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A Study Evaluating Intensive Chemotherapy With or Without Glasdegib or Azacitidine With or Without Glasdegib In Patients With Previously Untreated Acute Myeloid Leukemia (BRIGHT AML1019)

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ClinicalTrials.gov Identifier: NCT03416179
Recruitment Status : Completed
First Posted : January 31, 2018
Results First Posted : June 25, 2021
Last Update Posted : April 21, 2023
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Leukemia, Myeloid, Acute
Interventions Drug: glasdegib
Drug: daunorubicin + cytarabine
Drug: azacitidine
Drug: Placebo
Drug: cytarabine
Procedure: HSCT
Enrollment 730
Recruitment Details This study evaluated glasdegib in intensive and non-intensive chemotherapy populations. Intensive study: Glasdegib was studied in combination with cytarabine and daunorubicin for the treatment of adult participants with previously untreated acute myeloid leukemia (AML). Non-intensive study: Glasdegib was studied in combination with azacitidine for the treatment of adult participants with previously untreated AML who were not candidates for intensive induction chemotherapy.
Pre-assignment Details

Inadvertently 1 participant was enrolled twice into the study resulting in enrollment number as 730. However, a total of 729 participants were randomized and received treatment in the study.

Although participation of participants was terminated by the sponsor, the study was considered completed as participants were fully enrolled as planned.
Arm/Group Title Intensive Study: Glasdegib + Cytarabine + Daunorubicin Intensive Study: Placebo + Cytarabine + Daunorubicin Non-intensive Study: Glasdegib + Azacitidine Non-intensive Study: Placebo + Azacitidine
Hide Arm/Group Description Participants received first induction therapy (28 days) (backbone chemotherapy+experimental therapy). Backbone chemotherapy: Cytarabine 100 milligram per square meter (mg/m^2) daily by intravenous (IV) infusion for 7 days along with daunorubicin 60 mg/m^2 daily IV for 3 days. Depending upon bone marrow blast or investigator judgement participants had second induction i.e. received either same backbone therapy or cytarabine 100 mg/m^2 IV daily for 5 days and daunorubicin 60 mg/m^2 IV daily for 2 days. Participants with less than (<) 5% bone marrow blasts entered into consolation phase- treated with either or both of following: 1) cytarabine 1 to 3 gram per square meter (gm/m^2) IV for adults greater than or equals to (>=) 60 to <60 years twice daily on Days 1, 3, and 5 for 4 cycle (each cycle 28 day) or cytarabine per local prescribing information. 2) Received hematopoietic stem cell transplantation (HSCT) per local standard of care. Experimental Therapy: Participants were to receive Glasdegib 100 milligram (mg) tablet orally (PO) once daily (QD) from Day 1 of chemotherapy up to 28 days in both induction until 2 consecutive complete remission (CR) minimal residual disease (MRD)-negative central laboratory results, whichever came first (1.6 year). Participants received first induction therapy (28 days) (backbone chemotherapy+experimental therapy). Backbone chemotherapy: Cytarabine 100 mg/m^2 daily by IV infusion for 7 days along with daunorubicin 60 mg/m^2 daily IV for 3 days. Depending upon bone marrow blast or investigator judgement participants had second induction i.e. received either same backbone therapy or cytarabine 100 mg/m^2 IV daily for 5 days and daunorubicin 60 mg/m^2 IV daily for 2 days. Participants with <5% bone marrow blasts entered into consolation phase- treated with either or both of following: 1) cytarabine 1 to 3 gram/m^2 IV for adults >=60 to <60 years twice daily on Days 1, 3, and 5 for 4 cycle (each cycle 28 day) or cytarabine per local prescribing information. 2) Received HSCT per local standard of care. Experimental Therapy: Participants were to receive Glasdegib 100 mg matching placebo tablet PO QD from Day 1 of chemotherapy up to 28 days in both induction until 2 consecutive CR MRD-negative central laboratory results, whichever came first (1.8 year). Participants received chemotherapy with azacitidine 75 mg/m^2 SC injection or IV infusion from Day 1 up to Day 7 of each cycle (28 day) and continued for at least 6 cycles or until unacceptable toxicity, participant refusal or death, whichever occurred first. Participants also were to receive glasdegib 100 mg PO QD from Day 1 of chemotherapy until clinical benefit or disease progression, unacceptable toxicity, consent withdrawal, or death, whichever occurred first. Eligible participants underwent HSCT per local standard of care and were to receive glasdegib unless 2 consecutive negative MRD assessments (3 year). Participants received chemotherapy with azacitidine 75 mg/m^2 SC injection or IV infusion from Day 1 up to Day 7 of each cycle (28 day) and continued for at least 6 cycles or until unacceptable toxicity, participants refusal or death, whichever occurred first. Participants also received glasdegib 100 mg tablet matching placebo PO QD from Day 1 of chemotherapy until clinical benefit or disease progression, unacceptable toxicity, consent withdrawal, or death, whichever occurred first. Eligible participants underwent HSCT per local standard of care and were to receive glasdegib matching placebo unless 2 consecutive negative MRD assessments (2.44 year).
Period Title: Overall Study
Started 201 203 163 162
Treated 198 201 162 160
Completed 0 1 13 6
Not Completed 201 202 150 156
Reason Not Completed
Death             90             87             117             113
Withdrawal by Subject             15             20             6             9
Lost to Follow-up             1             1             0             3
Study participation terminated by Sponsor             93             91             26             31
Other             2             3             1             0
Arm/Group Title Intensive Study: Glasdegib + Cytarabine + Daunorubicin Intensive Study: Placebo + Cytarabine + Daunorubicin Non-intensive Study: Glasdegib + Azacitidine Non-intensive Study: Placebo + Azacitidine Total
Hide Arm/Group Description Participants received first induction therapy (28 days) (backbone chemotherapy+experimental therapy). Backbone chemotherapy: Cytarabine 100 mg/m^2 daily by IV infusion for 7 days along with daunorubicin 60 mg/m^2 daily IV for 3 days. Depending upon bone marrow blast or investigator judgement participants had second induction i.e. received either same backbone therapy or cytarabine 100 mg/m^2 IV daily for 5 days and daunorubicin 60 mg/m^2 IV daily for 2 days. Participants with <5% bone marrow blasts entered into consolation phase- treated with either or both of following: 1) cytarabine 1 to 3 gm/m^2 IV for adults >=60 to <60 years twice daily on Days 1, 3, and 5 for 4 cycle (each cycle 28 day) or cytarabine per local prescribing information. 2) Received HSCT per local standard of care. Experimental Therapy: Participants were to receive Glasdegib 100 mg tablet PO QD from Day 1 of chemotherapy up to 28 days in both induction until 2 consecutive CRMRD-negative central laboratory results, whichever came first (1.6 year). Participants received first induction therapy (28 days) (backbone chemotherapy+experimental therapy). Backbone chemotherapy: Cytarabine 100 mg/m^2 daily by IV infusion for 7 days along with daunorubicin 60 mg/m^2 daily IV for 3 days. Depending upon bone marrow blast or investigator judgement participants had second induction i.e. received either same backbone therapy or cytarabine 100 mg/m^2 IV daily for 5 days and daunorubicin 60 mg/m^2 IV daily for 2 days. Participants with <5% bone marrow blasts entered into consolation phase- treated with either or both of following: 1) cytarabine 1 to 3 gram/m^2 IV for adults >=60 to <60 years twice daily on Days 1, 3, and 5 for 4 cycle (each cycle 28 day) or cytarabine per local prescribing information. 2) Received HSCT per local standard of care. Experimental Therapy: Participants were to receive Glasdegib 100 mg matching placebo tablet PO QD from Day 1 of chemotherapy up to 28 days in both induction until 2 consecutive CR MRD-negative central laboratory results, whichever came first (1.8 year). Participants received chemotherapy with azacitidine 75 mg/m^2 SC injection or IV infusion from Day 1 up to Day 7 of each cycle (28 day) and continued for at least 6 cycles or until unacceptable toxicity, participant refusal or death, whichever occurred first. Participants also were to receive glasdegib 100 mg PO QD from Day 1 of chemotherapy until clinical benefit or disease progression, unacceptable toxicity, consent withdrawal, or death, whichever occurred first. Eligible participants underwent HSCT per local standard of care and were to receive glasdegib unless 2 consecutive negative MRD assessments (3 year). Participants received chemotherapy with azacitidine 75 mg/m^2 SC injection or IV infusion from Day 1 up to Day 7 of each cycle (28 day) and continued for at least 6 cycles or until unacceptable toxicity, participants refusal or death, whichever occurred first. Participants also received glasdegib 100 mg tablet matching placebo PO QD from Day 1 of chemotherapy until clinical benefit or disease progression, unacceptable toxicity, consent withdrawal, or death, whichever occurred first. Eligible participants underwent HSCT per local standard of care and were to receive glasdegib matching placebo unless 2 consecutive negative MRD assessments (2.44 year). Total of all reporting groups
Overall Number of Baseline Participants 201 203 163 162 729
Hide Baseline Analysis Population Description
Full analysis (FA) set included all randomized participants.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 201 participants 203 participants 163 participants 162 participants 729 participants
56.55  (12.60) 55.38  (13.61) 73.19  (7.17) 73.14  (6.82) 63.63  (13.79)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 201 participants 203 participants 163 participants 162 participants 729 participants
Female
71
  35.3%
97
  47.8%
97
  59.5%
89
  54.9%
354
  48.6%
Male
130
  64.7%
106
  52.2%
66
  40.5%
73
  45.1%
375
  51.4%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 201 participants 203 participants 163 participants 162 participants 729 participants
Hispanic or Latino
19
   9.5%
12
   5.9%
12
   7.4%
16
   9.9%
59
   8.1%
Not Hispanic or Latino
166
  82.6%
171
  84.2%
140
  85.9%
139
  85.8%
616
  84.5%
Unknown or Not Reported
16
   8.0%
20
   9.9%
11
   6.7%
7
   4.3%
54
   7.4%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 201 participants 203 participants 163 participants 162 participants 729 participants
American Indian or Alaska Native
1
   0.5%
0
   0.0%
0
   0.0%
0
   0.0%
1
   0.1%
Asian
66
  32.8%
57
  28.1%
51
  31.3%
44
  27.2%
218
  29.9%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
3
   1.5%
3
   1.5%
1
   0.6%
7
   4.3%
14
   1.9%
White
110
  54.7%
123
  60.6%
97
  59.5%
99
  61.1%
429
  58.8%
More than one race
1
   0.5%
0
   0.0%
0
   0.0%
0
   0.0%
1
   0.1%
Unknown or Not Reported
20
  10.0%
20
   9.9%
14
   8.6%
12
   7.4%
66
   9.1%
1.Primary Outcome
Title Intensive Study: Overall Survival (OS)
Hide Description OS is defined as the time from the date of randomization to the date of death due to any cause. Participants last known to be alive were to be censored at the date of last contact.
