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A Study To Evaluate PF-04449913 With Chemotherapy In Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome

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ClinicalTrials.gov Identifier: NCT01546038
Recruitment Status : Completed
First Posted : March 7, 2012
Results First Posted : May 23, 2018
Last Update Posted : March 3, 2020
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Acute Myeloid Leukemia
Interventions Drug: PF-04449913
Drug: Low dose ARA-C (LDAC)
Drug: Decitabine
Drug: Daunorubicin
Drug: Cytarabine
Enrollment 255
Recruitment Details  
Pre-assignment Details Phase 1B:Unfit(unfit for intensive chemotherapy)participants with prior decitabine or azacitidine for high risk MDS or AHD(antecedent hematologic disease)were eligible for the LDAC arm only;with prior cytarabine were eligible for decitabine arm only.Phase 2:Participant's treatment arm assignment was based on the fit or unfit status at screening.
Arm/Group Title Phase 1B: Glasdegib 100 mg + LDAC Phase 1B: Glasdegib 200 mg + LDAC Phase 1B: Glasdegib 100 mg + Decitabine Phase 1B: Glasdegib 200 mg + Decitabine Phase 1B: Glasdegib 100 mg + Cytarabine/Daunorubicin Phase 1B: Glasdegib 200 mg + Cytarabine/Daunorubicin Phase 2 Fit: Glasdegib 100 mg + Cytarabine/Daunorubicin Phase 2 Unfit: Glasdegib 100 mg + LDAC Phase 2 Unfit: LDAC Alone
Hide Arm/Group Description Participants received oral doses of glasdegib (PF-04449913) tablets 100 milligram (mg) starting on Day 3 of Cycle 1 for pharmacokinetic (PK) assessment purposes and thereafter once daily (QD) and continuously for 28-day cycles (starting on Day 1 for all other cycles). Low dose Ara-C (LDAC) was given at a dose of 20 mg subcutaneously twice daily (BID) on Days 1-10 of the 28-day cycles. Participants received oral doses of glasdegib tablets 200 mg starting on Day 3 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28-day cycles. In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg. Participants who had glasdegib dose reduction were reported as the starting glasdegib dose level received. Two (2) participants in this cohort had dose reduction to 100 mg starting from Cycle 2/Day 1 and Cycle 2/Day 16, respectively. Participants received oral doses of glasdegib tablets 100 mg starting on Day 2 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). Decitabine was given at a dose of 20 mg/m^2 as an intravenous (IV) infusion over 1 hour on Days 1-5 of the 28-day cycles. Participants received oral doses of glasdegib tablets 200 mg starting on Day 2 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). Decitabine was given at a dose of 20 mg/m^2 as an IV infusion over 1 hour on Days 1-5 of the 28-day cycles.In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg. Participants who had glasdegib dose reduction were reported as the starting glasdegib dose level received. Two (2) participants in this cohort had dose reduction to 100 mg starting from Cycle 1/Day 24 and Cycle 5/Day 1, respectively. Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days. Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 200 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg.One (1) participant in this cohort had dose reduction to 100 mg starting from Consolidation Cycle 1/Day 21. Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days. Participants received oral doses of glasdegib tablets 100 mg QD in 28-day cycles on a continuous basis, starting on Day 1 of Cycle 1. LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28-day cycles. Participants received LDAC subcutaneously at a dose of 20 mg BID on Days 1-10 of the 28-day cycles.
Period Title: Overall Study
Started 17 6 4 3 16 6 71 88 44
Received Treatment 17 6 4 3 16 6 69 84 41
Completed 1 0 0 0 6 2 18 4 1
Not Completed 16 6 4 3 10 4 53 84 43
Reason Not Completed
Death             15             6             4             2             9             3             46             76             39
Lost to Follow-up             0             0             0             0             1             0             2             1             0
Withdrawal by Subject             1             0             0             1             0             1             3             3             1
: Randomized, not treated             0             0             0             0             0             0             2             4             3
Arm/Group Title Phase 1B: Glasdegib + LDAC Phase 1B: Glasdegib + Decitabine Phase 1B: Glasdegib + Cytarabine/Daunorubicin Phase 2 Fit: Glasdegib 100 mg + Cytarabine/Daunorubicin Phase 2 Unfit: Glasdegib 100 mg + LDAC Phase 2 Unfit: LDAC Alone Total
Hide Arm/Group Description Included all participants who received oral glasdegib in combination with LDAC in phase 1B portion. Included all participants who received oral glasdegib in combination with decitabine in phase 1B portion. Included all participants who received oral glasdegib in combination with cytarabine/daunorubicin in phase 1B portion. Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days. Participants received oral doses of glasdegib tablets 100 mg QD in 28-day cycles on a continuous basis, starting on Day 1 of Cycle 1. LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28-day cycles. Participants received LDAC subcutaneously at a dose of 20 mg BID on Days 1-10 of the 28-day cycles. Total of all reporting groups
Overall Number of Baseline Participants 23 7 22 71 88 44 255
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 23 participants 7 participants 22 participants 71 participants 88 participants 44 participants 255 participants
75.8  (6.5) 75.0  (4.4) 54.9  (12.7) 61.9  (9.6) 76.2  (6.2) 74.5  (4.9) 66.8  (13.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 23 participants 7 participants 22 participants 71 participants 88 participants 44 participants 255 participants
Female
8
  34.8%
2
  28.6%
10
  45.5%
28
  39.4%
19
  21.6%
18
  40.9%
85
  33.3%
Male
15
  65.2%
5
  71.4%
12
  54.5%
43
  60.6%
69
  78.4%
26
  59.1%
170
  66.7%
1.Primary Outcome
Title Number of Participants With Dose-limiting Toxicities (DLTs) at Phase 1B
Hide Description A DLT was any of the following adverse events (AEs) in Cycle 1 and considered by the investigator possibly related to glasdegib in combination with chemotherapy: (1) Grade >= 3 non-hematologic toxicity, excluding Grade >= 3 infection, fever (including febrile neutropenia), infusion related AEs, electrolyte abnormalities and ALT/AST elevation that returned to Grade <= 1 or baseline within 7 days; (2) prolonged myelosuppression that lasted longer than 42 days from the point of detection, defined as absolute neutrophil count (ANC) < 500/microliter(mcL) or platelet count < 10 *10^9/L with a normal bone marrow (<5% blasts and no evidence of disease or dysplasia); (3) inability to deliver at least 80% of the planned study doses for all agents in a combination due to non-hematologic toxicities; (4) Delay of >28 days in receiving the next scheduled cycle due to persisting non-hematologic toxicities. Arm A: Glasdegib+LDAC; Arm B: Glasdegib+Decitabine; Arm C: Glasdegib+Cytarabine/Daunorubicin.
Time Frame Arms A and B: Cycle 1, Day 1 to Day 28; Arm C: Cycle 1, Day -3 to Day 21 or to Day 28 depending on when the next chemotherapy cycle was started
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol analysis set: all enrolled participants in the dose escalation component who received at least 1 dose of glasdegib and of the co-administered chemotherapeutics and who did not have major treatment deviations during the DLT monitoring period.
Arm/Group Title Phase 1B: Glasdegib 100 mg + LDAC Phase 1B: Glasdegib 200 mg + LDAC Phase 1B: Glasdegib 100 mg + Decitabine Phase 1B: Glasdegib 200 mg + Decitabine Phase 1B: Glasdegib 100 mg + Cytarabine/Daunorubicin Phase 1B: Glasdegib 200 mg + Cytarabine/Daunorubicin
Hide Arm/Group Description:
Participants received oral doses of glasdegib (PF-04449913) tablets 100 milligram (mg) starting on Day 3 of Cycle 1 for pharmacokinetic (PK) assessment purposes and thereafter once daily (QD) and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously twice daily (BID) on Days 1-10 of the 28-day cycles.
Participants received oral doses of glasdegib tablets 200 mg starting on Day 3 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28-day cycles. In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg. Participants who had glasdegib dose reduction were reported as the starting glasdegib dose level received. Two (2) participants in this cohort had dose reduction to 100 mg starting from Cycle 2/Day 1 and Cycle 2/Day 16, respectively.
Participants received oral doses of glasdegib tablets 100 mg starting on Day 2 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). Decitabine was given at a dose of 20 mg/m^2 as an intravenous (IV) infusion over 1 hour on Days 1-5 of the 28-day cycles.
Participants received oral doses of glasdegib tablets 200 mg starting on Day 2 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). Decitabine was given at a dose of 20 mg/m^2 as an IV infusion over 1 hour on Days 1-5 of the 28-day cycles.In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg. Participants who had glasdegib dose reduction were reported as the starting glasdegib dose level received. Two (2) participants in this cohort had dose reduction to 100 mg starting from Cycle 1/Day 24 and Cycle 5/Day 1, respectively.
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 200 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg.One (1) participant in this cohort had dose reduction to 100 mg starting from Consolidation Cycle 1/Day 21.
Overall Number of Participants Analyzed 3 5 4 2 6 6
Measure Type: Number
Unit of Measure: Participants
0 0 0 0 1 0
2.Primary Outcome
Title Percentage of Participants With Complete Response (CR) at Phase 2 Fit
Hide Description For AML participants:CR were those with repeat bone marrow showing <5% myeloblasts,spicules present and no Auer rods, peripheral blood showing neutrophils>=1000/mcL and platelets>=100,000/mcL, transfusion independent and no extramedullary disease. For MDS participants:CR were those with repeat bone marrow showing <=5% myeloblasts, peripheral blood showing neutrophils>=1000/mcL, platelets>=100,000/mcL, 0% blast and hemoglobin (Hgb)>= 11 g/dL, normal maturation of all cell lines.
Time Frame 4 years
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set: all enrolled participants of Phase 2 Fit arm who received at least 1 dose of study medication. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.
Arm/Group Title Phase 2 Fit: Glasdegib 100 mg + Cytarabine/Daunorubicin
Hide Arm/Group Description:
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.
Overall Number of Participants Analyzed 69
Measure Type: Number
Number (80% Confidence Interval)
Unit of Measure: Percentage of participants
Total participants Number Analyzed 69 participants
42.0
(34.4 to 49.6)
Participants >= 55 years old Number Analyzed 60 participants
36.7
(28.7 to 44.6)
Participants < 55 years old Number Analyzed 9 participants
77.8
(60.0 to 95.5)
3.Primary Outcome
Title Overall Survival (OS) at Phase 2 Unfit
Hide Description OS was defined as duration from the date of randomization to the date of death from any cause. Kaplan-Meier (KM) method was used to estimate median OS. In this method, every participant had a follow-up time which was associated with an indicator, 1=event (death in our case), and 0 =censored. If the participants were not known to have died, time to date of last known to be alive was used as to calculate the follow-up time and indicator was 0 for these participants. KM method estimates the median OS based on the K-M curve. The K-M curve only drops when we had an event and censor data are the ticks in the graph. To estimate median OS, the K-M curve usually will be smoothed first and a line will be drawn at 50%. The median OS is the point when K-M curve and the horizontal hit. Survival status was collected every month for the first 2 months after discontinuation of study treatment and thereafter every 2 months until death or 4 years from time of randomization for each participant.
Time Frame Randomization to Follow-up (4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set: all randomized participants of Phase 2 Unfit arm.
Arm/Group Title Phase 2 Unfit: Glasdegib 100 mg + LDAC Phase 2 Unfit: LDAC Alone
Hide Arm/Group Description:
Participants received oral doses of glasdegib tablets 100 mg QD in 28-day cycles on a continuous basis, starting on Day 1 of Cycle 1. LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28 day cycles.
Participants received LDAC subcutaneously at a dose of 20 mg BID on Days 1-10 of the 28 day cycles.
Overall Number of Participants Analyzed 88 44
Median (80% Confidence Interval)
Unit of Measure: Months
8.8
(6.9 to 9.9)
4.9
(3.5 to 6.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Phase 2 Unfit: Glasdegib 100 mg + LDAC, Phase 2 Unfit: LDAC Alone
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0020
Comments 1-sided p-value from the log-rank test stratified by prognosis stratum according to Interactive Voice Response System (IVRS).
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.569
Confidence Interval (2-Sided) 80%
0.441 to 0.734
Estimation Comments Based on the Cox proportional hazards model stratified by prognosis stratum according to IVRS.
4.Secondary Outcome
Title Overall Survival (OS) at Phase 1B
Hide Description OS was defined as duration from the date of randomization to the date of death from any cause. Kaplan-Meier (KM) method was used to estimate median OS. In this method, every participant had a follow-up time which was associated with an indicator, 1=event (death in our case), and 0 =censored. If the participants were not known to have died, time to date of last known to be alive was used as to calculate the follow-up time and indicator was 0 for these participants. KM method estimates the median OS based on the K-M curve. The K-M curve only drops when we had an event and censor data are the ticks in the graph. To estimate median OS, the K-M curve usually will be smoothed first and a line will be drawn at 50%. The median OS is the point when K-M curve and the horizontal hit. Survival status was collected every month for the first 2 months after discontinuation of study treatment and thereafter every 2 months until death or 4 years from each participant's first dose.
Time Frame First dose to Follow-up (4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set: all enrolled participants of Phase 1B portion who received at least 1 dose of study medication.
Arm/Group Title Phase 1B: Glasdegib + LDAC Phase 1B: Glasdegib + Decitabine Phase 1B: Glasdegib + Cytarabine/Daunorubicin
Hide Arm/Group Description:
Included all participants who received oral glasdegib in combination with LDAC in phase 1B portion.
Included all participants who received oral glasdegib in combination with decitabine in phase 1B portion.
Included all participants who received oral glasdegib in combination with cytarabine/daunorubicin in phase 1B portion.
Overall Number of Participants Analyzed 23 7 22
Median (80% Confidence Interval)
Unit of Measure: Months
4.4
(2.5 to 6.6)
11.5
(4.5 to 17.4)
37.8 [1] 
(14.5 to NA)
[1]
The upper bound of 80% CI was not estimable, as 10 (45.5%) participants were censored for no longer being followed for survival
5.Secondary Outcome
Title Overall Survival (OS) at Phase 2 Fit
Hide Description OS was defined as duration from the date of randomization to the date of death from any cause. Kaplan-Meier (KM) method was used to estimate median OS. In this method, every participant had a follow-up time which was associated with an indicator, 1=event (death in our case), and 0 =censored. If the participants were not known to have died, time to date of last known to be alive was used as to calculate the follow-up time and indicator was 0 for these participants. KM method estimates the median OS based on the K-M curve. The K-M curve only drops when we had an event and censor data are the ticks in the graph. To estimate median OS, the K-M curve usually will be smoothed first and a line will be drawn at 50%. The median OS is the point when K-M curve and the horizontal hit. Survival status was collected every month for the first 2 months after discontinuation of study treatment and thereafter every 2 months until death or 4 years from each participant's first dose.
Time Frame First dose to Follow-up (4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set: all enrolled participants of Phase 2 Fit arm who received at least 1 dose of study medication. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.
Arm/Group Title Phase 2 Fit: Glasdegib 100 mg + Cytarabine/Daunorubicin
Hide Arm/Group Description:
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.
Overall Number of Participants Analyzed 69
Median (80% Confidence Interval)
Unit of Measure: Months
Total participants Number Analyzed 69 participants
14.9
(13.4 to 19.3)
Participants >= 55 years old Number Analyzed 60 participants
14.7
(13.1 to 17.7)
Participants < 55 years old Number Analyzed 9 participants
NA [1] 
(11.0 to NA)
[1]
Number of deaths was 4 until the study completion, not enough for OS calculation.
6.Secondary Outcome
Title Percentage of Participants With CR / Complete Response With Incomplete Blood Count Recovery (CRi) at Phase 1B
Hide Description For AML participants:CR were those with repeat bone marrow showing <5% myeloblasts,spicules present and no Auer rods, peripheral blood showing neutrophils>=1000/mcL and platelets>=100,000/mcL, transfusion independent and no extramedullary disease. For MDS participants:CR were those with repeat bone marrow showing <=5% myeloblasts, peripheral blood showing neutrophils>=1000/mcL, platelets>=100,000/mcL, 0% blast and hemoglobin (Hgb)>= 11 g/dL, normal maturation of all cell lines.For AML and MDS participants, complete response with incomplete blood count recovery(CRi)were those with repeat bone marrow showing <5% myeloblasts with either platelets or neutrophils not recovered (platelets <100,000/mcL or neutrophils <1000/mcL).
Time Frame 4 years
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set: all enrolled participants of Phase 1B portion who received at least 1 dose of study medication.
Arm/Group Title Phase 1B: Glasdegib + LDAC Phase 1B: Glasdegib + Decitabine Phase 1B: Glasdegib + Cytarabine/Daunorubicin
Hide Arm/Group Description:
Included all participants who received oral glasdegib in combination with LDAC in phase 1B portion.
Included all participants who received oral glasdegib in combination with decitabine in phase 1B portion.
Included all participants who received oral glasdegib in combination with cytarabine/daunorubicin in phase 1B portion.
Overall Number of Participants Analyzed 23 7 22
Measure Type: Number
Number (80% Confidence Interval)
Unit of Measure: Percentage of participants
8.7
(2.3 to 21.5)
28.6
(7.9 to 59.6)
54.5
(38.9 to 69.5)
7.Secondary Outcome
Title Percentage of Participants With Complete Response (CR) at Phase 2 Unfit
Hide Description For AML participants:CR were those with repeat bone marrow showing <5% myeloblasts,spicules present and no Auer rods, peripheral blood showing neutrophils>=1000/mcL and platelets>=100,000/mcL, transfusion independent and no extramedullary disease. For MDS participants:CR were those with repeat bone marrow showing <=5% myeloblasts, peripheral blood showing neutrophils>=1000/mcL, platelets>=100,000/mcL, 0% blast and hemoglobin (Hgb)>= 11 g/dL, normal maturation of all cell lines.
Time Frame 4 years
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set: all randomized participants of Phase 2 Unfit arm.
Arm/Group Title Phase 2 Unfit: Glasdegib 100 mg + LDAC Phase 2 Unfit: LDAC Alone
Hide Arm/Group Description:
Participants received oral doses of glasdegib tablets 100 mg QD in 28-day cycles on a continuous basis, starting on Day 1 of Cycle 1. LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28 day cycles.
Participants received LDAC subcutaneously at a dose of 20 mg BID on Days 1-10 of the 28 day cycles.
Overall Number of Participants Analyzed 88 44
Measure Type: Number
Number (80% Confidence Interval)
Unit of Measure: Percentage of participants
18.2
(12.9 to 23.5)
2.3
(0.0 to 5.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Phase 2 Unfit: Glasdegib 100 mg + LDAC, Phase 2 Unfit: LDAC Alone
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0112
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.2755
Confidence Interval (2-Sided) 80%
1.3057 to 13.9994
Estimation Comments Based on the Cox proportional hazards model stratified by prognosis stratum according to IVRS.
8.Secondary Outcome
Title Percentage of Participants With Disease-specific Efficacy for Acute Myeloid Leukemia (AML) at Phase 2 Fit and Unfit
Hide Description AML participants,disease specific efficacy measures included:CRi;Morphologic Leukemia Free State(MLFS)(bone marrow<5%myeloblasts with spicules and no blasts with auer rods,neutrophils<1000/mcL and platelets<100,000/mcL);partial remission(PR)(bone marrow myeloblasts decrease to 5-25&>=50%decrease from start, neutrophils>=1000/mcL, platelets>=100,000/mcL);PR with incomplete blood count recovery(PRi)(bone marrow myeloblasts decrease to 5-25&>=50%decrease from start,neutrophils<1000/mcL or platelets<100,000/mcL);minor response(MR)(bone marrow myeloblasts decrease to>=25% from start);stable disease(SD)(bone marrow myeloblasts stable+/-25% from screening value);cytogenetic complete response(CRc)(bone marrow<5%myeloblasts, neutrophils>1000/mcL, platelets>100,000/mcL and normal cytogenetics),molecular complete response(CRm)(bone marrow<5%myeloblasts, neutrophils>1000/mcL, platelets>100,000/mcL and molecular-negative).
Time Frame 4 years
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Hide Analysis Population Description
AML participants in the Full analysis set: all enrolled participants of Phase 2 Fit arm who received at least 1 dose of study medication, and all randomized participants of Phase 2 Unfit arm.
Arm/Group Title Phase 2 Fit: Glasdegib 100 mg + Cytarabine/Daunorubicin Phase 2 Unfit: Glasdegib 100 mg + LDAC Phase 2 Unfit: LDAC Alone
Hide Arm/Group Description:
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.
Participants received oral doses of glasdegib tablets 100 mg QD in 28-day cycles on a continuous basis, starting on Day 1 of Cycle 1. LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28 day cycles.
Participants received LDAC subcutaneously at a dose of 20 mg BID on Days 1-10 of the 28 day cycles.
