0/17 (0.00%)	0
Radicular pain † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	1/21 (4.76%)	1	0/66 (0.00%)	0	0/100 (0.00%)	0	0/17 (0.00%)	0
Seizure † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	1	2/100 (2.00%)	2	0/17 (0.00%)	0
Syncope † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	1	5/100 (5.00%)	6	0/17 (0.00%)	0
Psychiatric disorders
Confusional state † 1	0/5 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	2	0/17 (0.00%)	0
Mental status changes † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	1/21 (4.76%)	1	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Renal and urinary disorders
Acute kidney injury † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/12 (8.33%)	1	3/13 (23.08%)	3	3/21 (14.29%)	4	5/66 (7.58%)	5	14/100 (14.00%)	16	1/17 (5.88%)	1
Renal failure † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	1	1/100 (1.00%)	1	1/17 (5.88%)	2
Renal injury † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	1/13 (7.69%)	1	0/21 (0.00%)	0	0/66 (0.00%)	0	0/100 (0.00%)	0	0/17 (0.00%)	0
Renal tubular necrosis † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	1/21 (4.76%)	1	1/66 (1.52%)	1	0/100 (0.00%)	0	0/17 (0.00%)	0
Urinary retention † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	1	0/100 (0.00%)	0	0/17 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Acute promyelocytic leukaemia differentiation syndrome † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Acute respiratory distress syndrome † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	1/21 (4.76%)	1	0/66 (0.00%)	0	0/100 (0.00%)	0	0/17 (0.00%)	0
Acute respiratory failure † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	3/100 (3.00%)	4	0/17 (0.00%)	0
Aspiration † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	1	0/100 (0.00%)	0	0/17 (0.00%)	0
Dyspnoea † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	1/13 (7.69%)	1	0/21 (0.00%)	0	1/66 (1.52%)	1	2/100 (2.00%)	2	0/17 (0.00%)	0
Epistaxis † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	1/21 (4.76%)	1	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Haemoptysis † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	1/21 (4.76%)	2	0/66 (0.00%)	0	0/100 (0.00%)	0	0/17 (0.00%)	0
Hypoxia † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	1/13 (7.69%)	1	1/21 (4.76%)	1	2/66 (3.03%)	2	3/100 (3.00%)	4	0/17 (0.00%)	0
Laryngeal mass † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	1/13 (7.69%)	1	0/21 (0.00%)	0	0/66 (0.00%)	0	0/100 (0.00%)	0	0/17 (0.00%)	0
Lung infiltration † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Pleural effusion † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	2/66 (3.03%)	2	2/100 (2.00%)	3	0/17 (0.00%)	0
Pneumonitis † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	1	0/100 (0.00%)	0	0/17 (0.00%)	0
Pulmonary embolism † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	1	0/100 (0.00%)	0	1/17 (5.88%)	1
Pulmonary haemorrhage † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Respiratory distress † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	2/66 (3.03%)	2	2/100 (2.00%)	2	0/17 (0.00%)	0
Respiratory failure † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	1/21 (4.76%)	2	1/66 (1.52%)	1	11/100 (11.00%)	13	1/17 (5.88%)	1
Skin and subcutaneous tissue disorders
Acute febrile neutrophilic dermatosis † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	2/66 (3.03%)	2	2/100 (2.00%)	2	0/17 (0.00%)	0
Angioedema † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	1	1/100 (1.00%)	1	0/17 (0.00%)	0
Rash papular † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	1/21 (4.76%)	1	0/66 (0.00%)	0	0/100 (0.00%)	0	0/17 (0.00%)	0
Skin lesion † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Vascular disorders
Deep vein thrombosis † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Embolism † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	0/100 (0.00%)	0	0/17 (0.00%)	0
Haematoma † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	2	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	1	1/100 (1.00%)	1	0/17 (0.00%)	0
Haemorrhage † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Hypertension † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	0/100 (0.00%)	0	1/17 (5.88%)	1
Hypotension † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	1/12 (8.33%)	1	0/13 (0.00%)	0	0/21 (0.00%)	0	3/66 (4.55%)	4	4/100 (4.00%)	4	0/17 (0.00%)	0
Orthostatic hypotension † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Phlebitis deep † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	1	0/100 (0.00%)	0	0/17 (0.00%)	0
1 Term from vocabulary, MedDRA 20; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Gilterinib 20 mg in Escalation Phase		Gilterinib 40 mg in Escalation Phase		Gilterinib 80 mg in Escalation Phase		Gilterinib 120 mg in Escalation Phase		Gilterinib 200 mg in Escalation Phase		Gilterinib 300 mg in Escalation Phase		Gilterinib 450 mg in Escalation Phase		Gilterinib 20 mg in Expansion Phase		Gilterinib 40 mg in Expansion Phase		Gilterinib 80 mg in Expansion Phase		Gilterinib 120 mg in Expansion Phase		Gilterinib 200 mg in Expansion Phase		Gilterinib 300 mg in Expansion Phase
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/5 (100.00%)		2/3 (66.67%)		3/3 (100.00%)		3/3 (100.00%)		3/3 (100.00%)		3/3 (100.00%)		3/3 (100.00%)		12/12 (100.00%)		12/13 (92.31%)		20/21 (95.24%)		62/66 (93.94%)		97/100 (97.00%)		16/17 (94.12%)
Blood and lymphatic system disorders
Anaemia † 1	2/5 (40.00%)	2	0/3 (0.00%)	0	1/3 (33.33%)	3	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	2/12 (16.67%)	4	4/13 (30.77%)	4	7/21 (33.33%)	10	27/66 (40.91%)	84	33/100 (33.00%)	65	6/17 (35.29%)	6
