A Study Evaluating the Safety, Efficacy and Pharmacokinetics of Venetoclax Combined With Chemotherapy in Participants With B-Cell Non-Hodgkin's Lymphoma (NHL) and DLBCL

• ClinicalTrials.gov Identifier: NCT02055820
• Recruitment Status: Completed
• First Posted: February 5, 2014
• Results First Posted: December 20, 2018
• Last Update Posted: June 11, 2020
• Sponsor: Hoffmann-La Roche
• Collaborator: AbbVie
• Information provided by (Responsible Party): Hoffmann-La Roche

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Lymphoma, Non-Hodgkin
• Interventions: Drug: Venetoclax; Drug: Cyclophosphamide; Drug: Obinutuzumab; Drug: Rituximab; Drug: Doxorubicin; Drug: Vincristine; Drug: Prednisone
• Enrollment: 267

Participant Flow

Recruitment Details	At start the trial had a randomised-controlled component, until July 2016 once the arm B (Gazyva) got closed following the publication of results of another trial. Since July 2016, the trial was single-arm, not randomised anymore, and kept including patients in only 1 arm (Arm A, rituximab).
Pre-assignment Details	The data reported for participant flow is based on safety population, which includes all participants who received at least one dose of study medication.

Arm/Group Title	Venetoclax 200 mg +R-CHOP	Venetoclax 400 mg +R-CHOP	Venetoclax 600 mg +R-CHOP	Venetoclax 800 mg +R-CHOP	Venetoclax 800 mg +R-CHOP Phase II	Venetoclax 200 mg +G-CHOP	Venetoclax 400 mg +G-CHOP	Venetoclax 600 mg +G-CHOP	Venetoclax 800 mg + G-CHOP A	Venetoclax 800 mg +G-CHOP B
Arm/Group Description	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase II: Participants received 6 cycles of CHOP and 8 cycles of venetoclax (at dose determined in Phase I) + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. In this arm venetoclax was administered as follows: Cycle 1 Days 4-10; Cycles 2-8 Days 1-10, Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. In this arm venetoclax was administered as follows: Cycle 1 Days 4-8; Cycles 2-8 Days 1-5. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.
Period Title: Phase I: Dose-Finding
Started	7	3	8	6	0	7	7	6	6	6
Completed	6	3	7	3	0	5	5	6	6	6
Not Completed	1	0	1	3	0	2	2	0	0	0
Reason Not Completed
Death	1	0	1	2	0	1	1	0	0	0
Withdrawal by Subject	0	0	0	0	0	1	0	0	0	0
Lost to Follow-up	0	0	0	1	0	0	1	0	0	0
Period Title: Phase II: Expansion
Started	0	0	0	0	208	0	0	0	0	0
Completed	0	0	0	0	159	0	0	0	0	0
Not Completed	0	0	0	0	49	0	0	0	0	0
Reason Not Completed
Death	0	0	0	0	33	0	0	0	0	0
Lost to Follow-up	0	0	0	0	4	0	0	0	0	0
Withdrawal by Subject	0	0	0	0	12	0	0	0	0	0

Baseline Characteristics

Arm/Group Title		Venetoclax 200 mg +R-CHOP	Venetoclax 400 mg +R-CHOP	Venetoclax 600 mg +R-CHOP	Venetoclax 800 mg +R-CHOP	Venetoclax 800 mg +R-CHOP Phase II	Venetoclax 200 mg +G-CHOP	Venetoclax 400 mg +G-CHOP	Venetoclax 600 mg +G-CHOP	Venetoclax 800 mg + G-CHOP A	Venetoclax 800 mg +G-CHOP B	Total
Arm/Group Description		Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase II: Participants received 6 cycles of CHOP and 8 cycles of venetoclax (at dose determined in Phase I) + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. In this arm venetoclax was administered as follows: Cycle 1 Days 4-10; Cycles 2-8 Days 1-10, Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. In this arm venetoclax was administered as follows: Cycle 1 Days 4-8; Cycles 2-8 Days 1-5. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Total of all reporting groups
Overall Number of Baseline Participants		7	3	8	6	208	7	7	6	6	6	264
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	7 participants	3 participants	8 participants	6 participants	208 participants	7 participants	7 participants	6 participants	6 participants	6 participants	264 participants
		67.0 (9.2)	61.0 (13.1)	57.0 (9.5)	56.3 (11.9)	61.4 (12.8)	52.1 (16.2)	60.9 (6.3)	66.7 (4.2)	60.5 (13.7)	66.8 (6.7)	61.2 (12.5)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	7 participants	3 participants	8 participants	6 participants	208 participants	7 participants	7 participants	6 participants	6 participants	6 participants	264 participants
	Female	3 42.9%	2 66.7%	2 25.0%	2 33.3%	94 45.2%	2 28.6%	5 71.4%	4 66.7%	4 66.7%	2 33.3%	120 45.5%
	Male	4 57.1%	1 33.3%	6 75.0%	4 66.7%	114 54.8%	5 71.4%	2 28.6%	2 33.3%	2 33.3%	4 66.7%	144 54.5%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	7 participants	3 participants	8 participants	6 participants	208 participants	7 participants	7 participants	6 participants	6 participants	6 participants	264 participants
	Hispanic or Latino	0 0.0%	0 0.0%	0 0.0%	0 0.0%	4 1.9%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	4 1.5%
	Not Hispanic or Latino	6 85.7%	1 33.3%	2 25.0%	3 50.0%	151 72.6%	6 85.7%	3 42.9%	4 66.7%	5 83.3%	6 100.0%	187 70.8%
	Unknown or Not Reported	1 14.3%	2 66.7%	6 75.0%	3 50.0%	53 25.5%	1 14.3%	4 57.1%	2 33.3%	1 16.7%	0 0.0%	73 27.7%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	7 participants	3 participants	8 participants	6 participants	208 participants	7 participants	7 participants	6 participants	6 participants	6 participants	264 participants
	American Indian or Alaska Native	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%
	Asian	0 0.0%	0 0.0%	0 0.0%	0 0.0%	5 2.4%	0 0.0%	1 14.3%	0 0.0%	0 0.0%	0 0.0%	6 2.3%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%	0 0.0%	3 1.4%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	3 1.1%
	Black or African American	0 0.0%	0 0.0%	0 0.0%	0 0.0%	4 1.9%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	4 1.5%
	White	6 85.7%	1 33.3%	2 25.0%	2 33.3%	154 74.0%	7 100.0%	2 28.6%	4 66.7%	5 83.3%	4 66.7%	187 70.8%
	More than one race	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%
	Unknown or Not Reported	1 14.3%	2 66.7%	6 75.0%	4 66.7%	42 20.2%	0 0.0%	4 57.1%	2 33.3%	1 16.7%	2 33.3%	64 24.2%

Outcome Measures

1. Primary Outcome

Title	Safety: Number of Participants With Dose-Limiting Toxicities (DLTs)
Description	DLTs were reported according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0). Decrease in B cells, lymphopenia, and leukopenia caused by lymphopenia were not considered DLTs but instead were expected outcomes of study treatment. Any Grade >/= 3 adverse event, that was attributed to having a reasonable possibility of being related to the combined administration of venetoclax plus R-CHOP or G-CHOP, that could not be attributed by the investigator to an alternative, clearly identifiable cause such as tumor progression, concurrent illness or medical condition, or concomitant medication and that occurred during the DLT observation period (start of venetoclax treatment through end of Cycle 2) was considered a DLT for dose-escalation purposes. Grade 3 or 4 neutropenia or thrombocytopenia identified on Day 1 of Cycle 2 or 3, resulting in dose delay were considered DLTs.
Time Frame	Start of venetoclax administration (Cycle 1 Day 4 or 3 days after first CHOP dose) up to end of Cycle 2 (cycle length = 21 days)

Outcome Measure Data

Analysis Population Description

Safety population: All participants who enrolled in the study and received any amount of venetoclax or R-CHOP/G-CHOP were included in the safety population for safety analyses. Here, participants in the Dose Finding phase were analyzed.

Arm/Group Title	Venetoclax 200 mg + R-CHOP	Venetoclax 400 mg + R-CHOP	Venetoclax 600 mg + R-CHOP	Venetoclax 800mg + R-CHOP	Venetoclax 200mg + G-CHOP	Venetoclax 400mg + G-CHOP	Venetoclax 600mg + G-CHOP	Venetoclax 800 mg + G-CHOP A	Venetoclax 800 mg + G-CHOP B
Arm/Group Description:	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Venetoclax + G-CHOP 800 mg A Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. In this arm venetoclax was delivered in Cycle 1 on Days 4-10 and Cycles 2-8 on Days 1-10. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. In this arm ventoclax was delivered in Cycle 1 on Days 4-8 and Cycles 2-8 on Days 1-5. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.
Overall Number of Participants Analyzed	7	3	8	6	7	7	6	6	6
Measure Type: Number; Unit of Measure: Participants
	1	0	1	0	2	1	1	0	0

2. Primary Outcome

Title	Percentage of Previously Untreated DLBCL Participants With Complete Response (CR) Defined by Positron Emission Tomography-Computed Tomography (PET/CT) Scan Using the Modified Lugano Classification Assessed by Independent Review Committee (IRC)
Description	CR was defined as follows according to modified Lugano classification for PET/CT-based response: Lymph nodes and extra-lymphatic sites with score 1, 2, or 3 with or without a residual mass on 5-point scale with 1) no uptake above background; 2) uptake </= mediastinum; 3) uptake < mediastinum but </= liver. No evidence of fluorodeoxyglucose (FDG)-uptake disease in marrow. If the bone marrow was involved by lymphoma prior to treatment, the infiltrate must have cleared on repeat bone marrow biopsy
Time Frame	Baseline up to end of treatment (up to approximately 6 months)

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population: All participants who enrolled in the study were included in the ITT population. Data reported for all participants for whom data were available.

Arm/Group Title	Venetoclax + R-CHOP 800 mg Phase II
Arm/Group Description:	Phase II: Participants received 6 cycles of CHOP and 8 cycles of venetoclax (at dose determined in Phase I) + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.
Overall Number of Participants Analyzed	211
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
	68.2; (61.50 to 74.47)

3. Primary Outcome

Title	Percentage of Participants With CR Defined by PET/CT Scan in Previously Untreated DLBCL Co-Expressing Both Bcl-2 and c-Myc Proteins (DE-DLBCL) Participants Assessed by IRC
Description	CR was defined as follows according to modified Lugano classification for PET/CT-based response: Lymph nodes and extra-lymphatic sites with score 1, 2, or 3 with or without a residual mass on 5-point scale with 1) no uptake above background; 2) uptake </= mediastinum; 3) uptake < mediastinum but </= liver. No evidence of fluorodeoxyglucose (FDG)-uptake disease in marrow. If the bone marrow was involved by lymphoma prior to treatment, the infiltrate must have cleared on repeat bone marrow biopsy.
Time Frame	Baseline up to end of treatment (up to approximately 6 months)

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population: All participants who enrolled in the study were included in the ITT population. Data reported for subgroup of the ITT, DE Participants.