Overall Number of Participants Analyzed 64 78 38
Measure Type: Number
Number (80% Confidence Interval)
Unit of Measure: Percentage of participants
CRi
10.9
(6.2 to 17.7)
5.1
(2.3 to 10.0)
2.6
(0.3 to 9.9)
MLFS
7.8
(3.8 to 14.0)
2.6
(0.7 to 6.7)
0.0
(0.0 to 5.9)
PR
1.6
(0.2 to 5.9)
6.4
(3.2 to 11.6)
2.6
(0.3 to 9.9)
PRi
1.6
(0.2 to 5.9)
1.3
(0.1 to 4.9)
0.0
(0.0 to 5.9)
MR
10.9
(6.2 to 17.7)
6.4
(3.2 to 11.6)
10.5
(4.7 to 19.9)
SD
6.3
(2.8 to 12.1)
16.7
(11.3 to 23.4)
21.1
(12.7 to 31.9)
CRc
35.9
(27.9 to 44.7)
11.5
(7.1 to 17.6)
0.0
(0.0 to 5.9)
CRm
37.5
(29.4 to 46.2)
16.7
(11.3 to 23.4)
2.6
(0.3 to 9.9)
9.Secondary Outcome
Title Percentage of Participants With Disease-specific Efficacy for Myelodysplastic Syndrome (MDS) at Phase 2 Fit and Unfit
Hide Description For all MDS participants, disease specific efficacy measures included: CRi (bone marrow showing <5% myeloblasts with platelets <100,000/mcL or neutrophils <1000/mcL, including confirmed and unconfirmed responses); PR (repeat bone marrow myeloblasts showing decreased by >= 50% decrease but still >5%, peripheral blood showing neutrophils >= 1,000/mcL, platelets >= 100,000/mcL and Hgb>=11g/dL; including confirmed and unconfirmed responses); SD (including confirmed and unconfirmed responses, failure to achieve PR and no evidence of progression for >8 weeks); marrow complete response (mCR) (bone marrow showing <=5% myeloblasts and decreased by >= 50%), partial cytogenetic response (>=50% reduction of chromosomal abnormality) and complete cytogenetic response (CRc) (disappearance of chromosomal abnormality with no appearance of now ones).
Time Frame 4 years
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Hide Analysis Population Description
MDS participants in the Full analysis set: all enrolled participants of Phase 2 Fit arm who received at least 1 dose of study medication, and all randomized participants of Phase 2 Unfit arm.
Arm/Group Title Phase 2 Fit: Glasdegib 100 mg + Cytarabine/Daunorubicin Phase 2 Unfit: Glasdegib 100 mg + LDAC Phase 2 Unfit: LDAC Alone
Hide Arm/Group Description:
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.
Participants received oral doses of glasdegib tablets 100 mg QD in 28-day cycles on a continuous basis, starting on Day 1 of Cycle 1. LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28 day cycles.
Participants received LDAC subcutaneously at a dose of 20 mg BID on Days 1-10 of the 28 day cycles.
Overall Number of Participants Analyzed 5 10 6
Measure Type: Number
Number (80% Confidence Interval)
Unit of Measure: Percentage of participants
mCR
0.0
(0.0 to 36.9)
10.0
(1.0 to 33.7)
0.0
(0.0 to 31.9)
PR
0.0
(0.0 to 36.9)
0.0
(0.0 to 20.6)
0.0
(0.0 to 31.9)
SD
0.0
(0.0 to 36.9)
0.0
(0.0 to 20.6)
33.3
(9.3 to 66.7)
CRi
20.0
(2.1 to 58.4)
10.0
(1.0 to 33.7)
0.0
(0.0 to 31.9)
Unconfirmed SD
0.0
(0.0 to 36.9)
10.0
(1.0 to 33.7)
0.0
(0.0 to 31.9)
Unconfirmed CRi
0.0
(0.0 to 36.9)
10.0
(1.0 to 33.7)
0.0
(0.0 to 31.9)
mCR (CRi not included)
0.0
(0.0 to 36.9)
10.0
(1.0 to 33.7)
0.0
(0.0 to 31.9)
CRc
60.0
(24.7 to 88.8)
10.0
(1.0 to 33.7)
0.0
(0.0 to 31.9)
10.Secondary Outcome
Title Maximum Observed Plasma Concentration (Cmax) of Glasdegib in Participants Receiving Glasdegib and LDAC at Phase 1B on Cycle 1/Day 10 and Cycle 1/Day 21
Hide Description [Not Specified]
Time Frame Pre-dose, 0.5, 1, 2, 4, 6 and 24 hours post-dose on Cycle 1/Day 10 and Cycle 1/Day 21
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Hide Analysis Population Description
Dose compliant group:Participants who had at least 4 days of uninterrupted dosing for a multiple dose PK assessment were considered to be at steady state,part of the "dose compliant" group.
Arm/Group Title Phase 1B: Glasdegib 100 mg + LDAC Phase 1B: Glasdegib 200 mg + LDAC
Hide Arm/Group Description:
Participants received oral doses of glasdegib (PF-04449913) tablets 100 milligram (mg) starting on Day 3 of Cycle 1 for pharmacokinetic (PK) assessment purposes and thereafter once daily (QD) and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously twice daily (BID) on Days 1-10 of the 28-day cycles.
Participants received oral doses of glasdegib tablets 200 mg starting on Day 3 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28-day cycles. In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg. Participants who had glasdegib dose reduction were reported as the starting glasdegib dose level received. Two (2) participants in this cohort had dose reduction to 100 mg starting from Cycle 2/Day 1 and Cycle 2/Day 16, respectively.
Overall Number of Participants Analyzed 17 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
Cycle 1/Day 10 Number Analyzed 13 participants 6 participants
1074
(63%)
1942
(75%)
Cycle 1/Day 21 Number Analyzed 8 participants 5 participants
1242
(56%)
2577
(104%)
11.Secondary Outcome
Title Time to Cmax (Tmax) of Glasdegib in Participants Receiving Glasdegib and LDAC at Phase 1B on Cycle 1/Day 10 and Cycle 1/Day 21
Hide Description [Not Specified]
Time Frame Pre-dose, 0.5, 1, 2, 4, 6 and 24 hours post-dose on Cycle 1/Day 10 and Cycle 1/Day 21
Hide Outcome Measure Data
Hide Analysis Population Description
Dose compliant group:Participants who had at least 4 days of uninterrupted dosing for a multiple dose PK assessment were considered to be at steady state,part of the "dose compliant" group.
Arm/Group Title Phase 1B: Glasdegib 100 mg + LDAC Phase 1B: Glasdegib 200 mg + LDAC
Hide Arm/Group Description:
Participants received oral doses of glasdegib (PF-04449913) tablets 100 milligram (mg) starting on Day 3 of Cycle 1 for pharmacokinetic (PK) assessment purposes and thereafter once daily (QD) and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously twice daily (BID) on Days 1-10 of the 28-day cycles.
Participants received oral doses of glasdegib tablets 200 mg starting on Day 3 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28-day cycles. In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg. Participants who had glasdegib dose reduction were reported as the starting glasdegib dose level received. Two (2) participants in this cohort had dose reduction to 100 mg starting from Cycle 2/Day 1 and Cycle 2/Day 16, respectively.
Overall Number of Participants Analyzed 17 6
Median (Full Range)
Unit of Measure: Hours
Cycle 1/Day 10 Number Analyzed 13 participants 6 participants
1.75
(0.750 to 24.0)
4.00
(1.02 to 24.0)
Cycle 1/Day 21 Number Analyzed 8 participants 5 participants
1.34
(0.533 to 2.00)
4.00
(1.00 to 6.00)
12.Secondary Outcome
Title Area Under the Plasma Concentration-time Profile From Time 0 to Dosing Interval (AUCtau) of Glasdegib in Participants Receiving Glasdegib and LDAC at Phase 1B on Cycle 1/Day 10 and Cycle 1/Day 21
Hide Description [Not Specified]
Time Frame Pre-dose, 0.5, 1, 2, 4, 6 and 24 hours post-dose on Cycle 1/Day 10 and Cycle 1/Day 21
Hide Outcome Measure Data
Hide Analysis Population Description
Dose compliant group:Participants who had at least 4 days of uninterrupted dosing for a multiple dose PK assessment were considered to be at steady state,part of the "dose compliant" group.
Arm/Group Title Phase 1B: Glasdegib 100 mg + LDAC Phase 1B: Glasdegib 200 mg + LDAC
Hide Arm/Group Description:
Participants received oral doses of glasdegib (PF-04449913) tablets 100 milligram (mg) starting on Day 3 of Cycle 1 for pharmacokinetic (PK) assessment purposes and thereafter once daily (QD) and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously twice daily (BID) on Days 1-10 of the 28-day cycles.
Participants received oral doses of glasdegib tablets 200 mg starting on Day 3 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28-day cycles. In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg. Participants who had glasdegib dose reduction were reported as the starting glasdegib dose level received. Two (2) participants in this cohort had dose reduction to 100 mg starting from Cycle 2/Day 1 and Cycle 2/Day 16, respectively.
Overall Number of Participants Analyzed 17 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*hr/mL
Cycle 1/Day 10 Number Analyzed 10 participants 4 participants
15020
(49%)
28600
(17%)
Cycle 1/Day 21 Number Analyzed 8 participants 4 participants
16660
(43%)
31400
(119%)
13.Secondary Outcome
Title Cmax of Glasdegib in Participants Receiving Glasdegib and Decitabine at Phase 1B on Cycle 1/Day 10 and Cycle 2/Day 1
Hide Description [Not Specified]
Time Frame Pre-dose, 0.5, 1, 2, 4, 6 and 24 hours post-dose on Cycle 1/Day 10; pre-dose, 0.5, 1, 2, 6 and 24 hours post-dose on Cycle 2/Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
Dose compliant group:Participants who had at least 4 days of uninterrupted dosing for a multiple dose PK assessment were considered to be at steady state,part of the "dose compliant" group.
Arm/Group Title Phase 1B: Glasdegib 100 mg + Decitabine Phase 1B: Glasdegib 200 mg + Decitabine
Hide Arm/Group Description:
Participants received oral doses of glasdegib tablets 100 mg starting on Day 2 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). Decitabine was given at a dose of 20 mg/m^2 as an intravenous (IV) infusion over 1 hour on Days 1-5 of the 28-day cycles.
Participants received oral doses of glasdegib tablets 200 mg starting on Day 2 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). Decitabine was given at a dose of 20 mg/m^2 as an IV infusion over 1 hour on Days 1-5 of the 28-day cycles.In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg. Participants who had glasdegib dose reduction were reported as the starting glasdegib dose level received. Two (2) participants in this cohort had dose reduction to 100 mg starting from Cycle 1/Day 24 and Cycle 5/Day 1, respectively.
Overall Number of Participants Analyzed 4 3
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
Cycle 1/Day 10 Number Analyzed 3 participants 3 participants
1718
(28%)
2381
(28%)
Cycle 2/Day 1 Number Analyzed 3 participants 2 participants
1826
(44%)
NA [1] 
(NA%)
[1]
Based on pre-specified criteria, statistical analysis was not performed if fewer than 3 participants have reportable parameter values.
14.Secondary Outcome
Title Tmax of Glasdegib in Participants Receiving Glasdegib and Decitabine at Phase 1B on Cycle 1/Day 10 and Cycle 2/Day 1
Hide Description [Not Specified]
Time Frame Pre-dose, 0.5, 1, 2, 4, 6 and 24 hours post-dose on Cycle 1/Day 10; pre-dose, 0.5, 1, 2, 6 and 24 hours post-dose on Cycle 2/Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
Dose compliant group:Participants who had at least 4 days of uninterrupted dosing for a multiple dose PK assessment were considered to be at steady state,part of the "dose compliant" group.
Arm/Group Title Phase 1B: Glasdegib 100 mg + Decitabine Phase 1B: Glasdegib 200 mg + Decitabine
Hide Arm/Group Description:
Participants received oral doses of glasdegib tablets 100 mg starting on Day 2 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). Decitabine was given at a dose of 20 mg/m^2 as an intravenous (IV) infusion over 1 hour on Days 1-5 of the 28-day cycles.
Participants received oral doses of glasdegib tablets 200 mg starting on Day 2 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). Decitabine was given at a dose of 20 mg/m^2 as an IV infusion over 1 hour on Days 1-5 of the 28-day cycles.In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg. Participants who had glasdegib dose reduction were reported as the starting glasdegib dose level received. Two (2) participants in this cohort had dose reduction to 100 mg starting from Cycle 1/Day 24 and Cycle 5/Day 1, respectively.
Overall Number of Participants Analyzed 4 3
Median (Full Range)
Unit of Measure: Hours
Cycle 1/Day 10 Number Analyzed 3 participants 3 participants
2.00
(0.500 to 24.0)
2.05
(1.00 to 5.97)
Cycle 2/Day 1 Number Analyzed 3 participants 2 participants
1.03
(0.567 to 2.00)
NA [1] 
(NA to NA)
[1]
Based on pre-specified criteria, statistical analysis was not performed if fewer than 3 participants have reportable parameter values.
15.Secondary Outcome
Title AUCtau of Glasdegib in Participants Receiving Glasdegib and Decitabine at Phase 1B on Cycle 1/Day 10 and Cycle 2/Day 1
Hide Description [Not Specified]
Time Frame Pre-dose, 0.5, 1, 2, 4, 6 and 24 hours post-dose on Cycle 1/Day 10; pre-dose, 0.5, 1, 2, 6 and 24 hours post-dose on Cycle 2/Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
Dose compliant group:Participants who had at least 4 days of uninterrupted dosing for a multiple dose PK assessment were considered to be at steady state,part of the "dose compliant" group.
Arm/Group Title Phase 1B: Glasdegib 100 mg + Decitabine Phase 1B: Glasdegib 200 mg + Decitabine
Hide Arm/Group Description:
Participants received oral doses of glasdegib tablets 100 mg starting on Day 2 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). Decitabine was given at a dose of 20 mg/m^2 as an intravenous (IV) infusion over 1 hour on Days 1-5 of the 28-day cycles.
Participants received oral doses of glasdegib tablets 200 mg starting on Day 2 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). Decitabine was given at a dose of 20 mg/m^2 as an IV infusion over 1 hour on Days 1-5 of the 28-day cycles.In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg. Participants who had glasdegib dose reduction were reported as the starting glasdegib dose level received. Two (2) participants in this cohort had dose reduction to 100 mg starting from Cycle 1/Day 24 and Cycle 5/Day 1, respectively.
Overall Number of Participants Analyzed 4 3
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*hr/mL
Cycle 1/Day 10 Number Analyzed 2 participants 3 participants
NA [1] 
(NA%)
28380
(11%)
Cycle 2/Day 1 Number Analyzed 3 participants 2 participants
17060
(29%)
NA [2] 
(NA%)
[1]
Based on pre-specified criteria, statistical analysis was not performed if fewer than 3 participants have reportable parameter values. Individual AUCtau values are 17700 and 26300 ng*hr/mL.
[2]
Based on pre-specified criteria, statistical analysis was not performed if fewer than 3 participants have reportable parameter values.
16.Secondary Outcome
Title Cmax of Glasdegib in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3 and Day 10
Hide Description [Not Specified]
Time Frame Pre-dose, 0.5, 1, 6 and 24 hours post-dose on Induction Cycle 1/Day 3; pre-dose, 0.5, 1, 4, 6 and 24 hours post-dose on Induction Cycle 1/Day 10
Hide Outcome Measure Data
Hide Analysis Population Description
Dose compliant group:Participants who had at least 4 days of uninterrupted dosing for a multiple dose PK assessment were considered to be at steady state,part of the "dose compliant" group.
Arm/Group Title Phase 1B: Glasdegib 100 mg + Cytarabine/Daunorubicin Phase 1B: Glasdegib 200 mg + Cytarabine/Daunorubicin
Hide Arm/Group Description:
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 200 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg.One (1) participant in this cohort had dose reduction to 100 mg starting from Consolidation Cycle 1/Day 21.
Overall Number of Participants Analyzed 16 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
Induction Cycle 1/Day 3 Number Analyzed 14 participants 6 participants
674.2
(45%)
1622
(25%)
Induction Cycle 1/Day 10 Number Analyzed 15 participants 6 participants
1135
(43%)
2371
(43%)
17.Secondary Outcome
Title Tmax of Glasdegib in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3 and Day 10
Hide Description [Not Specified]
Time Frame Pre-dose, 0.5, 1, 6 and 24 hours post-dose on Induction Cycle 1/Day 3; pre-dose, 0.5, 1, 4, 6 and 24 hours post-dose on Induction Cycle 1/Day 10
Hide Outcome Measure Data
Hide Analysis Population Description
Dose compliant group:Participants who had at least 4 days of uninterrupted dosing for a multiple dose PK assessment were considered to be at steady state,part of the "dose compliant" group.
Arm/Group Title Phase 1B: Glasdegib 100 mg + Cytarabine/Daunorubicin Phase 1B: Glasdegib 200 mg + Cytarabine/Daunorubicin
Hide Arm/Group Description:
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 200 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg.One (1) participant in this cohort had dose reduction to 100 mg starting from Consolidation Cycle 1/Day 21.
Overall Number of Participants Analyzed 16 6
Median (Full Range)
Unit of Measure: Hours
Induction Cycle 1/Day 3 Number Analyzed 14 participants 6 participants
5.99
(0.467 to 25.2)
6.00
(1.00 to 6.07)
Induction Cycle 1/Day 10 Number Analyzed 15 participants 6 participants
4.08
(0.500 to 24.7)
1.04
(0.583 to 4.12)
18.Secondary Outcome
Title AUCtau of Glasdegib in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3 and Day 10
Hide Description [Not Specified]
Time Frame Pre-dose, 0.5, 1, 6 and 24 hours post-dose on Induction Cycle 1/Day 3; pre-dose, 0.5, 1, 4, 6 and 24 hours post-dose on Induction Cycle 1/Day 10
Hide Outcome Measure Data
Hide Analysis Population Description
Dose compliant group:Participants who had at least 4 days of uninterrupted dosing for a multiple dose PK assessment were considered to be at steady state,part of the "dose compliant" group.
Arm/Group Title Phase 1B: Glasdegib 100 mg + Cytarabine/Daunorubicin Phase 1B: Glasdegib 200 mg + Cytarabine/Daunorubicin
Hide Arm/Group Description:
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 200 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg.One (1) participant in this cohort had dose reduction to 100 mg starting from Consolidation Cycle 1/Day 21.
Overall Number of Participants Analyzed 16 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*hr/mL
Induction Cycle 1/Day 3 Number Analyzed 12 participants 5 participants
9332
(56%)
22840
(43%)
Induction Cycle 1/Day 10 Number Analyzed 13 participants 5 participants
16300
(46%)
26370
(39%)
19.Secondary Outcome
Title Cmax of LDAC and Ara-U in Participants Receiving Glasdegib and LDAC at Phase 1B on Cycle 1/Day 2 and Cycle 1/Day 10
Hide Description Ara-U is the major metabolite of cytarabine. LDAC (low dose cytarabine) is rapidly degraded to the stable metabolite Ara-U, Cmax levels of both LDAC and Ara-U were reported.
Time Frame Pre-dose, 0.25, 0.5, 1, 2, 4 and 6 hours post-dose on Cycle 1/Day 2 and Cycle 1/Day 10
Hide Outcome Measure Data
Hide Analysis Population Description
PK concentration population: all treated participants who had at least 1 concentration of any of the study drugs.
Arm/Group Title Phase 1B: Glasdegib 100 mg + LDAC Phase 1B: Glasdegib 200 mg + LDAC
Hide Arm/Group Description:
Participants received oral doses of glasdegib (PF-04449913) tablets 100 milligram (mg) starting on Day 3 of Cycle 1 for pharmacokinetic (PK) assessment purposes and thereafter once daily (QD) and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously twice daily (BID) on Days 1-10 of the 28-day cycles.
Participants received oral doses of glasdegib tablets 200 mg starting on Day 3 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28-day cycles. In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg. Participants who had glasdegib dose reduction were reported as the starting glasdegib dose level received. Two (2) participants in this cohort had dose reduction to 100 mg starting from Cycle 2/Day 1 and Cycle 2/Day 16, respectively.
Overall Number of Participants Analyzed 17 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
LDAC Cycle 1/Day 2 Number Analyzed 16 participants 6 participants
58.50
(58%)
100.1
(29%)
LDAC Cycle 1/Day 10 Number Analyzed 12 participants 6 participants
63.01
(88%)
132.5
(39%)
Ara-U Cycle 1/Day 2 Number Analyzed 17 participants 6 participants
379.5
(34%)
569.7
(29%)
Ara-U Cycle 1/Day 10 Number Analyzed 12 participants 6 participants
452.2
(36%)
652.0
(27%)
20.Secondary Outcome
Title Tmax of LDAC and Ara-U in Participants Receiving Glasdegib and LDAC at Phase 1B on Cycle 1/Day 2 and Cycle 1/Day 10
Hide Description Ara-U is the major metabolite of cytarabine. LDAC (low dose cytarabine) is rapidly degraded to the stable metabolite Ara-U, Tmax levels of both LDAC and Ara-U were reported.