Time Frame Baseline up to 25 months
Hide Outcome Measure Data
Hide Analysis Population Description
FA set included all randomized participants.
Arm/Group Title Intensive Study: Glasdegib + Cytarabine + Daunorubicin Intensive Study: Placebo + Cytarabine + Daunorubicin
Hide Arm/Group Description:
Participants received first induction therapy (28 days) (backbone chemotherapy+experimental therapy). Backbone chemotherapy: Cytarabine 100 mg/m^2 daily by IV infusion for 7 days along with daunorubicin 60 mg/m^2 daily IV for 3 days. Depending upon bone marrow blast or investigator judgement participants had second induction i.e. received either same backbone therapy or cytarabine 100 mg/m^2 IV daily for 5 days and daunorubicin 60 mg/m^2 IV daily for 2 days. Participants with <5% bone marrow blasts entered into consolation phase- treated with either or both of following: 1) cytarabine 1 to 3 gm/m^2 IV for adults >=60 to <60 years twice daily on Days 1, 3, and 5 for 4 cycle (each cycle 28 day) or cytarabine per local prescribing information. 2) Received HSCT per local standard of care. Experimental Therapy: Participants were to receive Glasdegib 100 mg tablet PO QD from Day 1 of chemotherapy up to 28 days in both induction until 2 consecutive CRMRD-negative central laboratory results, whichever came first (1.6 year).
Participants received first induction therapy (28 days) (backbone chemotherapy+experimental therapy). Backbone chemotherapy: Cytarabine 100 mg/m^2 daily by IV infusion for 7 days along with daunorubicin 60 mg/m^2 daily IV for 3 days. Depending upon bone marrow blast or investigator judgement participants had second induction i.e. received either same backbone therapy or cytarabine 100 mg/m^2 IV daily for 5 days and daunorubicin 60 mg/m^2 IV daily for 2 days. Participants with <5% bone marrow blasts entered into consolation phase- treated with either or both of following: 1) cytarabine 1 to 3 gram/m^2 IV for adults >=60 to <60 years twice daily on Days 1, 3, and 5 for 4 cycle (each cycle 28 day) or cytarabine per local prescribing information. 2) Received HSCT per local standard of care. Experimental Therapy: Participants were to receive Glasdegib 100 mg matching placebo tablet PO QD from Day 1 of chemotherapy up to 28 days in both induction until 2 consecutive CR MRD-negative central laboratory results, whichever came first (1.8 year).
Overall Number of Participants Analyzed 201 203
Median (95% Confidence Interval)
Unit of Measure: months
17.3
(15.2 to 18.5)
20.4 [1] 
(17.6 to NA)
[1]
Upper limit of 95 % CI was not estimable due to low number of participants with events.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Intensive Study: Glasdegib + Cytarabine + Daunorubicin, Intensive Study: Placebo + Cytarabine + Daunorubicin
Comments Hazard ratio based on Cox proportional hazards model; under proportional hazards, hazard ratio less than (<) 1 indicated a reduction in hazard rate in favor of Glasdegib 100 mg PO + Cytarabine 100 mg/m^2 IV + Daunorubicin 60 mg/m^2 compared to Placebo + Cytarabine 100 mg/m^2 IV + Daunorubicin 60 mg/m^2.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6579
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.08
Confidence Interval (2-Sided) 95%
0.755 to 1.532
Estimation Comments [Not Specified]
2.Primary Outcome
Title Non-intensive Study: Overall Survival (OS)
Hide Description OS is defined as the time from the date of randomization to the date of death due to any cause. Participants last known to be alive were to be censored at the date of last contact.
Time Frame Baseline up to 25 months
Hide Outcome Measure Data
Hide Analysis Population Description
FA set included all randomized participants.
Arm/Group Title Non-intensive Study: Glasdegib + Azacitidine Non-intensive Study: Placebo + Azacitidine
Hide Arm/Group Description:
Participants received chemotherapy with azacitidine 75 mg/m^2 SC injection or IV infusion from Day 1 up to Day 7 of each cycle (28 day) and continued for at least 6 cycles or until unacceptable toxicity, participant refusal or death, whichever occurred first. Participants also were to receive glasdegib 100 mg PO QD from Day 1 of chemotherapy until clinical benefit or disease progression, unacceptable toxicity, consent withdrawal, or death, whichever occurred first. Eligible participants underwent HSCT per local standard of care and were to receive glasdegib unless 2 consecutive negative MRD assessments (3 year).
Participants received chemotherapy with azacitidine 75 mg/m^2 SC injection or IV infusion from Day 1 up to Day 7 of each cycle (28 day) and continued for at least 6 cycles or until unacceptable toxicity, participants refusal or death, whichever occurred first. Participants also received glasdegib 100 mg tablet matching placebo PO QD from Day 1 of chemotherapy until clinical benefit or disease progression, unacceptable toxicity, consent withdrawal, or death, whichever occurred first. Eligible participants underwent HSCT per local standard of care and were to receive glasdegib matching placebo unless 2 consecutive negative MRD assessments (2.44 year).
Overall Number of Participants Analyzed 163 162
Median (95% Confidence Interval)
Unit of Measure: months
10.3
(7.7 to 12.4)
10.6
(8.4 to 13.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Non-intensive Study: Glasdegib + Azacitidine, Non-intensive Study: Placebo + Azacitidine
Comments Hazard ratio based on Cox proportional hazards model; under proportional hazards, hazard ratio < 1 indicated a reduction in hazard rate in favor of Glasdegib 100 mg PO QD + Azacitidine compared to Placebo + Azacitidine
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5955
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.04
Confidence Interval (2-Sided) 95%
0.775 to 1.388
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Intensive Study: Percentage of Participants Who Improved in Fatigue Score Measured by the MD Anderson Symptom Inventory -Acute Myelogenous Leukemia/Myelodysplastic Syndrome (MDASI-AML/MDS) Questionnaire
Hide Description MDASI-AML/MDS: consists of 23 items, 13-item core cancer symptoms (pain, fatigue, nausea, disturbed sleep, distress, shortness of breath, problem remembering, lack of appetite, drowsiness, dry mouth, sadness, vomiting, and numbness), 4-item AML/MDS specific symptoms (malaise, diarrhea, muscle weakness, and skin problems), and 6 areas of interference (general activity, mood, work, walking, relations with other people, and enjoyment of life). "Fatigue" was measured at the participants' worst level in last 24 hours by asking participants to respond to each item on an 0-10 numeric rating scale (NRS), where 0 = "not present" and 10 = "as bad as you can imagine". Percentage of participants who had improvement in "fatigue" symptoms reported in this outcome measure.