Febrile neutropenia † 1	1/5 (20.00%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	2/12 (16.67%)	2	0/13 (0.00%)	0	1/21 (4.76%)	1	7/66 (10.61%)	8	15/100 (15.00%)	20	3/17 (17.65%)	3
Hyperfibrinogenaemia † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	0/100 (0.00%)	0	1/17 (5.88%)	1
Leukocytosis † 1	1/5 (20.00%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	1/13 (7.69%)	1	1/21 (4.76%)	1	4/66 (6.06%)	4	4/100 (4.00%)	6	2/17 (11.76%)	2
Lymphadenopathy † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	1	0/100 (0.00%)	0	1/17 (5.88%)	1
Neutropenia † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	5/66 (7.58%)	28	12/100 (12.00%)	29	2/17 (11.76%)	2
Thrombocytopenia † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	1/13 (7.69%)	1	3/21 (14.29%)	6	12/66 (18.18%)	27	19/100 (19.00%)	44	2/17 (11.76%)	2
Cardiac disorders
Angina pectoris † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	2/12 (16.67%)	3	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	2/100 (2.00%)	2	0/17 (0.00%)	0
Atrial fibrillation † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	1/21 (4.76%)	1	3/66 (4.55%)	3	5/100 (5.00%)	5	0/17 (0.00%)	0
Atrial flutter † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	1/13 (7.69%)	1	0/21 (0.00%)	0	0/66 (0.00%)	0	0/100 (0.00%)	0	0/17 (0.00%)	0
Palpitations † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	2/21 (9.52%)	2	0/66 (0.00%)	0	3/100 (3.00%)	3	0/17 (0.00%)	0
Pericardial effusion † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/12 (8.33%)	1	0/13 (0.00%)	0	1/21 (4.76%)	1	1/66 (1.52%)	1	3/100 (3.00%)	3	0/17 (0.00%)	0
Sinus bradycardia † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/12 (0.00%)	0	0/13 (0.00%)	0	1/21 (4.76%)	1	0/66 (0.00%)	0	2/100 (2.00%)	2	0/17 (0.00%)	0
Sinus tachycardia † 1	0/5 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/12 (8.33%)	1	2/13 (15.38%)	2	1/21 (4.76%)	2	2/66 (3.03%)	2	6/100 (6.00%)	7	0/17 (0.00%)	0
Tachycardia † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/12 (8.33%)	1	0/13 (0.00%)	0	1/21 (4.76%)	1	1/66 (1.52%)	1	12/100 (12.00%)	13	0/17 (0.00%)	0
Ear and labyrinth disorders
Ear discomfort † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/12 (8.33%)	1	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	0/100 (0.00%)	0	0/17 (0.00%)	0
Ear pain † 1	1/5 (20.00%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	2/12 (16.67%)	2	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	3/100 (3.00%)	3	0/17 (0.00%)	0
Endocrine disorders
Hypothyroidism † 1	1/5 (20.00%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	1	3/100 (3.00%)	3	0/17 (0.00%)	0
Eye disorders
Blepharitis † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	4/66 (6.06%)	4	2/100 (2.00%)	2	0/17 (0.00%)	0
Cataract † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	4/66 (6.06%)	6	0/100 (0.00%)	0	0/17 (0.00%)	0
Cataract nuclear † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	1/13 (7.69%)	1	0/21 (0.00%)	0	1/66 (1.52%)	1	0/100 (0.00%)	0	0/17 (0.00%)	0
Conjunctival haemorrhage † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/12 (8.33%)	1	0/13 (0.00%)	0	4/21 (19.05%)	4	0/66 (0.00%)	0	3/100 (3.00%)	3	0/17 (0.00%)	0
Dry eye † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	1/21 (4.76%)	1	8/66 (12.12%)	10	6/100 (6.00%)	7	0/17 (0.00%)	0
Eye oedema † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Eye pruritus † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	1	1/100 (1.00%)	1	1/17 (5.88%)	1
Glaucoma † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	1/13 (7.69%)	1	0/21 (0.00%)	0	0/66 (0.00%)	0	0/100 (0.00%)	0	0/17 (0.00%)	0
Lacrimation increased † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	2/66 (3.03%)	3	0/100 (0.00%)	0	0/17 (0.00%)	0
Periorbital oedema † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	2/21 (9.52%)	2	3/66 (4.55%)	3	5/100 (5.00%)	9	0/17 (0.00%)	0
Retinal exudates † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	0/100 (0.00%)	0	0/17 (0.00%)	0
Retinal haemorrhage † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	3/66 (4.55%)	3	0/100 (0.00%)	0	0/17 (0.00%)	0
Vision blurred † 1	1/5 (20.00%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	1/21 (4.76%)	1	5/66 (7.58%)	8	6/100 (6.00%)	6	0/17 (0.00%)	0
Vitreous detachment † 1	1/5 (20.00%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	1	0/100 (0.00%)	0	0/17 (0.00%)	0
Vitreous floaters † 1	1/5 (20.00%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	4/66 (6.06%)	4	3/100 (3.00%)	3	0/17 (0.00%)	0
Gastrointestinal disorders
Abdominal distension † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/12 (8.33%)	1	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	1	7/100 (7.00%)	8	1/17 (5.88%)	1
Abdominal pain † 1	1/5 (20.00%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	1/3 (33.33%)	1	1/12 (8.33%)	1	1/13 (7.69%)	1	1/21 (4.76%)	1	5/66 (7.58%)	6	15/100 (15.00%)	19	0/17 (0.00%)	0
Abdominal pain lower † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	1	0/100 (0.00%)	0	0/17 (0.00%)	0
Abdominal pain upper † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/12 (8.33%)	1	0/13 (0.00%)	0	0/21 (0.00%)	0	3/66 (4.55%)	3	1/100 (1.00%)	1	1/17 (5.88%)	1
Abdominal tenderness † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/12 (8.33%)	1	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	0/100 (0.00%)	0	0/17 (0.00%)	0
Aphthous ulcer † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	0/100 (0.00%)	0	1/17 (5.88%)	1
Colitis † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	2/66 (3.03%)	2	2/100 (2.00%)	2	0/17 (0.00%)	0