Time Frame Pre-dose, 0.25, 0.5, 1, 2, 4 and 6 hours post-dose on Cycle 1/Day 2 and Cycle 1/Day 10
Hide Outcome Measure Data
Hide Analysis Population Description
PK parameter analysis set: all treated participants who had at least 1 of the PK parameters of interest for any of the study drugs.
Arm/Group Title Phase 1B: Glasdegib 100 mg + LDAC Phase 1B: Glasdegib 200 mg + LDAC
Hide Arm/Group Description:
Participants received oral doses of glasdegib (PF-04449913) tablets 100 milligram (mg) starting on Day 3 of Cycle 1 for pharmacokinetic (PK) assessment purposes and thereafter once daily (QD) and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously twice daily (BID) on Days 1-10 of the 28-day cycles.
Participants received oral doses of glasdegib tablets 200 mg starting on Day 3 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28-day cycles. In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg. Participants who had glasdegib dose reduction were reported as the starting glasdegib dose level received. Two (2) participants in this cohort had dose reduction to 100 mg starting from Cycle 2/Day 1 and Cycle 2/Day 16, respectively.
Overall Number of Participants Analyzed 17 6
Median (Full Range)
Unit of Measure: Hours
LDAC Cycle 1/Day 2 Number Analyzed 16 participants 6 participants
0.250
(0.233 to 1.00)
0.250
(0.250 to 0.500)
LDAC Cycle 1/Day 10 Number Analyzed 12 participants 6 participants
0.325
(0.233 to 1.00)
0.250
(0.233 to 0.500)
Ara-U Cycle 1/Day 2 Number Analyzed 17 participants 6 participants
3.97
(1.00 to 6.05)
4.00
(1.00 to 6.00)
Ara-U Cycle 1/Day 10 Number Analyzed 12 participants 6 participants
2.00
(0.000 to 6.00)
1.99
(1.02 to 4.08)
21.Secondary Outcome
Title Area Under the Plasma Concentration-time Profile From Time 0 to Infinity (AUCinf) of LDAC in Participants Receiving Glasdegib and LDAC at Phase 1B on Cycle 1/Day 2 and Cycle 1/Day 10
Hide Description [Not Specified]
Time Frame Pre-dose, 0.25, 0.5, 1, 2, 4 and 6 hours post-dose on Cycle 1/Day 2 and Cycle 1/Day 10
Hide Outcome Measure Data
Hide Analysis Population Description
PK parameter analysis set: all treated participants who had at least 1 of the PK parameters of interest for any of the study drugs.
Arm/Group Title Phase 1B: Glasdegib 100 mg + LDAC Phase 1B: Glasdegib 200 mg + LDAC
Hide Arm/Group Description:
Participants received oral doses of glasdegib (PF-04449913) tablets 100 milligram (mg) starting on Day 3 of Cycle 1 for pharmacokinetic (PK) assessment purposes and thereafter once daily (QD) and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously twice daily (BID) on Days 1-10 of the 28-day cycles.
Participants received oral doses of glasdegib tablets 200 mg starting on Day 3 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28-day cycles. In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg. Participants who had glasdegib dose reduction were reported as the starting glasdegib dose level received. Two (2) participants in this cohort had dose reduction to 100 mg starting from Cycle 2/Day 1 and Cycle 2/Day 16, respectively.
Overall Number of Participants Analyzed 17 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*hr/mL
LDAC Cycle 1/Day 2 Number Analyzed 14 participants 6 participants
71.10
(28%)
89.35
(28%)
LDAC Cycle 1/Day 10 Number Analyzed 9 participants 5 participants
92.28
(25%)
143.9
(24%)
22.Secondary Outcome
Title Area Under the Plasma Concentration-time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of LDAC and Ara-U in Participants Receiving Glasdegib and LDAC at Phase 1B on Cycle 1/Day 2 and Cycle 1/Day 10
Hide Description Ara-U is the major metabolite of cytarabine. LDAC (low dose cytarabine) is rapidly degraded to the stable metabolite Ara-U. Area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration (AUClast) levels of both LDAC and Ara-U were reported.
Time Frame Pre-dose, 0.25, 0.5, 1, 2, 4 and 6 hours post-dose on Cycle 1/Day 2 and Cycle 1/Day 10
Hide Outcome Measure Data
Hide Analysis Population Description
PK parameter analysis set: all treated participants who had at least 1 of the PK parameters of interest for any of the study drugs.
Arm/Group Title Phase 1B: Glasdegib 100 mg + LDAC Phase 1B: Glasdegib 200 mg + LDAC
Hide Arm/Group Description:
Participants received oral doses of glasdegib (PF-04449913) tablets 100 milligram (mg) starting on Day 3 of Cycle 1 for pharmacokinetic (PK) assessment purposes and thereafter once daily (QD) and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously twice daily (BID) on Days 1-10 of the 28-day cycles.
Participants received oral doses of glasdegib tablets 200 mg starting on Day 3 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28-day cycles. In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg. Participants who had glasdegib dose reduction were reported as the starting glasdegib dose level received. Two (2) participants in this cohort had dose reduction to 100 mg starting from Cycle 2/Day 1 and Cycle 2/Day 16, respectively.
Overall Number of Participants Analyzed 17 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*hr/mL
LDAC Cycle 1/Day 2 Number Analyzed 16 participants 6 participants
62.55
(41%)
87.49
(29%)
LDAC Cycle 1/Day 10 Number Analyzed 12 participants 6 participants
65.56
(76%)
134.8
(26%)
Ara-U Cycle 1/Day 2 Number Analyzed 17 participants 6 participants
2036
(36%)
3050
(29%)
Ara-U Cycle 1/Day 10 Number Analyzed 12 participants 6 participants
2283
(43%)
3528
(29%)
23.Secondary Outcome
Title Cmax of Decitabine in Participants Receiving Glasdegib and Decitabine at Phase 1B on Cycle 1/Day 1 and Cycle 1/Day 2
Hide Description [Not Specified]
Time Frame Pre-dose, 0.5 hour from start of infusion, 1 hour (at end of infusion) and 2, 3 and 4 hours from start of infusion on Cycle 1/Day 1 and Cycle 1/Day 2
Hide Outcome Measure Data
Hide Analysis Population Description
PK concentration population: all treated participants who had at least 1 concentration of any of the study drugs.
Arm/Group Title Phase 1B: Glasdegib 100 mg + Decitabine Phase 1B: Glasdegib 200 mg + Decitabine
Hide Arm/Group Description:
Participants received oral doses of glasdegib tablets 100 mg starting on Day 2 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). Decitabine was given at a dose of 20 mg/m^2 as an intravenous (IV) infusion over 1 hour on Days 1-5 of the 28-day cycles.
Participants received oral doses of glasdegib tablets 200 mg starting on Day 3 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28-day cycles. In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg. Participants who had glasdegib dose reduction were reported as the starting glasdegib dose level received. Two (2) participants in this cohort had dose reduction to 100 mg starting from Cycle 2/Day 1 and Cycle 2/Day 16, respectively.
Overall Number of Participants Analyzed 4 3
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
Cycle 1/Day 1 Number Analyzed 3 participants 3 participants
113.4
(59%)
174.2
(113%)
Cycle 1/Day 2 Number Analyzed 3 participants 3 participants
127.9
(43%)
121.7
(37%)
24.Secondary Outcome
Title Tmax of Decitabine in Participants Receiving Glasdegib and Decitabine at Phase 1B on Cycle 1/Day 1 and Cycle 1/Day 2
Hide Description [Not Specified]
Time Frame Pre-dose, 0.5 hour from start of infusion, 1 hour (at end of infusion) and 2, 3 and 4 hours from start of infusion on Cycle 1/Day 1 and Cycle 1/Day 2
Hide Outcome Measure Data
Hide Analysis Population Description
PK parameter analysis set: all treated participants who had at least 1 of the PK parameters of interest for any of the study drugs.
Arm/Group Title Phase 1B: Glasdegib 100 mg + Decitabine Phase 1B: Glasdegib 200 mg + Decitabine
Hide Arm/Group Description:
Participants received oral doses of glasdegib tablets 100 mg starting on Day 2 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). Decitabine was given at a dose of 20 mg/m^2 as an intravenous (IV) infusion over 1 hour on Days 1-5 of the 28-day cycles.
Participants received oral doses of glasdegib tablets 200 mg starting on Day 3 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28-day cycles. In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg. Participants who had glasdegib dose reduction were reported as the starting glasdegib dose level received. Two (2) participants in this cohort had dose reduction to 100 mg starting from Cycle 2/Day 1 and Cycle 2/Day 16, respectively.
Overall Number of Participants Analyzed 4 3
Median (Full Range)
Unit of Measure: Hours
Cycle 1/Day 1 Number Analyzed 3 participants 3 participants
0.75
(0.50 to 1.0)
0.53
(0.52 to 0.75)
Cycle 1/Day 2 Number Analyzed 3 participants 3 participants
0.58
(0.53 to 0.95)
0.53
(0.52 to 1.3)
25.Secondary Outcome
Title AUCinf of Decitabine in Participants Receiving Glasdegib and Decitabine at Phase 1B on Cycle 1/Day 1 and Cycle 1/Day 2
Hide Description [Not Specified]
Time Frame Pre-dose, 0.5 hour from start of infusion, 1 hour (at end of infusion) and 2, 3 and 4 hours from start of infusion on Cycle 1/Day 1 and Cycle 1/Day 2
Hide Outcome Measure Data
Hide Analysis Population Description
PK parameter analysis set: all treated participants who had at least 1 of the PK parameters of interest for any of the study drugs.
Arm/Group Title Phase 1B: Glasdegib 100 mg + Decitabine Phase 1B: Glasdegib 200 mg + Decitabine
Hide Arm/Group Description:
Participants received oral doses of glasdegib tablets 100 mg starting on Day 2 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). Decitabine was given at a dose of 20 mg/m^2 as an intravenous (IV) infusion over 1 hour on Days 1-5 of the 28-day cycles.
Participants received oral doses of glasdegib tablets 200 mg starting on Day 3 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28-day cycles. In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg. Participants who had glasdegib dose reduction were reported as the starting glasdegib dose level received. Two (2) participants in this cohort had dose reduction to 100 mg starting from Cycle 2/Day 1 and Cycle 2/Day 16, respectively.
Overall Number of Participants Analyzed 4 3
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*hr/mL
Cycle 1/Day 1 Number Analyzed 3 participants 3 participants
133.4
(71%)
251.5
(140%)
Cycle 1/Day 2 Number Analyzed 2 participants 2 participants
NA [1] 
(NA%)
NA [2] 
(NA%)
[1]
Based on pre-specified criteria, statistical analysis was not performed if fewer than 3 participants have reportable parameter values. Individual AUCinf values are 265 and 1040 ng*hr/mL.
[2]
Based on pre-specified criteria, statistical analysis was not performed if fewer than 3 participants have reportable parameter values. Individual AUCinf values are 154 and 216 ng*hr/mL.
26.Secondary Outcome
Title AUCtau of Cytarabine and Ara-U in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3
Hide Description Ara-U is the major metabolite of cytarabine. LDAC (low dose cytarabine) is rapidly degraded to the stable metabolite Ara-U, levels of both cytarabine and Ara-U were reported.
Time Frame Pre-dose, 6 and 24 hours post start of cytarabine infusion on Induction Cycle 1/Day 3
Hide Outcome Measure Data
Hide Analysis Population Description
PK parameter analysis set: all treated participants who had at least 1 of the PK parameters of interest for any of the study drugs.
Arm/Group Title Phase 1B: Glasdegib 100 mg + Cytarabine/Daunorubicin Phase 1B: Glasdegib 200 mg + Cytarabine/Daunorubicin
Hide Arm/Group Description:
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 200 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg.One (1) participant in this cohort had dose reduction to 100 mg starting from Consolidation Cycle 1/Day 21.
Overall Number of Participants Analyzed 9 2
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*hr/mL
Cytarabine
1070
(211%)
NA [1] 
(NA%)
Ara-U
28420
(32%)
NA [2] 
(NA%)
[1]
Based on pre-specified criteria, statistical analysis was not performed if fewer than 3 participants have reportable parameter values. Individual AUCtau values are 276 and 879 ng*hr/mL.
[2]
Based on pre-specified criteria, statistical analysis was not performed if fewer than 3 participants have reportable parameter values. Individual AUCtau values are 32430 and 45900 ng*hr/mL.
27.Secondary Outcome
Title Cmax of Daunorubicin and Daunorubicinol in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3
Hide Description Daunorubicinol is the major metabolite of daunorubicin, which has anti-neoplastic activity. Cmax values of daunorubicin and daunorubicinol are reported.
Time Frame Pre-dose, 0.25, 0.5, 1, 4, 6, 24 hours post administration of daunorubicin on Induction Cycle 1/Day 3
Hide Outcome Measure Data
Hide Analysis Population Description
PK concentration population: all treated participants who had at least 1 concentration of any of the study drugs.
Arm/Group Title Phase 1B: Glasdegib 100 mg + Cytarabine/Daunorubicin Phase 1B: Glasdegib 200 mg + Cytarabine/Daunorubicin
Hide Arm/Group Description:
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 200 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg.One (1) participant in this cohort had dose reduction to 100 mg starting from Consolidation Cycle 1/Day 21.
Overall Number of Participants Analyzed 15 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
Daunorubicin
275.3
(153%)
341.0
(82%)
Daunorubicinol
195.4
(139%)
233.4
(46%)
28.Secondary Outcome
Title Tmax of Daunorubicin and Daunorubicinol in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3
Hide Description Daunorubicinol is the major metabolite of daunorubicin, which has anti-neoplastic activity. Tmax values of daunorubicin and daunorubicinol are reported.
Time Frame Pre-dose, 0.25, 0.5, 1, 4, 6, 24 hours post administration of daunorubicin on Induction Cycle 1/Day 3
Hide Outcome Measure Data
Hide Analysis Population Description
PK parameter analysis set: all treated participants who had at least 1 of the PK parameters of interest for any of the study drugs.
Arm/Group Title Phase 1B: Glasdegib 100 mg + Cytarabine/Daunorubicin Phase 1B: Glasdegib 200 mg + Cytarabine/Daunorubicin
Hide Arm/Group Description:
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 200 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg.One (1) participant in this cohort had dose reduction to 100 mg starting from Consolidation Cycle 1/Day 21.
Overall Number of Participants Analyzed 15 6
Median (Full Range)
Unit of Measure: Hours
Daunorubicin
0.500
(0.217 to 1.72)
0.492
(0.250 to 0.600)
Daunorubicinol
1.00
(0.217 to 5.90)
0.642
(0.283 to 4.00)
29.Secondary Outcome
Title AUCtau of Daunorubicin and Daunorubicinol in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3
Hide Description Daunorubicinol is the major metabolite of daunorubicin, which has anti-neoplastic activity. AUCtau values of daunorubicin and daunorubicinol are reported.
Time Frame Pre-dose, 0.25, 0.5, 1, 4, 6, 24 hours post administration of daunorubicin on Induction Cycle 1/Day 3
Hide Outcome Measure Data
Hide Analysis Population Description
PK parameter analysis set: all treated participants who had at least 1 of the PK parameters of interest for any of the study drugs.
Arm/Group Title Phase 1B: Glasdegib 100 mg + Cytarabine/Daunorubicin Phase 1B: Glasdegib 200 mg + Cytarabine/Daunorubicin
Hide Arm/Group Description:
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 200 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg.One (1) participant in this cohort had dose reduction to 100 mg starting from Consolidation Cycle 1/Day 21.
Overall Number of Participants Analyzed 16 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*hr/mL
Daunorubicin Number Analyzed 14 participants 4 participants
499.3
(61%)
424.9
(38%)
Daunorubicinol Number Analyzed 15 participants 5 participants
2152
(24%)
2712
(33%)
30.Secondary Outcome
Title Pre-dose Plasma Concentration (Ctrough) of Glasdegib in Phase 2 Fit on Induction Cycle 1/Day 10
Hide Description [Not Specified]
Time Frame Pre-dose, 1 and 4 hours post-dose on Induction Cycle 1/Day 10
Hide Outcome Measure Data
Hide Analysis Population Description
Dose compliant, non CYP3A4 group: dose compliant group participants who did not have administration of any strong or moderate CYP3A4 inhibitors.
Arm/Group Title Phase 2 Fit: Glasdegib 100 mg + Cytarabine/Daunorubicin
Hide Arm/Group Description:
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.
Overall Number of Participants Analyzed 42
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
308.7
(74%)
31.Secondary Outcome
Title Cmax of Glasdegib in Participants Receiving Glasdegib and LDAC at Phase 2 Unfit on Cycle 1/Day 10
Hide Description [Not Specified]
Time Frame Pre-dose, 1, 2, 4, and 6 hour post-dose on Cycle 1/Day 10
Hide Outcome Measure Data
Hide Analysis Population Description
Dose compliant, non CYP3A4 group: dose compliant group participants who did not have administration of any strong or moderate CYP3A4 inhibitors.
Arm/Group Title Phase 2 Unfit: Glasdegib 100 mg + LDAC
Hide Arm/Group Description:
Participants received oral doses of glasdegib tablets 100 mg QD in 28-day cycles on a continuous basis, starting on Day 1 of Cycle 1. LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28 day cycles.
Overall Number of Participants Analyzed 41
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
1252
(0.667% to 5.83%)
32.Secondary Outcome
Title Tmax of Glasdegib in Participants Receiving Glasdegib and LDAC at Phase 2 Unfit on Cycle 1/Day 10
Hide Description [Not Specified]
Time Frame Pre-dose, 1, 2, 4, and 6 hour post-dose on Cycle 1/Day 10
Hide Outcome Measure Data
Hide Analysis Population Description
Dose compliant, non CYP3A4 group: dose compliant group participants who did not have administration of any strong or moderate CYP3A4 inhibitors.
Arm/Group Title Phase 2 Unfit: Glasdegib 100 mg + LDAC
Hide Arm/Group Description:
Participants received oral doses of glasdegib tablets 100 mg QD in 28-day cycles on a continuous basis, starting on Day 1 of Cycle 1. LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28 day cycles.
Overall Number of Participants Analyzed 41
Median (Full Range)
Unit of Measure: Hours
1.67
(0.667 to 5.83)
33.Secondary Outcome
Title AUCtau of Glasdegib in Participants Receiving Glasdegib and LDAC at Phase 2 Unfit on Cycle 1/Day 10
Hide Description [Not Specified]
Time Frame Pre-dose, 1, 2, 4, and 6 hour post-dose on Cycle 1/Day 10
Hide Outcome Measure Data
Hide Analysis Population Description
Dose compliant, non CYP3A4 group: dose compliant group participants who did not have administration of any strong or moderate CYP3A4 inhibitors.
Arm/Group Title Phase 2 Unfit: Glasdegib 100 mg + LDAC
Hide Arm/Group Description:
Participants received oral doses of glasdegib tablets 100 mg QD in 28-day cycles on a continuous basis, starting on Day 1 of Cycle 1. LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28 day cycles.
Overall Number of Participants Analyzed 37
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*hr/mL
17210
(0.667% to 5.83%)
34.Secondary Outcome
Title Number of Participants With Disease-related Gene Mutations at Phase 1B
Hide Description Peripheral blood and bone marrow aspirate were collected for baseline mutational analyses. Genetic abnormalities frequently associated with AML were analyzed. These genetic abnormalities included known mutations in the genes NPM1, CEBPA, FLT3, RUNX1, IDH1, IDH2, KIT, K Ras, N Ras and WT1. Additional genes with mutations known to be associated with AML and MDS such as TET2 and DNMT3A were also evaluated.
Time Frame Baseline (Cycle 1/Day 1 pre-dose for Glasdegib + LDAC and Glasdegib + Decitabine Arms; Induction Cycle 1/Day -3 pre-dose for Glasdegib +Cytarabine/Daunorubicin Arm)
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacodynamic (PD) analysis set: all enrolled participants in the Phase 1B portion who received at least 1 dose of glasdegib; responders and non-responders in each arm with at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.
Arm/Group Title Phase 1B: Glasdegib + LDAC (Biomarker, Responder) Phase 1B: Glasdegib + LDAC (Biomarker, Non-Responder) Phase 1B: Glasdegib + Decitabine (Biomarker,Responder) Phase 1B: Glasdegib + Decitabine (Biomaker,Non-Responder) Phase 1B: Glasdegib + Cytarabine/Dauno (Biomarker, Responder) Phase 1B: Glasdegib+Cytarabine/Dauno(Biomarker,Non-Responder)
Hide Arm/Group Description:
AML participants who achieved CR, CRi, MLFS, PR, or PRi (AML investigator reported best overall response), and MDS participants who achieved CR, mCR, PR, or SD (MDS investigator reported best overall response).