Arm/Group Title	Venetoclax + R-CHOP 800 mg Phase II
Arm/Group Description:	Phase II: Participants received 6 cycles of CHOP and 8 cycles of venetoclax (at dose determined in Phase I) + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.
Overall Number of Participants Analyzed	81
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
	66.7; (55.32 to 76.76)

4. Secondary Outcome

Title	Venetoclax Plasma PK: Area Under the Plasma Concentration-Time Curve (AUC)
Description	AUC was calculated based on measurement of venetoclax concentration in plasma over time. Venetoclax exposure was pooled across Phase I and II for the R-CHOP 800 mg cohorts. Data are reported as hour*micrograms per milliliter (hr*mcg/mL)
Time Frame	Predose (within 30 minutes) & 2, 4, 6, 8 hours (Hr) postdose on Cycle 1 Day 4 (cycle length = 21 days)

Outcome Measure Data

Analysis Population Description

PK evaluable population: All patients who received study drug and provided at least one post-treatment PK sample for whom data were available. Reporting according to study drug received. One participant mistakenly received only 100 mg instead of the planned 200 mg dose and was reported in a separate arm for PK outcome measures.

Arm/Group Title	Venetoclax 800mg + R-CHOP	Venetoclax 200 mg + R-CHOP	Venetoclax 400 mg + R-CHOP	Venetoclax 600 mg + R-CHOP	Venetoclax + R-CHOP 800 mg	Venetoclax 200mg + G-CHOP	Venetoclax 400mg + G-CHOP	Venetoclax 600mg + G-CHOP	Venetoclax + G-CHOP 800mg
Arm/Group Description:	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I and II: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.
Overall Number of Participants Analyzed	1	6	4	8	124	7	7	6	10
Mean (Standard Deviation); Unit of Measure: hr*mcg/mL
	.66 [1] (NA)	2.51 (.97)	3.87 (2.41)	3.70 (1.59)	4.51 (2.32)	2.55 (1.13)	4.33 (1.31)	5.13 (2.41)	6.20 (1.71)

[1]

N/A as there is only one participant in this cohort

5. Secondary Outcome

Title	Venetoclax Plasma PK: Time to Maximum Observed Plasma Concentration (Tmax)
Description	Tmax was determined based on measurement of venetoclax concentrations in plasma over time. Venetoclax exposure was pooled across Phase I and II for the R-CHOP 800 mg cohorts.
Time Frame	Predose (within 30 minutes) & 2, 4, 6, 8 Hr postdose on Cycle 1 Day 4 (cycle length = 21 days)

Outcome Measure Data

Analysis Population Description

PK evaluable population: All patients who received study drug and provided at least one post-treatment PK sample for whom data were available. Reporting according to study drug received. One participant mistakenly received only 100 mg instead of the planned 200 mg dose and was reported in a separate arm for PK outcome measures.

Arm/Group Title	Venetoclax + R-CHOP 100 mg	Venetoclax 200 mg + R-CHOP	Venetoclax 400 mg + R-CHOP	Venetoclax 600 mg + R-CHOP	Venetoclax 800mg + R-CHOP	Venetoclax 200mg + G-CHOP	Venetoclax 400mg + G-CHOP	Venetoclax 600mg + G-CHOP	Venetoclax + G-CHOP 800 mg
Arm/Group Description:	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.
Overall Number of Participants Analyzed	1	6	4	8	124	7	7	6	10
Mean (Standard Deviation); Unit of Measure: Hour
	4.0 [1] (NA)	4.59 (1.08)	6.50 (1.91)	5.52 (2.07)	5.53 (1.55)	5.72 (1.42)	6.56 (1.51)	5.30 (2.38)	5.79 (1.47)

[1]

N/A as there is only one participant in this cohort

6. Secondary Outcome

Title	Venetoclax Plasma PK: Maximum Observed Plasma Concentration (Cmax)
Description	Cmax was determined based on measurement of venetoclax concentrations in plasma over time. Venetoclax exposure was pooled across Phase I and II for the R-CHOP 800 mg cohorts. Data are reported as micrograms per milliliter
Time Frame	Predose (within 30 minutes) & 2, 4, 6, 8 Hr postdose on Cycle 1 Day 4 (cycle length = 21 days)

Outcome Measure Data

Analysis Population Description

PK evaluable population: All patients who received study drug and provided at least one post-treatment PK sample for whom data were available. Reporting according to study drug received. One participant mistakenly received only 100 mg instead of the planned 200 mg dose and was reported in a separate arm for PK outcome measures.

Arm/Group Title	Venetoclax + R-CHOP 100 mg	Venetoclax 200 mg + R-CHOP	Venetoclax 400 mg + R-CHOP	Venetoclax 600 mg + R-CHOP	Venetoclax 800mg + R-CHOP	Venetoclax 200mg + G-CHOP	Venetoclax 400mg + G-CHOP	Venetoclax 600mg + G-CHOP	Venetoclax + G-CHOP 800 mg
Arm/Group Description:	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.
Overall Number of Participants Analyzed	1	6	4	8	124	7	7	6	10
Mean (Standard Deviation); Unit of Measure: Ug/ML
	.09 [1] (NA)	.58 (.32)	.92 (.64)	.85 (.33)	1.15 (.48)	.52 (.21)	1.26 (.30)	1.00 (.58)	1.54 (.37)

[1]

N/A as there is only one participant in this cohort

7. Secondary Outcome

Title	Venetoclax Plasma PK: Minimum Plasma Concentration (Cmin) Within the Dosing Interval
Description	Cmin was determined based on measurement of venetoclax concentrations in plasma over time. Venetoclax exposure was pooled across Phase I and II for the R-CHOP 800 mg cohorts.
Time Frame	Predose (within 30 minutes) & 2, 4, 6, 8 Hr postdose on Cycle 1 Day 4 (cycle length = 21 days)

Outcome Measure Data

Analysis Population Description

PK evaluable population: All patients who received study drug and provided at least one post-treatment PK sample for whom data were available. Reporting according to study drug received. One participant mistakenly received only 100 mg instead of the planned 200 mg dose and was reported in a separate arm for PK outcome measures.

Arm/Group Title	Venetoclax + R-CHOP 100 mg	Venetoclax 200 mg + R-CHOP	Venetoclax 400 mg + R-CHOP	Venetoclax 600 mg + R-CHOP	Venetoclax 800mg + R-CHOP	Venetoclax 200mg + G-CHOP	Venetoclax 400mg + G-CHOP	Venetoclax 600mg + G-CHOP	Venetoclax + G-CHOP 800 mg
Arm/Group Description:	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.
Overall Number of Participants Analyzed	1	3	2	4	126	7	5	5	6
Mean (Standard Deviation); Unit of Measure: mcg/mL
	0.0714 (0.00)	0.522 (0.441)	0.253 (0.247)	0.387 (0.141)	0.640 (0.451)	0.134 (0.107)	0.395 (0.381)	0.612 (0.535)	0.628 (0.395)

8. Secondary Outcome

Title	Prednisone Plasma PK: AUC
Description	AUC was determined based on measurement of Predisone concentrations in plasma over time.
Time Frame	Predose (within 30 minutes) and 0.5, 1, 2, 4, 6 Hr after prednisone dose on Day 1 of Cycle 1 and 2 (cycle length = 21 days)

Outcome Measure Data

Analysis Population Description

PK evaluable population: All participants who received study drug and provided at least one post-treatment PK sample. A similar dose strength of prednisone (100 mg) was administered across the treatment arms/venetoclax dose groups. Hence, the data are presented as an overall summary in Cycles 1 and 2.

Arm/Group Title		Venetoclax PK Popluation
Arm/Group Description:		All participants in the study. Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. Phase II: Participants received 6 cycles of CHOP and 8 cycles of venetoclax (at dose determined in Phase I) + obinutuzumab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.
Overall Number of Participants Analyzed		54
Mean (Standard Deviation); Unit of Measure: hr*mcg/mL
Cycle 1, Day 1	Number Analyzed	52 participants
		195 (72.8)
Cycle 2, Day 1	Number Analyzed	54 participants
		184 (81.2)

9. Secondary Outcome

Title	Prednisone Plasma PK: Tmax
Description	Tmax was determined based on measurement of Predisone concentrations in plasma over time.
Time Frame	Predose (within 30 minutes) and 0.5, 1, 2, 4, 6 Hr after prednisone dose on Day 1 of Cycle 1 and 2 (cycle length = 21 days)

Outcome Measure Data

Analysis Population Description

PK evaluable population: All patients who received study drug and provided at least one post-treatment PK sample for whom data were available. A similar dose strength of prednisone (100 mg) was administered across the treatment arms/venetoclax dose groups. Hence, the data are presented as an overall summary in Cycles 1 and 2.

Arm/Group Title		Venetoclax PK Popluation
Arm/Group Description:		All participants in the study. Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. Phase II: Participants received 6 cycles of CHOP and 8 cycles of venetoclax (at dose determined in Phase I) + obinutuzumab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.
Overall Number of Participants Analyzed		54
Mean (Standard Deviation); Unit of Measure: Hour
Cycle 1, Day 1	Number Analyzed	52 participants
		2.19 (1.61)
Cycle 2, Day 1	Number Analyzed	54 participants
		3.80 (2.52)

10. Secondary Outcome

Title	Prednisone Plasma PK: Cmax
Description	Cmax was determined based on measurement of Predisone concentrations in plasma over time.
Time Frame	Predose (within 30 minutes) and 0.5, 1, 2, 4, 6 Hr after prednisone dose on Day 1 of Cycle 1 and 2 (cycle length = 21 days)

Outcome Measure Data

Analysis Population Description

PK evaluable population: All patients who received study drug and provided at least one post-treatment PK sample for whom data were available. A similar dose strength of prednisone (100 mg) was administered across the treatment arms/venetoclax dose groups. Hence, the data are presented as an overall summary in Cycles 1 and 2.

Arm/Group Title		Venetoclax PK Popluation
Arm/Group Description:		All participants in the study. Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. Phase II: Participants received 6 cycles of CHOP and 8 cycles of venetoclax (at dose determined in Phase I) + obinutuzumab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.
Overall Number of Participants Analyzed		54
Mean (Standard Deviation); Unit of Measure: Ng/ML
Cycle 1, Day 1	Number Analyzed	52 participants
		49.9 (28.7)
Cycle 2, Day 1	Number Analyzed	54 participants
		43.2 (17.6)

11. Secondary Outcome

Title	Rituximab PK: Cmax
Description	Cmax was determined using the post-dose rituximab plasma concentrations at the 800 mg Venetoclax Dose using the end of infusion time point on Cycle 1 Day 1.
Time Frame	End of Infusion on Cycle 1 Day 1 (cycle length = 21 days)

Outcome Measure Data

Analysis Population Description

PK evaluable population: All patients who received study drug and provided at least one post-treatment PK sample for whom data were available. The Cmax of rituximab is presented at the 800 mg Venetoclax dose group. Hence, the data is not presented by the treatment arms/Venetoclax dose groups.