Time Frame Post-baseline up to Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
FA set included all randomized participants.
Arm/Group Title Intensive Study: Glasdegib + Cytarabine + Daunorubicin Intensive Study: Placebo + Cytarabine + Daunorubicin
Hide Arm/Group Description:
Participants received first induction therapy (28 days) (backbone chemotherapy+experimental therapy). Backbone chemotherapy: Cytarabine 100 mg/m^2 daily by IV infusion for 7 days along with daunorubicin 60 mg/m^2 daily IV for 3 days. Depending upon bone marrow blast or investigator judgement participants had second induction i.e. received either same backbone therapy or cytarabine 100 mg/m^2 IV daily for 5 days and daunorubicin 60 mg/m^2 IV daily for 2 days. Participants with <5% bone marrow blasts entered into consolation phase- treated with either or both of following: 1) cytarabine 1 to 3 gm/m^2 IV for adults >=60 to <60 years twice daily on Days 1, 3, and 5 for 4 cycle (each cycle 28 day) or cytarabine per local prescribing information. 2) Received HSCT per local standard of care. Experimental Therapy: Participants were to receive Glasdegib 100 mg tablet PO QD from Day 1 of chemotherapy up to 28 days in both induction until 2 consecutive CRMRD-negative central laboratory results, whichever came first (1.6 year).
Participants received first induction therapy (28 days) (backbone chemotherapy+experimental therapy). Backbone chemotherapy: Cytarabine 100 mg/m^2 daily by IV infusion for 7 days along with daunorubicin 60 mg/m^2 daily IV for 3 days. Depending upon bone marrow blast or investigator judgement participants had second induction i.e. received either same backbone therapy or cytarabine 100 mg/m^2 IV daily for 5 days and daunorubicin 60 mg/m^2 IV daily for 2 days. Participants with <5% bone marrow blasts entered into consolation phase- treated with either or both of following: 1) cytarabine 1 to 3 gram/m^2 IV for adults >=60 to <60 years twice daily on Days 1, 3, and 5 for 4 cycle (each cycle 28 day) or cytarabine per local prescribing information. 2) Received HSCT per local standard of care. Experimental Therapy: Participants were to receive Glasdegib 100 mg matching placebo tablet PO QD from Day 1 of chemotherapy up to 28 days in both induction until 2 consecutive CR MRD-negative central laboratory results, whichever came first (1.8 year).
Overall Number of Participants Analyzed 201 203
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
17.41
(12.17 to 22.66)
17.24
(12.05 to 22.44)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Intensive Study: Glasdegib + Cytarabine + Daunorubicin, Intensive Study: Placebo + Cytarabine + Daunorubicin
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5095
Comments [Not Specified]
Method Mantel Haenszel
Comments [Not Specified]
4.Secondary Outcome
Title Non-intensive Study: Percentage of Participants Who Improved in Fatigue Score Measured by the MDASI-AML/MDS Questionnaire at Week 12
Hide Description MDASI-AML/MDS: consists of 23 items, 13-item core cancer symptoms (pain, fatigue, nausea, disturbed sleep, distress, shortness of breath, problem remembering, lack of appetite, drowsiness, dry mouth, sadness, vomiting, and numbness), 4-item AML/MDS specific symptoms (malaise, diarrhea, muscle weakness, and skin problems), and 6 areas of interference (general activity, mood, work, walking, relations with other people, and enjoyment of life). "Fatigue" was measured at the participants' worst level in last 24 hours by asking participants to respond to each item on an 0-10 NRS, where 0 = "not present" and 10 = "as bad as you can imagine". Percentage of participants who had improvement in "fatigue" symptoms reported in this outcome measure.
Time Frame Post-baseline up to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
FA set included all randomized participants.
Arm/Group Title Non-intensive Study: Glasdegib + Azacitidine Non-intensive Study: Placebo + Azacitidine
Hide Arm/Group Description:
Participants received chemotherapy with azacitidine 75 mg/m^2 SC injection or IV infusion from Day 1 up to Day 7 of each cycle (28 day) and continued for at least 6 cycles or until unacceptable toxicity, participant refusal or death, whichever occurred first. Participants also were to receive glasdegib 100 mg PO QD from Day 1 of chemotherapy until clinical benefit or disease progression, unacceptable toxicity, consent withdrawal, or death, whichever occurred first. Eligible participants underwent HSCT per local standard of care and were to receive glasdegib unless 2 consecutive negative MRD assessments (3 year).
Participants received chemotherapy with azacitidine 75 mg/m^2 SC injection or IV infusion from Day 1 up to Day 7 of each cycle (28 day) and continued for at least 6 cycles or until unacceptable toxicity, participants refusal or death, whichever occurred first. Participants also received glasdegib 100 mg tablet matching placebo PO QD from Day 1 of chemotherapy until clinical benefit or disease progression, unacceptable toxicity, consent withdrawal, or death, whichever occurred first. Eligible participants underwent HSCT per local standard of care and were to receive glasdegib matching placebo unless 2 consecutive negative MRD assessments (2.44 year).
Overall Number of Participants Analyzed 163 162
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
11.66
(6.73 to 16.58)
15.43
(9.87 to 21.00)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Non-intensive Study: Glasdegib + Azacitidine, Non-intensive Study: Placebo + Azacitidine
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8359
Comments [Not Specified]
Method Mantel Haenszel
Comments [Not Specified]
5.Secondary Outcome
Title Intensive Study: Percentage of Participants With Complete Remission Without Negative Minimal Residual Disease (CRMRD-neg)
Hide Description Complete remission (CR) was defined based on 2017 European LeukemiaNet (ELN) recommendations. CR: Bone marrow blasts <5 percentage (%); absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count (ANC) greater than equal to (>=) 1.0*10^9/Liter (L); platelet count >=100*10^9/L. CRMRD-neg: CR with negativity for a genetic marker by reverse transcription quantitative polymerase chain reaction (RT-qPCR), or CR with negativity by Multiparameter Flow Cytometry (MFC).
Time Frame Day 1 up to maximum of 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
FA set included all randomized participants.
Arm/Group Title Intensive Study: Glasdegib + Cytarabine + Daunorubicin Intensive Study: Placebo + Cytarabine + Daunorubicin
Hide Arm/Group Description:
Participants received first induction therapy (28 days) (backbone chemotherapy+experimental therapy). Backbone chemotherapy: Cytarabine 100 mg/m^2 daily by IV infusion for 7 days along with daunorubicin 60 mg/m^2 daily IV for 3 days. Depending upon bone marrow blast or investigator judgement participants had second induction i.e. received either same backbone therapy or cytarabine 100 mg/m^2 IV daily for 5 days and daunorubicin 60 mg/m^2 IV daily for 2 days. Participants with <5% bone marrow blasts entered into consolation phase- treated with either or both of following: 1) cytarabine 1 to 3 gm/m^2 IV for adults >=60 to <60 years twice daily on Days 1, 3, and 5 for 4 cycle (each cycle 28 day) or cytarabine per local prescribing information. 2) Received HSCT per local standard of care. Experimental Therapy: Participants were to receive Glasdegib 100 mg tablet PO QD from Day 1 of chemotherapy up to 28 days in both induction until 2 consecutive CRMRD-negative central laboratory results, whichever came first (1.6 year).
Participants received first induction therapy (28 days) (backbone chemotherapy+experimental therapy). Backbone chemotherapy: Cytarabine 100 mg/m^2 daily by IV infusion for 7 days along with daunorubicin 60 mg/m^2 daily IV for 3 days. Depending upon bone marrow blast or investigator judgement participants had second induction i.e. received either same backbone therapy or cytarabine 100 mg/m^2 IV daily for 5 days and daunorubicin 60 mg/m^2 IV daily for 2 days. Participants with <5% bone marrow blasts entered into consolation phase- treated with either or both of following: 1) cytarabine 1 to 3 gram/m^2 IV for adults >=60 to <60 years twice daily on Days 1, 3, and 5 for 4 cycle (each cycle 28 day) or cytarabine per local prescribing information. 2) Received HSCT per local standard of care. Experimental Therapy: Participants were to receive Glasdegib 100 mg matching placebo tablet PO QD from Day 1 of chemotherapy up to 28 days in both induction until 2 consecutive CR MRD-negative central laboratory results, whichever came first (1.8 year).