Constipation † 1	1/5 (20.00%)	1	1/3 (33.33%)	1	1/3 (33.33%)	1	2/3 (66.67%)	2	1/3 (33.33%)	1	1/3 (33.33%)	1	0/3 (0.00%)	0	1/12 (8.33%)	2	1/13 (7.69%)	1	5/21 (23.81%)	5	12/66 (18.18%)	14	32/100 (32.00%)	36	1/17 (5.88%)	1
Diarrhoea † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	1/3 (33.33%)	1	0/3 (0.00%)	0	1/3 (33.33%)	2	1/3 (33.33%)	2	1/12 (8.33%)	1	2/13 (15.38%)	2	5/21 (23.81%)	12	27/66 (40.91%)	44	45/100 (45.00%)	71	5/17 (29.41%)	6
Dry mouth † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/12 (8.33%)	1	1/13 (7.69%)	1	2/21 (9.52%)	2	4/66 (6.06%)	4	10/100 (10.00%)	10	1/17 (5.88%)	1
Dyspepsia † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/12 (8.33%)	1	0/13 (0.00%)	0	0/21 (0.00%)	0	3/66 (4.55%)	3	3/100 (3.00%)	3	0/17 (0.00%)	0
Dysphagia † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/12 (8.33%)	1	0/13 (0.00%)	0	0/21 (0.00%)	0	2/66 (3.03%)	2	7/100 (7.00%)	8	2/17 (11.76%)	2
Gastrointestinal haemorrhage † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	1/21 (4.76%)	1	0/66 (0.00%)	0	4/100 (4.00%)	5	0/17 (0.00%)	0
Gingival bleeding † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/12 (0.00%)	0	1/13 (7.69%)	2	1/21 (4.76%)	1	2/66 (3.03%)	2	2/100 (2.00%)	2	0/17 (0.00%)	0
Gingival pain † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	1/13 (7.69%)	1	0/21 (0.00%)	0	1/66 (1.52%)	1	1/100 (1.00%)	1	0/17 (0.00%)	0
Haemorrhoids † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/12 (8.33%)	1	1/13 (7.69%)	1	1/21 (4.76%)	1	1/66 (1.52%)	1	6/100 (6.00%)	8	0/17 (0.00%)	0
Melaena † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/12 (8.33%)	1	0/13 (0.00%)	0	1/21 (4.76%)	1	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Mouth haemorrhage † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	1/3 (33.33%)	1	0/12 (0.00%)	0	0/13 (0.00%)	0	1/21 (4.76%)	1	2/66 (3.03%)	2	8/100 (8.00%)	9	0/17 (0.00%)	0
Mouth ulceration † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	1/21 (4.76%)	1	4/66 (6.06%)	5	4/100 (4.00%)	5	1/17 (5.88%)	1
Nausea † 1	2/5 (40.00%)	3	0/3 (0.00%)	0	2/3 (66.67%)	3	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/12 (8.33%)	1	3/13 (23.08%)	3	4/21 (19.05%)	5	15/66 (22.73%)	22	28/100 (28.00%)	37	1/17 (5.88%)	1
Oesophagitis † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	1	1/100 (1.00%)	1	1/17 (5.88%)	1
Oral mucosal blistering † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	2/21 (9.52%)	2	2/66 (3.03%)	2	1/100 (1.00%)	3	1/17 (5.88%)	1
Oral pain † 1	1/5 (20.00%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	1	2/100 (2.00%)	3	0/17 (0.00%)	0
Proctalgia † 1	1/5 (20.00%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	1	0/100 (0.00%)	0	0/17 (0.00%)	0
Rectal haemorrhage † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/12 (8.33%)	1	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	1	4/100 (4.00%)	4	0/17 (0.00%)	0
Salivary hypersecretion † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	1/13 (7.69%)	1	0/21 (0.00%)	0	0/66 (0.00%)	0	0/100 (0.00%)	0	0/17 (0.00%)	0
Stomatitis † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	1/3 (33.33%)	1	1/12 (8.33%)	1	1/13 (7.69%)	1	0/21 (0.00%)	0	8/66 (12.12%)	9	14/100 (14.00%)	15	1/17 (5.88%)	1
Tongue coated † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/12 (8.33%)	2	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Vomiting † 1	1/5 (20.00%)	1	0/3 (0.00%)	0	2/3 (66.67%)	2	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	2/12 (16.67%)	3	1/13 (7.69%)	1	5/21 (23.81%)	6	13/66 (19.70%)	16	22/100 (22.00%)	31	1/17 (5.88%)	1
General disorders
Asthenia † 1	1/5 (20.00%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	2	0/3 (0.00%)	0	2/12 (16.67%)	2	0/13 (0.00%)	0	3/21 (14.29%)	3	6/66 (9.09%)	8	19/100 (19.00%)	20	0/17 (0.00%)	0
Chills † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/12 (8.33%)	1	0/13 (0.00%)	0	1/21 (4.76%)	1	5/66 (7.58%)	5	12/100 (12.00%)	15	0/17 (0.00%)	0
Face oedema † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/12 (8.33%)	1	0/13 (0.00%)	0	2/21 (9.52%)	3	2/66 (3.03%)	2	2/100 (2.00%)	2	0/17 (0.00%)	0
Fatigue † 1	1/5 (20.00%)	1	0/3 (0.00%)	0	1/3 (33.33%)	2	0/3 (0.00%)	0	3/3 (100.00%)	6	1/3 (33.33%)	2	1/3 (33.33%)	3	4/12 (33.33%)	5	5/13 (38.46%)	6	8/21 (38.10%)	11	27/66 (40.91%)	38	32/100 (32.00%)	47	4/17 (23.53%)	4
Gait disturbance † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Generalised oedema † 1	1/5 (20.00%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	1	2/100 (2.00%)	2	1/17 (5.88%)	1
Local swelling † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	0/100 (0.00%)	0	1/17 (5.88%)	1
Localised oedema † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	1/21 (4.76%)	1	1/66 (1.52%)	2	5/100 (5.00%)	5	0/17 (0.00%)	0
Malaise † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	2/66 (3.03%)	3	5/100 (5.00%)	5	0/17 (0.00%)	0
Mucosal inflammation † 1	0/5 (0.00%)	0	1/3 (33.33%)	1	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	7/66 (10.61%)	9	11/100 (11.00%)	13	0/17 (0.00%)	0
Nodule † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	1/21 (4.76%)	1	1/66 (1.52%)	2	0/100 (0.00%)	0	1/17 (5.88%)	1
Oedema † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/12 (8.33%)	1	0/13 (0.00%)	0	3/21 (14.29%)	5	3/66 (4.55%)	5	6/100 (6.00%)	7	0/17 (0.00%)	0
Oedema peripheral † 1	0/5 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	1/3 (33.33%)	1	1/3 (33.33%)	1	4/12 (33.33%)	4	2/13 (15.38%)	2	5/21 (23.81%)	11	17/66 (25.76%)	22	31/100 (31.00%)	48	1/17 (5.88%)	2
Pain † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	6/66 (9.09%)	7	6/100 (6.00%)	9	0/17 (0.00%)	0
Peripheral swelling † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/12 (8.33%)	1	0/13 (0.00%)	0	1/21 (4.76%)	2	3/66 (4.55%)	4	4/100 (4.00%)	6	0/17 (0.00%)	0