AML subjects who did not achieve CR, CRi, MLFS, PR, or PRi; and MDS subjects who did not achieve CR, mCR, PR or SD were defined as non-responders for best overall response.
AML participants who achieved CR, CRi, MLFS, PR, or PRi (AML investigator reported best overall response), and MDS participants who achieved CR, mCR, PR, or SD (MDS investigator reported best overall response).
AML participants who did not achieve CR, CRi, MLFS, PR, or PRi; and MDS participants who did not achieve CR, mCR, PR or SD were defined as non-responders for best overall response.
AML subjects who achieved CR, CRi, MLFS, PR, or PRi (AML investigator reported best overall response), and MDS subjects who achieved CR, mCR, PR, or SD (MDS investigator reported best overall response). Dauno is short for daunorubicin.
AML participants who did not achieve CR, CRi, MLFS, PR, or PRi; and MDS participants who did not achieve CR, mCR, PR or SD were defined as non-responders for best overall response. Dauno is short for daunorubicin.
Overall Number of Participants Analyzed 0 9 0 1 11 1
Measure Type: Number
Unit of Measure: Participants
CEBPA (CCAAT/enhancer-binding protein alpha) 3 0 2 0
DNMT3A (DNA [cytosine-5]-methyltransferase 3A) 2 0 0 0
FLT3 (Fms-like tyrosine kinase 3) 1 0 2 0
FLT3-ITD (FLT3 internal tandem duplications) 0 0 1 0
IDH1 (Isocitrate dehydrogenase 1) 1 0 0 0
IDH2 (Isocitrate dehydrogenase 2) 0 0 2 0
KIT(Tyrosine-protein kinase Kit) 0 1 0 0
KRAS(Kirsten rat sarcoma 2 viral oncogene homolog) 1 0 0 0
NPM1 (Nucleophosmin) 0 0 4 0
NRAS(Neuroblastoma RAS viral oncogene homolog) 5 0 1 0
RUNX1 (Runt related transcription factor 1) 1 0 1 0
TET2 (Tet methylcytosine dioxygenase 2) 3 0 1 0
WT1 (Wilm's tumour tumor suppressor gene1) 0 0 0 0
35.Secondary Outcome
Title Serum Levels of Circulating Protein Analytes at Phase 1B - Baseline
Hide Description Serum levels were determined for 38 circulating proteins. Values showing statistically significant, ≥2-fold difference compared with baseline are reported here.
Time Frame Baseline (Induction Cycle 1/Day -3 pre-dose)
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacodynamic (PD) analysis set: all enrolled participants in the Phase 1B portion who received at least 1 dose of glasdegib, and had at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.
Arm/Group Title Phase 1B: Glasdegib + Cytarabine/Daunorubicin
Hide Arm/Group Description:
Included all participants who received oral glasdegib in combination with cytarabine/daunorubicin in phase 1B portion.
Overall Number of Participants Analyzed 22
Median (Full Range)
Unit of Measure: pg/mL
MMP-3 (Matrix metalloproteinase-3)
10200
(1700 to 44000)
IL-8 (Interleukin-8)
10.7
(0.00 to 71.00)
BDNF (Brain-derived neurotrophic factor)
1200
(0.00 to 22000)
IL-5 (Interleukin-5)
0.00
(0.00 to 0.00)
VEGF (Vascular endothelial growth factor)
88.00
(32.00 to 2000.00)
MCP-1 (Monocyte chemotactic protein-1)
180.5
(0.00 to 1850.00)
ITAC:Interferon-inducible T-cell α chemoattractant
0.00
(0.00 to 1900.00)
36.Secondary Outcome
Title Serum Levels of Circulating Protein Analytes at Phase 1B - Induction Cycle 1/Day 3
Hide Description Serum levels were determined for 38 circulating proteins. Values showing statistically significant, ≥2-fold difference compared with baseline are reported here. Statistically significant, >=2-fold baseline difference was only seen for MMP-3 (Matrix metalloproteinase-3) at Induction Cycle 1/Day 3.
Time Frame Induction Cycle 1/Day 3, 1 Hour Post dose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacodynamic (PD) analysis set: all enrolled participants in the Phase 1B portion who received at least 1 dose of glasdegib, and had at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.
Arm/Group Title Phase 1B: Glasdegib + Cytarabine/Daunorubicin
Hide Arm/Group Description:
Included all participants who received oral glasdegib in combination with cytarabine/daunorubicin in phase 1B portion.
Overall Number of Participants Analyzed 21
Median (Full Range)
Unit of Measure: pg/mL
20000
(1600 to 111000)
37.Secondary Outcome
Title Serum Levels of Circulating Protein Analytes at Phase 1B - Induction Cycle 1/Day 10
Hide Description Serum levels were determined for 38 circulating proteins. Values showing statistically significant, ≥2-fold difference compared with baseline are reported here.
Time Frame Induction Cycle 1/Day 10, 1 Hour Post dose
Hide Outcome Measure Data
Hide Analysis Population Description
PD analysis set: all enrolled participants in the Phase 1B portion who received at least 1 dose of glasdegib, and had at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.
Arm/Group Title Phase 1B: Glasdegib + Cytarabine/Daunorubicin
Hide Arm/Group Description:
Included all participants who received oral glasdegib in combination with cytarabine/daunorubicin in phase 1B portion.
Overall Number of Participants Analyzed 21
Median (Full Range)
Unit of Measure: pg/mL
IL-8
37.00
(7.90 to 128.00)
BDNF
200
(0.00 to 2800)
IL-5
99.00
(0.00 to 2440.00)
VEGF
51.00
(0.00 to 149.00)
MCP-1
684.00
(368.00 to 9780.00)
ITAC
0.00
(0.00 to 218.00)
38.Secondary Outcome
Title Baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 1B
Hide Description Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. A total of 38 proteins were analyzed. The data of analytes for which the serum level showed statistically significant correlation with clinical response in Arm C are reported. Baseline levels statistically associated with best overall response was only seen in SDF-1 (stromal cell-derived factor 1) in glasdegib+cytarabine/daunorubicin arm.
Time Frame Baseline (Cycle 1/Day 1 pre-dose for Glasdegib + LDAC and Glasdegib + Decitabine Arms; Induction Cycle 1/Day -3 pre-dose for Glasdegib +Cytarabine/Daunorubicin Arm)
Hide Outcome Measure Data
Hide Analysis Population Description
PD analysis set: all enrolled participants in the Phase 1B portion who received at least 1 dose of glasdegib, and had at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.
Arm/Group Title Phase 1B: Glasdegib + Cytarabine/Dauno (Biomarker, Responder) Phase 1B: Glasdegib+Cytarabine/Dauno(Biomarker,Non-Responder)
Hide Arm/Group Description:
AML subjects who achieved CR, CRi, MLFS, PR, or PRi (AML investigator reported best overall response), and MDS subjects who achieved CR, mCR, PR, or SD (MDS investigator reported best overall response). Dauno is short for daunorubicin.
AML participants who did not achieve CR, CRi, MLFS, PR, or PRi; and MDS participants who did not achieve CR, mCR, PR or SD were defined as non-responders for best overall response. Dauno is short for daunorubicin.
Overall Number of Participants Analyzed 14 8
Median (Full Range)
Unit of Measure: pg/mL
2275.00
(1600.00 to 3700.00)
3275.00
(1950.00 to 4730.00)
39.Secondary Outcome
Title Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 1B - Induction Cycle 1/Lead-In
Hide Description Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. A total of 38 proteins were analyzed. The data of analytes for which the serum level showed statistically significant correlation with clinical response are reported. Post-baseline levels statistically significant associated with best overall response was only seen for MMP-3 (Matrix metalloproteinase-3) at Induction Cycle 1/Lead-in.
Time Frame Induction Cycle 1/Lead-in, 1 Hour Post dose
Hide Outcome Measure Data
Hide Analysis Population Description
PD analysis set: all enrolled participants in the Phase 1B portion who received at least 1 dose of glasdegib, and had at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.
Arm/Group Title Phase 1B: Glasdegib + Cytarabine/Dauno (Biomarker, Responder) Phase 1B: Glasdegib+Cytarabine/Dauno(Biomarker,Non-Responder)
Hide Arm/Group Description:
AML subjects who achieved CR, CRi, MLFS, PR, or PRi (AML investigator reported best overall response), and MDS subjects who achieved CR, mCR, PR, or SD (MDS investigator reported best overall response). Dauno is short for daunorubicin.
AML participants who did not achieve CR, CRi, MLFS, PR, or PRi; and MDS participants who did not achieve CR, mCR, PR or SD were defined as non-responders for best overall response. Dauno is short for daunorubicin.
Overall Number of Participants Analyzed 14 8
Median (Full Range)
Unit of Measure: ng/mL
8.90
(2.20 to 51.00)
10.50
(6.50 to 19.00)
40.Secondary Outcome
Title Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 1B - Induction Cycle 1/Day 3
Hide Description Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. A total of 38 proteins were analyzed. The data of analytes for which the serum level showed statistically significant correlation with clinical response are reported. Post-baseline levels statistically significant associated with best overall response was only seen for SDF-1 (Stromal cell-derived factor 1) at Induction Cycle 1/Day 3.
Time Frame Induction Cycle 1/Day 3, 1 Hour Post dose
Hide Outcome Measure Data
Hide Analysis Population Description
PD analysis set: all enrolled participants in the Phase 1B portion who received at least 1 dose of glasdegib, and had at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.
Arm/Group Title Phase 1B: Glasdegib + Cytarabine/Dauno (Biomarker, Responder) Phase 1B: Glasdegib+Cytarabine/Dauno(Biomarker,Non-Responder)
Hide Arm/Group Description:
AML subjects who achieved CR, CRi, MLFS, PR, or PRi (AML investigator reported best overall response), and MDS subjects who achieved CR, mCR, PR, or SD (MDS investigator reported best overall response). Dauno is short for daunorubicin.
AML participants who did not achieve CR, CRi, MLFS, PR, or PRi; and MDS participants who did not achieve CR, mCR, PR or SD were defined as non-responders for best overall response. Dauno is short for daunorubicin.
Overall Number of Participants Analyzed 13 8
Median (Full Range)
Unit of Measure: pg/mL
2510.00
(1530.00 to 3520.00)
3260.00
(1350.00 to 4430.00)
41.Secondary Outcome
Title Number of Participants With Disease-related Gene Mutations at Phase 2 Fit and Unfit
Hide Description Peripheral blood and bone marrow aspirate were collected for baseline mutational analyses. Genetic abnormalities frequently associated with AML were analyzed. These genetic abnormalities included known mutations in the genes NPM1, CEBPA, FLT3, RUNX1, IDH1, IDH2, KIT, K Ras, N Ras and WT1. Additional genes with mutations known to be associated with AML and MDS such as TET2 and DNMT3A were also evaluated.
Time Frame Baseline (Induction Cycle 1/Day -3 pre-dose for Phase 2 Fit; Cycle 1/Day 1 pre-dose for Phase 2 Unfit)
Hide Outcome Measure Data
Hide Analysis Population Description
PD analysis set: all enrolled participants in the Phase 2 Fit and Unfit portion who received at least 1 dose of glasdegib; responders and non-responders in each arm with at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.
Arm/Group Title Phase 2 Fit (Biomarker, Responder) Phase 2 Fit (Biomarker,Non-Responder) Phase 2 Unfit: Glasdegib 100 mg + LDAC (Biomarker, Responder) Phase 2 Unfit: Glasdegib 100 mg+LDAC(Biomarker, Non-Responder) Phase 2 Unfit: LDAC Alone (Biomarker, Responder) Phase 2 Unfit: LDAC Alone (Biomarker, Non-Responder)
Hide Arm/Group Description:
AML participants who achieved CR, CRi, MLFS, PR, or PRi (AML investigator reported best overall response), and MDS participants who achieved CR, mCR, PR, or SD (MDS investigator reported best overall response).
AML participants who did not achieve CR, CRi, MLFS, PR, or PRi; and MDS participants who did not achieve CR, mCR, PR or SD were defined as non-responders for best overall response.
AML subjects who achieved CR, CRi, MLFS, PR, or PRi (AML investigator reported best overall response), and MDS subjects who achieved CR, mCR, PR, or SD (MDS investigator reported best overall response).
AML subjects who did not achieve CR, CRi, MLFS, PR, or PRi; and MDS subjects who did not achieve CR, mCR, PR or SD were defined as non-responders for best overall response.
AML subjects who achieved CR, CRi, MLFS, PR, or PRi (AML investigator reported best overall response), and MDS subjects who achieved CR, mCR, PR, or SD (MDS investigator reported best overall response).
AML subjects who did not achieve CR, CRi, MLFS, PR, or PRi; and MDS subjects who did not achieve CR, mCR, PR or SD were defined as non-responders for best overall response.
Overall Number of Participants Analyzed 32 18 21 40 1 26
Measure Type: Number
Unit of Measure: Participants
CEBPA 6 3 3 5 0 3
DNMT3A 12 6 2 13 0 6
FLT3 3 2 1 4 0 0
FLT3-ITD 2 1 1 2 0 2
IDH1 2 1 5 5 0 2
IDH2 5 4 2 10 0 5
KIT 2 1 1 2 0 1
KRAS 0 1 0 2 0 2
NPM1 12 3 2 3 0 1
NRAS 5 1 1 4 0 3
RUNX1 7 7 10 18 0 7
TET2 7 5 7 8 1 8
WT1 0 1 1 2 0 1
42.Secondary Outcome
Title Serum Levels of Circulating Protein Analytes at Phase 2 Fit - Induction Cycle 1/Day 3
Hide Description Serum levels were determined for 38 circulating proteins. Selected values showing statistically significant difference compared with baseline are reported here.
Time Frame Induction Cycle 1/Day 3, 1 Hour Post dose
Hide Outcome Measure Data
Hide Analysis Population Description
PD analysis set: all enrolled participants in the Phase 2 Fit portion who received at least 1 dose of glasdegib, and had at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.
Arm/Group Title Phase 2 Fit: Glasdegib 100 mg + Cytarabine/Daunorubicin
Hide Arm/Group Description:
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.
Overall Number of Participants Analyzed 57
Median (Full Range)
Unit of Measure: pg/mL
Factor VII(activated blood coagulation factor VII)
318000
(56000 to 620000)
BDNF
700
(0 to 6200)
MMP-3
21000
(1700 to 107000)
IL-8
28.00
(0.00 to 139.00)
ITAC
14.00
(0.00 to 535.00)
43.Secondary Outcome
Title Serum Levels of Circulating Protein Analytes at Phase 2 Fit - Induction Cycle 1/Day 10
Hide Description Serum levels were determined for 38 circulating proteins. Selected values showing statistically significant difference compared with baseline are reported here.
Time Frame Induction Cycle 1/Day 10, 1 Hour Post dose
Hide Outcome Measure Data
Hide Analysis Population Description
PD analysis set: all enrolled participants in the Phase 2 Fit portion who received at least 1 dose of glasdegib, and had at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.
Arm/Group Title Phase 2 Fit: Glasdegib 100 mg + Cytarabine/Daunorubicin
Hide Arm/Group Description:
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.
Overall Number of Participants Analyzed 62
Median (Full Range)
Unit of Measure: pg/mL
IL-1β (Interleukin-1β)
8.50
(0.00 to 15.00)
IL-6
17.00
(0.00 to 7320.00)
Factor VII
292500
(45000 to 641000)
BDNF
300
(0 to 15000)
VEGF
69.00
(0.00 to 140.00)
MCP-1
594.00
(126.00 to 21200.00)
MMP-3
12000
(3000 to 93000)
IL-8
55.00
(0.00 to 8930.00)
IL-5
85.00
(0.00 to 2240.00)
ITAC
0.00
(0.00 to 46.00)
44.Secondary Outcome
Title Serum Levels of Circulating Protein Analytes at Phase 2 Fit - Consolidation Cycle 1/Day 1
Hide Description Serum levels were determined for 38 circulating proteins. Selected values showing statistically significant difference compared with baseline are reported here.
Time Frame Consolidation Cycle 1/Day 1, 1 Hour Post dose
Hide Outcome Measure Data
Hide Analysis Population Description
PD analysis set: all enrolled participants in the Phase 2 Fit portion who received at least 1 dose of glasdegib, and had at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.
Arm/Group Title Phase 2 Fit: Glasdegib 100 mg + Cytarabine/Daunorubicin
Hide Arm/Group Description:
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.
Overall Number of Participants Analyzed 24
Median (Full Range)
Unit of Measure: pg/mL
MIP-1β (Macrophage Inflammatory Protein-1β)
226.00
(0.00 to 6160.00)
BDNF
7000
(370 to 38000)
VEGF
232.50
(41.00 to 834.00)
IL-8
9.90
(0.00 to 514.00)
ITAC
41.50
(10.00 to 117.00)
45.Secondary Outcome
Title Serum Levels of Circulating Protein Analytes at Phase 2 Fit - Consolidation Cycle 1/Day 10
Hide Description Serum levels were determined for 38 circulating proteins. Selected values showing statistically significant difference compared with baseline are reported here.
Time Frame Consolidation Cycle 1/Day 10, Pre-dose
Hide Outcome Measure Data
Hide Analysis Population Description
PD analysis set: all enrolled participants in the Phase 2 Fit portion who received at least 1 dose of glasdegib, and had at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.
Arm/Group Title Phase 2 Fit: Glasdegib 100 mg + Cytarabine/Daunorubicin
Hide Arm/Group Description:
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.
Overall Number of Participants Analyzed 20
Median (Full Range)
Unit of Measure: pg/mL
MIP-1β
239.50
(0.00 to 6560.00)
MCP-1
581.00
(192.00 to 3880.00)
MMP-3
12000
(2700 to 48000)
IL-8
11.00
(0.00 to 74.00)
ITAC
4.10
(0.00 to 27.00)
46.Secondary Outcome
Title Serum Levels of Circulating Protein Analytes at Phase 2 Fit - End of Treatment
Hide Description Serum levels were determined for 38 circulating proteins. Selected values showing statistically significant difference compared with baseline are reported here.
Time Frame End of Treatment (maximum of 12 cycles from start of therapy or until disease progression or relapse, participant refusal or unacceptable toxicity occurred, whichever came first, an average of 1 year)
Hide Outcome Measure Data
Hide Analysis Population Description
PD analysis set: all enrolled participants in the Phase 2 Fit portion who received at least 1 dose of glasdegib, and had at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.
Arm/Group Title Phase 2 Fit: Glasdegib 100 mg + Cytarabine/Daunorubicin
Hide Arm/Group Description:
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.
Overall Number of Participants Analyzed 42
Median (Full Range)
Unit of Measure: pg/mL
MIP-1β
338.00
(0.00 to 4480.00)
VEGF
133.00
(0.00 to 2880.00)
MCP-1
277.00
(0.00 to 7450.00)
47.Secondary Outcome
Title Baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Fit
Hide Description Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. A total of 38 proteins were analyzed. Selected data of analyte for which the serum level showed statistically significant correlation with clinical response are reported.
Time Frame Baseline (Induction Cycle 1/Day -3 pre-dose)
Hide Outcome Measure Data
Hide Analysis Population Description
PD analysis set: all enrolled participants in the Phase 2 Fit portion who received at least 1 dose of glasdegib, and had at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.
Arm/Group Title Phase 2 Fit (Biomarker, Responder) Phase 2 Fit (Biomarker, Non-Responder)
Hide Arm/Group Description:
AML subjects who achieved CR, CRi, MLFS, PR, or PRi (AML investigator reported best overall response), and MDS subjects who achieved CR, mCR, PR, or SD (MDS investigator reported best overall response).
AML subjects who did not achieve CR, CRi, MLFS, PR, or PRi; and MDS subjects who did not achieve CR, mCR, PR or SD were defined as non-responders for best overall response.
Overall Number of Participants Analyzed 43 22
Median (Full Range)
Unit of Measure: pg/mL
323.00
(158.00 to 419.00)
362.00
(225.00 to 758.00)
48.Secondary Outcome
Title Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Fit - Induction Cycle 1/Day 3
Hide Description Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. A total of 38 proteins were analyzed. Selected data of analyte for which the serum level showed statistically significant correlation with clinical response are reported.
Time Frame Induction Cycle 1/Day 3, 1 Hour Post dose
Hide Outcome Measure Data
Hide Analysis Population Description
PD analysis set: all enrolled participants in the Phase 2 Fit portion who received at least 1 dose of glasdegib, and had at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.
Arm/Group Title Phase 2 Fit (Biomarker, Responder) Phase 2 Fit (Biomarker, Non-Responder)
Hide Arm/Group Description:
AML subjects who achieved CR, CRi, MLFS, PR, or PRi (AML investigator reported best overall response), and MDS subjects who achieved CR, mCR, PR, or SD (MDS investigator reported best overall response).