Arm/Group Title	Venetoclax 800 mg
Arm/Group Description:	All participants in the study, who received 800 mg venetoclax. Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. Phase II: Participants received 6 cycles of CHOP and 8 cycles of venetoclax (at dose determined in Phase I) + obinutuzumab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.
Overall Number of Participants Analyzed	7
Mean (Standard Deviation); Unit of Measure: mcg/mL
	173 (39.4)

12. Secondary Outcome

Title	Rituximab PK: Cmin Within the Dosing Interval
Description	Cmin was determined using the pre-dose rituximab plasma concentrations at the 800 mg Venetoclax Dose on Day 1 of Cycle 2.
Time Frame	Pre-dose on Cycle 2 Day 1 (cycle length = 21 days)

Outcome Measure Data

Analysis Population Description

PK evaluable population: All patients who received study drug and provided at least one post-treatment PK sample for whom data were available. The Cmin of rituximab is presented at the 800 mg Venetoclax dose group. Hence, the data is not presented by the treatment arms/Venetoclax dose groups.

Arm/Group Title	Venetoclax 800 mg
Arm/Group Description:	All participants in the study, who received 800 mg venetoclax. Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. Phase II: Participants received 6 cycles of CHOP and 8 cycles of venetoclax (at dose determined in Phase I) + obinutuzumab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.
Overall Number of Participants Analyzed	8
Mean (Standard Deviation); Unit of Measure: mcg/mL
	26.1 (13)

13. Secondary Outcome

Title	Obinutuzumab PK: Cmax
Description	Cmax was determined using the post-dose obinutuzumab plasma concentrations at the 800 mg Venetoclax Dose using the end of infusion time point on Cycle 1 Day 1.
Time Frame	End of Infusion on Cycle 1 Day 1 (cycle length = 21 days)

Outcome Measure Data

Analysis Population Description

PK evaluable population: All patients who received study drug and provided at least one post-treatment PK sample for whom data were available. The Cmax of obinutuzumab is presented at the 800 mg Venetoclax dose group. Hence, the data is not presented by the treatment arms/Venetoclax dose groups.

Arm/Group Title	Venetoclax 800 mg
Arm/Group Description:	All participants in the study, who received 800 mg venetoclax. Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. Phase II: Participants received 6 cycles of CHOP and 8 cycles of venetoclax (at dose determined in Phase I) + obinutuzumab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.
Overall Number of Participants Analyzed	10
Mean (Standard Deviation); Unit of Measure: mcg/mL
	326 (76)

14. Secondary Outcome

Title	Cyclophosphamide PK: Cmax
Description	Cmax was determined using the post-dose Cyclophosphamide plasma concentrations on Cycle 1 Day 1.
Time Frame	End of Infusion on Cycle 1 Day 1 (cycle length = 21 days)

Outcome Measure Data

Analysis Population Description

PK evaluable population: All patients who received study drug and provided at least one post-treatment PK sample for whom data were available. Given a single dose strength of Cyclophosphamide was administered across the different Venetoclax dose groups and treatment arms, hence the data are presented as an overall summary.

Arm/Group Title	Venetoclax PK Popluation
Arm/Group Description:	All participants in the study. Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. Phase II: Participants received 6 cycles of CHOP and 8 cycles of venetoclax (at dose determined in Phase I) + obinutuzumab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.
Overall Number of Participants Analyzed	36
Mean (Standard Deviation); Unit of Measure: mcg/mL
	32.1 (7.51)

15. Secondary Outcome

Title	Doxorubicin PK: Cmax
Description	Cmax was determined using the post-dose Doxorubicin plasma concentrations.
Time Frame	End of Infusion on Cycle 1 Day 1 (cycle length = 21 days)

Outcome Measure Data

Analysis Population Description

PK evaluable population: All patients who received study drug and provided at least one post-treatment PK sample for whom data were available. Given a single dose strength of Doxorubicin was administered across the different Venetoclax dose groups and treatment arms, hence the data are presented as an overall summary.

Arm/Group Title	Venetoclax PK Popluation
Arm/Group Description:	All participants in the study. Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. Phase II: Participants received 6 cycles of CHOP and 8 cycles of venetoclax (at dose determined in Phase I) + obinutuzumab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.
Overall Number of Participants Analyzed	24
Mean (Standard Deviation); Unit of Measure: mcg/mL
	1260 (911)

16. Secondary Outcome

Title	Vincristine PK: Cmax
Description	Cmax was determined using the post-dose Vincristine plasma concentrations.
Time Frame	End of Infusion on Cycle 1 Day 1 (cycle length = 21 days)

Outcome Measure Data

Analysis Population Description

PK evaluable population: All patients who received study drug and provided at least one post-treatment PK sample for whom data were available. Given a single dose strength of Vincristine was administered across the different Venetoclax dose groups and treatment arms, hence the data are presented as an overall summary.

Arm/Group Title	Venetoclax PK Popluation
Arm/Group Description:	All participants in the study. Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. Phase II: Participants received 6 cycles of CHOP and 8 cycles of venetoclax (at dose determined in Phase I) + obinutuzumab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.
Overall Number of Participants Analyzed	28
Mean (Standard Deviation); Unit of Measure: mcg/mL
	54.0 (44.6)

17. Secondary Outcome

Title	Percentage of Participants With Objective Response Defined as Partial Response (PR) or Complete Response (CR) Defined by Positron Emission Tomography-Computed Tomography (PET/CT) Using the Modified Lugano Classification Assessed by IRC
Description	Objective Response defined as PR (partial response) or CR (complete response) at end of treatment. CR: Lymph nodes and extra-lymphatic sites with score 1, 2 or 3 on a 5-point scale (with a higher score being a worse outcome). No evidence of fluorodeoxyglucose (FDG)-uptake disease in marrow. If the bone marrow was involved by lymphoma prior to treatment, the infiltrate must have cleared on repeat bone marrow biopsy. PR: Lymph nodes and extralymphatic sites with score of 4 or 5 on the 5-point scale with reduced uptake compared with baseline and residual mass(es) of any size. CT-based response criteria for PR must also be met. No new lesions. In bone marrow residual uptake could be higher than in normal marrow but must be reduced compared with baseline; persistent focal changes in the marrow to be considered for further evaluation with magnetic resonance imaging (MRI) or biopsy or an interval scan. OR=PR+CR
Time Frame	Baseline to end of treatment (up to approximately 6 months)

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population: All participants who enrolled in the study were included in the ITT population. Data reported for all participants for whom data were available.

Arm/Group Title	Venetoclax + R-CHOP 800 mg Phase II
Arm/Group Description:	Phase II: Participants received 6 cycles of CHOP and 8 cycles of venetoclax (at dose determined in Phase I) + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.
Overall Number of Participants Analyzed	211
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of Participants
	81.5; (75.61 to 86.51)

18. Secondary Outcome

Title	Percentage of Participants Who Are Alive and Without Disease Progression at Month 12
Description	Progressive disease (PD) was determined using the modified Lugano classification criteria. For PET-CT-based PD: Score 4 (uptake moderately > liver) or 5 (uptake markedly higher than liver and/or new lesions) with an increase in intensity of uptake from baseline in target nodes and nodal lesions, new FDG-uptake foci of extranodal lesions consistent with lymphoma at interim or end-of-treatment assessment, no non-measured lesions, new FDG-uptake foci consistent with lymphoma, new or recurrent FDG-uptake foci in bone marrow. For CT-based PD: >/= 50% decrease in SPD of up to 6 target measureable nodes and extranodal sites; non-measured lesion should be absent/normal, have regressed, but not increased; no new lesions.
Time Frame	Month 12

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population: All participants who enrolled in the study were included in the ITT population. Data reported for all participants for whom data were available.

Arm/Group Title	Venetoclax 200 mg + R-CHOP	Venetoclax 400 mg + R-CHOP	Venetoclax 600 mg + R-CHOP	Venetoclax 800mg + R-CHOP	Venetoclax + R-CHOP 800 mg Phase II	Venetoclax 200mg + G-CHOP	Venetoclax 400mg + G-CHOP	Venetoclax 600mg + G-CHOP	Venetoclax 800 mg + G-CHOP A	Venetoclax 800 mg + G-CHOP B
Arm/Group Description:	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase II: Participants received 6 cycles of CHOP and 8 cycles of venetoclax (at dose determined in Phase I) + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Venetoclax + G-CHOP 800 mg A Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. In this arm venetoclax was delivered in Cycle 1 on Days 4-10 and Cycles 2-8 on Days 1-10. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. In this arm ventoclax was delivered in Cycle 1 on Days 4-8 and Cycles 2-8 on Days 1-5. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.
Overall Number of Participants Analyzed	7	3	8	6	211	7	7	6	6	6
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of Participants
	85.71; (59.79 to 100.00)	100.00; (100.00 to 100.00)	87.50; (64.58 to 100.00)	66.67; (28.95 to 100.00)	88.99; (82.65 to 92.10)	100.00; (100.00 to 100.00)	75.00; (32.57 to 100.00)	100.00; (100.00 to 100.00)	100.00; (100.00 to 100.00)	100.00; (100.00 to 100.00)

19. Secondary Outcome

Title	Percentage of Participants With CR Defined by Computed Tomography (CT) Scan Using the Modified Lugano Classification
Description	CR was defined as follows according to modified Lugano classification for CT-based response: Target nodes/nodal masses must have regressed to </= 1.5 cm in longest transverse diameter of a lesion (LDi), no extra-lymphatic sites of disease, absence of non-measured lesions, organ enlargement must have regressed to normal, no new lesions, and if the bone marrow was involved by lymphoma prior to treatment, the infiltrate must have cleared on repeat bone marrow biopsy.
Time Frame	Baseline up to end of treatment (approx. 6 months)

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population: All participants who enrolled in the study were included in the ITT population. Data reported for all participants for whom data were available.