Pyrexia † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/12 (8.33%)	1	3/13 (23.08%)	3	3/21 (14.29%)	3	18/66 (27.27%)	25	24/100 (24.00%)	33	3/17 (17.65%)	3
Serositis † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	0/100 (0.00%)	0	0/17 (0.00%)	0
Hepatobiliary disorders
Hyperbilirubinaemia † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	2/21 (9.52%)	2	2/66 (3.03%)	2	6/100 (6.00%)	12	0/17 (0.00%)	0
Immune system disorders
Graft versus host disease † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/12 (8.33%)	1	0/13 (0.00%)	0	0/21 (0.00%)	0	3/66 (4.55%)	4	0/100 (0.00%)	0	0/17 (0.00%)	0
Seasonal allergy † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/12 (8.33%)	1	0/13 (0.00%)	0	1/21 (4.76%)	1	1/66 (1.52%)	1	1/100 (1.00%)	1	0/17 (0.00%)	0
Infections and infestations
Abscess limb † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/12 (8.33%)	1	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	0/100 (0.00%)	0	0/17 (0.00%)	0
Bacteraemia † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	2/21 (9.52%)	2	3/66 (4.55%)	3	2/100 (2.00%)	2	0/17 (0.00%)	0
Candida infection † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	4/66 (6.06%)	4	2/100 (2.00%)	2	0/17 (0.00%)	0
Cellulitis † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	2/21 (9.52%)	3	5/66 (7.58%)	6	1/100 (1.00%)	1	0/17 (0.00%)	0
Clostridium difficile infection † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	1/13 (7.69%)	1	1/21 (4.76%)	1	4/66 (6.06%)	4	2/100 (2.00%)	2	0/17 (0.00%)	0
Enterococcal bacteraemia † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	1	2/100 (2.00%)	2	1/17 (5.88%)	1
Gingivitis † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	1/13 (7.69%)	1	0/21 (0.00%)	0	0/66 (0.00%)	0	0/100 (0.00%)	0	0/17 (0.00%)	0
Herpes virus infection † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/12 (8.33%)	1	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Herpes zoster † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	1/13 (7.69%)	1	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Influenza † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	1	5/100 (5.00%)	5	0/17 (0.00%)	0
Laryngitis fungal † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/12 (8.33%)	1	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	0/100 (0.00%)	0	0/17 (0.00%)	0
Lip infection † 1	1/5 (20.00%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Lung infection † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	1/13 (7.69%)	1	0/21 (0.00%)	0	2/66 (3.03%)	2	5/100 (5.00%)	5	0/17 (0.00%)	0
Oral candidiasis † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/12 (8.33%)	1	0/13 (0.00%)	0	1/21 (4.76%)	1	0/66 (0.00%)	0	2/100 (2.00%)	2	0/17 (0.00%)	0
Oral herpes † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/12 (8.33%)	1	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	2	0/100 (0.00%)	0	0/17 (0.00%)	0
Pharyngitis † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/12 (8.33%)	2	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Pneumonia † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	1/21 (4.76%)	2	5/66 (7.58%)	6	5/100 (5.00%)	6	0/17 (0.00%)	0
Sinusitis † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	1/12 (8.33%)	1	0/13 (0.00%)	0	1/21 (4.76%)	1	2/66 (3.03%)	2	1/100 (1.00%)	1	0/17 (0.00%)	0
Skin infection † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	1/13 (7.69%)	1	1/21 (4.76%)	1	3/66 (4.55%)	3	3/100 (3.00%)	3	0/17 (0.00%)	0
Upper respiratory tract infection † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	2	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	2/13 (15.38%)	2	1/21 (4.76%)	1	7/66 (10.61%)	9	5/100 (5.00%)	11	0/17 (0.00%)	0
Urinary tract infection † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	2/21 (9.52%)	2	9/66 (13.64%)	9	5/100 (5.00%)	7	0/17 (0.00%)	0
Urinary tract infection bacterial † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	1/21 (4.76%)	1	4/66 (6.06%)	7	3/100 (3.00%)	4	0/17 (0.00%)	0
Urinary tract infection enterococcal † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	2/12 (16.67%)	2	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Injury, poisoning and procedural complications
Contusion † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	1/12 (8.33%)	1	1/13 (7.69%)	1	3/21 (14.29%)	3	3/66 (4.55%)	3	10/100 (10.00%)	11	0/17 (0.00%)	0
Fall † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	1/12 (8.33%)	1	0/13 (0.00%)	0	2/21 (9.52%)	2	11/66 (16.67%)	15	18/100 (18.00%)	22	0/17 (0.00%)	0
Incision site pain † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/12 (8.33%)	1	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	0/100 (0.00%)	0	0/17 (0.00%)	0
Infusion related reaction † 1	1/5 (20.00%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	3/100 (3.00%)	5	0/17 (0.00%)	0
Periorbital haemorrhage † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	1/21 (4.76%)	1	0/66 (0.00%)	0	0/100 (0.00%)	0	1/17 (5.88%)	1
Post procedural haemorrhage † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	1/21 (4.76%)	1	0/66 (0.00%)	0	0/100 (0.00%)	0	0/17 (0.00%)	0
Procedural pain † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	1	1/100 (1.00%)	1	1/17 (5.88%)	1
Stoma site pain † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/12 (8.33%)	2	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	0/100 (0.00%)	0	0/17 (0.00%)	0
Transfusion reaction † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	2	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	1/21 (4.76%)	1	3/66 (4.55%)	3	1/100 (1.00%)	1	1/17 (5.88%)	1
Investigations
Activated partial thromboplastin time prolonged † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	1/12 (8.33%)	2	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	1	4/100 (4.00%)	5	0/17 (0.00%)	0