AML subjects who did not achieve CR, CRi, MLFS, PR, or PRi; and MDS subjects who did not achieve CR, mCR, PR or SD were defined as non-responders for best overall response.
Overall Number of Participants Analyzed 37 20
Mean (Full Range)
Unit of Measure: pg/mL
3.20
(0.00 to 26.00)
10.90
(0.00 to 63.00)
49.Secondary Outcome
Title Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Fit - Induction Cycle 1/Day 10
Hide Description Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. A total of 38 proteins were analyzed. Selected data of analyte for which the serum level showed statistically significant correlation with clinical response are reported.
Time Frame Induction Cycle 1/Day 10, 1 Hour Post dose
Hide Outcome Measure Data
Hide Analysis Population Description
PD analysis set: all enrolled participants in the Phase 2 Fit portion who received at least 1 dose of glasdegib, and had at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.
Arm/Group Title Phase 2 Fit (Biomarker, Responder) Phase 2 Fit (Biomarker, Non-Responder)
Hide Arm/Group Description:
AML subjects who achieved CR, CRi, MLFS, PR, or PRi (AML investigator reported best overall response), and MDS subjects who achieved CR, mCR, PR, or SD (MDS investigator reported best overall response).
AML subjects who did not achieve CR, CRi, MLFS, PR, or PRi; and MDS subjects who did not achieve CR, mCR, PR or SD were defined as non-responders for best overall response.
Overall Number of Participants Analyzed 42 20
Mean (Full Range)
Unit of Measure: pg/mL
1.20
(0.00 to 18.00)
6.60
(0.00 to 88.00)
50.Secondary Outcome
Title Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Fit - End of Treatment
Hide Description Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. A total of 38 proteins were analyzed. Selected data of analytes for which the serum level showed statistically significant correlation with clinical response are reported.
Time Frame End of Treatment (maximum of 12 cycles from start of therapy or until disease progression or relapse, participant refusal or unacceptable toxicity occurred, whichever came first, an average of 1 year)
Hide Outcome Measure Data
Hide Analysis Population Description
PD analysis set: all enrolled participants in the Phase 2 Fit portion who received at least 1 dose of glasdegib, and had at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.
Arm/Group Title Phase 2 Fit (Biomarker, Responder) Phase 2 Fit (Biomarker, Non-Responder)
Hide Arm/Group Description:
AML subjects who achieved CR, CRi, MLFS, PR, or PRi (AML investigator reported best overall response), and MDS subjects who achieved CR, mCR, PR, or SD (MDS investigator reported best overall response).
AML subjects who did not achieve CR, CRi, MLFS, PR, or PRi; and MDS subjects who did not achieve CR, mCR, PR or SD were defined as non-responders for best overall response.
Overall Number of Participants Analyzed 27 15
Median (Full Range)
Unit of Measure: pg/mL
IL-1β
9.70
(0.00 to 20.00)
6.70
(0.00 to 20.00)
IL-15 (Interleukin-15)
700
(0 to 1300)
600
(0 to 850)
51.Secondary Outcome
Title Serum Levels of Circulating Protein Analytes at Phase 2 Unfit - Cycle 1/Day 1
Hide Description Serum levels were determined for 38 circulating proteins. Selected value showing statistically significant difference compared with baseline is reported here.
Time Frame Cycle 1/Day 1, 1 Hour Post dose
Hide Outcome Measure Data
Hide Analysis Population Description
PD analysis set: all enrolled participants in the Phase 2 Unfit portion who received at least 1 dose of glasdegib, and had at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.
Arm/Group Title Phase 2 Unfit: Glasdegib 100 mg + LDAC
Hide Arm/Group Description:
Participants received oral doses of glasdegib tablets 100 mg QD in 28-day cycles on a continuous basis, starting on Day 1 of Cycle 1. LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28 day cycles.
Overall Number of Participants Analyzed 18
Median (Full Range)
Unit of Measure: pg/mL
483.00
(40.00 to 1230.00)
52.Secondary Outcome
Title Serum Levels of Circulating Protein Analytes at Phase 2 Unfit - Cycle 1/Day 10
Hide Description Serum levels were determined for 38 circulating proteins. Selected values showing statistically significant differences compared with baseline are reported here. ITAC (Interferon-inducible T-cell α chemoattractant) level in LDAC alone arm at Cycle 1/Day 10 exhibited non-significant change from baseline but similar trends as in Glasdegib 100 mg+LDAC arm.
Time Frame Cycle 1/Day 10, Pre-dose
Hide Outcome Measure Data
Hide Analysis Population Description
PD analysis set: all enrolled participants in the Phase 2 Unfit portion who received at least 1 dose of glasdegib, and had at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.
Arm/Group Title Phase 2 Unfit: Glasdegib 100 mg + LDAC Phase 2 Unfit: LDAC Alone
Hide Arm/Group Description:
Participants received oral doses of glasdegib tablets 100 mg QD in 28-day cycles on a continuous basis, starting on Day 1 of Cycle 1. LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28 day cycles.
Participants received LDAC subcutaneously at a dose of 20 mg BID on Days 1-10 of the 28 day cycles.
Overall Number of Participants Analyzed 66 24
Median (Full Range)
Unit of Measure: pg/mL
BDNF
500
(0 to 7200)
200
(0 to 5100)
ITAC
7.5
(0.00 to 226.00)
0.00
(0.00 to 71.00)
53.Secondary Outcome
Title Baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Unfit
Hide Description Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. A total of 38 proteins were analyzed. The data of analytes for which the serum level showed statistically significant correlation with clinical response are reported.
Time Frame Baseline (Cycle 1/Day 1 pre-dose)
Hide Outcome Measure Data
Hide Analysis Population Description
PD analysis set: all enrolled participants in the Phase 2 Unfit portion who received at least 1 dose of glasdegib, and had at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.
Arm/Group Title Phase 2 Unfit: Glasdegib 100 mg + LDAC (Biomarker, Responder) Phase 2 Unfit: Glasdegib 100 mg+LDAC(Biomarker, Non-Responder)
Hide Arm/Group Description:
AML subjects who achieved CR, CRi, MLFS, PR, or PRi (AML investigator reported best overall response), and MDS subjects who achieved CR, mCR, PR, or SD (MDS investigator reported best overall response).
AML subjects who did not achieve CR, CRi, MLFS, PR, or PRi; and MDS subjects who did not achieve CR, mCR, PR or SD were defined as non-responders for best overall response.
Overall Number of Participants Analyzed 28 44
Median (Full Range)
Unit of Measure: pg/mL
BDNF
2000
(170 to 22000)
900
(0 to 12000)
ICAM-1 (Intercellular cell adhesion molecule-1)
128000
(37000 to 287000)
161000
(82000 to 580000)
6CKINE
223.50
(53.00 to 679.00)
318.00
(128.00 to 911.00)
BAFF (B-cell activating factor)
704.50
(116.00 to 3000.00)
1295.00
(199.00 to 6190.00)
MIP-3β
275.00
(86.00 to 2060.00)
414.50
(109.00 to 2130.00)
Eotaxin-1 (C-C motif chemokine 11)
169.00
(0.00 to 333.00)
0.00
(0.00 to 260.00)
54.Secondary Outcome
Title Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Unfit - Cycle 1/Day 1
Hide Description Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. A total of 38 proteins were analyzed. Selected data of analytes for which the serum level showed statistically significant correlation with clinical response are reported.
Time Frame Cycle 1/Day 1, 1 Hour Post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
PD analysis set: all enrolled participants in the Phase 2 Unfit portion who received at least 1 dose of glasdegib, and had at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.
Arm/Group Title Phase 2 Unfit: Glasdegib 100 mg + LDAC (Biomarker, Responder) Phase 2 Unfit: Glasdegib 100 mg+LDAC(Biomarker, Non-Responder)
Hide Arm/Group Description:
AML subjects who achieved CR, CRi, MLFS, PR, or PRi (AML investigator reported best overall response), and MDS subjects who achieved CR, mCR, PR, or SD (MDS investigator reported best overall response).
AML subjects who did not achieve CR, CRi, MLFS, PR, or PRi; and MDS subjects who did not achieve CR, mCR, PR or SD were defined as non-responders for best overall response.
Overall Number of Participants Analyzed 6 12
Median (Full Range)
Unit of Measure: pg/mL
Factor VII:activated blood coagulation factor VII
311500
(48000 to 661000)
234500
(147000 to 676000)
IL-6 (Interleukin-6)
0.00
(0.00 to 3.50)
6.80
(0.00 to 62.00)
55.Secondary Outcome
Title Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Unfit - End of Treatment
Hide Description Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. A total of 38 proteins were analyzed. Selected data of analyte for which the serum level showed statistically significant correlation with clinical response are reported.
Time Frame End of Treatment (maximum of 12 cycles from start of therapy or until disease progression or relapse, participant refusal or unacceptable toxicity occurred, whichever came first, an average of 1 year)
Hide Outcome Measure Data
Hide Analysis Population Description
PD analysis set: all enrolled participants in the Phase 2 Unfit portion who received at least 1 dose of glasdegib, and had at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.
Arm/Group Title Phase 2 Unfit: Glasdegib 100 mg + LDAC (Biomarker, Responder) Phase 2 Unfit: Glasdegib 100 mg+LDAC(Biomarker, Non-Responder)
Hide Arm/Group Description:
AML subjects who achieved CR, CRi, MLFS, PR, or PRi (AML investigator reported best overall response), and MDS subjects who achieved CR, mCR, PR, or SD (MDS investigator reported best overall response).
AML subjects who did not achieve CR, CRi, MLFS, PR, or PRi; and MDS subjects who did not achieve CR, mCR, PR or SD were defined as non-responders for best overall response.
Overall Number of Participants Analyzed 17 18
Median (Full Range)
Unit of Measure: pg/mL
0.00
(0.00 to 45.00)
9.40
(0.00 to 52.00)
56.Secondary Outcome
Title Ratios of mRNA Levels to Baseline at Phase 2 Fit - Induction Cycle 1/Day 3
Hide Description Whole blood mRNA analyses were performed on 21 mRNA candidates. Values showing statistically significant, ≥2-fold differences compared with baseline are reported here. CDKN1A: cyclin-dependent kinase inhibitor 1A; SMO: mRNA encoding the glasdegib target Smoothened; PTCH2: Patched 2; MYCN: Neuroblastoma Myc oncogene.
Time Frame Baseline (Induction Cycle 1/Day -3 pre-dose); Induction Cycle 1/Day 3, 1 Hour Post dose
Hide Outcome Measure Data
Hide Analysis Population Description
PD analysis set: all enrolled participants in Phase 2 Fit who received at least 1 dose of glasdegib, had at least 1 PD parameter with a baseline and an adequate post treatment assessment.
Arm/Group Title Phase 2 Fit: Glasdegib 100 mg + Cytarabine/Daunorubicin
Hide Arm/Group Description:
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.
Overall Number of Participants Analyzed 62
Median (Full Range)
Unit of Measure: ratio
CDKN1A Number Analyzed 54 participants
2.40
(0.08 to 53.17)
SMO Number Analyzed 18 participants
4.80
(0.06 to 51.22)
PTCH2 Number Analyzed 10 participants
0.60
(0.03 to 2.66)
MYCN Number Analyzed 38 participants
0.20
(0.00 to 248.53)
57.Secondary Outcome
Title Ratios of mRNA Levels to Baseline at Phase 2 Fit - End of Treatment
Hide Description Whole blood mRNA analyses were performed on 21 mRNA candidates. Selected values showing statistically significant differences compared with baseline are reported here. CCND2:G1/S-Specific Cyclin D2; MSI2: Musashi RNA Binding Protein 2; PTCH2: Patched 2.
Time Frame Baseline (Induction Cycle 1/Day -3 pre-dose); End of Treatment (maximum of 12 cycles from start of therapy or until disease progression or relapse, participant refusal or unacceptable toxicity occurred, whichever came first, an average of 1 year)
Hide Outcome Measure Data
Hide Analysis Population Description
PD analysis set: all enrolled participants in Phase 2 Fit who received at least 1 dose of glasdegib, had at least 1 PD parameter with a baseline and an adequate post treatment assessment.
Arm/Group Title Phase 2 Fit: Glasdegib 100 mg + Cytarabine/Daunorubicin
Hide Arm/Group Description:
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.
Overall Number of Participants Analyzed 62
Median (Full Range)
Unit of Measure: ratio
CCND2 Number Analyzed 42 participants
0.80
(0.23 to 3.23)
MSI2 Number Analyzed 42 participants
0.80
(0.31 to 4.58)
PTCH2 Number Analyzed 12 participants
0.70
(0.29 to 1.90)
58.Secondary Outcome
Title Ratios of mRNA Levels to Baseline at Phase 2 Unfit - End of Treatment
Hide Description Whole blood mRNA analyses were performed on 21 mRNA candidates. Only the analytes showing statistically significant change from baseline are reported here.
Time Frame Baseline (Cycle 1/Day 1 pre-dose); End of Treatment (maximum of 12 cycles from start of therapy or until disease progression or relapse, participant refusal or unacceptable toxicity occurred, whichever came first, an average of 1 year)
Hide Outcome Measure Data
Hide Analysis Population Description
PD analysis set:all enrolled participants in Phase 2 Unfit who received at least 1 dose of glasdegib, had at least 1 PD parameter with a baseline and an adequate post treatment assessment.
Arm/Group Title Phase 2 Unfit: Glasdegib 100 mg + LDAC
Hide Arm/Group Description:
Participants received oral doses of glasdegib tablets 100 mg QD in 28-day cycles on a continuous basis, starting on Day 1 of Cycle 1. LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28 day cycles.
Overall Number of Participants Analyzed 47
Median (Full Range)
Unit of Measure: ratio
CCND2 Number Analyzed 30 participants
0.70
(0.06 to 2.35)
SMO Number Analyzed 20 participants
0.40
(0.09 to 8.09)
CCND1 Number Analyzed 17 participants
0.40
(0.10 to 13.33)
59.Secondary Outcome
Title Baseline mRNA Levels Associated With Best Overall Response at Phase 2 Fit
Hide Description Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. Whole blood mRNA analyses were performed on 21 mRNA candidates. Baseline mRNA level showing statistically significant correlation with clinical response are reported. Baseline mRNA levels statistically significant associated with best overall response was only seen for CCND2 (G1/S-Specific Cyclin D2).
Time Frame Baseline (Induction Cycle 1/Day -3 pre-dose)
Hide Outcome Measure Data
Hide Analysis Population Description
PD analysis set: all enrolled participants in the Phase 2 Fit portion who received at least 1 dose of glasdegib, and had at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.
Arm/Group Title Phase 2 Fit (Biomarker, Responder) Phase 2 Fit (Biomarker, Non-Responder)
Hide Arm/Group Description:
AML subjects who achieved CR, CRi, MLFS, PR, or PRi (AML investigator reported best overall response), and MDS subjects who achieved CR, mCR, PR, or SD (MDS investigator reported best overall response).
AML subjects who did not achieve CR, CRi, MLFS, PR, or PRi; and MDS subjects who did not achieve CR, mCR, PR or SD were defined as non-responders for best overall response.
Overall Number of Participants Analyzed 39 22
Median (Full Range)
Unit of Measure: Normalized expression units
10.9
(1.61 to 25.26)
14.80
(5.03 to 23.74)
60.Secondary Outcome
Title Baseline mRNA Levels Associated With Best Overall Response at Phase 2 Unfit
Hide Description Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. Whole blood mRNA analyses were performed on 21 mRNA candidates. Baseline mRNA level showing statistically significant correlation with clinical response are reported. FOXM1: Forkhead box M1; PTCH1: Patched 1.
Time Frame Baseline (Cycle 1/Day 1 pre-dose)
Hide Outcome Measure Data
Hide Analysis Population Description
PD analysis set:all enrolled participants in Phase 2 Unfit who received at least 1 dose of glasdegib, had at least 1 PD parameter with a baseline and an adequate post treatment assessment.
Arm/Group Title Phase 2 Unfit: Glasdegib 100 mg + LDAC (Biomarker, Responder) Phase 2 Unfit: Glasdegib 100 mg+LDAC(Biomarker, Non-Responder)
Hide Arm/Group Description:
AML subjects who achieved CR, CRi, MLFS, PR, or PRi (AML investigator reported best overall response), and MDS subjects who achieved CR, mCR, PR, or SD (MDS investigator reported best overall response).
AML subjects who did not achieve CR, CRi, MLFS, PR, or PRi; and MDS subjects who did not achieve CR, mCR, PR or SD were defined as non-responders for best overall response.
Overall Number of Participants Analyzed 33 55
Median (Full Range)
Unit of Measure: Normalized expression units
FOXM1 Number Analyzed 15 participants 28 participants
0.20
(0.05 to 0.77)
0.40
(0.09 to 1.86)
PTCH1 Number Analyzed 14 participants 27 participants
0.20
(0.07 to 0.58)
0.10
(0.01 to 0.42)
61.Secondary Outcome
Title Ratios of mRNA Levels to Baseline Associated With Best Overall Response at Phase 2 Fit
Hide Description Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. Whole blood mRNA analyses were performed on 21 mRNA candidates. Ratios of mRNA level to baseline showing statistically significant correlation with clinical response are reported.
Time Frame Baseline (Induction Cycle 1/Day -3 pre-dose); End of Treatment (maximum of 12 cycles from start of therapy or until disease progression or relapse, participant refusal or unacceptable toxicity occurred, whichever came first, an average of 1 year)
Hide Outcome Measure Data
Hide Analysis Population Description
PD analysis set: all enrolled participants in Phase 2 Fit who received at least 1 dose of glasdegib, had at least 1 PD parameter with a baseline and an adequate post treatment assessment.
Arm/Group Title Phase 2 Fit (Biomarker, Responder) Phase 2 Fit (Biomarker, Non-Responder)
Hide Arm/Group Description:
AML subjects who achieved CR, CRi, MLFS, PR, or PRi (AML investigator reported best overall response), and MDS subjects who achieved CR, mCR, PR, or SD (MDS investigator reported best overall response).
AML subjects who did not achieve CR, CRi, MLFS, PR, or PRi; and MDS subjects who did not achieve CR, mCR, PR or SD were defined as non-responders for best overall response.
Overall Number of Participants Analyzed 45 26
Median (Full Range)
Unit of Measure: ratio
CCNE1 Number Analyzed 26 participants 13 participants
0.60
(0.21 to 1.65)
1.10
(0.28 to 3.82)
MSI2 Number Analyzed 28 participants 14 participants
0.90
(0.31 to 4.58)
0.50
(0.33 to 1.86)
62.Secondary Outcome
Title Ratios of mRNA Levels Associated With Best Overall Response at Phase 2 Unfit
Hide Description Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. Whole blood mRNA analyses were performed on 21 mRNA candidates. Ratios of mRNA level to baseline showing statistically significant correlation with clinical response are reported. Ratios of mRNA levels to baseline statistically significant associated with best overall response was only seen for MYCN (Neuroblastoma Myc oncogene) at Cycle 1/Day 1.
Time Frame Baseline (Cycle 1/Day 1 pre-dose); Cycle 1/Day 1, 1 Hour Post dose
Hide Outcome Measure Data
Hide Analysis Population Description
PD analysis set: all enrolled participants in the Phase 2 Unfit portion who received at least 1 dose of glasdegib, and had at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.
Arm/Group Title Phase 2 Unfit: Glasdegib 100 mg + LDAC (Biomarker, Responder) Phase 2 Unfit: Glasdegib 100 mg+LDAC(Biomarker, Non-Responder)
Hide Arm/Group Description:
AML participants who achieved CR, CRi, MLFS, PR, or PRi (AML investigator reported best overall response), and MDS participants who achieved CR, mCR, PR, or SD (MDS investigator reported best overall response).
AML subjects who did not achieve CR, CRi, MLFS, PR, or PRi; and MDS subjects who did not achieve CR, mCR, PR or SD were defined as non-responders for best overall response.
Overall Number of Participants Analyzed 33 55
Median (Full Range)
Unit of Measure: ratio
1.60
(0.50 to 40.25)
0.50
(0.03 to 20.60)
63.Secondary Outcome
Title Number of Participants With Corrected QT Interval Using Fridericia's Formula (QTcF) Values Meeting Predefined Criteria at Phase 1B
Hide Description Maximum absolute values and increases from baseline were summarized for QTcF interval (time from the beginning of Q wave to the end of T wave corresponding to electrical systole corrected for heart rate using Fridericia's formula). Number of participants with QTcF meeting the following criteria is presented: QTcF interval:<450 msec; QTcF interval: 450 to <480 msec; QTcF interval: 480 to <500 msec; QTcF interval >=500 msec; QTcF interval increase from baseline: <30 msec; QTcF interval increase from baseline: 30 to <60 msec; QTcF interval increase from baseline >=60 msec. Arms in the time frame description are defined as: Arm A, Glasdegib +LDAC; Arm B, Glasdegib + Decitabine; Arm C, Glasdegib + Cytarabine/Daunorubicin. End of treatment in the time frame were defined as: maximum of 12 cycles from start of therapy or until disease progression or relapse, participant refusal or unacceptable toxicity occurred, whichever came first.