Arm/Group Title	Venetoclax + R-CHOP 800 mg Phase II
Arm/Group Description:	Phase II: Participants received 6 cycles of CHOP and 8 cycles of venetoclax (at dose determined in Phase I) + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.
Overall Number of Participants Analyzed	211
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of Participants
	37.4; (30.89 to 44.35)

20. Secondary Outcome

Title	Safety: Percentage of Participants With Adverse Events
Description	An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Time Frame	Baseline up to approximately 36 months

Outcome Measure Data

Analysis Population Description

Safety population: All patients who enrolled in the study and received any amount of venetoclax or R-CHOP/G-CHOP were included in the safety population for safety analyses

Arm/Group Title	Venetoclax 200 mg + R-CHOP	Venetoclax 400 mg + R-CHOP	Venetoclax 600 mg + R-CHOP	Venetoclax 800mg + R-CHOP	Venetoclax + R-CHOP 800 mg Phase II	Venetoclax 200mg + G-CHOP	Venetoclax 400mg + G-CHOP	Venetoclax 600mg + G-CHOP	Venetoclax 800 mg + G-CHOP A	Venetoclax 800 mg + G-CHOP B
Arm/Group Description:	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase II: Participants received 6 cycles of CHOP and 8 cycles of venetoclax (at dose determined in Phase I) + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Venetoclax + G-CHOP 800 mg A Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. In this arm venetoclax was delivered in Cycle 1 on Days 4-10 and Cycles 2-8 on Days 1-10. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. In this arm ventoclax was delivered in Cycle 1 on Days 4-8 and Cycles 2-8 on Days 1-5. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.
Overall Number of Participants Analyzed	7	3	8	6	208	7	7	6	6	6
Measure Type: Number; Unit of Measure: Percentage of Participants
	100.00	100.00	100.00	100.00	99.0	100.00	100.00	100.00	100.00	100.00

21. Secondary Outcome

Title	Safety: Percentage of Participants Maintaining Relative Dose Intensity of CHOP Chemotherapy
Description	Maintenance of relative dose intensity was defined as a dose intensity of >/= 90%.
Time Frame	Baseline up to Cycle 6 (cycle length = 21 days)

Outcome Measure Data

Analysis Population Description

Safety population: All patients who enrolled in the study and received any amount of venetoclax or R-CHOP/G-CHOP were included in the safety population for safety analyses. Overall R-CHOP and G-CHOP arms were analyzed for this outcome measure.

Arm/Group Title		Venetoclax + R-CHOP Arm	Venetoclax 600mg + G-CHOP
Arm/Group Description:		Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + rituximab. Each cycle consisted of 21 days. Phase II: Participants received 6 cycles of CHOP and 8 cycles of venetoclax (at dose determined in Phase I) + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.
Overall Number of Participants Analyzed		232	32
Measure Type: Number; Unit of Measure: Percentage of participants
Cyclophosphamide	Number Analyzed	229 participants	31 participants
		89.5	77.4
Doxorubicin	Number Analyzed	229 participants	31 participants
		88.6	77.4
Vincristine	Number Analyzed	232 participants	32 participants
		86.6	78.1
Prednisone	Number Analyzed	231 participants	32 participants
		87.4	81.3

22. Secondary Outcome

Title	Relative Dose Intensity of Venetoclax
Description	Dose intensity was categorized as < 80%, 80% to < 85%, 85% to < 90%, or >/= 90%.
Time Frame	Baseline up to Cycle 6 (cycle length = 21 days)

Outcome Measure Data

Analysis Population Description

Safety population: All patients who enrolled in the study and received any amount of venetoclax or R-CHOP/G-CHOP were included in the safety population for safety analyses

Arm/Group Title		Venetoclax 200 mg + R-CHOP	Venetoclax 400 mg + R-CHOP	Venetoclax 600 mg + R-CHOP	Venetoclax 800mg + R-CHOP	Venetoclax + R-CHOP 800 mg Phase II	Venetoclax 200mg + G-CHOP	Venetoclax 400mg + G-CHOP	Venetoclax 600mg + G-CHOP	Venetoclax + G-CHOP 800 mg	Venetoclax + G-CHOP 800mg B
Arm/Group Description:		Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase II: Participants received 6 cycles of CHOP and 8 cycles of venetoclax (at dose determined in Phase I) + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days.
Overall Number of Participants Analyzed		7	3	8	6	208	7	7	6	6	6
Measure Type: Number; Unit of Measure: Percentage of Partcipants
<80%	Number Analyzed	7 participants	3 participants	8 participants	6 participants	204 participants	7 participants	7 participants	6 participants	6 participants	6 participants
		71.4	0.00	12.5	0.00	26.0	100.00	14.3	50.0	83.3	100.0
80-<85%	Number Analyzed	7 participants	3 participants	8 participants	6 participants	204 participants	7 participants	7 participants	6 participants	6 participants	6 participants
		0.00	0.00	12.5	0.00	3.4	0.00	14.3	16.7	0.00	0.00
85-<90%	Number Analyzed	7 participants	3 participants	8 participants	6 participants	204 participants	7 participants	7 participants	6 participants	6 participants	6 participants
		0.00	0.00	12.5	0.00	2.9	0.00	0.00	0.00	16.7	0.00
>=90%	Number Analyzed	7 participants	3 participants	8 participants	6 participants	204 participants	7 participants	7 participants	6 participants	6 participants	6 participants
		28.6	100.00	62.5	100.00	67.6	0.00	71.4	33.3	0.00	0.00