Alanine aminotransferase increased † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	1/3 (33.33%)	1	1/12 (8.33%)	2	1/13 (7.69%)	1	3/21 (14.29%)	9	16/66 (24.24%)	26	25/100 (25.00%)	46	2/17 (11.76%)	3
Aspartate aminotransferase increased † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	1/3 (33.33%)	1	1/3 (33.33%)	1	2/3 (66.67%)	4	1/12 (8.33%)	3	1/13 (7.69%)	1	3/21 (14.29%)	9	20/66 (30.30%)	33	35/100 (35.00%)	61	1/17 (5.88%)	2
Blood alkaline phosphatase increased † 1	1/5 (20.00%)	1	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	1/3 (33.33%)	1	1/12 (8.33%)	1	0/13 (0.00%)	0	3/21 (14.29%)	12	10/66 (15.15%)	12	15/100 (15.00%)	19	0/17 (0.00%)	0
Blood bilirubin increased † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/12 (8.33%)	2	2/13 (15.38%)	3	3/21 (14.29%)	3	1/66 (1.52%)	1	12/100 (12.00%)	22	0/17 (0.00%)	0
Blood creatine phosphokinase increased † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	5/66 (7.58%)	9	15/100 (15.00%)	27	1/17 (5.88%)	1
Blood creatinine increased † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/12 (8.33%)	1	2/13 (15.38%)	2	4/21 (19.05%)	9	13/66 (19.70%)	23	19/100 (19.00%)	40	1/17 (5.88%)	1
Blood lactate dehydrogenase increased † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	1/13 (7.69%)	1	0/21 (0.00%)	0	3/66 (4.55%)	4	7/100 (7.00%)	9	0/17 (0.00%)	0
Blood phosphorus decreased † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	1/13 (7.69%)	1	0/21 (0.00%)	0	1/66 (1.52%)	1	0/100 (0.00%)	0	0/17 (0.00%)	0
Blood thyroid stimulating hormone increased † 1	1/5 (20.00%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	0/100 (0.00%)	0	0/17 (0.00%)	0
Blood urea increased † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	2/100 (2.00%)	2	1/17 (5.88%)	1
Cardiac murmur † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	2/21 (9.52%)	2	1/66 (1.52%)	1	0/100 (0.00%)	0	0/17 (0.00%)	0
Chest X-ray abnormal † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	1/13 (7.69%)	1	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Electrocardiogram QT prolonged † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	1/21 (4.76%)	1	9/66 (13.64%)	13	9/100 (9.00%)	11	0/17 (0.00%)	0
International normalised ratio increased † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/12 (8.33%)	1	1/13 (7.69%)	2	1/21 (4.76%)	1	4/66 (6.06%)	7	5/100 (5.00%)	7	1/17 (5.88%)	1
Liver function test increased † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	1/21 (4.76%)	2	1/66 (1.52%)	1	3/100 (3.00%)	4	1/17 (5.88%)	1
Neutrophil count decreased † 1	1/5 (20.00%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	2	0/3 (0.00%)	0	2/12 (16.67%)	4	0/13 (0.00%)	0	1/21 (4.76%)	1	8/66 (12.12%)	16	14/100 (14.00%)	29	0/17 (0.00%)	0
Platelet count decreased † 1	1/5 (20.00%)	3	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	2	1/3 (33.33%)	1	2/12 (16.67%)	8	3/13 (23.08%)	4	1/21 (4.76%)	1	12/66 (18.18%)	26	17/100 (17.00%)	37	1/17 (5.88%)	1
Transaminases increased † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	1/21 (4.76%)	1	5/66 (7.58%)	5	5/100 (5.00%)	6	1/17 (5.88%)	1
Ultrasound liver abnormal † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	0/100 (0.00%)	0	1/17 (5.88%)	1
Volume blood increased † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	1/13 (7.69%)	1	0/21 (0.00%)	0	0/66 (0.00%)	0	0/100 (0.00%)	0	0/17 (0.00%)	0
Weight decreased † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/12 (8.33%)	1	1/13 (7.69%)	1	0/21 (0.00%)	0	3/66 (4.55%)	3	6/100 (6.00%)	7	0/17 (0.00%)	0
Weight increased † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	2/66 (3.03%)	5	12/100 (12.00%)	18	0/17 (0.00%)	0
White blood cell count decreased † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	4/66 (6.06%)	14	13/100 (13.00%)	30	0/17 (0.00%)	0
Metabolism and nutrition disorders
Decreased appetite † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	2/3 (66.67%)	3	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/12 (8.33%)	1	1/13 (7.69%)	1	3/21 (14.29%)	4	11/66 (16.67%)	13	19/100 (19.00%)	21	1/17 (5.88%)	1
Dehydration † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	1/13 (7.69%)	2	0/21 (0.00%)	0	1/66 (1.52%)	1	10/100 (10.00%)	10	0/17 (0.00%)	0
Fluid overload † 1	0/5 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	2/66 (3.03%)	2	2/100 (2.00%)	2	0/17 (0.00%)	0
Fluid retention † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	2/100 (2.00%)	2	0/17 (0.00%)	0
Hypercalcaemia † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	1/13 (7.69%)	1	0/21 (0.00%)	0	0/66 (0.00%)	0	0/100 (0.00%)	0	0/17 (0.00%)	0
Hyperglycaemia † 1	1/5 (20.00%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	2/3 (66.67%)	2	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	5/66 (7.58%)	7	14/100 (14.00%)	16	0/17 (0.00%)	0
Hyperkalaemia † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/12 (0.00%)	0	1/13 (7.69%)	1	1/21 (4.76%)	2	5/66 (7.58%)	6	9/100 (9.00%)	10	0/17 (0.00%)	0
Hyperphosphataemia † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/12 (8.33%)	1	0/13 (0.00%)	0	1/21 (4.76%)	2	2/66 (3.03%)	2	1/100 (1.00%)	1	0/17 (0.00%)	0
Hyperuricaemia † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	2/13 (15.38%)	2	0/21 (0.00%)	0	4/66 (6.06%)	4	10/100 (10.00%)	11	0/17 (0.00%)	0
Hypoalbuminaemia † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	1/12 (8.33%)	2	1/13 (7.69%)	1	4/21 (19.05%)	15	7/66 (10.61%)	15	18/100 (18.00%)	28	1/17 (5.88%)	2
Hypocalcaemia † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	1/12 (8.33%)	1	2/13 (15.38%)	2	3/21 (14.29%)	17	11/66 (16.67%)	23	23/100 (23.00%)	50	1/17 (5.88%)	1