Overall Number of Participants Analyzed 201 203
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
5.0
(2.4 to 9.0)
5.4
(2.7 to 9.5)
6.Secondary Outcome
Title Non-intensive Study: Percentage of Participants With Complete Remission Without Negative Minimal Residual Disease (CRMRD-neg)
Hide Description CR was defined based on 2017 ELN recommendations. CR: Bone marrow blasts <5%; absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; ANC >=1.0*10^9/L; platelet count >=100*10^9/L. CRMRDneg: CR with negativity for a genetic marker by RT-qPCR, or CR with negativity by MFC.
Time Frame Day 1 up to maximum of 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
FA set included all randomized participants.
Arm/Group Title Non-intensive Study: Glasdegib + Azacitidine Non-intensive Study: Placebo + Azacitidine
Hide Arm/Group Description:
Participants received chemotherapy with azacitidine 75 mg/m^2 SC injection or IV infusion from Day 1 up to Day 7 of each cycle (28 day) and continued for at least 6 cycles or until unacceptable toxicity, participant refusal or death, whichever occurred first. Participants also were to receive glasdegib 100 mg PO QD from Day 1 of chemotherapy until clinical benefit or disease progression, unacceptable toxicity, consent withdrawal, or death, whichever occurred first. Eligible participants underwent HSCT per local standard of care and were to receive glasdegib unless 2 consecutive negative MRD assessments (3 year).
Participants received chemotherapy with azacitidine 75 mg/m^2 SC injection or IV infusion from Day 1 up to Day 7 of each cycle (28 day) and continued for at least 6 cycles or until unacceptable toxicity, participants refusal or death, whichever occurred first. Participants also received glasdegib 100 mg tablet matching placebo PO QD from Day 1 of chemotherapy until clinical benefit or disease progression, unacceptable toxicity, consent withdrawal, or death, whichever occurred first. Eligible participants underwent HSCT per local standard of care and were to receive glasdegib matching placebo unless 2 consecutive negative MRD assessments (2.44 year).
Overall Number of Participants Analyzed 163 162
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
1.8
(0.4 to 5.3)
0.6
(0.0 to 3.4)
7.Secondary Outcome
Title Intensive Study: Percentage of Participants With Complete Remission Including Negative Minimal Residual Disease (CRMRD-neg)
Hide Description CR was defined based on 2017 ELN recommendations. CR: Bone marrow blasts <5%; absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; ANC >=1.0*10^9/L; platelet count >=100*10^9/L. CRMRDneg: CR with negativity for a genetic marker by RT-qPCR, or CR with negativity by MFC.
Time Frame Day 1 up to maximum of 2 years
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Hide Analysis Population Description
FA set included all randomized participants.
Arm/Group Title Intensive Study: Glasdegib + Cytarabine + Daunorubicin Intensive Study: Placebo + Cytarabine + Daunorubicin
Hide Arm/Group Description:
Participants received first induction therapy (28 days) (backbone chemotherapy+experimental therapy). Backbone chemotherapy: Cytarabine 100 mg/m^2 daily by IV infusion for 7 days along with daunorubicin 60 mg/m^2 daily IV for 3 days. Depending upon bone marrow blast or investigator judgement participants had second induction i.e. received either same backbone therapy or cytarabine 100 mg/m^2 IV daily for 5 days and daunorubicin 60 mg/m^2 IV daily for 2 days. Participants with <5% bone marrow blasts entered into consolation phase- treated with either or both of following: 1) cytarabine 1 to 3 gm/m^2 IV for adults >=60 to <60 years twice daily on Days 1, 3, and 5 for 4 cycle (each cycle 28 day) or cytarabine per local prescribing information. 2) Received HSCT per local standard of care. Experimental Therapy: Participants were to receive Glasdegib 100 mg tablet PO QD from Day 1 of chemotherapy up to 28 days in both induction until 2 consecutive CRMRD-negative central laboratory results, whichever came first (1.6 year).
Participants received first induction therapy (28 days) (backbone chemotherapy+experimental therapy). Backbone chemotherapy: Cytarabine 100 mg/m^2 daily by IV infusion for 7 days along with daunorubicin 60 mg/m^2 daily IV for 3 days. Depending upon bone marrow blast or investigator judgement participants had second induction i.e. received either same backbone therapy or cytarabine 100 mg/m^2 IV daily for 5 days and daunorubicin 60 mg/m^2 IV daily for 2 days. Participants with <5% bone marrow blasts entered into consolation phase- treated with either or both of following: 1) cytarabine 1 to 3 gram/m^2 IV for adults >=60 to <60 years twice daily on Days 1, 3, and 5 for 4 cycle (each cycle 28 day) or cytarabine per local prescribing information. 2) Received HSCT per local standard of care. Experimental Therapy: Participants were to receive Glasdegib 100 mg matching placebo tablet PO QD from Day 1 of chemotherapy up to 28 days in both induction until 2 consecutive CR MRD-negative central laboratory results, whichever came first (1.8 year).
Overall Number of Participants Analyzed 201 203
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
49.3
(42.1 to 56.4)
47.3
(40.3 to 54.4)
8.Secondary Outcome
Title Non-intensive Study: Percentage of Participants With Complete Remission (CR) Including Negative Minimal Residual Disease (CRMRD-neg)
Hide Description CR was defined based on 2017 ELN recommendations. CR: Bone marrow blasts <5%; absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; ANC >=1.0*10^9/L; platelet count >=100*10^9/L. CRMRDneg: CR with negativity for a genetic marker by RT-qPCR, or CR with negativity by MFC.
Time Frame Day 1 up to maximum of 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
FA set included all randomized participants.
Arm/Group Title Non-intensive Study: Glasdegib + Azacitidine Non-intensive Study: Placebo + Azacitidine
Hide Arm/Group Description:
Participants received chemotherapy with azacitidine 75 mg/m^2 SC injection or IV infusion from Day 1 up to Day 7 of each cycle (28 day) and continued for at least 6 cycles or until unacceptable toxicity, participant refusal or death, whichever occurred first. Participants also were to receive glasdegib 100 mg PO QD from Day 1 of chemotherapy until clinical benefit or disease progression, unacceptable toxicity, consent withdrawal, or death, whichever occurred first. Eligible participants underwent HSCT per local standard of care and were to receive glasdegib unless 2 consecutive negative MRD assessments (3 year).
Participants received chemotherapy with azacitidine 75 mg/m^2 SC injection or IV infusion from Day 1 up to Day 7 of each cycle (28 day) and continued for at least 6 cycles or until unacceptable toxicity, participants refusal or death, whichever occurred first. Participants also received glasdegib 100 mg tablet matching placebo PO QD from Day 1 of chemotherapy until clinical benefit or disease progression, unacceptable toxicity, consent withdrawal, or death, whichever occurred first. Eligible participants underwent HSCT per local standard of care and were to receive glasdegib matching placebo unless 2 consecutive negative MRD assessments (2.44 year).
Overall Number of Participants Analyzed 163 162
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
19.6
(13.8 to 26.6)
13.0
(8.2 to 19.1)
9.Secondary Outcome
Title Intensive Study: Percentage of Participants With Complete Remission With Incomplete Hematologic Recovery (CRi)
Hide Description CR was defined based on 2017 ELN recommendations. CR: MRD (positive or unknown), bone marrow blasts <5%; absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; ANC less than (<) 1.0*10^9/L; platelet count <100 × 10^9/L. CRi (included CR [includes CRMRD-neg]): not qualifying for CR, neutropenia <1.0*10^9/L or platelets <100*10^9, absence of extramedullary disease, and absence of blasts with Auer rods.
Time Frame Day 1 up to maximum of 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
FA set included all randomized participants.