Adverse Events

Time Frame	Baseline up to approximately 67 months
Adverse Event Reporting Description	Safety population: All participants, who were enrolled in the study and received any amount of venetoclax or R-CHOP/G-CHOP were included in the safety population.
Arm/Group Title	Venetoclax 200 mg +R-CHOP		Venetoclax 400 mg +R-CHOP		Venetoclax 600 mg +R-CHOP		Venetoclax 800 mg +R-CHOP		Venetoclax 800 mg +R-CHOP Phase II		Venetoclax 200 mg +G-CHOP		Venetoclax 400 mg +G-CHOP		Venetoclax 600 mg +G-CHOP		Venetoclax 800 mg + G-CHOP A		Venetoclax 800 mg +G-CHOP B
Arm/Group Description	Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.		Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.		Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.		Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.		Phase II: Participants received 6 cycles of CHOP and 8 cycles of venetoclax (at dose determined in Phase I) + rituximab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.		Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.		Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.		Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.		Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. In this arm venetoclax was administered as follows: Cycle 1 Days 4-10; Cycles 2-8 Days 1-10, Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.		Phase I: Participants received 6 cycles of CHOP and 8 cycles of venetoclax + obinutuzumab. Each cycle consisted of 21 days. In this arm venetoclax was administered as follows: Cycle 1 Days 4-8; Cycles 2-8 Days 1-5. Participants who experienced ongoing response without excessive toxicity could receive up to eight cycles of CHOP following discussion between the investigator and the Medical Monitor.
All-Cause Mortality
	Venetoclax 200 mg +R-CHOP		Venetoclax 400 mg +R-CHOP		Venetoclax 600 mg +R-CHOP		Venetoclax 800 mg +R-CHOP		Venetoclax 800 mg +R-CHOP Phase II		Venetoclax 200 mg +G-CHOP		Venetoclax 400 mg +G-CHOP		Venetoclax 600 mg +G-CHOP		Venetoclax 800 mg + G-CHOP A		Venetoclax 800 mg +G-CHOP B
	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	1/7 (14.29%)		0/3 (0.00%)		1/8 (12.50%)		4/6 (66.67%)		33/208 (15.87%)		1/7 (14.29%)		1/7 (14.29%)		0/6 (0.00%)		0/6 (0.00%)		0/6 (0.00%)
Serious Adverse Events
	Venetoclax 200 mg +R-CHOP		Venetoclax 400 mg +R-CHOP		Venetoclax 600 mg +R-CHOP		Venetoclax 800 mg +R-CHOP		Venetoclax 800 mg +R-CHOP Phase II		Venetoclax 200 mg +G-CHOP		Venetoclax 400 mg +G-CHOP		Venetoclax 600 mg +G-CHOP		Venetoclax 800 mg + G-CHOP A		Venetoclax 800 mg +G-CHOP B
	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	5/7 (71.43%)		2/3 (66.67%)		4/8 (50.00%)		3/6 (50.00%)		116/208 (55.77%)		5/7 (71.43%)		4/7 (57.14%)		3/6 (50.00%)		5/6 (83.33%)		5/6 (83.33%)
Blood and lymphatic system disorders
AGRANULOCYTOSIS † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
ANAEMIA † 1	0/7 (0.00%)	0	1/3 (33.33%)	1	0/8 (0.00%)	0	0/6 (0.00%)	0	4/208 (1.92%)	4	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
FEBRILE NEUTROPENIA † 1	3/7 (42.86%)	5	0/3 (0.00%)	0	1/8 (12.50%)	2	2/6 (33.33%)	3	57/208 (27.40%)	89	1/7 (14.29%)	1	2/7 (28.57%)	2	0/6 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	3
HAEMOLYTIC ANAEMIA † 1	1/7 (14.29%)	1	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	0/208 (0.00%)	0	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
LEUKOPENIA † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
NEUTROPENIA † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	19/208 (9.13%)	24	1/7 (14.29%)	1	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1
THROMBOCYTOPENIA † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	2/208 (0.96%)	2	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	2/6 (33.33%)	4	0/6 (0.00%)	0
Cardiac disorders
ACUTE CORONARY SYNDROME † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	0/208 (0.00%)	0	1/7 (14.29%)	1	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
ATRIAL FIBRILLATION † 1	1/7 (14.29%)	1	1/3 (33.33%)	1	0/8 (0.00%)	0	0/6 (0.00%)	0	6/208 (2.88%)	6	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
ATRIOVENTRICULAR BLOCK † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	2/208 (0.96%)	2	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
CARDIAC ARREST † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	0/208 (0.00%)	0	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1
CARDIAC FAILURE † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
CARDIAC FAILURE CONGESTIVE † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
CARDIOGENIC SHOCK † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
CARDIOMYOPATHY † 1	0/7 (0.00%)	0	1/3 (33.33%)	1	0/8 (0.00%)	0	0/6 (0.00%)	0	0/208 (0.00%)	0	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
LEFT VENTRICULAR FAILURE † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
MYOCARDIAL ISCHAEMIA † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
SINUS TACHYCARDIA † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
SUPRAVENTRICULAR TACHYCARDIA † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
TACHYCARDIA † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1
Eye disorders
OPTIC NEUROPATHY † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Gastrointestinal disorders
DIARRHOEA † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	4/208 (1.92%)	4	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
DIVERTICULAR PERFORATION † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	2	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
DUODENAL STENOSIS † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
DYSPHAGIA † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	0/208 (0.00%)	0	0/7 (0.00%)	0	0/7 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0
ENTEROCOLITIS † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
GASTRIC DILATATION † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
GASTRIC PERFORATION † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
GASTRIC STENOSIS † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
GASTRIC ULCER † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
GASTRIC ULCER PERFORATION † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	0/208 (0.00%)	0	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0
GASTROINTESTINAL PAIN † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
HAEMATEMESIS † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
ILEAL PERFORATION † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
ILEUS † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	0/208 (0.00%)	0	0/7 (0.00%)	0	0/7 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0
NAUSEA † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
OBSTRUCTION GASTRIC † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
OESOPHAGEAL STENOSIS † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	0/208 (0.00%)	0	1/7 (14.29%)	1	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
PANCREATITIS † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	2/208 (0.96%)	2	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
RECTAL HAEMORRHAGE † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
SMALL INTESTINAL OBSTRUCTION † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	2	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
STOMATITIS † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
UPPER GASTROINTESTINAL HAEMORRHAGE † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
VOMITING † 1	0/7 (0.00%)	0	1/3 (33.33%)	1	0/8 (0.00%)	0	0/6 (0.00%)	0	5/208 (2.40%)	5	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
General disorders
ASTHENIA † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	0/208 (0.00%)	0	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0
FATIGUE † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	2/208 (0.96%)	2	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
INFLAMMATION † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
PYREXIA † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	7/208 (3.37%)	7	1/7 (14.29%)	2	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
SUDDEN CARDIAC DEATH † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Hepatobiliary disorders
BILE DUCT STONE † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
CHOLECYSTITIS † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	0/208 (0.00%)	0	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1
CHOLECYSTITIS ACUTE † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
DRUG-INDUCED LIVER INJURY † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	0/208 (0.00%)	0	1/7 (14.29%)	1	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Immune system disorders
HYPOGAMMAGLOBULINAEMIA † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Infections and infestations
ACUTE SINUSITIS † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
ATYPICAL PNEUMONIA † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	2/208 (0.96%)	2	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
BACTERIAL SEPSIS † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
BRONCHITIS † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
CELLULITIS † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
CLOSTRIDIUM COLITIS † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
CLOSTRIDIUM DIFFICILE INFECTION † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
DEVICE RELATED INFECTION † 1	1/7 (14.29%)	1	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	0/208 (0.00%)	0	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
DIVERTICULITIS † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	0/208 (0.00%)	0	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0
EMPYEMA † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	0/208 (0.00%)	0	0/7 (0.00%)	0	1/7 (14.29%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
ESCHERICHIA PYELONEPHRITIS † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
ESCHERICHIA URINARY TRACT INFECTION † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
GASTROENTERITIS † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
GASTROENTERITIS NOROVIRUS † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	1/6 (16.67%)	1	0/208 (0.00%)	0	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
HERPES SIMPLEX † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
INFECTION † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	4/208 (1.92%)	5	1/7 (14.29%)	1	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
INFLUENZA † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	2/208 (0.96%)	2	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
LOWER RESPIRATORY TRACT INFECTION † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	2/208 (0.96%)	2	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
LUNG INFECTION † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	3/208 (1.44%)	4	0/7 (0.00%)	0	1/7 (14.29%)	1	0/6 (0.00%)	0	1/6 (16.67%)	2	0/6 (0.00%)	0
MENINGITIS VIRAL † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	1/6 (16.67%)	1	0/208 (0.00%)	0	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
NASOPHARYNGITIS † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
OOPHORITIS † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	0/208 (0.00%)	0	0/7 (0.00%)	0	1/7 (14.29%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
ORAL CANDIDIASIS † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
ORAL HERPES † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
PNEUMOCYSTIS JIROVECII INFECTION † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
PNEUMOCYSTIS JIROVECII PNEUMONIA † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	2/208 (0.96%)	2	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1
PNEUMONIA † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	9/208 (4.33%)	9	1/7 (14.29%)	1	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
PNEUMONIA RESPIRATORY SYNCYTIAL VIRAL † 1	1/7 (14.29%)	1	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	0/208 (0.00%)	0	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
PSEUDOMONAL SEPSIS † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	2/208 (0.96%)	3	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
RECTAL ABSCESS † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
RESPIRATORY TRACT INFECTION † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
RHINOVIRUS INFECTION † 1	1/7 (14.29%)	1	0/3 (0.00%)	0	1/8 (12.50%)	1	0/6 (0.00%)	0	0/208 (0.00%)	0	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
SEPSIS † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	1/6 (16.67%)	1	6/208 (2.88%)	6	0/7 (0.00%)	0	0/7 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0
SIALOADENITIS † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
SINUSITIS † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
SKIN INFECTION † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
STAPHYLOCOCCAL SEPSIS † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
UPPER RESPIRATORY TRACT INFECTION † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
URINARY TRACT INFECTION † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	2/208 (0.96%)	2	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
URINARY TRACT INFECTION PSEUDOMONAL † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
VASCULAR DEVICE INFECTION † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	2/208 (0.96%)	2	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Injury, poisoning and procedural complications
CONTUSION † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
INFUSION RELATED REACTION † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	1/8 (12.50%)	1	0/6 (0.00%)	0	1/208 (0.48%)	2	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
LIGAMENT RUPTURE † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	1/8 (12.50%)	1	0/6 (0.00%)	0	0/208 (0.00%)	0	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
POST LUMBAR PUNCTURE SYNDROME † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	1/7 (14.29%)	1	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
SPINAL FRACTURE † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
TOXICITY TO VARIOUS AGENTS † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Investigations
BLOOD POTASSIUM INCREASED † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	0/208 (0.00%)	0	1/7 (14.29%)	1	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
C-REACTIVE PROTEIN INCREASED † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	2	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Metabolism and nutrition disorders
DECREASED APPETITE † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
DEHYDRATION † 1	1/7 (14.29%)	1	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
DIABETES MELLITUS INADEQUATE CONTROL † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	2/208 (0.96%)	2	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
HYPERKALAEMIA † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	0/208 (0.00%)	0	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1	1/6 (16.67%)	1
HYPOKALAEMIA † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
HYPONATRAEMIA † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
TUMOUR LYSIS SYNDROME † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	1/8 (12.50%)	1	0/6 (0.00%)	0	0/208 (0.00%)	0	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Musculoskeletal and connective tissue disorders
BACK PAIN † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
JOINT SWELLING † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
PAIN IN EXTREMITY † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	2/208 (0.96%)	2	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
SPONDYLOLISTHESIS † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
ACUTE MYELOID LEUKAEMIA † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	3/208 (1.44%)	3	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
ADENOLYMPHOMA † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
GLIOBLASTOMA † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
HISTIOCYTOSIS † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	0/208 (0.00%)	0	0/7 (0.00%)	0	0/7 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0
LUNG NEOPLASM MALIGNANT † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	0/208 (0.00%)	0	1/7 (14.29%)	1	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
MYELODYSPLASTIC SYNDROME † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	1/8 (12.50%)	1	0/6 (0.00%)	0	2/208 (0.96%)	2	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Nervous system disorders
CAROTID SINUS SYNDROME † 1	1/7 (14.29%)	1	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	0/208 (0.00%)	0	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
EPILEPSY † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
HYPOGLOSSAL NERVE PARESIS † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
POLYNEUROPATHY † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
PRESYNCOPE † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
SYNCOPE † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	2/208 (0.96%)	3	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
TRANSIENT ISCHAEMIC ATTACK † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Psychiatric disorders
CONFUSIONAL STATE † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	0/208 (0.00%)	0	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0
PSYCHOTIC DISORDER † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	0/208 (0.00%)	0	1/7 (14.29%)	1	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Renal and urinary disorders