Hypochloraemia † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	0/100 (0.00%)	0	1/17 (5.88%)	1
Hypoglycaemia † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/12 (8.33%)	1	0/13 (0.00%)	0	0/21 (0.00%)	0	2/66 (3.03%)	2	3/100 (3.00%)	4	0/17 (0.00%)	0
Hypokalaemia † 1	1/5 (20.00%)	1	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	5/12 (41.67%)	9	2/13 (15.38%)	3	2/21 (9.52%)	11	10/66 (15.15%)	20	25/100 (25.00%)	33	0/17 (0.00%)	0
Hypomagnesaemia † 1	1/5 (20.00%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/12 (8.33%)	2	1/13 (7.69%)	1	3/21 (14.29%)	3	13/66 (19.70%)	19	17/100 (17.00%)	25	0/17 (0.00%)	0
Hyponatraemia † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	2	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	1/13 (7.69%)	1	2/21 (9.52%)	8	8/66 (12.12%)	16	20/100 (20.00%)	26	1/17 (5.88%)	1
Hypophosphataemia † 1	1/5 (20.00%)	2	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/12 (8.33%)	1	0/13 (0.00%)	0	1/21 (4.76%)	1	6/66 (9.09%)	10	11/100 (11.00%)	13	2/17 (11.76%)	2
Hypoproteinaemia † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	2/100 (2.00%)	2	0/17 (0.00%)	0
Hypovolaemia † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	2/100 (2.00%)	2	0/17 (0.00%)	0
Iron overload † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	4/66 (6.06%)	4	0/100 (0.00%)	0	0/17 (0.00%)	0
Musculoskeletal and connective tissue disorders
Arthralgia † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	4/21 (19.05%)	4	12/66 (18.18%)	15	16/100 (16.00%)	23	1/17 (5.88%)	1
Back pain † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/12 (8.33%)	2	0/13 (0.00%)	0	2/21 (9.52%)	2	8/66 (12.12%)	9	9/100 (9.00%)	11	0/17 (0.00%)	0
Bone pain † 1	1/5 (20.00%)	1	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/12 (8.33%)	1	0/13 (0.00%)	0	1/21 (4.76%)	1	1/66 (1.52%)	1	7/100 (7.00%)	7	0/17 (0.00%)	0
Flank pain † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Muscle spasms † 1	0/5 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	1/21 (4.76%)	1	3/66 (4.55%)	4	4/100 (4.00%)	4	0/17 (0.00%)	0
Muscular weakness † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/12 (0.00%)	0	1/13 (7.69%)	1	0/21 (0.00%)	0	7/66 (10.61%)	7	4/100 (4.00%)	4	0/17 (0.00%)	0
Musculoskeletal chest pain † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	1/13 (7.69%)	1	0/21 (0.00%)	0	1/66 (1.52%)	1	0/100 (0.00%)	0	0/17 (0.00%)	0
Musculoskeletal pain † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	1/21 (4.76%)	1	2/66 (3.03%)	2	7/100 (7.00%)	7	0/17 (0.00%)	0
Myalgia † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	1/12 (8.33%)	1	1/13 (7.69%)	1	0/21 (0.00%)	0	5/66 (7.58%)	5	12/100 (12.00%)	14	0/17 (0.00%)	0
Myopathy † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	0/100 (0.00%)	0	1/17 (5.88%)	1
Neck pain † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	1/13 (7.69%)	1	0/21 (0.00%)	0	4/66 (6.06%)	5	3/100 (3.00%)	3	0/17 (0.00%)	0
Pain in extremity † 1	0/5 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	1/3 (33.33%)	1	1/3 (33.33%)	1	1/3 (33.33%)	1	1/3 (33.33%)	1	1/12 (8.33%)	1	0/13 (0.00%)	0	2/21 (9.52%)	3	10/66 (15.15%)	13	11/100 (11.00%)	15	0/17 (0.00%)	0
Pain in jaw † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	2/12 (16.67%)	2	0/13 (0.00%)	0	1/21 (4.76%)	1	1/66 (1.52%)	1	0/100 (0.00%)	0	0/17 (0.00%)	0
Nervous system disorders
Cognitive disorder † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	2/100 (2.00%)	2	0/17 (0.00%)	0
Dizziness † 1	0/5 (0.00%)	0	1/3 (33.33%)	1	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/12 (8.33%)	1	1/13 (7.69%)	1	5/21 (23.81%)	6	17/66 (25.76%)	19	26/100 (26.00%)	34	0/17 (0.00%)	0
Dysaesthesia † 1	1/5 (20.00%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	4/66 (6.06%)	6	9/100 (9.00%)	10	0/17 (0.00%)	0
Dysgeusia † 1	0/5 (0.00%)	0	1/3 (33.33%)	1	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	2/12 (16.67%)	2	1/13 (7.69%)	1	1/21 (4.76%)	1	9/66 (13.64%)	9	11/100 (11.00%)	12	2/17 (11.76%)	2
Headache † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	2	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	2/12 (16.67%)	2	1/13 (7.69%)	1	3/21 (14.29%)	4	10/66 (15.15%)	14	14/100 (14.00%)	20	0/17 (0.00%)	0
Hyperaesthesia † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	2/66 (3.03%)	2	4/100 (4.00%)	4	0/17 (0.00%)	0
Lethargy † 1	1/5 (20.00%)	1	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	2/21 (9.52%)	2	1/66 (1.52%)	1	3/100 (3.00%)	3	1/17 (5.88%)	1
Memory impairment † 1	1/5 (20.00%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	0/100 (0.00%)	0	0/17 (0.00%)	0
Neuropathy peripheral † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	2	0/12 (0.00%)	0	0/13 (0.00%)	0	1/21 (4.76%)	1	7/66 (10.61%)	9	5/100 (5.00%)	6	2/17 (11.76%)	2
Paraesthesia † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	6/66 (9.09%)	7	7/100 (7.00%)	12	1/17 (5.88%)	1
Peripheral sensory neuropathy † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/12 (8.33%)	1	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Presyncope † 1	1/5 (20.00%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	3/66 (4.55%)	3	7/100 (7.00%)	8	0/17 (0.00%)	0
Sciatica † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	1/13 (7.69%)	1	0/21 (0.00%)	0	0/66 (0.00%)	0	0/100 (0.00%)	0	0/17 (0.00%)	0
Somnolence † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	1/13 (7.69%)	1	1/21 (4.76%)	1	1/66 (1.52%)	1	2/100 (2.00%)	2	0/17 (0.00%)	0
Syncope † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	2/66 (3.03%)	3	6/100 (6.00%)	6	0/17 (0.00%)	0
Tremor † 1	1/5 (20.00%)	1	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	2	6/100 (6.00%)	7	0/17 (0.00%)	0