Arm/Group Title Intensive Study: Glasdegib + Cytarabine + Daunorubicin Intensive Study: Placebo + Cytarabine + Daunorubicin
Hide Arm/Group Description:
Participants received first induction therapy (28 days) (backbone chemotherapy+experimental therapy). Backbone chemotherapy: Cytarabine 100 mg/m^2 daily by IV infusion for 7 days along with daunorubicin 60 mg/m^2 daily IV for 3 days. Depending upon bone marrow blast or investigator judgement participants had second induction i.e. received either same backbone therapy or cytarabine 100 mg/m^2 IV daily for 5 days and daunorubicin 60 mg/m^2 IV daily for 2 days. Participants with <5% bone marrow blasts entered into consolation phase- treated with either or both of following: 1) cytarabine 1 to 3 gm/m^2 IV for adults >=60 to <60 years twice daily on Days 1, 3, and 5 for 4 cycle (each cycle 28 day) or cytarabine per local prescribing information. 2) Received HSCT per local standard of care. Experimental Therapy: Participants were to receive Glasdegib 100 mg tablet PO QD from Day 1 of chemotherapy up to 28 days in both induction until 2 consecutive CRMRD-negative central laboratory results, whichever came first (1.6 year).
Participants received first induction therapy (28 days) (backbone chemotherapy+experimental therapy). Backbone chemotherapy: Cytarabine 100 mg/m^2 daily by IV infusion for 7 days along with daunorubicin 60 mg/m^2 daily IV for 3 days. Depending upon bone marrow blast or investigator judgement participants had second induction i.e. received either same backbone therapy or cytarabine 100 mg/m^2 IV daily for 5 days and daunorubicin 60 mg/m^2 IV daily for 2 days. Participants with <5% bone marrow blasts entered into consolation phase- treated with either or both of following: 1) cytarabine 1 to 3 gram/m^2 IV for adults >=60 to <60 years twice daily on Days 1, 3, and 5 for 4 cycle (each cycle 28 day) or cytarabine per local prescribing information. 2) Received HSCT per local standard of care. Experimental Therapy: Participants were to receive Glasdegib 100 mg matching placebo tablet PO QD from Day 1 of chemotherapy up to 28 days in both induction until 2 consecutive CR MRD-negative central laboratory results, whichever came first (1.8 year).
Overall Number of Participants Analyzed 201 203
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
1.5
(0.3 to 4.3)
5.4
(2.7 to 9.5)
10.Secondary Outcome
Title Non-intensive Study: Percentage of Participants With Complete Remission With Incomplete Hematologic Recovery (CRi)
Hide Description CR was defined based on 2017 ELN recommendations. CR: MRD (positive or unknown), bone marrow blasts <5%; absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; ANC <1.0*10^9/L; platelet count <100 × 10^9/L. CRi (included CR [includes CRMRD-neg]): not qualifying for CR, neutrophil <0.5*10^9/L or platelets <50*10^9, absence of extramedullary disease, and absence of blasts with Auer rods.
Time Frame Day 1 up to maximum of 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
FA set included all randomized participants.
Arm/Group Title Non-intensive Study: Glasdegib + Azacitidine Non-intensive Study: Placebo + Azacitidine
Hide Arm/Group Description:
Participants received chemotherapy with azacitidine 75 mg/m^2 SC injection or IV infusion from Day 1 up to Day 7 of each cycle (28 day) and continued for at least 6 cycles or until unacceptable toxicity, participant refusal or death, whichever occurred first. Participants also were to receive glasdegib 100 mg PO QD from Day 1 of chemotherapy until clinical benefit or disease progression, unacceptable toxicity, consent withdrawal, or death, whichever occurred first. Eligible participants underwent HSCT per local standard of care and were to receive glasdegib unless 2 consecutive negative MRD assessments (3 year).
Participants received chemotherapy with azacitidine 75 mg/m^2 SC injection or IV infusion from Day 1 up to Day 7 of each cycle (28 day) and continued for at least 6 cycles or until unacceptable toxicity, participants refusal or death, whichever occurred first. Participants also received glasdegib 100 mg tablet matching placebo PO QD from Day 1 of chemotherapy until clinical benefit or disease progression, unacceptable toxicity, consent withdrawal, or death, whichever occurred first. Eligible participants underwent HSCT per local standard of care and were to receive glasdegib matching placebo unless 2 consecutive negative MRD assessments (2.44 year).
Overall Number of Participants Analyzed 163 162
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
2.5
(0.7 to 6.2)
4.9
(2.2 to 9.5)
11.Secondary Outcome
Title Intensive Study: Percentage of Participants With Morphologic Leukemia-free State (MLFS)
Hide Description MLFS was defined based on 2017 ELN recommendations. MLFS: MRD (positive or unknown), bone marrow blasts <5%, no hematologic recovery required, marrow should not be aplastic, at least 200 cells enumerated or cellularity absence of extramedullary disease >=10%, and absence of blasts with Auer rods.
Time Frame Day 1 up to maximum of 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
FA set included all randomized participants.
Arm/Group Title Intensive Study: Glasdegib + Cytarabine + Daunorubicin Intensive Study: Placebo + Cytarabine + Daunorubicin
Hide Arm/Group Description:
Participants received first induction therapy (28 days) (backbone chemotherapy+experimental therapy). Backbone chemotherapy: Cytarabine 100 mg/m^2 daily by IV infusion for 7 days along with daunorubicin 60 mg/m^2 daily IV for 3 days. Depending upon bone marrow blast or investigator judgement participants had second induction i.e. received either same backbone therapy or cytarabine 100 mg/m^2 IV daily for 5 days and daunorubicin 60 mg/m^2 IV daily for 2 days. Participants with <5% bone marrow blasts entered into consolation phase- treated with either or both of following: 1) cytarabine 1 to 3 gm/m^2 IV for adults >=60 to <60 years twice daily on Days 1, 3, and 5 for 4 cycle (each cycle 28 day) or cytarabine per local prescribing information. 2) Received HSCT per local standard of care. Experimental Therapy: Participants were to receive Glasdegib 100 mg tablet PO QD from Day 1 of chemotherapy up to 28 days in both induction until 2 consecutive CRMRD-negative central laboratory results, whichever came first (1.6 year).
Participants received first induction therapy (28 days) (backbone chemotherapy+experimental therapy). Backbone chemotherapy: Cytarabine 100 mg/m^2 daily by IV infusion for 7 days along with daunorubicin 60 mg/m^2 daily IV for 3 days. Depending upon bone marrow blast or investigator judgement participants had second induction i.e. received either same backbone therapy or cytarabine 100 mg/m^2 IV daily for 5 days and daunorubicin 60 mg/m^2 IV daily for 2 days. Participants with <5% bone marrow blasts entered into consolation phase- treated with either or both of following: 1) cytarabine 1 to 3 gram/m^2 IV for adults >=60 to <60 years twice daily on Days 1, 3, and 5 for 4 cycle (each cycle 28 day) or cytarabine per local prescribing information. 2) Received HSCT per local standard of care. Experimental Therapy: Participants were to receive Glasdegib 100 mg matching placebo tablet PO QD from Day 1 of chemotherapy up to 28 days in both induction until 2 consecutive CR MRD-negative central laboratory results, whichever came first (1.8 year).
Overall Number of Participants Analyzed 201 203
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
1.5
(0.3 to 4.3)
2.0
(0.5 to 5.0)
12.Secondary Outcome
Title Non-intensive Study: Percentage of Participants With Morphologic Leukemia-free State (MLFS)
Hide Description MLFS was defined based on 2017 ELN recommendations. MLFS: MRD (positive or unknown), bone marrow blasts <5%, no hematologic recovery required, marrow should not be aplastic, at least 200 cells enumerated or cellularity absence of extramedullary disease >=10%, and absence of blasts with Auer rods.
Time Frame Day 1 up to maximum of 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
FA set included all randomized participants.
Arm/Group Title Non-intensive Study: Glasdegib + Azacitidine Non-intensive Study: Placebo + Azacitidine
Hide Arm/Group Description:
Participants received chemotherapy with azacitidine 75 mg/m^2 SC injection or IV infusion from Day 1 up to Day 7 of each cycle (28 day) and continued for at least 6 cycles or until unacceptable toxicity, participant refusal or death, whichever occurred first. Participants also were to receive glasdegib 100 mg PO QD from Day 1 of chemotherapy until clinical benefit or disease progression, unacceptable toxicity, consent withdrawal, or death, whichever occurred first. Eligible participants underwent HSCT per local standard of care and were to receive glasdegib unless 2 consecutive negative MRD assessments (3 year).