Time Frame 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
QTc analysis set: all participants enrolled in the study having at least 1 ECG assessment after receiving at least 1 dose of glasdegib.
Arm/Group Title Phase 1B: Glasdegib + LDAC Phase 1B: Glasdegib + Decitabine Phase 1B: Glasdegib + Cytarabine/Daunorubicin
Hide Arm/Group Description:
Included all participants who received oral glasdegib in combination with LDAC in phase 1B portion.
Included all participants who received oral glasdegib in combination with decitabine in phase 1B portion.
Included all participants who received oral glasdegib in combination with cytarabine/daunorubicin in phase 1B portion.
Overall Number of Participants Analyzed 21 7 22
Measure Type: Number
Unit of Measure: Participants
QTcF interval increase < 30 msec 16 2 14
QTcF interval increase: 30 to < 60 msec 5 3 6
QTcF interval increase >= 60 msec 0 2 2
Maximum QTcF interval < 450 msec 10 4 10
Maximum QTcF interval: 450 to < 480 msec 11 2 10
Maximum QTcF interval: 480 to < 500 msec 0 0 1
Maximum QTcF interval >= 500 msec 0 1 1
64.Secondary Outcome
Title Number of Participants With Corrected QT Interval Using Fridericia's Formula (QTcF) Values Meeting Predefined Criteria at Phase 2 Fit and Unfit
Hide Description Maximum absolute values and increases from baseline were summarized for QTcF interval (time from the beginning of Q wave to the end of T wave corresponding to electrical systole corrected for heart rate using Fridericia's formula). Number of participants with QTcF meeting the following criteria is presented:QTcF interval:<450 msec; QTcF interval: 450 to <480 msec; QTcF interval: 480 to <500 msec; QTcF interval >=500 msec; QTcF interval increase from baseline: <30 msec; QTcF interval increase from baseline: 30 to <60 msec; QTcF interval increase from baseline >=60 msec. End of treatment in the time frame were defined as: maximum of 12 cycles from start of therapy or until disease progression or relapse, participant refusal or unacceptable toxicity occurred, whichever came first.
Time Frame 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
QTc analysis set: all participants enrolled in the study having at least 1 ECG assessment after receiving at least 1 dose of glasdegib.
Arm/Group Title Phase 2 Fit: Glasdegib 100 mg + Cytarabine/Daunorubicin Phase 2 Unfit: Glasdegib 100 mg + LDAC Phase 2 Unfit: LDAC Alone
Hide Arm/Group Description:
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.
Participants received oral doses of glasdegib tablets 100 mg QD in 28-day cycles on a continuous basis, starting on Day 1 of Cycle 1. LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28 day cycles.
Participants received LDAC subcutaneously at a dose of 20 mg BID on Days 1-10 of the 28 day cycles.
Overall Number of Participants Analyzed 68 83 17
Measure Type: Number
Unit of Measure: Participants
QTcF interval increase < 30 msec 41 60 12
QTcF interval increase: 30 to < 60 msec 21 19 4
QTcF interval increase >= 60 msec 6 4 1
Maximum QTcF interval < 450 msec 46 46 8
Maximum QTcF interval: 450 to < 480 msec 18 29 4
Maximum QTcF interval: 480 to < 500 msec 3 3 3
Maximum QTcF interval >= 500 msec 1 5 2
65.Secondary Outcome
Title Number of Participants With Treatment-emergent Adverse Events (AEs) at Phase 1B (All Causality)
Hide Description An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event did not necessarily had a causal relationship with the treatment or usage. Treatment Emergent AEs were those with initial onset or increasing in severity after the first dose of study medication and occurred within 28 days post last dose. AEs were graded by the investigator according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 : Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE.
Time Frame 4 years
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Safety analysis set: all enrolled participants who received at least 1 dose of any of the study medications for each drug combination.
Arm/Group Title Phase 1B: Glasdegib + LDAC Phase 1B: Glasdegib + Decitabine Phase 1B: Glasdegib + Cytarabine/Daunorubicin
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Included all participants who received oral glasdegib in combination with LDAC in phase 1B portion.
Included all participants who received oral glasdegib in combination with decitabine in phase 1B portion.
Included all participants who received oral glasdegib in combination with cytarabine/daunorubicin in phase 1B portion.
Overall Number of Participants Analyzed 23 7 22
Measure Type: Number
Unit of Measure: Participants
Grade 1 AEs 1 1 0
Grade 2 AEs 2 0 3
Grade 3 AEs 3 1 8
Grade 4 AEs 10 4 10
Grade 5 AEs 7 1 1
Missing or unknown AEs 0 0 0
66.Secondary Outcome
Title Number of Participants With Treatment-emergent AEs at Phase 1B (Treatment-related)
Hide Description An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event did not necessarily had a causal relationship with the treatment or usage. Treatment Emergent AEs were those with initial onset or increasing in severity after the first dose of study medication and occurred within 28 days post last dose. Treatment-related AEs were AEs related to glasdegib and/or backbone chemotherapy. AEs were graded by the investigator according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 : Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE.
Time Frame 4 years
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Safety analysis set: all enrolled participants who received at least 1 dose of any of the study medications for each drug combination.
Arm/Group Title Phase 1B: Glasdegib + LDAC Phase 1B: Glasdegib + Decitabine Phase 1B: Glasdegib + Cytarabine/Daunorubicin
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Included all participants who received oral glasdegib in combination with LDAC in phase 1B portion.
Included all participants who received oral glasdegib in combination with decitabine in phase 1B portion.
Included all participants who received oral glasdegib in combination with cytarabine/daunorubicin in phase 1B portion.
Overall Number of Participants Analyzed 23 7 22
Measure Type: Number
Unit of Measure: Participants
Grade 1 AEs 3 2 2
Grade 2 AEs 2 0 7
Grade 3 AEs 7 0 3
Grade 4 AEs 6 4 10
Grade 5 AEs 3 0 0
Missing or unknown AEs 0 0 0
67.Secondary Outcome
Title Number of Participants With Treatment-emergent AEs Categorized by Seriousness at Phase 1B
Hide Description An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event did not necessarily had a causal relationship with the treatment or usage. Treatment Emergent AEs were those with initial onset or increasing in severity after the first dose of study medication and occurred within 28 days post last dose. An serious adverse event (SAE) was any untoward medical occurrence at any dose that: resulted in death; was life threatening (immediate risk of death); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); resulted in congenital anomaly/birth defect.
Time Frame 4 years
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Safety analysis set: all enrolled participants who received at least 1 dose of any of the study medications for each drug combination.
Arm/Group Title Phase 1B: Glasdegib 100 mg + LDAC Phase 1B: Glasdegib 200 mg + LDAC Phase 1B: Glasdegib 100 mg + Decitabine Phase 1B: Glasdegib 200 mg + Decitabine Phase 1B: Glasdegib 100 mg + Cytarabine/Daunorubicin Phase 1B: Glasdegib 200 mg + Cytarabine/Daunorubicin
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Participants received oral doses of glasdegib (PF-04449913) tablets 100 milligram (mg) starting on Day 3 of Cycle 1 for pharmacokinetic (PK) assessment purposes and thereafter once daily (QD) and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously twice daily (BID) on Days 1-10 of the 28-day cycles.
Participants received oral doses of glasdegib tablets 200 mg starting on Day 3 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28-day cycles. In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg. Participants who had glasdegib dose reduction were reported as the starting glasdegib dose level received. Two (2) participants in this cohort had dose reduction to 100 mg starting from Cycle 2/Day 1 and Cycle 2/Day 16, respectively.
Participants received oral doses of glasdegib tablets 100 mg starting on Day 2 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). Decitabine was given at a dose of 20 mg/m^2 as an intravenous (IV) infusion over 1 hour on Days 1-5 of the 28-day cycles.
Participants received oral doses of glasdegib tablets 200 mg starting on Day 2 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). Decitabine was given at a dose of 20 mg/m^2 as an IV infusion over 1 hour on Days 1-5 of the 28-day cycles.In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg. Participants who had glasdegib dose reduction were reported as the starting glasdegib dose level received. Two (2) participants in this cohort had dose reduction to 100 mg starting from Cycle 1/Day 24 and Cycle 5/Day 1, respectively.
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 200 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg.One (1) participant in this cohort had dose reduction to 100 mg starting from Consolidation Cycle 1/Day 21.
Overall Number of Participants Analyzed 17 6 4 3 16 6
Measure Type: Number
Unit of Measure: Participants
AEs 17 6 4 3 16 6
SAEs 13 5 4 2 10 3
68.Secondary Outcome
Title Number of Participants With Treatment-emergent AEs at Phase 2 Fit and Unfit (All Causality)
Hide Description An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event did not necessarily had a causal relationship with the treatment or usage. Treatment Emergent AEs were those with initial onset or increasing in severity after the first dose of study medication and occurred within 28 days post last dose. AEs were graded by the investigator according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 : Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE.
Time Frame 4 years
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Safety analysis set: all enrolled participants who received at least 1 dose of any of the study medications for each drug combination.
Arm/Group Title Phase 2 Fit: Glasdegib 100 mg + Cytarabine/Daunorubicin Phase 2 Unfit: Glasdegib 100 mg + LDAC Phase 2 Unfit: LDAC Alone
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Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.
Participants received oral doses of glasdegib tablets 100 mg QD in 28-day cycles on a continuous basis, starting on Day 1 of Cycle 1. LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28 day cycles.
Participants received LDAC subcutaneously at a dose of 20 mg BID on Days 1-10 of the 28 day cycles.
Overall Number of Participants Analyzed 69 84 41
Measure Type: Number
Unit of Measure: Participants
Grade 1 AEs 0 2 0
Grade 2 AEs 1 4 1
Grade 3 AEs 11 15 8
Grade 4 AEs 52 39 15
Grade 5 AEs 5 24 17
Missing or unknown AEs 0 0 0
69.Secondary Outcome
Title Number of Participants With Treatment-emergent AEs at Phase 2 Fit and Unfit (Treatment-related)
Hide Description An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event did not necessarily had a causal relationship with the treatment or usage. Treatment Emergent AEs were those with initial onset or increasing in severity after the first dose of study medication and occurred within 28 days post last dose. Treatment-related AEs were AEs related to glasdegib and/or backbone chemotherapy. AEs were graded by the investigator according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 : Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE.
Time Frame 4 years
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Safety analysis set: all enrolled participants who received at least 1 dose of any of the study medications for each drug combination.
Arm/Group Title Phase 2 Fit: Glasdegib 100 mg + Cytarabine/Daunorubicin Phase 2 Unfit: Glasdegib 100 mg + LDAC Phase 2 Unfit: LDAC Alone
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Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.
Participants received oral doses of glasdegib tablets 100 mg QD in 28-day cycles on a continuous basis, starting on Day 1 of Cycle 1. LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28 day cycles.
Participants received LDAC subcutaneously at a dose of 20 mg BID on Days 1-10 of the 28 day cycles.
Overall Number of Participants Analyzed 69 84 41
Measure Type: Number
Unit of Measure: Participants
Grade 1 AEs 0 4 4
Grade 2 AEs 4 9 6
Grade 3 AEs 15 20 3
Grade 4 AEs 46 34 10
Grade 5 AEs 1 1 1
Missing or unknown AEs 0 0 0
70.Secondary Outcome
Title Number of Participants With Treatment-emergent AEs Categorized by Seriousness at Phase 2 Fit and Unfit
Hide Description An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event did not necessarily had a causal relationship with the treatment or usage. Treatment Emergent AEs were those with initial onset or increasing in severity after the first dose of study medication and occurred within 28 days post last dose. An serious adverse event (SAE) was any untoward medical occurrence at any dose that: resulted in death; was life threatening (immediate risk of death); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); resulted in congenital anomaly/birth defect.
Time Frame 4 years
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Safety analysis set: all enrolled participants who received at least 1 dose of any of the study medications for each drug combination.
Arm/Group Title Phase 2 Fit: Glasdegib 100 mg + Cytarabine/Daunorubicin Phase 2 Unfit: Glasdegib 100 mg + LDAC Phase 2 Unfit: LDAC Alone
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Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.
Participants received oral doses of glasdegib tablets 100 mg QD in 28-day cycles on a continuous basis, starting on Day 1 of Cycle 1. LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28 day cycles.
Participants received LDAC subcutaneously at a dose of 20 mg BID on Days 1-10 of the 28 day cycles.
Overall Number of Participants Analyzed 69 84 41
Measure Type: Number
Unit of Measure: Participants
AEs 69 84 41
SAEs 35 68 32
Time Frame 4 years
Adverse Event Reporting Description The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. All-cause mortality reflects the number of deaths from start of treatment to and including 28 days after last dose. Safety analysis set was evaluated.
 
Arm/Group Title Phase 1B: Glasdegib 100 mg + LDAC Phase 1B: Glasdegib 200 mg + LDAC Phase 1B: Glasdegib 100 mg + Decitabine Phase 1B: Glasdegib 200 mg + Decitabine Phase 1B: Glasdegib 100 mg + Cytarabine/Daunorubicin Phase 1B: Glasdegib 200 mg + Cytarabine/Daunorubicin Phase 2 Fit: Glasdegib 100 mg + Cytarabine/Daunorubicin Phase 2 Unfit: Glasdegib 100 mg + LDAC Phase 2 Unfit: LDAC Alone
Hide Arm/Group Description Participants received oral doses of glasdegib (PF-04449913) tablets 100 milligram (mg) starting on Day 3 of Cycle 1 for pharmacokinetic (PK) assessment purposes and thereafter once daily (QD) and continuously for 28-day cycles (starting on Day 1 for all other cycles). Low dose Ara-C (LDAC) was given at a dose of 20 mg subcutaneously twice daily (BID) on Days 1-10 of the 28-day cycles. Participants received oral doses of glasdegib tablets 200 mg starting on Day 3 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28-day cycles. In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg. Participants who had glasdegib dose reduction were reported as the starting glasdegib dose level received. Two (2) participants in this cohort had dose reduction to 100 mg starting from Cycle 2/Day 1 and Cycle 2/Day 16, respectively. Participants received oral doses of glasdegib tablets 100 mg starting on Day 2 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). Decitabine was given at a dose of 20 mg/m^2 as an intravenous (IV) infusion over 1 hour on Days 1-5 of the 28-day cycles. Participants received oral doses of glasdegib tablets 200 mg starting on Day 2 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). Decitabine was given at a dose of 20 mg/m^2 as an IV infusion over 1 hour on Days 1-5 of the 28-day cycles.In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg. Participants who had glasdegib dose reduction were reported as the starting glasdegib dose level received. Two (2) participants in this cohort had dose reduction to 100 mg starting from Cycle 1/Day 24 and Cycle 5/Day 1, respectively. Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days. Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 200 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg.One (1) participant in this cohort had dose reduction to 100 mg starting from Consolidation Cycle 1/Day 21. Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days. Participants received oral doses of glasdegib tablets 100 mg QD in 28-day cycles on a continuous basis, starting on Day 1 of Cycle 1. LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28-day cycles. Participants received LDAC subcutaneously at a dose of 20 mg BID on Days 1-10 of the 28-day cycles.