Product Issues
Device occlusion † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	0/100 (0.00%)	0	1/17 (5.88%)	1
Psychiatric disorders
Agitation † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	1/13 (7.69%)	1	1/21 (4.76%)	1	0/66 (0.00%)	0	3/100 (3.00%)	3	0/17 (0.00%)	0
Anxiety † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/12 (8.33%)	1	1/13 (7.69%)	1	1/21 (4.76%)	1	5/66 (7.58%)	5	6/100 (6.00%)	6	0/17 (0.00%)	0
Confusional state † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	1/13 (7.69%)	2	3/21 (14.29%)	3	4/66 (6.06%)	4	10/100 (10.00%)	12	1/17 (5.88%)	1
Depression † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	1/21 (4.76%)	1	3/66 (4.55%)	3	6/100 (6.00%)	6	0/17 (0.00%)	0
Disorientation † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	1/13 (7.69%)	1	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Insomnia † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	2/12 (16.67%)	2	1/13 (7.69%)	1	3/21 (14.29%)	3	8/66 (12.12%)	9	13/100 (13.00%)	14	1/17 (5.88%)	1
Mental status changes † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/12 (0.00%)	0	1/13 (7.69%)	1	2/21 (9.52%)	2	0/66 (0.00%)	0	2/100 (2.00%)	2	1/17 (5.88%)	1
Sleep disorder † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	2/21 (9.52%)	2	0/66 (0.00%)	0	0/100 (0.00%)	0	0/17 (0.00%)	0
Renal and urinary disorders
Dysuria † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	1/21 (4.76%)	1	3/66 (4.55%)	3	7/100 (7.00%)	8	0/17 (0.00%)	0
Haematuria † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	1/21 (4.76%)	2	3/66 (4.55%)	4	6/100 (6.00%)	6	0/17 (0.00%)	0
Pollakiuria † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	2/3 (66.67%)	2	0/3 (0.00%)	0	0/12 (0.00%)	0	1/13 (7.69%)	1	0/21 (0.00%)	0	0/66 (0.00%)	0	7/100 (7.00%)	7	0/17 (0.00%)	0
Urinary incontinence † 1	1/5 (20.00%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	1/21 (4.76%)	1	5/66 (7.58%)	6	4/100 (4.00%)	5	0/17 (0.00%)	0
Urinary retention † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	1/21 (4.76%)	2	0/66 (0.00%)	0	7/100 (7.00%)	8	0/17 (0.00%)	0
Reproductive system and breast disorders
Nipple pain † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	1/13 (7.69%)	1	0/21 (0.00%)	0	0/66 (0.00%)	0	0/100 (0.00%)	0	0/17 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Atelectasis † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/12 (8.33%)	1	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Cough † 1	1/5 (20.00%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	2/12 (16.67%)	3	1/13 (7.69%)	1	7/21 (33.33%)	7	18/66 (27.27%)	27	26/100 (26.00%)	29	3/17 (17.65%)	3
Dysphonia † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	2	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	1	2/100 (2.00%)	2	1/17 (5.88%)	1
Dyspnoea † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	3/12 (25.00%)	4	5/13 (38.46%)	5	4/21 (19.05%)	5	19/66 (28.79%)	23	28/100 (28.00%)	38	2/17 (11.76%)	2
Dyspnoea exertional † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	1/21 (4.76%)	1	6/66 (9.09%)	7	3/100 (3.00%)	3	1/17 (5.88%)	1
Epistaxis † 1	0/5 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	1/3 (33.33%)	1	3/12 (25.00%)	3	3/13 (23.08%)	3	3/21 (14.29%)	3	16/66 (24.24%)	18	20/100 (20.00%)	24	4/17 (23.53%)	4
Haemoptysis † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	2/66 (3.03%)	2	2/100 (2.00%)	2	0/17 (0.00%)	0
Hypoxia † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	1/12 (8.33%)	1	1/13 (7.69%)	1	2/21 (9.52%)	2	5/66 (7.58%)	8	11/100 (11.00%)	14	0/17 (0.00%)	0
Nasal congestion † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/12 (0.00%)	0	0/13 (0.00%)	0	3/21 (14.29%)	4	3/66 (4.55%)	4	9/100 (9.00%)	9	0/17 (0.00%)	0
Oropharyngeal pain † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	2/12 (16.67%)	2	2/13 (15.38%)	2	0/21 (0.00%)	0	5/66 (7.58%)	6	8/100 (8.00%)	11	0/17 (0.00%)	0
Pharyngeal disorder † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	1/13 (7.69%)	1	0/21 (0.00%)	0	0/66 (0.00%)	0	0/100 (0.00%)	0	0/17 (0.00%)	0
Pleural effusion † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	1/12 (8.33%)	1	0/13 (0.00%)	0	1/21 (4.76%)	1	2/66 (3.03%)	2	10/100 (10.00%)	14	0/17 (0.00%)	0
Rales † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/12 (8.33%)	1	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	1	1/100 (1.00%)	1	0/17 (0.00%)	0
Rhinorrhoea † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Sinus pain † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/12 (8.33%)	1	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	0/100 (0.00%)	0	0/17 (0.00%)	0
Tachypnoea † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	2	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Upper-airway cough syndrome † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	4/66 (6.06%)	4	2/100 (2.00%)	3	0/17 (0.00%)	0
Wheezing † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/12 (8.33%)	1	0/13 (0.00%)	0	0/21 (0.00%)	0	2/66 (3.03%)	2	5/100 (5.00%)	6	0/17 (0.00%)	0
Skin and subcutaneous tissue disorders
Alopecia † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/12 (8.33%)	1	0/13 (0.00%)	0	0/21 (0.00%)	0	5/66 (7.58%)	6	0/100 (0.00%)	0	0/17 (0.00%)	0
Blood blister † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	1	2/100 (2.00%)	2	1/17 (5.88%)	1
Decubitus ulcer † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	1/21 (4.76%)	1	1/66 (1.52%)	1	2/100 (2.00%)	3	0/17 (0.00%)	0
Dermatitis acneiform † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	1/13 (7.69%)	1	0/21 (0.00%)	0	0/66 (0.00%)	0	0/100 (0.00%)	0	0/17 (0.00%)	0
Drug eruption † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	1/21 (4.76%)	1	5/66 (7.58%)	5	4/100 (4.00%)	4	0/17 (0.00%)	0