ACUTE KIDNEY INJURY † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	2/208 (0.96%)	2	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
CHRONIC OBSTRUCTIVE PULMONARY DISEASE † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
COUGH † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
DYSPNOEA † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	2/208 (0.96%)	2	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
HAEMOPTYSIS † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
INTERSTITIAL LUNG DISEASE † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	1/8 (12.50%)	1	0/6 (0.00%)	0	0/208 (0.00%)	0	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
ORGANISING PNEUMONIA † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	1/7 (14.29%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
PLEURAL EFFUSION † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
PNEUMOTHORAX † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
PRODUCTIVE COUGH † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
PULMONARY EMBOLISM † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	1/7 (14.29%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Skin and subcutaneous tissue disorders
RASH MACULO-PAPULAR † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Vascular disorders
EMBOLISM † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	0/208 (0.00%)	0	0/7 (0.00%)	0	1/7 (14.29%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
HYPOTENSION † 1	1/7 (14.29%)	1	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	2/208 (0.96%)	2	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
1 Term from vocabulary, MedDRA version 22.0; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0.05%
	Venetoclax 200 mg +R-CHOP		Venetoclax 400 mg +R-CHOP		Venetoclax 600 mg +R-CHOP		Venetoclax 800 mg +R-CHOP		Venetoclax 800 mg +R-CHOP Phase II		Venetoclax 200 mg +G-CHOP		Venetoclax 400 mg +G-CHOP		Venetoclax 600 mg +G-CHOP		Venetoclax 800 mg + G-CHOP A		Venetoclax 800 mg +G-CHOP B
	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	7/7 (100.00%)		3/3 (100.00%)		8/8 (100.00%)		6/6 (100.00%)		204/208 (98.08%)		7/7 (100.00%)		7/7 (100.00%)		6/6 (100.00%)		6/6 (100.00%)		6/6 (100.00%)
Blood and lymphatic system disorders
ANAEMIA † 1	4/7 (57.14%)	9	0/3 (0.00%)	0	1/8 (12.50%)	1	2/6 (33.33%)	2	73/208 (35.10%)	117	1/7 (14.29%)	1	1/7 (14.29%)	1	1/6 (16.67%)	4	5/6 (83.33%)	8	4/6 (66.67%)	5
FEBRILE NEUTROPENIA † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	1/8 (12.50%)	1	1/6 (16.67%)	3	9/208 (4.33%)	10	0/7 (0.00%)	0	4/7 (57.14%)	7	0/6 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0
HAEMOLYTIC ANAEMIA † 1	1/7 (14.29%)	1	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	0/208 (0.00%)	0	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
LEUKOPENIA † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	23/208 (11.06%)	47	0/7 (0.00%)	0	0/7 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0
NEUTROPENIA † 1	4/7 (57.14%)	9	2/3 (66.67%)	8	6/8 (75.00%)	18	3/6 (50.00%)	10	134/208 (64.42%)	409	2/7 (28.57%)	2	4/7 (57.14%)	17	5/6 (83.33%)	13	6/6 (100.00%)	16	2/6 (33.33%)	10
PANCYTOPENIA † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	1/8 (12.50%)	1	1/6 (16.67%)	1	0/208 (0.00%)	0	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
THROMBOCYTOPENIA † 1	4/7 (57.14%)	7	1/3 (33.33%)	2	3/8 (37.50%)	5	0/6 (0.00%)	0	52/208 (25.00%)	89	2/7 (28.57%)	3	3/7 (42.86%)	7	2/6 (33.33%)	6	4/6 (66.67%)	15	2/6 (33.33%)	5
Cardiac disorders
ANGINA PECTORIS † 1	1/7 (14.29%)	1	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	0/208 (0.00%)	0	0/7 (0.00%)	0	0/7 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0
ATRIAL FIBRILLATION † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	1/8 (12.50%)	1	0/6 (0.00%)	0	7/208 (3.37%)	8	1/7 (14.29%)	1	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1
CARDIAC FAILURE † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	1/7 (14.29%)	1	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
PALPITATIONS † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	1/8 (12.50%)	1	0/6 (0.00%)	0	8/208 (3.85%)	8	0/7 (0.00%)	0	1/7 (14.29%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
TACHYCARDIA † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	1/8 (12.50%)	1	0/6 (0.00%)	0	3/208 (1.44%)	3	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1
Congenital, familial and genetic disorders
ICHTHYOSIS † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	1/8 (12.50%)	1	0/6 (0.00%)	0	0/208 (0.00%)	0	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Ear and labyrinth disorders
EAR PAIN † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	1/7 (14.29%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
TINNITUS † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	1/7 (14.29%)	1	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Eye disorders
DRY EYE † 1	1/7 (14.29%)	1	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	4/208 (1.92%)	4	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
EYE PAIN † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0
LACRIMATION INCREASED † 1	2/7 (28.57%)	2	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	3/208 (1.44%)	3	0/7 (0.00%)	0	0/7 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0
PHOTOPHOBIA † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	0/208 (0.00%)	0	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1
VISION BLURRED † 1	1/7 (14.29%)	1	0/3 (0.00%)	0	1/8 (12.50%)	1	0/6 (0.00%)	0	7/208 (3.37%)	7	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
VITREOUS FLOATERS † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0
Gastrointestinal disorders
ABDOMINAL DISCOMFORT † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	4/208 (1.92%)	4	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0
ABDOMINAL DISTENSION † 1	2/7 (28.57%)	2	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	14/208 (6.73%)	15	0/7 (0.00%)	0	1/7 (14.29%)	1	0/6 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0
ABDOMINAL PAIN † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	1/8 (12.50%)	1	1/6 (16.67%)	1	30/208 (14.42%)	38	0/7 (0.00%)	0	1/7 (14.29%)	1	1/6 (16.67%)	1	3/6 (50.00%)	4	1/6 (16.67%)	1
ABDOMINAL PAIN UPPER † 1	0/7 (0.00%)	0	1/3 (33.33%)	1	1/8 (12.50%)	1	0/6 (0.00%)	0	7/208 (3.37%)	12	1/7 (14.29%)	1	1/7 (14.29%)	1	0/6 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0
CONSTIPATION † 1	1/7 (14.29%)	1	2/3 (66.67%)	2	3/8 (37.50%)	3	2/6 (33.33%)	2	67/208 (32.21%)	78	6/7 (85.71%)	7	3/7 (42.86%)	3	2/6 (33.33%)	2	2/6 (33.33%)	2	1/6 (16.67%)	1
DENTAL CARIES † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1
DENTAL CYST † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	0/208 (0.00%)	0	0/7 (0.00%)	0	1/7 (14.29%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
DIARRHOEA † 1	3/7 (42.86%)	10	2/3 (66.67%)	4	2/8 (25.00%)	2	3/6 (50.00%)	5	79/208 (37.98%)	133	5/7 (71.43%)	5	3/7 (42.86%)	6	2/6 (33.33%)	3	2/6 (33.33%)	4	1/6 (16.67%)	1
DRY MOUTH † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	5/208 (2.40%)	5	0/7 (0.00%)	0	0/7 (0.00%)	0	1/6 (16.67%)	2	1/6 (16.67%)	1	0/6 (0.00%)	0
DYSPEPSIA † 1	1/7 (14.29%)	1	1/3 (33.33%)	1	0/8 (0.00%)	0	1/6 (16.67%)	1	22/208 (10.58%)	27	1/7 (14.29%)	1	1/7 (14.29%)	1	1/6 (16.67%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0
DYSPHAGIA † 1	1/7 (14.29%)	1	0/3 (0.00%)	0	0/8 (0.00%)	0	1/6 (16.67%)	1	7/208 (3.37%)	9	1/7 (14.29%)	1	1/7 (14.29%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
FLATULENCE † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	4/208 (1.92%)	4	0/7 (0.00%)	0	1/7 (14.29%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
GASTRIC ULCER † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	0/208 (0.00%)	0	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0
GASTROINTESTINAL DISORDER † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	0/208 (0.00%)	0	0/7 (0.00%)	0	1/7 (14.29%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
GASTROOESOPHAGEAL REFLUX DISEASE † 1	1/7 (14.29%)	1	0/3 (0.00%)	0	1/8 (12.50%)	1	2/6 (33.33%)	2	6/208 (2.88%)	7	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0
GINGIVAL PAIN † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	1/6 (16.67%)	1	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0
HAEMORRHOIDS † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	1/6 (16.67%)	1	15/208 (7.21%)	17	0/7 (0.00%)	0	1/7 (14.29%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
MOUTH ULCERATION † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	1/8 (12.50%)	2	0/6 (0.00%)	0	7/208 (3.37%)	7	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
NAUSEA † 1	3/7 (42.86%)	3	2/3 (66.67%)	4	1/8 (12.50%)	1	5/6 (83.33%)	7	108/208 (51.92%)	172	3/7 (42.86%)	5	4/7 (57.14%)	7	3/6 (50.00%)	4	5/6 (83.33%)	10	4/6 (66.67%)	6
ORAL PAIN † 1	1/7 (14.29%)	1	0/3 (0.00%)	0	0/8 (0.00%)	0	1/6 (16.67%)	1	3/208 (1.44%)	3	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
PROCTALGIA † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	1/6 (16.67%)	1	2/208 (0.96%)	2	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
STOMATITIS † 1	2/7 (28.57%)	2	1/3 (33.33%)	1	1/8 (12.50%)	1	2/6 (33.33%)	2	24/208 (11.54%)	29	0/7 (0.00%)	0	0/7 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0
TOOTHACHE † 1	1/7 (14.29%)	1	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	2/208 (0.96%)	2	1/7 (14.29%)	1	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
VOMITING † 1	0/7 (0.00%)	0	1/3 (33.33%)	1	1/8 (12.50%)	1	2/6 (33.33%)	6	64/208 (30.77%)	111	5/7 (71.43%)	5	4/7 (57.14%)	8	0/6 (0.00%)	0	4/6 (66.67%)	6	1/6 (16.67%)	1
General disorders
ASTHENIA † 1	2/7 (28.57%)	2	1/3 (33.33%)	2	2/8 (25.00%)	2	0/6 (0.00%)	0	33/208 (15.87%)	41	2/7 (28.57%)	2	0/7 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0
CHEST PAIN † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	12/208 (5.77%)	12	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1
CHILLS † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	1/6 (16.67%)	1	12/208 (5.77%)	15	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
FATIGUE † 1	5/7 (71.43%)	5	0/3 (0.00%)	0	3/8 (37.50%)	3	2/6 (33.33%)	4	81/208 (38.94%)	104	5/7 (71.43%)	7	2/7 (28.57%)	2	2/6 (33.33%)	2	3/6 (50.00%)	4	1/6 (16.67%)	1
FEELING ABNORMAL † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	1/7 (14.29%)	1	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
GAIT DISTURBANCE † 1	1/7 (14.29%)	1	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	3/208 (1.44%)	3	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
INFLUENZA LIKE ILLNESS † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	3/208 (1.44%)	4	1/7 (14.29%)	1	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
INFUSION SITE EXTRAVASATION † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	0/208 (0.00%)	0	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1
MALAISE † 1	2/7 (28.57%)	2	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	5/208 (2.40%)	5	1/7 (14.29%)	2	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
MUCOSAL INFLAMMATION † 1	1/7 (14.29%)	1	0/3 (0.00%)	0	2/8 (25.00%)	2	1/6 (16.67%)	1	19/208 (9.13%)	28	1/7 (14.29%)	1	3/7 (42.86%)	3	0/6 (0.00%)	0	1/6 (16.67%)	1	1/6 (16.67%)	1
NON-CARDIAC CHEST PAIN † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	1/6 (16.67%)	1	0/208 (0.00%)	0	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
OEDEMA † 1	1/7 (14.29%)	1	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	3/208 (1.44%)	4	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
OEDEMA PERIPHERAL † 1	2/7 (28.57%)	2	0/3 (0.00%)	0	2/8 (25.00%)	2	0/6 (0.00%)	0	23/208 (11.06%)	26	0/7 (0.00%)	0	1/7 (14.29%)	1	0/6 (0.00%)	0	3/6 (50.00%)	3	1/6 (16.67%)	1
PAIN † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	7/208 (3.37%)	8	1/7 (14.29%)	1	1/7 (14.29%)	1	0/6 (0.00%)	0	1/6 (16.67%)	1	2/6 (33.33%)	2
PYREXIA † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	1/8 (12.50%)	1	2/6 (33.33%)	2	50/208 (24.04%)	68	0/7 (0.00%)	0	5/7 (71.43%)	7	2/6 (33.33%)	2	1/6 (16.67%)	1	2/6 (33.33%)	2
UNEVALUABLE EVENT † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	1/6 (16.67%)	1	0/208 (0.00%)	0	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Hepatobiliary disorders
CHOLELITHIASIS † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	0/208 (0.00%)	0	0/7 (0.00%)	0	0/7 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0
HYPERBILIRUBINAEMIA † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	3/208 (1.44%)	5	1/7 (14.29%)	1	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Immune system disorders
HYPERSENSITIVITY † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	0/208 (0.00%)	0	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1
HYPOGAMMAGLOBULINAEMIA † 1	1/7 (14.29%)	1	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Infections and infestations
ANORECTAL INFECTION † 1	1/7 (14.29%)	1	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	0/208 (0.00%)	0	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
BRONCHITIS † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	1/8 (12.50%)	2	0/6 (0.00%)	0	16/208 (7.69%)	18	0/7 (0.00%)	0	1/7 (14.29%)	1	1/6 (16.67%)	1	0/6 (0.00%)	0	1/6 (16.67%)	1
CAMPYLOBACTER GASTROENTERITIS † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	1/8 (12.50%)	1	0/6 (0.00%)	0	0/208 (0.00%)	0	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
CANDIDA INFECTION † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	3/208 (1.44%)	3	0/7 (0.00%)	0	1/7 (14.29%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
CELLULITIS † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	1/7 (14.29%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
CELLULITIS ORBITAL † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	0/208 (0.00%)	0	0/7 (0.00%)	0	1/7 (14.29%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
CLOSTRIDIUM DIFFICILE COLITIS † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	3/208 (1.44%)	3	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0
CLOSTRIDIUM DIFFICILE INFECTION † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	1/7 (14.29%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
CONJUNCTIVITIS † 1	1/7 (14.29%)	1	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	2/208 (0.96%)	2	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
DEVICE RELATED INFECTION † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0
ENTEROVIRUS INFECTION † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	1/7 (14.29%)	1	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
ERYSIPELAS † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	0/208 (0.00%)	0	0/7 (0.00%)	0	0/7 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0
FURUNCLE † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	0/208 (0.00%)	0	0/7 (0.00%)	0	1/7 (14.29%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
HERPES SIMPLEX † 1	1/7 (14.29%)	1	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
HERPES ZOSTER † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	1/7 (14.29%)	1	1/6 (16.67%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0
INFLUENZA † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	2/208 (0.96%)	2	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0
LUNG INFECTION † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	4/208 (1.92%)	5	1/7 (14.29%)	1	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
NASOPHARYNGITIS † 1	1/7 (14.29%)	1	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	8/208 (3.85%)	9	0/7 (0.00%)	0	1/7 (14.29%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1
ORAL CANDIDIASIS † 1	1/7 (14.29%)	1	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	8/208 (3.85%)	9	0/7 (0.00%)	0	0/7 (0.00%)	0	1/6 (16.67%)	1	1/6 (16.67%)	1	1/6 (16.67%)	1
ORAL FUNGAL INFECTION † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	2/208 (0.96%)	2	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1
ORAL HERPES † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	5/208 (2.40%)	6	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0
PNEUMOCYSTIS JIROVECII PNEUMONIA † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	1/6 (16.67%)	1	0/208 (0.00%)	0	1/7 (14.29%)	1	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
PNEUMONIA † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	5/208 (2.40%)	5	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0
PSEUDOMONAL BACTERAEMIA † 1	1/7 (14.29%)	1	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	0/208 (0.00%)	0	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
RHINITIS † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	7/208 (3.37%)	7	0/7 (0.00%)	0	0/7 (0.00%)	0	1/6 (16.67%)	2	0/6 (0.00%)	0	0/6 (0.00%)	0
SEPSIS † 1	1/7 (14.29%)	1	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	0/208 (0.00%)	0	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
SINUSITIS BACTERIAL † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	0/208 (0.00%)	0	0/7 (0.00%)	0	1/7 (14.29%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
SKIN INFECTION † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	3/208 (1.44%)	3	0/7 (0.00%)	0	1/7 (14.29%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
STAPHYLOCOCCAL INFECTION † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	1/7 (14.29%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
TOOTH ABSCESS † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0
UPPER RESPIRATORY TRACT INFECTION † 1	1/7 (14.29%)	1	0/3 (0.00%)	0	0/8 (0.00%)	0	1/6 (16.67%)	1	12/208 (5.77%)	15	2/7 (28.57%)	2	0/7 (0.00%)	0	1/6 (16.67%)	1	1/6 (16.67%)	2	1/6 (16.67%)	1
URINARY TRACT INFECTION † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	16/208 (7.69%)	22	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