All-Cause Mortality
Phase 1B: Glasdegib 100 mg + LDAC Phase 1B: Glasdegib 200 mg + LDAC Phase 1B: Glasdegib 100 mg + Decitabine Phase 1B: Glasdegib 200 mg + Decitabine Phase 1B: Glasdegib 100 mg + Cytarabine/Daunorubicin Phase 1B: Glasdegib 200 mg + Cytarabine/Daunorubicin Phase 2 Fit: Glasdegib 100 mg + Cytarabine/Daunorubicin Phase 2 Unfit: Glasdegib 100 mg + LDAC Phase 2 Unfit: LDAC Alone
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   6/17 (35.29%)   1/6 (16.67%)   1/4 (25.00%)   0/3 (0.00%)   0/16 (0.00%)   1/6 (16.67%)   5/69 (7.25%)   26/84 (30.95%)   17/41 (41.46%) 
Hide Serious Adverse Events
Phase 1B: Glasdegib 100 mg + LDAC Phase 1B: Glasdegib 200 mg + LDAC Phase 1B: Glasdegib 100 mg + Decitabine Phase 1B: Glasdegib 200 mg + Decitabine Phase 1B: Glasdegib 100 mg + Cytarabine/Daunorubicin Phase 1B: Glasdegib 200 mg + Cytarabine/Daunorubicin Phase 2 Fit: Glasdegib 100 mg + Cytarabine/Daunorubicin Phase 2 Unfit: Glasdegib 100 mg + LDAC Phase 2 Unfit: LDAC Alone
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   13/17 (76.47%)   5/6 (83.33%)   4/4 (100.00%)   2/3 (66.67%)   10/16 (62.50%)   3/6 (50.00%)   35/69 (50.72%)   68/84 (80.95%)   32/41 (78.05%) 
Blood and lymphatic system disorders                   
Febrile neutropenia * 1  3/17 (17.65%)  3/6 (50.00%)  0/4 (0.00%)  1/3 (33.33%)  1/16 (6.25%)  1/6 (16.67%)  14/69 (20.29%)  24/84 (28.57%)  7/41 (17.07%) 
Neutropenia * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  2/69 (2.90%)  0/84 (0.00%)  0/41 (0.00%) 
Pancytopenia * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  1/69 (1.45%)  0/84 (0.00%)  2/41 (4.88%) 
Anaemia * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  6/84 (7.14%)  0/41 (0.00%) 
Disseminated intravascular coagulation * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  1/41 (2.44%) 
Granulocytopenia * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  1/41 (2.44%) 
Leukocytosis * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  1/84 (1.19%)  1/41 (2.44%) 
Lymphadenitis * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  1/84 (1.19%)  0/41 (0.00%) 
Thrombocytosis * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  1/84 (1.19%)  0/41 (0.00%) 
Cardiac disorders                   
Acute myocardial infarction * 1  1/17 (5.88%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  1/69 (1.45%)  0/84 (0.00%)  1/41 (2.44%) 
Cardiac failure congestive * 1  1/17 (5.88%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Angina pectoris * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  1/84 (1.19%)  0/41 (0.00%) 
Atrial fibrillation * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  1/84 (1.19%)  1/41 (2.44%) 
Cardiac arrest * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  2/84 (2.38%)  0/41 (0.00%) 
Cardiac failure * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  2/84 (2.38%)  0/41 (0.00%) 
Cardiogenic shock * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  1/41 (2.44%) 
Myocardial infarction * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  2/84 (2.38%)  1/41 (2.44%) 
Tachyarrhythmia * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  1/84 (1.19%)  0/41 (0.00%) 
Ventricular fibrillation * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  1/84 (1.19%)  0/41 (0.00%) 
Myocarditis * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  1/69 (1.45%)  0/84 (0.00%)  0/41 (0.00%) 
Tachycardia * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  1/69 (1.45%)  0/84 (0.00%)  0/41 (0.00%) 
Eye disorders                   
Mydriasis * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  1/84 (1.19%)  0/41 (0.00%) 
Gastrointestinal disorders                   
Gastrointestinal haemorrhage * 1  0/17 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  2/84 (2.38%)  0/41 (0.00%) 
Impaired gastric emptying * 1  1/17 (5.88%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Nausea * 1  0/17 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  1/84 (1.19%)  1/41 (2.44%) 
Neutropenic colitis * 1  1/17 (5.88%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Vomiting * 1  0/17 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  1/84 (1.19%)  1/41 (2.44%) 
Abdominal pain * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  2/69 (2.90%)  0/84 (0.00%)  0/41 (0.00%) 
Upper gastrointestinal haemorrhage * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  1/69 (1.45%)  0/84 (0.00%)  0/41 (0.00%) 
Diarrhoea * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  1/69 (1.45%)  0/84 (0.00%)  1/41 (2.44%) 
Colitis * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  1/84 (1.19%)  0/41 (0.00%) 
Constipation * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  1/84 (1.19%)  0/41 (0.00%) 
Gastrooesophageal reflux disease * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  1/84 (1.19%)  0/41 (0.00%) 
Haematemesis * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  1/84 (1.19%)  0/41 (0.00%) 
Lower gastrointestinal haemorrhage * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  1/41 (2.44%) 
Pancreatitis acute * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  1/84 (1.19%)  0/41 (0.00%) 
Retroperitoneal haematoma * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  1/84 (1.19%)  0/41 (0.00%) 
General disorders                   
Disease progression * 1  3/17 (17.65%)  1/6 (16.67%)  1/4 (25.00%)  0/3 (0.00%)  0/16 (0.00%)  1/6 (16.67%)  2/69 (2.90%)  10/84 (11.90%)  5/41 (12.20%) 
Fatigue * 1  1/17 (5.88%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  3/84 (3.57%)  0/41 (0.00%) 
Multiple organ dysfunction syndrome * 1  1/17 (5.88%)  0/6 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Nodule * 1  1/17 (5.88%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Pyrexia * 1  0/17 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  3/84 (3.57%)  1/41 (2.44%) 
Asthenia * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  1/41 (2.44%) 
Death * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  1/84 (1.19%)  0/41 (0.00%) 
General physical health deterioration * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  1/41 (2.44%) 
Mucosal inflammation * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  1/84 (1.19%)  0/41 (0.00%) 
Oedema * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  1/84 (1.19%)  0/41 (0.00%) 
Sudden death * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  2/84 (2.38%)  0/41 (0.00%) 
Hepatobiliary disorders                   
Cholecystitis * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  2/69 (2.90%)  0/84 (0.00%)  0/41 (0.00%) 
Infections and infestations                   
Appendicitis * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Bacteraemia * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  2/69 (2.90%)  1/84 (1.19%)  0/41 (0.00%) 
Cellulitis * 1  0/17 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/16 (0.00%)  1/6 (16.67%)  0/69 (0.00%)  1/84 (1.19%)  0/41 (0.00%) 
Clostridium difficile infection * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Enterobacter sepsis * 1  1/17 (5.88%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Enterocolitis infectious * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  2/16 (12.50%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Lower respiratory tract infection bacterial * 1  1/17 (5.88%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Neutropenic sepsis * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Pneumonia * 1  2/17 (11.76%)  0/6 (0.00%)  2/4 (50.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  4/69 (5.80%)  19/84 (22.62%)  7/41 (17.07%) 
Sepsis * 1  1/17 (5.88%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  6/69 (8.70%)  3/84 (3.57%)  5/41 (12.20%) 
Skin infection * 1  0/17 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  1/84 (1.19%)  0/41 (0.00%) 
Staphylococcal bacteraemia * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  1/6 (16.67%)  1/69 (1.45%)  0/84 (0.00%)  0/41 (0.00%) 
Septic shock * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  1/69 (1.45%)  2/84 (2.38%)  1/41 (2.44%) 
Abscess * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  1/84 (1.19%)  0/41 (0.00%) 
Aspergillus infection * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  1/84 (1.19%)  0/41 (0.00%) 
Clostridium difficile colitis * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  1/69 (1.45%)  1/84 (1.19%)  0/41 (0.00%) 
Cystitis * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  1/41 (2.44%) 
Device related infection * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  1/84 (1.19%)  0/41 (0.00%) 
Escherichia urinary tract infection * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  1/84 (1.19%)  0/41 (0.00%) 
Herpes zoster * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  1/84 (1.19%)  0/41 (0.00%) 
Infected dermal cyst * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  1/84 (1.19%)  0/41 (0.00%) 
Influenza * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  1/84 (1.19%)  1/41 (2.44%) 
Lung infection * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  1/84 (1.19%)  1/41 (2.44%) 
Otitis media chronic * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  1/84 (1.19%)  0/41 (0.00%) 
Pneumonia fungal * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  1/84 (1.19%)  0/41 (0.00%) 
Pseudomembranous colitis * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  1/41 (2.44%) 
Respiratory tract infection * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  1/84 (1.19%)  0/41 (0.00%) 
Septic encephalopathy * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  1/84 (1.19%)  0/41 (0.00%) 
Urogenital infection bacterial * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  1/41 (2.44%) 
Adenovirus infection * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  1/69 (1.45%)  0/84 (0.00%)  0/41 (0.00%) 
Arthritis bacterial * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  1/69 (1.45%)  0/84 (0.00%)  0/41 (0.00%) 
Mycobacterium avium complex infection * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  1/69 (1.45%)  0/84 (0.00%)  0/41 (0.00%) 
Pharyngitis * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  1/69 (1.45%)  0/84 (0.00%)  0/41 (0.00%) 
Pneumocystis jirovecii pneumonia * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  1/69 (1.45%)  0/84 (0.00%)  0/41 (0.00%) 
Pseudomonal sepsis * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  1/69 (1.45%)  0/84 (0.00%)  0/41 (0.00%) 
Tooth abscess * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  1/69 (1.45%)  0/84 (0.00%)  0/41 (0.00%) 
Abdominal infection * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  1/84 (1.19%)  0/41 (0.00%) 
Clostridial sepsis * 1  1/17 (5.88%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Injury, poisoning and procedural complications                   
Fall * 1  0/17 (0.00%)  2/6 (33.33%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  2/84 (2.38%)  0/41 (0.00%) 
Skin abrasion * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Infusion related reaction * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  1/69 (1.45%)  1/84 (1.19%)  0/41 (0.00%) 
Subdural haematoma * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  2/69 (2.90%)  0/84 (0.00%)  0/41 (0.00%) 
Femur fracture * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  1/84 (1.19%)  0/41 (0.00%) 
Subarachnoid haemorrhage * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Splenic rupture * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  1/41 (2.44%) 
Thoracic vertebral fracture * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  1/84 (1.19%)  0/41 (0.00%) 
Investigations                   
Lumbar puncture abnormal * 1  0/17 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Alanine aminotransferase increased * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  1/69 (1.45%)  0/84 (0.00%)  0/41 (0.00%) 
Aspartate aminotransferase increased * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  1/69 (1.45%)  0/84 (0.00%)  0/41 (0.00%) 
Laboratory test abnormal * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  1/41 (2.44%) 
Metabolism and nutrition disorders                   
Dehydration * 1  0/17 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Gout * 1  1/17 (5.88%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  1/84 (1.19%)  0/41 (0.00%) 
Hyperuricaemia * 1  1/17 (5.88%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Hyponatraemia * 1  0/17 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  1/69 (1.45%)  2/84 (2.38%)  0/41 (0.00%) 
Tumour lysis syndrome * 1  1/17 (5.88%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Decreased appetite * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  1/84 (1.19%)  0/41 (0.00%) 
Musculoskeletal and connective tissue disorders                   
Arthralgia * 1  0/17 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Myalgia * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  0/69 (0.00%)  1/84 (1.19%)  0/41 (0.00%) 
Back pain * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  1/69 (1.45%)  1/84 (1.19%)  0/41 (0.00%) 
Muscle spasms * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  1/84 (1.19%)  0/41 (0.00%) 
Muscular weakness * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  2/84 (2.38%)  0/41 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                   
Squamous cell carcinoma of skin * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  1/41 (2.44%) 
Nervous system disorders                   
Autonomic nervous system imbalance * 1  0/17 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Dizziness * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  1/3 (33.33%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Ischaemic stroke * 1  0/17 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Neurotoxicity * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Polyneuropathy * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Subarachnoid haemorrhage * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  0/69 (0.00%)  1/84 (1.19%)  0/41 (0.00%) 
Dyskinesia * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  1/69 (1.45%)  0/84 (0.00%)  0/41 (0.00%) 
Presyncope * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  1/69 (1.45%)  1/84 (1.19%)  0/41 (0.00%) 
Syncope * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  1/69 (1.45%)  4/84 (4.76%)  0/41 (0.00%) 
Cerebral haemorrhage * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  1/84 (1.19%)  0/41 (0.00%) 
Haemorrhage intracranial * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  3/84 (3.57%)  1/41 (2.44%) 
Peripheral sensorimotor neuropathy * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  1/84 (1.19%)  0/41 (0.00%) 
Transient ischaemic attack * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  1/84 (1.19%)  0/41 (0.00%) 
Cerebrovascular accident * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  1/84 (1.19%)  0/41 (0.00%) 
Psychiatric disorders                   
Bipolar II disorder * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Mental status changes * 1  0/17 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Confusional state * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  1/69 (1.45%)  0/84 (0.00%)  0/41 (0.00%) 
Renal and urinary disorders                   
Acute kidney injury * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  1/69 (1.45%)  3/84 (3.57%)  0/41 (0.00%) 
Respiratory, thoracic and mediastinal disorders                   
Acute respiratory distress syndrome * 1  1/17 (5.88%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  1/84 (1.19%)  0/41 (0.00%) 
Respiratory failure * 1  0/17 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Pleuritic pain * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  1/69 (1.45%)  0/84 (0.00%)  0/41 (0.00%) 
Pneumonitis * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  1/69 (1.45%)  0/84 (0.00%)  0/41 (0.00%) 
Cough * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  1/41 (2.44%) 
Dyspnoea * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  1/84 (1.19%)  0/41 (0.00%) 
Pleural effusion * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  1/84 (1.19%)  1/41 (2.44%) 
Pulmonary embolism * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  1/84 (1.19%)  0/41 (0.00%) 
Respiratory arrest * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  1/41 (2.44%) 
Respiratory distress * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  1/84 (1.19%)  0/41 (0.00%) 
Skin and subcutaneous tissue disorders                   
Rash generalised * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Rash maculo-papular * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Rash * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  1/84 (1.19%)  0/41 (0.00%) 
Skin toxicity * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  1/84 (1.19%)  0/41 (0.00%) 
Vascular disorders                   
Hypotension * 1  0/17 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  1/69 (1.45%)  0/84 (0.00%)  0/41 (0.00%) 
Haemorrhage * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  1/84 (1.19%)  0/41 (0.00%) 
Hypertension * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  1/84 (1.19%)  0/41 (0.00%) 
1
Term from vocabulary, MedDRA 21.1
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Phase 1B: Glasdegib 100 mg + LDAC Phase 1B: Glasdegib 200 mg + LDAC Phase 1B: Glasdegib 100 mg + Decitabine Phase 1B: Glasdegib 200 mg + Decitabine Phase 1B: Glasdegib 100 mg + Cytarabine/Daunorubicin Phase 1B: Glasdegib 200 mg + Cytarabine/Daunorubicin Phase 2 Fit: Glasdegib 100 mg + Cytarabine/Daunorubicin Phase 2 Unfit: Glasdegib 100 mg + LDAC Phase 2 Unfit: LDAC Alone
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   16/17 (94.12%)   6/6 (100.00%)   4/4 (100.00%)   3/3 (100.00%)   16/16 (100.00%)   6/6 (100.00%)   69/69 (100.00%)   82/84 (97.62%)   39/41 (95.12%) 
Blood and lymphatic system disorders                   
Anaemia * 1  3/17 (17.65%)  1/6 (16.67%)  2/4 (50.00%)  1/3 (33.33%)  4/16 (25.00%)  1/6 (16.67%)  28/69 (40.58%)  37/84 (44.05%)  17/41 (41.46%) 
Febrile neutropenia * 1  3/17 (17.65%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  8/16 (50.00%)  2/6 (33.33%)  38/69 (55.07%)  8/84 (9.52%)  4/41 (9.76%) 
Leukocytosis * 1  1/17 (5.88%)  0/6 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  6/84 (7.14%)  2/41 (4.88%) 
Leukopenia * 1  0/17 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  2/16 (12.50%)  1/6 (16.67%)  9/69 (13.04%)  0/84 (0.00%)  0/41 (0.00%) 
Lymphadenitis * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Neutropenia * 1  7/17 (41.18%)  0/6 (0.00%)  2/4 (50.00%)  2/3 (66.67%)  4/16 (25.00%)  1/6 (16.67%)  15/69 (21.74%)  13/84 (15.48%)  8/41 (19.51%) 
Spleen disorder * 1  1/17 (5.88%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Splenomegaly * 1  1/17 (5.88%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Thrombocytopenia * 1  6/17 (35.29%)  1/6 (16.67%)  2/4 (50.00%)  1/3 (33.33%)  3/16 (18.75%)  2/6 (33.33%)  23/69 (33.33%)  26/84 (30.95%)  11/41 (26.83%) 
Lymphadenopathy * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  4/69 (5.80%)  0/84 (0.00%)  0/41 (0.00%) 
Cardiac disorders                   
Angina pectoris * 1  1/17 (5.88%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Atrial fibrillation * 1  1/17 (5.88%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  5/69 (7.25%)  7/84 (8.33%)  1/41 (2.44%) 
Diastolic dysfunction * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Palpitations * 1  1/17 (5.88%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  4/69 (5.80%)  0/84 (0.00%)  0/41 (0.00%) 
Sinus bradycardia * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Sinus tachycardia * 1  0/17 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  7/69 (10.14%)  0/84 (0.00%)  0/41 (0.00%) 
Tachycardia * 1  1/17 (5.88%)  1/6 (16.67%)  0/4 (0.00%)  1/3 (33.33%)  0/16 (0.00%)  1/6 (16.67%)  5/69 (7.25%)  0/84 (0.00%)  0/41 (0.00%) 
Ventricular tachycardia * 1  1/17 (5.88%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Pericardial effusion * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  4/69 (5.80%)  0/84 (0.00%)  0/41 (0.00%) 
Endocrine disorders                   
Adrenal insufficiency * 1  0/17 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Hypothyroidism * 1  0/17 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Eye disorders                   
Diplopia * 1  0/17 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Eye haemorrhage * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  1/6 (16.67%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Ocular hyperaemia * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Photophobia * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Scleral pigmentation * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Vision blurred * 1  1/17 (5.88%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  2/16 (12.50%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Gastrointestinal disorders                   
Abdominal discomfort * 1  0/17 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Abdominal distension * 1  1/17 (5.88%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  2/16 (12.50%)  0/6 (0.00%)  10/69 (14.49%)  0/84 (0.00%)  0/41 (0.00%) 
Abdominal pain * 1  4/17 (23.53%)  0/6 (0.00%)  1/4 (25.00%)  1/3 (33.33%)  6/16 (37.50%)  0/6 (0.00%)  20/69 (28.99%)  15/84 (17.86%)  4/41 (9.76%) 
Abdominal pain upper * 1  2/17 (11.76%)  0/6 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  0/69 (0.00%)  7/84 (8.33%)  1/41 (2.44%) 
Anal fissure * 1  1/17 (5.88%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Anal haemorrhage * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  1/6 (16.67%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Angina bullosa haemorrhagica * 1  0/17 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Ascites * 1  1/17 (5.88%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Constipation * 1  7/17 (41.18%)  3/6 (50.00%)  2/4 (50.00%)  1/3 (33.33%)  10/16 (62.50%)  3/6 (50.00%)  32/69 (46.38%)  21/84 (25.00%)  6/41 (14.63%) 
Diarrhoea * 1  8/17 (47.06%)  2/6 (33.33%)  2/4 (50.00%)  0/3 (0.00%)  10/16 (62.50%)  6/6 (100.00%)  49/69 (71.01%)  24/84 (28.57%)  9/41 (21.95%) 
Diverticulum * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  1/6 (16.67%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Dry mouth * 1  1/17 (5.88%)  0/6 (0.00%)  0/4 (0.00%)  1/3 (33.33%)  2/16 (12.50%)  1/6 (16.67%)  10/69 (14.49%)  0/84 (0.00%)  0/41 (0.00%) 
Dyspepsia * 1  0/17 (0.00%)  0/6 (0.00%)  2/4 (50.00%)  0/3 (0.00%)  4/16 (25.00%)  1/6 (16.67%)  12/69 (17.39%)  0/84 (0.00%)  0/41 (0.00%) 
Dysphagia * 1  1/17 (5.88%)  0/6 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Faeces discoloured * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  1/3 (33.33%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Flatulence * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  4/69 (5.80%)  0/84 (0.00%)  0/41 (0.00%) 
Gastritis * 1  0/17 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Gastrooesophageal reflux disease * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  2/6 (33.33%)  6/69 (8.70%)  0/84 (0.00%)  0/41 (0.00%) 
Gingival bleeding * 1  2/17 (11.76%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  1/6 (16.67%)  4/69 (5.80%)  0/84 (0.00%)  0/41 (0.00%) 
Gingival pain * 1  0/17 (0.00%)  1/6 (16.67%)  1/4 (25.00%)  0/3 (0.00%)  2/16 (12.50%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Haematemesis * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  1/6 (16.67%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Haematochezia * 1  0/17 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Haemorrhoidal haemorrhage * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  2/16 (12.50%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Haemorrhoids * 1  0/17 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  4/16 (25.00%)  2/6 (33.33%)  5/69 (7.25%)  7/84 (8.33%)  0/41 (0.00%) 
Hiatus hernia * 1  0/17 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Megacolon * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Mouth haemorrhage * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  5/69 (7.25%)  2/84 (2.38%)  4/41 (9.76%) 
Nausea * 1  6/17 (35.29%)  4/6 (66.67%)  4/4 (100.00%)  1/3 (33.33%)  14/16 (87.50%)  3/6 (50.00%)  40/69 (57.97%)  30/84 (35.71%)  5/41 (12.20%) 
Oral disorder * 1  1/17 (5.88%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  2/16 (12.50%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Oral mucosal blistering * 1  0/17 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Oral pain * 1  1/17 (5.88%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Pancreatitis * 1  0/17 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Proctalgia * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  2/16 (12.50%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Retching * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Stomatitis * 1  2/17 (11.76%)  0/6 (0.00%)  0/4 (0.00%)  2/3 (66.67%)  5/16 (31.25%)  0/6 (0.00%)  17/69 (24.64%)  0/84 (0.00%)  0/41 (0.00%) 
Tongue disorder * 1  0/17 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Tooth loss * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  1/6 (16.67%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Toothache * 1  0/17 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  2/16 (12.50%)  0/6 (0.00%)  5/69 (7.25%)  0/84 (0.00%)  0/41 (0.00%) 
Vomiting * 1  1/17 (5.88%)  2/6 (33.33%)  1/4 (25.00%)  1/3 (33.33%)  5/16 (31.25%)  4/6 (66.67%)  25/69 (36.23%)  18/84 (21.43%)  4/41 (9.76%) 
Mouth ulceration * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  3/41 (7.32%) 
General disorders                   
Asthenia * 1  3/17 (17.65%)  1/6 (16.67%)  1/4 (25.00%)  2/3 (66.67%)  1/16 (6.25%)  0/6 (0.00%)  8/69 (11.59%)  10/84 (11.90%)  8/41 (19.51%) 