Dry skin † 1	1/5 (20.00%)	1	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	2/21 (9.52%)	4	3/66 (4.55%)	3	3/100 (3.00%)	5	0/17 (0.00%)	0
Ecchymosis † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	1/12 (8.33%)	1	0/13 (0.00%)	0	2/21 (9.52%)	3	3/66 (4.55%)	3	8/100 (8.00%)	8	1/17 (5.88%)	1
Eccrine squamous syringometaplasia † 1	0/5 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	0/100 (0.00%)	0	0/17 (0.00%)	0
Erythema † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	2/21 (9.52%)	2	3/66 (4.55%)	4	4/100 (4.00%)	4	1/17 (5.88%)	1
Erythema multiforme † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/12 (8.33%)	1	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Hyperhidrosis † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	3/21 (14.29%)	4	1/66 (1.52%)	1	4/100 (4.00%)	4	0/17 (0.00%)	0
Pain of skin † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	1/66 (1.52%)	1	5/100 (5.00%)	5	1/17 (5.88%)	1
Petechiae † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	2/12 (16.67%)	4	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	14/100 (14.00%)	14	1/17 (5.88%)	1
Photosensitivity reaction † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	1/13 (7.69%)	1	0/21 (0.00%)	0	1/66 (1.52%)	1	1/100 (1.00%)	1	0/17 (0.00%)	0
Pigmentation disorder † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/12 (8.33%)	1	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	0/17 (0.00%)	0
Pruritus † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	1/12 (8.33%)	1	0/13 (0.00%)	0	2/21 (9.52%)	2	0/66 (0.00%)	0	7/100 (7.00%)	12	0/17 (0.00%)	0
Rash † 1	0/5 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/12 (0.00%)	0	1/13 (7.69%)	1	0/21 (0.00%)	0	11/66 (16.67%)	11	11/100 (11.00%)	13	0/17 (0.00%)	0
Rash maculo-papular † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	2/12 (16.67%)	2	1/13 (7.69%)	1	1/21 (4.76%)	1	3/66 (4.55%)	3	7/100 (7.00%)	9	0/17 (0.00%)	0
Rash papular † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	1/13 (7.69%)	2	0/21 (0.00%)	0	0/66 (0.00%)	0	0/100 (0.00%)	0	1/17 (5.88%)	1
Skin lesion † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	1/21 (4.76%)	1	1/66 (1.52%)	1	5/100 (5.00%)	5	2/17 (11.76%)	4
Swelling face † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	2/66 (3.03%)	2	0/100 (0.00%)	0	0/17 (0.00%)	0
Vascular disorders
Flushing † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/12 (8.33%)	1	0/13 (0.00%)	0	0/21 (0.00%)	0	0/66 (0.00%)	0	1/100 (1.00%)	1	1/17 (5.88%)	1
Haematoma † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	1/12 (8.33%)	1	0/13 (0.00%)	0	1/21 (4.76%)	1	2/66 (3.03%)	2	6/100 (6.00%)	8	0/17 (0.00%)	0
Hot flush † 1	1/5 (20.00%)	1	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	0/21 (0.00%)	0	2/66 (3.03%)	2	2/100 (2.00%)	2	0/17 (0.00%)	0
Hypertension † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/12 (8.33%)	1	1/13 (7.69%)	1	1/21 (4.76%)	1	7/66 (10.61%)	7	16/100 (16.00%)	34	1/17 (5.88%)	2
Hypotension † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/12 (8.33%)	1	0/13 (0.00%)	0	3/21 (14.29%)	4	10/66 (15.15%)	11	25/100 (25.00%)	32	1/17 (5.88%)	1
Orthostatic hypotension † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	1/21 (4.76%)	2	3/66 (4.55%)	3	8/100 (8.00%)	8	0/17 (0.00%)	0
Pallor † 1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/12 (0.00%)	0	0/13 (0.00%)	0	2/21 (9.52%)	2	1/66 (1.52%)	1	0/100 (0.00%)	0	0/17 (0.00%)	0
1 Term from vocabulary, MedDRA 20; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Institute and/or Principal Investigator may publish trial data generated at their specific study site after Sponsor publication of the multi-center data. Sponsor must receive a site's manuscript prior to publication for review and comment as specified in the Investigator Agreement.

Results Point of Contact

• Name/Title: Clinical Trial Disclosure
• Organization: Astellas Pharma Global Development, Inc.
• Phone: 800-888-7704
• EMail: astellas.resultsdisclosure@astellas.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

James AJ, Smith CC, Litzow M, Perl AE, Altman JK, Shepard D, Kadokura T, Souda K, Patton M, Lu Z, Liu C, Moy S, Levis MJ, Bahceci E. Pharmacokinetic Profile of Gilteritinib: A Novel FLT-3 Tyrosine Kinase Inhibitor. Clin Pharmacokinet. 2020 Oct;59(10):1273-1290. doi: 10.1007/s40262-020-00888-w. Erratum In: Clin Pharmacokinet. 2021 Sep;60(9):1251.

Perl AE, Altman JK, Cortes J, Smith C, Litzow M, Baer MR, Claxton D, Erba HP, Gill S, Goldberg S, Jurcic JG, Larson RA, Liu C, Ritchie E, Schiller G, Spira AI, Strickland SA, Tibes R, Ustun C, Wang ES, Stuart R, Rollig C, Neubauer A, Martinelli G, Bahceci E, Levis M. Selective inhibition of FLT3 by gilteritinib in relapsed or refractory acute myeloid leukaemia: a multicentre, first-in-human, open-label, phase 1-2 study. Lancet Oncol. 2017 Aug;18(8):1061-1075. doi: 10.1016/S1470-2045(17)30416-3. Epub 2017 Jun 20. Erratum In: Lancet Oncol. 2017 Dec;18(12 ):e711. Lancet Oncol. 2018 Jul;19(7):e335. Lancet Oncol. 2019 Jun;20(6):e293.

Kasi PM, Litzow MR, Patnaik MM, Hashmi SK, Gangat N. Clonal evolution of AML on novel FMS-like tyrosine kinase-3 (FLT3) inhibitor therapy with evolving actionable targets. Leuk Res Rep. 2016 Jan 12;5:7-10. doi: 10.1016/j.lrr.2016.01.002. eCollection 2016.

• Responsible Party: Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )
• ClinicalTrials.gov Identifier: NCT02014558
• Other Study ID Numbers: 2215-CL-0101
• First Submitted: November 6, 2013
• First Posted: December 18, 2013
• Results First Submitted: December 19, 2018
• Results First Posted: February 20, 2019
• Last Update Posted: May 23, 2019