VASCULAR DEVICE INFECTION † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1
VIRAL UPPER RESPIRATORY TRACT INFECTION † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	1/8 (12.50%)	1	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
VULVOVAGINAL CANDIDIASIS † 1	1/7 (14.29%)	1	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	0/208 (0.00%)	0	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Injury, poisoning and procedural complications
FALL † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	4/208 (1.92%)	4	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0
HAND FRACTURE † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	1/6 (16.67%)	1	0/208 (0.00%)	0	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
INFUSION RELATED REACTION † 1	1/7 (14.29%)	1	2/3 (66.67%)	2	1/8 (12.50%)	1	2/6 (33.33%)	3	44/208 (21.15%)	48	4/7 (57.14%)	4	1/7 (14.29%)	1	2/6 (33.33%)	2	2/6 (33.33%)	3	3/6 (50.00%)	4
MUSCLE STRAIN † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	1/8 (12.50%)	1	0/6 (0.00%)	0	0/208 (0.00%)	0	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
PROCEDURAL PAIN † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	0/208 (0.00%)	0	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0
THERMAL BURN † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	1/6 (16.67%)	1	0/208 (0.00%)	0	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
TRACHEAL OBSTRUCTION † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	1/8 (12.50%)	1	0/6 (0.00%)	0	0/208 (0.00%)	0	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Investigations
ALANINE AMINOTRANSFERASE INCREASED † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	1/7 (14.29%)	1	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
ASPARTATE AMINOTRANSFERASE INCREASED † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	0/208 (0.00%)	0	1/7 (14.29%)	1	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
BLOOD MAGNESIUM DECREASED † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	0/208 (0.00%)	0	0/7 (0.00%)	0	0/7 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0
BLOOD POTASSIUM INCREASED † 1	1/7 (14.29%)	1	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	0/208 (0.00%)	0	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
COMPUTERISED TOMOGRAM THORAX ABNORMAL † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	0/208 (0.00%)	0	0/7 (0.00%)	0	1/7 (14.29%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
EJECTION FRACTION DECREASED † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	2/208 (0.96%)	2	1/7 (14.29%)	1	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
URINE OUTPUT DECREASED † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	0/208 (0.00%)	0	1/7 (14.29%)	1	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
WEIGHT DECREASED † 1	2/7 (28.57%)	3	0/3 (0.00%)	0	0/8 (0.00%)	0	1/6 (16.67%)	1	32/208 (15.38%)	33	0/7 (0.00%)	0	1/7 (14.29%)	1	0/6 (0.00%)	0	2/6 (33.33%)	2	1/6 (16.67%)	1
WEIGHT INCREASED † 1	1/7 (14.29%)	1	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	3/208 (1.44%)	3	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0
WHITE BLOOD CELL COUNT DECREASED † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	0/208 (0.00%)	0	1/7 (14.29%)	1	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Metabolism and nutrition disorders
DECREASED APPETITE † 1	1/7 (14.29%)	1	1/3 (33.33%)	1	1/8 (12.50%)	1	1/6 (16.67%)	1	42/208 (20.19%)	45	2/7 (28.57%)	2	2/7 (28.57%)	2	1/6 (16.67%)	1	2/6 (33.33%)	2	1/6 (16.67%)	1
DEHYDRATION † 1	1/7 (14.29%)	1	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	7/208 (3.37%)	11	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
FLUID RETENTION † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	2/208 (0.96%)	3	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0
GOUT † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	2/208 (0.96%)	2	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1
HYPERKALAEMIA † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	4/208 (1.92%)	4	0/7 (0.00%)	0	1/7 (14.29%)	1	1/6 (16.67%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0
HYPERPHOSPHATAEMIA † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	2/208 (0.96%)	2	1/7 (14.29%)	1	0/7 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0
HYPERURICAEMIA † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	1/8 (12.50%)	1	0/6 (0.00%)	0	2/208 (0.96%)	2	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
HYPOCALCAEMIA † 1	1/7 (14.29%)	1	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	3/208 (1.44%)	4	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
HYPOCHLORAEMIA † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	0/208 (0.00%)	0	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1
HYPOKALAEMIA † 1	3/7 (42.86%)	4	1/3 (33.33%)	1	2/8 (25.00%)	2	0/6 (0.00%)	0	35/208 (16.83%)	44	1/7 (14.29%)	1	2/7 (28.57%)	2	0/6 (0.00%)	0	1/6 (16.67%)	1	1/6 (16.67%)	1
HYPOMAGNESAEMIA † 1	1/7 (14.29%)	6	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	10/208 (4.81%)	12	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
HYPONATRAEMIA † 1	1/7 (14.29%)	2	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	4/208 (1.92%)	4	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1
HYPOPHOSPHATAEMIA † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	1/8 (12.50%)	1	0/6 (0.00%)	0	7/208 (3.37%)	9	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
TUMOUR LYSIS SYNDROME † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	1/6 (16.67%)	1	1/6 (16.67%)	1	0/6 (0.00%)	0
Musculoskeletal and connective tissue disorders
ARTHRALGIA † 1	2/7 (28.57%)	4	0/3 (0.00%)	0	0/8 (0.00%)	0	1/6 (16.67%)	1	22/208 (10.58%)	23	1/7 (14.29%)	1	2/7 (28.57%)	3	1/6 (16.67%)	2	0/6 (0.00%)	0	0/6 (0.00%)	0
BACK PAIN † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	1/8 (12.50%)	1	2/6 (33.33%)	2	29/208 (13.94%)	34	0/7 (0.00%)	0	2/7 (28.57%)	2	1/6 (16.67%)	1	0/6 (0.00%)	0	1/6 (16.67%)	1
BONE PAIN † 1	0/7 (0.00%)	0	1/3 (33.33%)	1	0/8 (0.00%)	0	1/6 (16.67%)	1	9/208 (4.33%)	10	2/7 (28.57%)	2	1/7 (14.29%)	2	2/6 (33.33%)	2	0/6 (0.00%)	0	1/6 (16.67%)	1
MUSCLE SPASMS † 1	1/7 (14.29%)	1	0/3 (0.00%)	0	1/8 (12.50%)	1	0/6 (0.00%)	0	5/208 (2.40%)	5	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
MUSCULAR WEAKNESS † 1	2/7 (28.57%)	2	0/3 (0.00%)	0	0/8 (0.00%)	0	1/6 (16.67%)	1	10/208 (4.81%)	10	0/7 (0.00%)	0	1/7 (14.29%)	1	0/6 (0.00%)	0	1/6 (16.67%)	1	1/6 (16.67%)	1
MUSCULOSKELETAL CHEST PAIN † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	3/208 (1.44%)	3	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1
MYALGIA † 1	1/7 (14.29%)	1	0/3 (0.00%)	0	1/8 (12.50%)	1	1/6 (16.67%)	1	12/208 (5.77%)	18	1/7 (14.29%)	1	0/7 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1	1/6 (16.67%)	1
PAIN IN EXTREMITY † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	1/6 (16.67%)	1	5/208 (2.40%)	5	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1
PAIN IN JAW † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	1/6 (16.67%)	1	0/208 (0.00%)	0	0/7 (0.00%)	0	1/7 (14.29%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
SQUAMOUS CELL CARCINOMA † 1	1/7 (14.29%)	1	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	0/208 (0.00%)	0	0/7 (0.00%)	0	1/7 (14.29%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
SQUAMOUS CELL CARCINOMA OF SKIN † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	0/208 (0.00%)	0	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1
Nervous system disorders
AGEUSIA † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	0/208 (0.00%)	0	1/7 (14.29%)	1	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
CAROTID SINUS SYNDROME † 1	1/7 (14.29%)	1	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	0/208 (0.00%)	0	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
COGNITIVE DISORDER † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	1/6 (16.67%)	2	0/208 (0.00%)	0	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
DISTURBANCE IN ATTENTION † 1	1/7 (14.29%)	1	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	1/7 (14.29%)	1	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
DIZZINESS † 1	1/7 (14.29%)	1	0/3 (0.00%)	0	2/8 (25.00%)	2	1/6 (16.67%)	1	24/208 (11.54%)	33	1/7 (14.29%)	1	1/7 (14.29%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0	2/6 (33.33%)	2
DYSGEUSIA † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	1/8 (12.50%)	1	1/6 (16.67%)	1	19/208 (9.13%)	19	1/7 (14.29%)	1	3/7 (42.86%)	3	1/6 (16.67%)	1	2/6 (33.33%)	2	4/6 (66.67%)	4
HEADACHE † 1	1/7 (14.29%)	1	0/3 (0.00%)	0	3/8 (37.50%)	3	1/6 (16.67%)	1	28/208 (13.46%)	31	3/7 (42.86%)	5	3/7 (42.86%)	3	1/6 (16.67%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0
HYPOAESTHESIA † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	4/208 (1.92%)	4	1/7 (14.29%)	1	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
LETHARGY † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	0/208 (0.00%)	0	1/7 (14.29%)	1	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1
MEMORY IMPAIRMENT † 1	1/7 (14.29%)	1	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	3/208 (1.44%)	3	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
NEUROPATHY PERIPHERAL † 1	2/7 (28.57%)	2	1/3 (33.33%)	2	3/8 (37.50%)	3	3/6 (50.00%)	3	28/208 (13.46%)	33	0/7 (0.00%)	0	2/7 (28.57%)	2	1/6 (16.67%)	1	1/6 (16.67%)	1	2/6 (33.33%)	3
PARAESTHESIA † 1	2/7 (28.57%)	2	0/3 (0.00%)	0	0/8 (0.00%)	0	1/6 (16.67%)	1	18/208 (8.65%)	26	0/7 (0.00%)	0	1/7 (14.29%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
PERIPHERAL MOTOR NEUROPATHY † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	2/208 (0.96%)	2	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1	1/6 (16.67%)	1
PERIPHERAL SENSORY NEUROPATHY † 1	3/7 (42.86%)	3	1/3 (33.33%)	1	2/8 (25.00%)	2	2/6 (33.33%)	2	14/208 (6.73%)	14	0/7 (0.00%)	0	1/7 (14.29%)	1	1/6 (16.67%)	1	1/6 (16.67%)	1	1/6 (16.67%)	1
POST HERPETIC NEURALGIA † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	0/208 (0.00%)	0	0/7 (0.00%)	0	0/7 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0
PRESYNCOPE † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	1/8 (12.50%)	1	0/6 (0.00%)	0	1/208 (0.48%)	1	1/7 (14.29%)	1	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
SYNCOPE † 1	1/7 (14.29%)	1	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	4/208 (1.92%)	8	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Psychiatric disorders
ANXIETY † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	1/6 (16.67%)	1	9/208 (4.33%)	9	1/7 (14.29%)	3	1/7 (14.29%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1
DEPRESSION † 1	1/7 (14.29%)	1	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	4/208 (1.92%)	5	0/7 (0.00%)	0	1/7 (14.29%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
INSOMNIA † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	2/8 (25.00%)	3	1/6 (16.67%)	1	14/208 (6.73%)	17	2/7 (28.57%)	2	2/7 (28.57%)	3	0/6 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1
MOOD SWINGS † 1	1/7 (14.29%)	1	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	0/208 (0.00%)	0	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Renal and urinary disorders
BLADDER HYPERTROPHY † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	1/6 (16.67%)	1	0/208 (0.00%)	0	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
DYSURIA † 1	0/7 (0.00%)	0	1/3 (33.33%)	1	0/8 (0.00%)	0	1/6 (16.67%)	1	3/208 (1.44%)	3	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
HAEMATURIA † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0
NOCTURIA † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	0/208 (0.00%)	0	0/7 (0.00%)	0	1/7 (14.29%)	1	0/6 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0
POLLAKIURIA † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	1/7 (14.29%)	1	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
RENAL FAILURE † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	0/208 (0.00%)	0	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1
URINARY INCONTINENCE † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	2/208 (0.96%)	2	0/7 (0.00%)	0	1/7 (14.29%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
URINARY TRACT PAIN † 1	1/7 (14.29%)	1	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Reproductive system and breast disorders
BREAST PAIN † 1	1/7 (14.29%)	1	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	0/208 (0.00%)	0	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
TESTICULAR PAIN † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	1/6 (16.67%)	1	0/208 (0.00%)	0	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
VAGINAL DISCHARGE † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	0/208 (0.00%)	0	0/7 (0.00%)	0	1/7 (14.29%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
VULVOVAGINAL DRYNESS † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	0/208 (0.00%)	0	0/7 (0.00%)	0	1/7 (14.29%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
COUGH † 1	2/7 (28.57%)	2	0/3 (0.00%)	0	3/8 (37.50%)	4	1/6 (16.67%)	1	51/208 (24.52%)	67	3/7 (42.86%)	3	2/7 (28.57%)	2	0/6 (0.00%)	0	3/6 (50.00%)	5	2/6 (33.33%)	2
DYSPNOEA † 1	2/7 (28.57%)	3	1/3 (33.33%)	2	0/8 (0.00%)	0	1/6 (16.67%)	1	22/208 (10.58%)	24	0/7 (0.00%)	0	1/7 (14.29%)	1	0/6 (0.00%)	0	1/6 (16.67%)	1	1/6 (16.67%)	1
DYSPNOEA EXERTIONAL † 1	0/7 (0.00%)	0	1/3 (33.33%)	1	1/8 (12.50%)	1	1/6 (16.67%)	1	4/208 (1.92%)	4	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
EPISTAXIS † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	3/208 (1.44%)	3	1/7 (14.29%)	1	0/7 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0
HICCUPS † 1	1/7 (14.29%)	1	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	4/208 (1.92%)	5	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
NASAL CONGESTION † 1	1/7 (14.29%)	1	0/3 (0.00%)	0	1/8 (12.50%)	1	1/6 (16.67%)	1	11/208 (5.29%)	11	2/7 (28.57%)	2	1/7 (14.29%)	1	0/6 (0.00%)	0	2/6 (33.33%)	4	1/6 (16.67%)	1
OROPHARYNGEAL PAIN † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	10/208 (4.81%)	13	1/7 (14.29%)	1	1/7 (14.29%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
PLEURAL EFFUSION † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	0/208 (0.00%)	0	0/7 (0.00%)	0	1/7 (14.29%)	1	1/6 (16.67%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0
PLEURITIC PAIN † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	0/208 (0.00%)	0	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0
PRODUCTIVE COUGH † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	8/208 (3.85%)	8	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1
RHINORRHOEA † 1	1/7 (14.29%)	1	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	11/208 (5.29%)	11	1/7 (14.29%)	1	0/7 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0	1/6 (16.67%)	1
SINUS PAIN † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	1/6 (16.67%)	1	0/208 (0.00%)	0	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0
VOCAL CORD DYSFUNCTION † 1	1/7 (14.29%)	1	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	0/208 (0.00%)	0	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
WHEEZING † 1	1/7 (14.29%)	1	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Skin and subcutaneous tissue disorders
ALOPECIA † 1	1/7 (14.29%)	2	0/3 (0.00%)	0	0/8 (0.00%)	0	3/6 (50.00%)	3	28/208 (13.46%)	29	0/7 (0.00%)	0	0/7 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0
DRY SKIN † 1	0/7 (0.00%)	0	1/3 (33.33%)	1	0/8 (0.00%)	0	0/6 (0.00%)	0	8/208 (3.85%)	9	0/7 (0.00%)	0	2/7 (28.57%)	2	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
ECCHYMOSIS † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	0/208 (0.00%)	0	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0
HYPERHIDROSIS † 1	1/7 (14.29%)	2	0/3 (0.00%)	0	0/8 (0.00%)	0	1/6 (16.67%)	1	3/208 (1.44%)	3	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0
NAIL DISCOLOURATION † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	1/8 (12.50%)	1	1/6 (16.67%)	1	3/208 (1.44%)	3	0/7 (0.00%)	0	1/7 (14.29%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
NIGHT SWEATS † 1	1/7 (14.29%)	1	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	4/208 (1.92%)	4	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
PIGMENTATION DISORDER † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	1/6 (16.67%)	1	0/208 (0.00%)	0	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
PRURITUS † 1	1/7 (14.29%)	1	1/3 (33.33%)	1	0/8 (0.00%)	0	0/6 (0.00%)	0	6/208 (2.88%)	8	0/7 (0.00%)	0	0/7 (0.00%)	0	1/6 (16.67%)	1	1/6 (16.67%)	2	0/6 (0.00%)	0
PURPURA † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1
RASH † 1	1/7 (14.29%)	1	0/3 (0.00%)	0	1/8 (12.50%)	1	0/6 (0.00%)	0	9/208 (4.33%)	9	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
RASH MACULO-PAPULAR † 1	1/7 (14.29%)	1	0/3 (0.00%)	0	0/8 (0.00%)	0	1/6 (16.67%)	1	5/208 (2.40%)	5	1/7 (14.29%)	1	0/7 (0.00%)	0	2/6 (33.33%)	2	0/6 (0.00%)	0	0/6 (0.00%)	0
SKIN HYPERPIGMENTATION † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	1/208 (0.48%)	1	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1
Vascular disorders
HOT FLUSH † 1	1/7 (14.29%)	1	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	2/208 (0.96%)	2	0/7 (0.00%)	0	0/7 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0
HYPOTENSION † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	0/6 (0.00%)	0	13/208 (6.25%)	15	1/7 (14.29%)	1	0/7 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	2	0/6 (0.00%)	0
THROMBOPHLEBITIS † 1	0/7 (0.00%)	0	0/3 (0.00%)	0	0/8 (0.00%)	0	1/6 (16.67%)	1	3/208 (1.44%)	3	1/7 (14.29%)	1	0/7 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
1 Term from vocabulary, MedDRA version 22.0; † 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.