Participants received chemotherapy with azacitidine 75 mg/m^2 SC injection or IV infusion from Day 1 up to Day 7 of each cycle (28 day) and continued for at least 6 cycles or until unacceptable toxicity, participants refusal or death, whichever occurred first. Participants also received glasdegib 100 mg tablet matching placebo PO QD from Day 1 of chemotherapy until clinical benefit or disease progression, unacceptable toxicity, consent withdrawal, or death, whichever occurred first. Eligible participants underwent HSCT per local standard of care and were to receive glasdegib matching placebo unless 2 consecutive negative MRD assessments (2.44 year).
Overall Number of Participants Analyzed 163 162
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
3.1
(1.0 to 7.0)
0.6
(0.0 to 3.4)
13.Secondary Outcome
Title Intensive Study: Percentage of Participants With Partial Remission (PR)
Hide Description PR was defined based on 2017 ELN recommendations. PR: MRD (positive or unknown); bone marrow blasts - decrease to 5-25% and decrease of pre-treatment bone marrow blast percentage by at least 50%; neutrophil count >=1.0*10^9/L; and platelets count >=100*10^9/L.
Time Frame Day 1 up to maximum of 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
FA set included all randomized participants.
Arm/Group Title Intensive Study: Glasdegib + Cytarabine + Daunorubicin Intensive Study: Placebo + Cytarabine + Daunorubicin
Hide Arm/Group Description:
Participants received first induction therapy (28 days) (backbone chemotherapy+experimental therapy). Backbone chemotherapy: Cytarabine 100 mg/m^2 daily by IV infusion for 7 days along with daunorubicin 60 mg/m^2 daily IV for 3 days. Depending upon bone marrow blast or investigator judgement participants had second induction i.e. received either same backbone therapy or cytarabine 100 mg/m^2 IV daily for 5 days and daunorubicin 60 mg/m^2 IV daily for 2 days. Participants with <5% bone marrow blasts entered into consolation phase- treated with either or both of following: 1) cytarabine 1 to 3 gm/m^2 IV for adults >=60 to <60 years twice daily on Days 1, 3, and 5 for 4 cycle (each cycle 28 day) or cytarabine per local prescribing information. 2) Received HSCT per local standard of care. Experimental Therapy: Participants were to receive Glasdegib 100 mg tablet PO QD from Day 1 of chemotherapy up to 28 days in both induction until 2 consecutive CRMRD-negative central laboratory results, whichever came first (1.6 year).
Participants received first induction therapy (28 days) (backbone chemotherapy+experimental therapy). Backbone chemotherapy: Cytarabine 100 mg/m^2 daily by IV infusion for 7 days along with daunorubicin 60 mg/m^2 daily IV for 3 days. Depending upon bone marrow blast or investigator judgement participants had second induction i.e. received either same backbone therapy or cytarabine 100 mg/m^2 IV daily for 5 days and daunorubicin 60 mg/m^2 IV daily for 2 days. Participants with <5% bone marrow blasts entered into consolation phase- treated with either or both of following: 1) cytarabine 1 to 3 gram/m^2 IV for adults >=60 to <60 years twice daily on Days 1, 3, and 5 for 4 cycle (each cycle 28 day) or cytarabine per local prescribing information. 2) Received HSCT per local standard of care. Experimental Therapy: Participants were to receive Glasdegib 100 mg matching placebo tablet PO QD from Day 1 of chemotherapy up to 28 days in both induction until 2 consecutive CR MRD-negative central laboratory results, whichever came first (1.8 year).
Overall Number of Participants Analyzed 201 203
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
5.0
(2.4 to 9.0)
4.4
(2.0 to 8.2)
14.Secondary Outcome
Title Non-intensive Study: Percentage of Participants With Partial Remission (PR)
Hide Description PR was defined based on 2017 ELN recommendations. PR: MRD (positive or unknown); bone marrow blasts - decrease to 5-25% and decrease of pre-treatment bone marrow blast percentage by at least 50%; neutrophil count >=1.0*10^9/L; and platelets count >=100*10^9/L.
Time Frame Day 1 up to maximum of 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
FA set included all randomized participants.
Arm/Group Title Non-intensive Study: Glasdegib + Azacitidine Non-intensive Study: Placebo + Azacitidine
Hide Arm/Group Description:
Participants received chemotherapy with azacitidine 75 mg/m^2 SC injection or IV infusion from Day 1 up to Day 7 of each cycle (28 day) and continued for at least 6 cycles or until unacceptable toxicity, participant refusal or death, whichever occurred first. Participants also were to receive glasdegib 100 mg PO QD from Day 1 of chemotherapy until clinical benefit or disease progression, unacceptable toxicity, consent withdrawal, or death, whichever occurred first. Eligible participants underwent HSCT per local standard of care and were to receive glasdegib unless 2 consecutive negative MRD assessments (3 year).
Participants received chemotherapy with azacitidine 75 mg/m^2 SC injection or IV infusion from Day 1 up to Day 7 of each cycle (28 day) and continued for at least 6 cycles or until unacceptable toxicity, participants refusal or death, whichever occurred first. Participants also received glasdegib 100 mg tablet matching placebo PO QD from Day 1 of chemotherapy until clinical benefit or disease progression, unacceptable toxicity, consent withdrawal, or death, whichever occurred first. Eligible participants underwent HSCT per local standard of care and were to receive glasdegib matching placebo unless 2 consecutive negative MRD assessments (2.44 year).
Overall Number of Participants Analyzed 163 162
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
2.5
(0.7 to 6.2)
4.9
(2.2 to 9.5)
15.Secondary Outcome
Title Non-intensive Study: Percentage of Participants With Complete Remission With Partial Hematologic Recovery (CRh)
Hide Description CRh: MRD (positive or unknown); bone marrow blasts <5%; assessed in non-intensive chemotherapy study only, not qualifying for CR, ie, both neutrophil >=0.5*10^9/L and platelets >=50*10^9/L must be met, but does not satisfy both neutrophils >=1*10^9/L and platelets >=100*10^9/L at the same time; absence of extramedullary disease; and absence of blasts with Auer rods.
Time Frame Day 1 up to maximum of 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
FA set included all randomized participants. This outcome measure was planned to be analyzed only in non-intensive study.
Arm/Group Title Non-intensive Study: Glasdegib + Azacitidine Non-intensive Study: Placebo + Azacitidine
Hide Arm/Group Description:
Participants received chemotherapy with azacitidine 75 mg/m^2 SC injection or IV infusion from Day 1 up to Day 7 of each cycle (28 day) and continued for at least 6 cycles or until unacceptable toxicity, participant refusal or death, whichever occurred first. Participants also were to receive glasdegib 100 mg PO QD from Day 1 of chemotherapy until clinical benefit or disease progression, unacceptable toxicity, consent withdrawal, or death, whichever occurred first. Eligible participants underwent HSCT per local standard of care and were to receive glasdegib unless 2 consecutive negative MRD assessments (3 year).
Participants received chemotherapy with azacitidine 75 mg/m^2 SC injection or IV infusion from Day 1 up to Day 7 of each cycle (28 day) and continued for at least 6 cycles or until unacceptable toxicity, participants refusal or death, whichever occurred first. Participants also received glasdegib 100 mg tablet matching placebo PO QD from Day 1 of chemotherapy until clinical benefit or disease progression, unacceptable toxicity, consent withdrawal, or death, whichever occurred first. Eligible participants underwent HSCT per local standard of care and were to receive glasdegib matching placebo unless 2 consecutive negative MRD assessments (2.44 year).
Overall Number of Participants Analyzed 163 162
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
3.1
(1.0 to 7.0)
3.1
(1.0 to 7.1)
16.Secondary Outcome
Title Intensive Study: Duration of Response (DoRi)
Hide Description DoRi: only defined for participants who have ever achieved CRi or better (included CR as well) on study as the time from date of first achieving CRi or better to the date of relapse after CRi or better or death due to any cause. CRi: not qualifying for CR, neutropenia <1.0*10^9/L or platelets <100*10^9, absence of extramedullary disease, and absence of blasts with Auer rods. CR was defined based on 2017 ELN recommendations. CR: Bone marrow blasts <5 %; absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; ANC >=1.0*10^9/L; platelet count >=100*10^9/L. Participants last known to be alive who were free from relapse after CRi or better were censored at the date of last disease assessment that verifies their status.
Time Frame From date of first achieving CRi or better to the date of relapse after CRi or better or death due to any cause (maximum up to 2 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The intensive cohort was terminated because of futility. Participants ended study intervention early and were not followed up as planned. Hence, DORi was not collected, analyzed and reported.