Catheter site pain * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Catheter site swelling * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  1/6 (16.67%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Chest discomfort * 1  1/17 (5.88%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Chest pain * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  2/6 (33.33%)  9/69 (13.04%)  9/84 (10.71%)  1/41 (2.44%) 
Chills * 1  1/17 (5.88%)  1/6 (16.67%)  0/4 (0.00%)  1/3 (33.33%)  5/16 (31.25%)  0/6 (0.00%)  21/69 (30.43%)  5/84 (5.95%)  1/41 (2.44%) 
Fatigue * 1  6/17 (35.29%)  1/6 (16.67%)  1/4 (25.00%)  2/3 (66.67%)  6/16 (37.50%)  2/6 (33.33%)  25/69 (36.23%)  26/84 (30.95%)  8/41 (19.51%) 
Gait disturbance * 1  0/17 (0.00%)  2/6 (33.33%)  1/4 (25.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Generalised oedema * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Hernia * 1  1/17 (5.88%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Influenza like illness * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Injection site pain * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Localised oedema * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Mucosal inflammation * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  1/6 (16.67%)  8/69 (11.59%)  6/84 (7.14%)  2/41 (4.88%) 
Nodule * 1  2/17 (11.76%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Non-cardiac chest pain * 1  0/17 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  3/16 (18.75%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Oedema * 1  0/17 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  1/6 (16.67%)  6/69 (8.70%)  0/84 (0.00%)  0/41 (0.00%) 
Oedema peripheral * 1  5/17 (29.41%)  1/6 (16.67%)  0/4 (0.00%)  1/3 (33.33%)  7/16 (43.75%)  2/6 (33.33%)  22/69 (31.88%)  22/84 (26.19%)  7/41 (17.07%) 
Pain * 1  1/17 (5.88%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  3/16 (18.75%)  0/6 (0.00%)  6/69 (8.70%)  4/84 (4.76%)  3/41 (7.32%) 
Performance status decreased * 1  2/17 (11.76%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Pyrexia * 1  5/17 (29.41%)  0/6 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  10/16 (62.50%)  1/6 (16.67%)  34/69 (49.28%)  23/84 (27.38%)  9/41 (21.95%) 
Thirst * 1  0/17 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Catheter site erythema * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  6/69 (8.70%)  0/84 (0.00%)  0/41 (0.00%) 
Catheter site haemorrhage * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  4/69 (5.80%)  0/84 (0.00%)  0/41 (0.00%) 
Hepatobiliary disorders                   
Cholelithiasis * 1  1/17 (5.88%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Hyperbilirubinaemia * 1  1/17 (5.88%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  4/69 (5.80%)  0/84 (0.00%)  0/41 (0.00%) 
Immune system disorders                   
Hypersensitivity * 1  1/17 (5.88%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Infections and infestations                   
Arthritis bacterial * 1  0/17 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Bacteraemia * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  1/6 (16.67%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Bronchiolitis * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  1/6 (16.67%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Candida infection * 1  1/17 (5.88%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Cellulitis * 1  1/17 (5.88%)  1/6 (16.67%)  1/4 (25.00%)  0/3 (0.00%)  0/16 (0.00%)  1/6 (16.67%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Clostridium difficile colitis * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  1/6 (16.67%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Clostridium difficile infection * 1  1/17 (5.88%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  2/16 (12.50%)  1/6 (16.67%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Device related infection * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Enterobacter bacteraemia * 1  1/17 (5.88%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Enterocolitis bacterial * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Enterocolitis infectious * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Folliculitis * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Fungal infection * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Genital infection viral * 1  0/17 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Nasopharyngitis * 1  1/17 (5.88%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Onychomycosis * 1  0/17 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Otitis media * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Pneumonia * 1  1/17 (5.88%)  1/6 (16.67%)  1/4 (25.00%)  0/3 (0.00%)  2/16 (12.50%)  1/6 (16.67%)  6/69 (8.70%)  9/84 (10.71%)  3/41 (7.32%) 
Pneumonia fungal * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  2/6 (33.33%)  4/69 (5.80%)  0/84 (0.00%)  0/41 (0.00%) 
Pulmonary mycosis * 1  1/17 (5.88%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Sepsis * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  1/6 (16.67%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Skin infection * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Staphylococcal bacteraemia * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  1/6 (16.67%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Staphylococcal infection * 1  2/17 (11.76%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Subcutaneous abscess * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Upper respiratory tract infection * 1  0/17 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Urinary tract infection * 1  0/17 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  1/3 (33.33%)  0/16 (0.00%)  1/6 (16.67%)  8/69 (11.59%)  5/84 (5.95%)  5/41 (12.20%) 
Viral infection * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  1/6 (16.67%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Oral herpes * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  3/84 (3.57%)  3/41 (7.32%) 
Injury, poisoning and procedural complications                   
Contusion * 1  1/17 (5.88%)  2/6 (33.33%)  1/4 (25.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  6/69 (8.70%)  5/84 (5.95%)  2/41 (4.88%) 
Fall * 1  0/17 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  1/6 (16.67%)  0/69 (0.00%)  9/84 (10.71%)  1/41 (2.44%) 
Infusion related reaction * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Post procedural haemorrhage * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Procedural headache * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Skin abrasion * 1  1/17 (5.88%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Vascular access complication * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Investigations                   
Alanine aminotransferase increased * 1  0/17 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  4/16 (25.00%)  1/6 (16.67%)  21/69 (30.43%)  0/84 (0.00%)  0/41 (0.00%) 
Amylase increased * 1  0/17 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Aspartate aminotransferase increased * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  2/16 (12.50%)  1/6 (16.67%)  17/69 (24.64%)  6/84 (7.14%)  1/41 (2.44%) 
Blood alkaline phosphatase increased * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  1/6 (16.67%)  13/69 (18.84%)  0/84 (0.00%)  0/41 (0.00%) 
Blood bilirubin increased * 1  0/17 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  2/16 (12.50%)  0/6 (0.00%)  19/69 (27.54%)  0/84 (0.00%)  0/41 (0.00%) 
Blood creatinine increased * 1  2/17 (11.76%)  2/6 (33.33%)  1/4 (25.00%)  1/3 (33.33%)  0/16 (0.00%)  1/6 (16.67%)  14/69 (20.29%)  9/84 (10.71%)  3/41 (7.32%) 
Blood fibrinogen decreased * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  1/6 (16.67%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Blood uric acid increased * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Chest X-ray abnormal * 1  1/17 (5.88%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Eastern Cooperative Oncology Group performance status worsened * 1  1/17 (5.88%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Electrocardiogram QT prolonged * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  1/6 (16.67%)  7/69 (10.14%)  7/84 (8.33%)  1/41 (2.44%) 
International normalised ratio increased * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  2/16 (12.50%)  0/6 (0.00%)  7/69 (10.14%)  3/84 (3.57%)  5/41 (12.20%) 
Karnofsky scale worsened * 1  1/17 (5.88%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Lipase increased * 1  0/17 (0.00%)  1/6 (16.67%)  1/4 (25.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Liver function test increased * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Lymphocyte count decreased * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  3/16 (18.75%)  0/6 (0.00%)  6/69 (8.70%)  0/84 (0.00%)  0/41 (0.00%) 
Neutrophil count decreased * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  12/69 (17.39%)  11/84 (13.10%)  1/41 (2.44%) 
Platelet count decreased * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  2/16 (12.50%)  0/6 (0.00%)  18/69 (26.09%)  14/84 (16.67%)  4/41 (9.76%) 
Weight decreased * 1  1/17 (5.88%)  1/6 (16.67%)  1/4 (25.00%)  0/3 (0.00%)  1/16 (6.25%)  1/6 (16.67%)  9/69 (13.04%)  17/84 (20.24%)  1/41 (2.44%) 
White blood cell count decreased * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  4/16 (25.00%)  0/6 (0.00%)  20/69 (28.99%)  13/84 (15.48%)  2/41 (4.88%) 
Activated partial thromboplastin time prolonged * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  5/69 (7.25%)  0/84 (0.00%)  0/41 (0.00%) 
Weight increased * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  4/69 (5.80%)  0/84 (0.00%)  0/41 (0.00%) 
C-reactive protein increased * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  6/84 (7.14%)  6/41 (14.63%) 
Metabolism and nutrition disorders                   
Decreased appetite * 1  1/17 (5.88%)  2/6 (33.33%)  1/4 (25.00%)  2/3 (66.67%)  2/16 (12.50%)  2/6 (33.33%)  26/69 (37.68%)  29/84 (34.52%)  5/41 (12.20%) 
Dehydration * 1  1/17 (5.88%)  1/6 (16.67%)  1/4 (25.00%)  0/3 (0.00%)  2/16 (12.50%)  0/6 (0.00%)  6/69 (8.70%)  0/84 (0.00%)  0/41 (0.00%) 
Gout * 1  1/17 (5.88%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  5/84 (5.95%)  2/41 (4.88%) 
Hyperkalaemia * 1  1/17 (5.88%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  6/69 (8.70%)  0/84 (0.00%)  0/41 (0.00%) 
Hypermagnesaemia * 1  0/17 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  4/69 (5.80%)  0/84 (0.00%)  0/41 (0.00%) 
Hypernatraemia * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  5/69 (7.25%)  0/84 (0.00%)  0/41 (0.00%) 
Hyperphosphataemia * 1  1/17 (5.88%)  0/6 (0.00%)  0/4 (0.00%)  1/3 (33.33%)  2/16 (12.50%)  1/6 (16.67%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Hyperuricaemia * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  2/16 (12.50%)  1/6 (16.67%)  0/69 (0.00%)  7/84 (8.33%)  1/41 (2.44%) 
Hypoalbuminaemia * 1  2/17 (11.76%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  3/16 (18.75%)  2/6 (33.33%)  18/69 (26.09%)  0/84 (0.00%)  0/41 (0.00%) 
Hypocalcaemia * 1  2/17 (11.76%)  0/6 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  5/16 (31.25%)  2/6 (33.33%)  22/69 (31.88%)  5/84 (5.95%)  1/41 (2.44%) 
Hypoglycaemia * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Hypokalaemia * 1  2/17 (11.76%)  3/6 (50.00%)  1/4 (25.00%)  0/3 (0.00%)  6/16 (37.50%)  2/6 (33.33%)  37/69 (53.62%)  13/84 (15.48%)  6/41 (14.63%) 
Hypomagnesaemia * 1  1/17 (5.88%)  1/6 (16.67%)  1/4 (25.00%)  0/3 (0.00%)  4/16 (25.00%)  2/6 (33.33%)  20/69 (28.99%)  8/84 (9.52%)  2/41 (4.88%) 
Hyponatraemia * 1  2/17 (11.76%)  0/6 (0.00%)  1/4 (25.00%)  1/3 (33.33%)  5/16 (31.25%)  1/6 (16.67%)  23/69 (33.33%)  10/84 (11.90%)  0/41 (0.00%) 
Hypophagia * 1  1/17 (5.88%)  0/6 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Hypophosphataemia * 1  1/17 (5.88%)  1/6 (16.67%)  1/4 (25.00%)  0/3 (0.00%)  3/16 (18.75%)  0/6 (0.00%)  15/69 (21.74%)  0/84 (0.00%)  0/41 (0.00%) 
Hypovolaemia * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  1/6 (16.67%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Metabolic acidosis * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Tumour lysis syndrome * 1  1/17 (5.88%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Vitamin D deficiency * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  1/6 (16.67%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Hyperglycaemia * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  13/69 (18.84%)  0/84 (0.00%)  0/41 (0.00%) 
Musculoskeletal and connective tissue disorders                   
Arthralgia * 1  1/17 (5.88%)  2/6 (33.33%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  1/6 (16.67%)  11/69 (15.94%)  10/84 (11.90%)  0/41 (0.00%) 
Back pain * 1  2/17 (11.76%)  1/6 (16.67%)  2/4 (50.00%)  2/3 (66.67%)  4/16 (25.00%)  1/6 (16.67%)  12/69 (17.39%)  9/84 (10.71%)  3/41 (7.32%) 
Bone pain * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  4/16 (25.00%)  0/6 (0.00%)  0/69 (0.00%)  2/84 (2.38%)  3/41 (7.32%) 
Joint effusion * 1  0/17 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Muscle spasms * 1  5/17 (29.41%)  1/6 (16.67%)  0/4 (0.00%)  2/3 (66.67%)  10/16 (62.50%)  2/6 (33.33%)  11/69 (15.94%)  19/84 (22.62%)  2/41 (4.88%) 
Muscular weakness * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  1/3 (33.33%)  1/16 (6.25%)  0/6 (0.00%)  0/69 (0.00%)  6/84 (7.14%)  0/41 (0.00%) 
Musculoskeletal pain * 1  0/17 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  3/16 (18.75%)  0/6 (0.00%)  7/69 (10.14%)  0/84 (0.00%)  0/41 (0.00%) 
Musculoskeletal stiffness * 1  0/17 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Myalgia * 1  1/17 (5.88%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  3/16 (18.75%)  1/6 (16.67%)  5/69 (7.25%)  5/84 (5.95%)  0/41 (0.00%) 
Neck pain * 1  0/17 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  4/69 (5.80%)  0/84 (0.00%)  0/41 (0.00%) 
Osteoarthritis * 1  0/17 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Pain in extremity * 1  1/17 (5.88%)  0/6 (0.00%)  1/4 (25.00%)  1/3 (33.33%)  4/16 (25.00%)  3/6 (50.00%)  9/69 (13.04%)  15/84 (17.86%)  2/41 (4.88%) 
Pain in jaw * 1  1/17 (5.88%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  1/6 (16.67%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Periarthritis * 1  0/17 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Plantar fasciitis * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Spinal pain * 1  0/17 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                   
Squamous cell carcinoma * 1  0/17 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Nervous system disorders                   
Ageusia * 1  0/17 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Amnesia * 1  0/17 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Central nervous system lesion * 1  0/17 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Cognitive disorder * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Dizziness * 1  1/17 (5.88%)  2/6 (33.33%)  1/4 (25.00%)  1/3 (33.33%)  1/16 (6.25%)  2/6 (33.33%)  12/69 (17.39%)  18/84 (21.43%)  4/41 (9.76%) 
Dysgeusia * 1  4/17 (23.53%)  4/6 (66.67%)  1/4 (25.00%)  1/3 (33.33%)  7/16 (43.75%)  1/6 (16.67%)  19/69 (27.54%)  21/84 (25.00%)  1/41 (2.44%) 
Headache * 1  3/17 (17.65%)  1/6 (16.67%)  1/4 (25.00%)  0/3 (0.00%)  9/16 (56.25%)  2/6 (33.33%)  22/69 (31.88%)  11/84 (13.10%)  5/41 (12.20%) 
Lethargy * 1  1/17 (5.88%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Memory impairment * 1  0/17 (0.00%)  1/6 (16.67%)  1/4 (25.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Mental impairment * 1  1/17 (5.88%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Paraesthesia * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Peroneal nerve palsy * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  1/3 (33.33%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Presyncope * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  1/3 (33.33%)  0/16 (0.00%)  1/6 (16.67%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Sedation * 1  1/17 (5.88%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Syncope * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  1/3 (33.33%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Hypoaesthesia * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  5/69 (7.25%)  0/84 (0.00%)  0/41 (0.00%) 
Psychiatric disorders                   
Agitation * 1  0/17 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  3/84 (3.57%)  3/41 (7.32%) 
Anxiety * 1  1/17 (5.88%)  2/6 (33.33%)  0/4 (0.00%)  0/3 (0.00%)  3/16 (18.75%)  1/6 (16.67%)  15/69 (21.74%)  3/84 (3.57%)  4/41 (9.76%) 
Apathy * 1  0/17 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Confusional state * 1  1/17 (5.88%)  1/6 (16.67%)  1/4 (25.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  4/69 (5.80%)  7/84 (8.33%)  0/41 (0.00%) 
Depressed mood * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Depression * 1  2/17 (11.76%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  2/6 (33.33%)  4/69 (5.80%)  0/84 (0.00%)  0/41 (0.00%) 
Disorientation * 1  1/17 (5.88%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Insomnia * 1  1/17 (5.88%)  0/6 (0.00%)  2/4 (50.00%)  0/3 (0.00%)  5/16 (31.25%)  0/6 (0.00%)  19/69 (27.54%)  10/84 (11.90%)  2/41 (4.88%) 
Panic attack * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  1/6 (16.67%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Delirium * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  4/69 (5.80%)  0/84 (0.00%)  0/41 (0.00%) 
Hallucination * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  5/69 (7.25%)  0/84 (0.00%)  0/41 (0.00%) 
Renal and urinary disorders                   
Acute kidney injury * 1  2/17 (11.76%)  0/6 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  3/16 (18.75%)  2/6 (33.33%)  8/69 (11.59%)  7/84 (8.33%)  1/41 (2.44%) 
Dysuria * 1  1/17 (5.88%)  0/6 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  4/69 (5.80%)  0/84 (0.00%)  0/41 (0.00%) 
Haematuria * 1  1/17 (5.88%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  5/69 (7.25%)  0/84 (0.00%)  0/41 (0.00%) 
Pollakiuria * 1  0/17 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  4/69 (5.80%)  0/84 (0.00%)  0/41 (0.00%) 
Proteinuria * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  4/69 (5.80%)  0/84 (0.00%)  0/41 (0.00%) 
Renal cyst * 1  1/17 (5.88%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Renal failure * 1  0/17 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Urinary retention * 1  1/17 (5.88%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Urinary incontinence * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  7/84 (8.33%)  0/41 (0.00%) 
Reproductive system and breast disorders                   
Pelvic pain * 1  0/17 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Vaginal haemorrhage * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Vulvovaginal pruritus * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Respiratory, thoracic and mediastinal disorders                   
Atelectasis * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  2/16 (12.50%)  1/6 (16.67%)  5/69 (7.25%)  0/84 (0.00%)  0/41 (0.00%) 
Cough * 1  4/17 (23.53%)  1/6 (16.67%)  1/4 (25.00%)  1/3 (33.33%)  1/16 (6.25%)  2/6 (33.33%)  14/69 (20.29%)  18/84 (21.43%)  7/41 (17.07%) 
Dysphonia * 1  1/17 (5.88%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Dyspnoea * 1  2/17 (11.76%)  0/6 (0.00%)  1/4 (25.00%)  1/3 (33.33%)  3/16 (18.75%)  2/6 (33.33%)  13/69 (18.84%)  21/84 (25.00%)  11/41 (26.83%) 
Dyspnoea exertional * 1  0/17 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Epistaxis * 1  1/17 (5.88%)  1/6 (16.67%)  1/4 (25.00%)  1/3 (33.33%)  3/16 (18.75%)  1/6 (16.67%)  11/69 (15.94%)  7/84 (8.33%)  6/41 (14.63%) 
Hypoxia * 1  2/17 (11.76%)  0/6 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  8/69 (11.59%)  0/84 (0.00%)  0/41 (0.00%) 
Lung infiltration * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Nasal congestion * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  7/69 (10.14%)  0/84 (0.00%)  0/41 (0.00%) 
Oropharyngeal pain * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  2/6 (33.33%)  12/69 (17.39%)  9/84 (10.71%)  0/41 (0.00%) 
Pleural effusion * 1  2/17 (11.76%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  9/69 (13.04%)  0/84 (0.00%)  0/41 (0.00%) 
Pleuritic pain * 1  1/17 (5.88%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Pulmonary fibrosis * 1  1/17 (5.88%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Pulmonary oedema * 1  0/17 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Respiratory failure * 1  0/17 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Rhinitis allergic * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  2/16 (12.50%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Rhinorrhoea * 1  1/17 (5.88%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  1/6 (16.67%)  5/69 (7.25%)  0/84 (0.00%)  0/41 (0.00%) 
Sinus congestion * 1  0/17 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Wheezing * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  7/69 (10.14%)  0/84 (0.00%)  0/41 (0.00%) 
Hiccups * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  5/69 (7.25%)  0/84 (0.00%)  0/41 (0.00%) 
Sinus pain * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Skin and subcutaneous tissue disorders                   
Alopecia * 1  1/17 (5.88%)  1/6 (16.67%)  1/4 (25.00%)  2/3 (66.67%)  4/16 (25.00%)  2/6 (33.33%)  16/69 (23.19%)  9/84 (10.71%)  0/41 (0.00%) 
Decubitus ulcer * 1  0/17 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Dermatitis acneiform * 1  0/17 (0.00%)  1/6 (16.67%)  1/4 (25.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Dry skin * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  2/16 (12.50%)  1/6 (16.67%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Ecchymosis * 1  0/17 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Erythema * 1  0/17 (0.00%)  2/6 (33.33%)  0/4 (0.00%)  0/3 (0.00%)  2/16 (12.50%)  0/6 (0.00%)  0/69 (0.00%)  7/84 (8.33%)  2/41 (4.88%) 
Macule * 1  1/17 (5.88%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Night sweats * 1  2/17 (11.76%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  1/6 (16.67%)  4/69 (5.80%)  0/84 (0.00%)  0/41 (0.00%) 
Pain of skin * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  1/3 (33.33%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Palmar erythema * 1  1/17 (5.88%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Panniculitis * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Petechiae * 1  2/17 (11.76%)  2/6 (33.33%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  1/6 (16.67%)  11/69 (15.94%)  7/84 (8.33%)  4/41 (9.76%) 
Plantar erythema * 1  1/17 (5.88%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Pruritus * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  4/16 (25.00%)  1/6 (16.67%)  10/69 (14.49%)  6/84 (7.14%)  1/41 (2.44%) 
Pruritus allergic * 1  1/17 (5.88%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Purpura * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Rash * 1  2/17 (11.76%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  3/16 (18.75%)  1/6 (16.67%)  14/69 (20.29%)  11/84 (13.10%)  1/41 (2.44%) 
Rash macular * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  1/6 (16.67%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Rash maculo-papular * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  3/16 (18.75%)  0/6 (0.00%)  9/69 (13.04%)  0/84 (0.00%)  0/41 (0.00%) 
Rash papular * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Skin disorder * 1  0/17 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Skin lesion * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  1/6 (16.67%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Skin ulcer * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Urticaria * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  1/6 (16.67%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Hyperhidrosis * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  9/69 (13.04%)  0/84 (0.00%)  0/41 (0.00%) 
Vascular disorders                   
Hypertension * 1  0/17 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  1/3 (33.33%)  3/16 (18.75%)  1/6 (16.67%)  12/69 (17.39%)  6/84 (7.14%)  1/41 (2.44%) 
Hypotension * 1  1/17 (5.88%)  2/6 (33.33%)  0/4 (0.00%)  0/3 (0.00%)  4/16 (25.00%)  0/6 (0.00%)  14/69 (20.29%)  12/84 (14.29%)  4/41 (9.76%) 
Ischaemia * 1  1/17 (5.88%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Phlebitis * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/16 (6.25%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Thrombophlebitis * 1  1/17 (5.88%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Venous thrombosis * 1  1/17 (5.88%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  0/84 (0.00%)  0/41 (0.00%) 
Pallor * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  1/84 (1.19%)  3/41 (7.32%) 
Haematoma * 1  0/17 (0.00%)  0/6 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/16 (0.00%)  0/6 (0.00%)  0/69 (0.00%)  5/84 (5.95%)  2/41 (4.88%) 
1
Term from vocabulary, MedDRA 21.1
*
Indicates events were collected by non-systematic assessment
[Not Specified]
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.
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
Phone: 1-800-718-1021
EMail: ClinicalTrials.gov_Inquiries@pfizer.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01546038    
Other Study ID Numbers: B1371003
2012-000684-24 ( EudraCT Number )
First Submitted: March 1, 2012
First Posted: March 7, 2012
Results First Submitted: December 11, 2017
Results First Posted: May 23, 2018
Last Update Posted: March 3, 2020