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.

Results Point of Contact

• Name/Title: Medical Communications
• Organization: Hoffmann-La Roche
• Phone: 800-821-8590
• EMail: genentech@druginfo.com

Publications of Results:

Zelenetz AD, Salles G, Mason KD, Casulo C, Le Gouill S, Sehn LH, Tilly H, Cartron G, Chamuleau MED, Goy A, Tam CS, Lugtenburg PJ, Petrich AM, Sinha A, Samineni D, Herter S, Ingalla E, Szafer-Glusman E, Klein C, Sampath D, Kornacker M, Mobasher M, Morschhauser F. Venetoclax plus R- or G-CHOP in non-Hodgkin lymphoma: results from the CAVALLI phase 1b trial. Blood. 2019 May 2;133(18):1964-1976. doi: 10.1182/blood-2018-11-880526. Epub 2019 Mar 8.

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

Samineni D, Huang W, Gibiansky L, Ding H, Zhang R, Li C, Sinha A, Rajwanshi R, Humphrey K, Bazeos A, Salem AH, Miles D. Population Pharmacokinetics and Exposure-Response Analyses for Venetoclax in Combination with R-CHOP in Relapsed/Refractory and Previously Untreated Patients with Diffuse Large B Cell Lymphoma. Adv Ther. 2022 Jan;39(1):598-618. doi: 10.1007/s12325-021-01919-z. Epub 2021 Nov 25.

Morschhauser F, Feugier P, Flinn IW, Gasiorowski R, Greil R, Illes A, Johnson NA, Larouche JF, Lugtenburg PJ, Patti C, Salles GA, Trneny M, de Vos S, Mir F, Samineni D, Kim SY, Jiang Y, Punnoose E, Sinha A, Clark E, Spielewoy N, Humphrey K, Bazeos A, Zelenetz AD. A phase 2 study of venetoclax plus R-CHOP as first-line treatment for patients with diffuse large B-cell lymphoma. Blood. 2021 Feb 4;137(5):600-609. doi: 10.1182/blood.2020006578. Erratum In: Blood. 2021 Apr 1;137(13):1844.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT02055820
• Other Study ID Numbers: GO27878; 2013-003749-40 ( EudraCT Number )
• First Submitted: February 4, 2014
• First Posted: February 5, 2014
• Results First Submitted: June 26, 2018
• Results First Posted: December 20, 2018
• Last Update Posted: June 11, 2020