Arm/Group Title Intensive Study: Glasdegib + Cytarabine + Daunorubicin Intensive Study: Placebo + Cytarabine + Daunorubicin
Hide Arm/Group Description:
Participants received first induction therapy (28 days) (backbone chemotherapy+experimental therapy). Backbone chemotherapy: Cytarabine 100 mg/m^2 daily by IV infusion for 7 days along with daunorubicin 60 mg/m^2 daily IV for 3 days. Depending upon bone marrow blast or investigator judgement participants had second induction i.e. received either same backbone therapy or cytarabine 100 mg/m^2 IV daily for 5 days and daunorubicin 60 mg/m^2 IV daily for 2 days. Participants with <5% bone marrow blasts entered into consolation phase- treated with either or both of following: 1) cytarabine 1 to 3 gm/m^2 IV for adults >=60 to <60 years twice daily on Days 1, 3, and 5 for 4 cycle (each cycle 28 day) or cytarabine per local prescribing information. 2) Received HSCT per local standard of care. Experimental Therapy: Participants were to receive Glasdegib 100 mg tablet PO QD from Day 1 of chemotherapy up to 28 days in both induction until 2 consecutive CRMRD-negative central laboratory results, whichever came first (1.6 year).
Participants received first induction therapy (28 days) (backbone chemotherapy+experimental therapy). Backbone chemotherapy: Cytarabine 100 mg/m^2 daily by IV infusion for 7 days along with daunorubicin 60 mg/m^2 daily IV for 3 days. Depending upon bone marrow blast or investigator judgement participants had second induction i.e. received either same backbone therapy or cytarabine 100 mg/m^2 IV daily for 5 days and daunorubicin 60 mg/m^2 IV daily for 2 days. Participants with <5% bone marrow blasts entered into consolation phase- treated with either or both of following: 1) cytarabine 1 to 3 gram/m^2 IV for adults >=60 to <60 years twice daily on Days 1, 3, and 5 for 4 cycle (each cycle 28 day) or cytarabine per local prescribing information. 2) Received HSCT per local standard of care. Experimental Therapy: Participants were to receive Glasdegib 100 mg matching placebo tablet PO QD from Day 1 of chemotherapy up to 28 days in both induction until 2 consecutive CR MRD-negative central laboratory results, whichever came first (1.8 year).
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
17.Secondary Outcome
Title Non-intensive Study: Duration of Response (DoRi) or (DoRh)
Hide Description DoRi: only defined for participants who have ever achieved CRi or better (included CR and CRh) on study as the time from date of first achieving CRi or better to the date of relapse after CRi or better or death due to any cause. DoRh: participants who had ever achieved CRh or better (included CR) on study as the time from date of first achieving CRh or better to the date of disease progression, or relapse after CRh or better, or death due to any cause. CRi: not qualifying for CR, neutrophil <0.5*10^9/L or platelets <50*10^9, absence of extramedullary disease, and absence of blasts with Auer rods. CRh: MRD (positive or unknown); bone marrow blasts <5%; assessed in non-intensive chemotherapy study only, not qualifying for CR, ie, both neutrophil >=0.5*10^9/L and platelets >=50*10^9/L must be met, but does not satisfy both neutrophils >=1*10^9/L and platelets >=100*10^9/L at the same time; absence of extramedullary disease; and absence of blasts with Auer rods.
Time Frame From date of first achieving CRi/CRh or better to the date of relapse/disease progression after CRi/CRh or better or death due to any cause (maximum up to 3 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The non-intensive cohort was terminated because of futility. Participants ended study intervention early and were not followed up as planned. Hence, DORi and DoRh was not collected, analyzed and reported.
Arm/Group Title Non-intensive Study: Glasdegib + Azacitidine Non-intensive Study: Placebo + Azacitidine
Hide Arm/Group Description:
Participants received chemotherapy with azacitidine 75 mg/m^2 SC injection or IV infusion from Day 1 up to Day 7 of each cycle (28 day) and continued for at least 6 cycles or until unacceptable toxicity, participant refusal or death, whichever occurred first. Participants also were to receive glasdegib 100 mg PO QD from Day 1 of chemotherapy until clinical benefit or disease progression, unacceptable toxicity, consent withdrawal, or death, whichever occurred first. Eligible participants underwent HSCT per local standard of care and were to receive glasdegib unless 2 consecutive negative MRD assessments (3 year).
Participants received chemotherapy with azacitidine 75 mg/m^2 SC injection or IV infusion from Day 1 up to Day 7 of each cycle (28 day) and continued for at least 6 cycles or until unacceptable toxicity, participants refusal or death, whichever occurred first. Participants also received glasdegib 100 mg tablet matching placebo PO QD from Day 1 of chemotherapy until clinical benefit or disease progression, unacceptable toxicity, consent withdrawal, or death, whichever occurred first. Eligible participants underwent HSCT per local standard of care and were to receive glasdegib matching placebo unless 2 consecutive negative MRD assessments (2.44 year).
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
18.Secondary Outcome
Title Non-intensive Study: Time to Response
Hide Description TTRi:Participants who achieved CRi or better, as the time from date of randomization to first documentation of response(CRi or better).TTRh:Participants who achieved CRh or better, as the time from date of randomization to first documentation of response(CRh or better). CRi:not qualifying for CR, neutrophil<0.5*10^9/L or platelets<50*10^9, absence of extramedullary disease,absence of blasts with Auer rods. CR was defined based on 2017 ELN recommendations. CR: Bone marrow blasts <5 %; absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; ANC >=1.0*10^9/L; platelet count >=100*10^9/L. CRh: MRD (positive or unknown); bone marrow blasts <5%; assessed in non-intensive chemotherapy study only, not qualifying for CR, ie, both neutrophil >=0.5*10^9/L and platelets >=50*10^9/L must be met, but does not satisfy both neutrophils >=1*10^9/L and platelets >=100*10^9/L at the same time; absence of extramedullary disease; and absence of blasts with Auer rods.
Time Frame From the date of randomization to the first documentation of response (CRi/CRh or better) (maximum up to 3 years)
Hide Outcome Measure Data
Hide Analysis Population Description
FA set included all randomized participants.
Arm/Group Title Non-intensive Study: Glasdegib + Azacitidine Non-intensive Study: Placebo + Azacitidine
Hide Arm/Group Description:
Participants received chemotherapy with azacitidine 75 mg/m^2 SC injection or IV infusion from Day 1 up to Day 7 of each cycle (28 day) and continued for at least 6 cycles or until unacceptable toxicity, participant refusal or death, whichever occurred first. Participants also were to receive glasdegib 100 mg PO QD from Day 1 of chemotherapy until clinical benefit or disease progression, unacceptable toxicity, consent withdrawal, or death, whichever occurred first. Eligible participants underwent HSCT per local standard of care and were to receive glasdegib unless 2 consecutive negative MRD assessments (3 year).
Participants received chemotherapy with azacitidine 75 mg/m^2 SC injection or IV infusion from Day 1 up to Day 7 of each cycle (28 day) and continued for at least 6 cycles or until unacceptable toxicity, participants refusal or death, whichever occurred first. Participants also received glasdegib 100 mg tablet matching placebo PO QD from Day 1 of chemotherapy until clinical benefit or disease progression, unacceptable toxicity, consent withdrawal, or death, whichever occurred first. Eligible participants underwent HSCT per local standard of care and were to receive glasdegib matching placebo unless 2 consecutive negative MRD assessments (2.44 year).
Overall Number of Participants Analyzed 163 162
Mean (Standard Deviation)
Unit of Measure: Months
TTRi 4.057  (1.9532) 4.093  (2.1809)
TTRh 4.334  (1.8853) 4.146  (2.1540)
19.Secondary Outcome
Title Intensive Study: Event-free Survival (EFS)
Hide Description EFS: Time from the date of randomization to the date of treatment failure (TF), relapse from CR, or death from any cause, whichever comes first. TF was defined as failure to achieve CR during the induction cycle (including the re-induction cycle if there is one) and the event date for TF is the day of randomization. CR was defined based on 2017 ELN recommendations. CR: Bone marrow blasts <5%; absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; ANC >=1.0*10^9/L; platelet count >=100*10^9/L.
Time Frame From the date of randomization to the date of TF, relapse from CR, or death from any cause, whichever comes first (maximum up to 2 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The intensive cohort was terminated because of futility. Participants ended study intervention early and were not followed up as planned. Hence, EFS was not collected, analyzed and reported.
Arm/Group Title Intensive Study: Glasdegib + Cytarabine + Daunorubicin Intensive Study: Placebo + Cytarabine + Daunorubicin
Hide Arm/Group Description:
Participants received first induction therapy (28 days) (backbone chemotherapy+experimental therapy). Backbone chemotherapy: Cytarabine 100 mg/m^2 daily by IV infusion for 7 days along with daunorubicin 60 mg/m^2 daily IV for 3 days. Depending upon bone marrow blast or investigator judgement participants had second induction i.e. received either same backbone therapy or cytarabine 100 mg/m^2 IV daily for 5 days and daunorubicin 60 mg/m^2 IV daily for 2 days. Participants with <5% bone marrow blasts entered into consolation phase- treated with either or both of following: 1) cytarabine 1 to 3 gm/m^2 IV for adults >=60 to <60 years twice daily on Days 1, 3, and 5 for 4 cycle (each cycle 28 day) or cytarabine per local prescribing information. 2) Received HSCT per local standard of care. Experimental Therapy: Participants were to receive Glasdegib 100 mg tablet PO QD from Day 1 of chemotherapy up to 28 days in both induction until 2 consecutive CRMRD-negative central laboratory results, whichever came first (1.6 year).
Participants received first induction therapy (28 days) (backbone chemotherapy+experimental therapy). Backbone chemotherapy: Cytarabine 100 mg/m^2 daily by IV infusion for 7 days along with daunorubicin 60 mg/m^2 daily IV for 3 days. Depending upon bone marrow blast or investigator judgement participants had second induction i.e. received either same backbone therapy or cytarabine 100 mg/m^2 IV daily for 5 days and daunorubicin 60 mg/m^2 IV daily for 2 days. Participants with <5% bone marrow blasts entered into consolation phase- treated with either or both of following: 1) cytarabine 1 to 3 gram/m^2 IV for adults >=60 to <60 years twice daily on Days 1, 3, and 5 for 4 cycle (each cycle 28 day) or cytarabine per local prescribing information. 2) Received HSCT per local standard of care. Experimental Therapy: Participants were to receive Glasdegib 100 mg matching placebo tablet PO QD from Day 1 of chemotherapy up to 28 days in both induction until 2 consecutive CR MRD-negative central laboratory results, whichever came first (1.8 year).
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
20.Secondary Outcome
Title Non-intensive Study: Event-free Survival (EFS)
Hide Description EFS: Time from the date of randomization to the date of TF, relapse from CR, or death from any cause, whichever comes first. TF was defined as failure to achieve CR during the induction cycle (including the re-induction cycle if there is one) and the event date for TF is the day of randomization. CR was defined based on 2017 ELN recommendations. CR: Bone marrow blasts <5%; absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; ANC >=1.0*10^9/L; platelet count >=100*10^9/L.
Time Frame From the date of randomization to the date of TF, relapse from CR, or death from any cause, whichever comes first (maximum up to 3 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The non-intensive cohort was terminated because of futility. Participants ended study intervention early and were not followed up as planned. Hence, EFS was not collected, analyzed and reported.
Arm/Group Title Non-intensive Study: Glasdegib + Azacitidine Non-intensive Study: Placebo + Azacitidine
Hide Arm/Group Description:
Participants received chemotherapy with azacitidine 75 mg/m^2 SC injection or IV infusion from Day 1 up to Day 7 of each cycle (28 day) and continued for at least 6 cycles or until unacceptable toxicity, participant refusal or death, whichever occurred first. Participants also were to receive glasdegib 100 mg PO QD from Day 1 of chemotherapy until clinical benefit or disease progression, unacceptable toxicity, consent withdrawal, or death, whichever occurred first. Eligible participants underwent HSCT per local standard of care and were to receive glasdegib unless 2 consecutive negative MRD assessments (3 year).
Participants received chemotherapy with azacitidine 75 mg/m^2 SC injection or IV infusion from Day 1 up to Day 7 of each cycle (28 day) and continued for at least 6 cycles or until unacceptable toxicity, participants refusal or death, whichever occurred first. Participants also received glasdegib 100 mg tablet matching placebo PO QD from Day 1 of chemotherapy until clinical benefit or disease progression, unacceptable toxicity, consent withdrawal, or death, whichever occurred first. Eligible participants underwent HSCT per local standard of care and were to receive glasdegib matching placebo unless 2 consecutive negative MRD assessments (2.44 year).
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
21.Secondary Outcome
Title Intensive Study: MD Anderson Symptom Inventory -Acute Myelogenous Leukemia/Myelodysplastic Syndrome (MDASI-AML/MDS) Score
Hide Description MDASI-AML/MDS: consists of 23 items, 13-item core cancer symptoms (pain, fatigue, nausea, disturbed sleep, distress, shortness of breath, problem remembering, lack of appetite, drowsiness, dry mouth, sadness, vomiting, and numbness), 4-item AML/MDS specific symptoms (malaise, diarrhea, muscle weakness, and skin problems), and 6 areas of interference (general activity, mood, work, walking, relations with other people, and enjoyment of life). The 13 core symptoms and 6 core interference items had highest frequency and/or severity in participants with various cancers and treatment types. It was measured at severity of symptoms and related interference at their worst level in last 24 hours by asking participants to respond to each item on an 0-10 NRS, where 0 = "not present" or "did not interfere" and 10 = "worst" or "interfered completely".
Time Frame Day 1 up to maximum of 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
The intensive cohort was terminated because of futility. Participants ended study intervention early and were not followed up as planned. Hence, MDASI-AML/MDS was not collected, analyzed and reported.
Arm/Group Title Intensive Study: Glasdegib + Cytarabine + Daunorubicin Intensive Study: Placebo + Cytarabine + Daunorubicin
Hide Arm/Group Description:
Participants received first induction therapy (28 days) (backbone chemotherapy+experimental therapy). Backbone chemotherapy: Cytarabine 100 mg/m^2 daily by IV infusion for 7 days along with daunorubicin 60 mg/m^2 daily IV for 3 days. Depending upon bone marrow blast or investigator judgement participants had second induction i.e. received either same backbone therapy or cytarabine 100 mg/m^2 IV daily for 5 days and daunorubicin 60 mg/m^2 IV daily for 2 days. Participants with <5% bone marrow blasts entered into consolation phase- treated with either or both of following: 1) cytarabine 1 to 3 gm/m^2 IV for adults >=60 to <60 years twice daily on Days 1, 3, and 5 for 4 cycle (each cycle 28 day) or cytarabine per local prescribing information. 2) Received HSCT per local standard of care. Experimental Therapy: Participants were to receive Glasdegib 100 mg tablet PO QD from Day 1 of chemotherapy up to 28 days in both induction until 2 consecutive CRMRD-negative central laboratory results, whichever came first (1.6 year).
Participants received first induction therapy (28 days) (backbone chemotherapy+experimental therapy). Backbone chemotherapy: Cytarabine 100 mg/m^2 daily by IV infusion for 7 days along with daunorubicin 60 mg/m^2 daily IV for 3 days. Depending upon bone marrow blast or investigator judgement participants had second induction i.e. received either same backbone therapy or cytarabine 100 mg/m^2 IV daily for 5 days and daunorubicin 60 mg/m^2 IV daily for 2 days. Participants with <5% bone marrow blasts entered into consolation phase- treated with either or both of following: 1) cytarabine 1 to 3 gram/m^2 IV for adults >=60 to <60 years twice daily on Days 1, 3, and 5 for 4 cycle (each cycle 28 day) or cytarabine per local prescribing information. 2) Received HSCT per local standard of care. Experimental Therapy: Participants were to receive Glasdegib 100 mg matching placebo tablet PO QD from Day 1 of chemotherapy up to 28 days in both induction until 2 consecutive CR MRD-negative central laboratory results, whichever came first (1.8 year).
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
22.Secondary Outcome
Title Non-intensive Study: MD Anderson Symptom Inventory -Acute Myelogenous Leukemia/Myelodysplastic Syndrome (MDASI-AML/MDS) Score
Hide Description MDASI-AML/MDS: consists of 23 items, 13-item core cancer symptoms (pain, fatigue, nausea, disturbed sleep, distress, shortness of breath, problem remembering, lack of appetite, drowsiness, dry mouth, sadness, vomiting, and numbness), 4-item AML/MDS specific symptoms (malaise, diarrhea, muscle weakness, and skin problems), and 6 areas of interference (general activity, mood, work, walking, relations with other people, and enjoyment of life). The 13 core symptoms and 6 core interference items had highest frequency and/or severity in participants with various cancers and treatment types. It was measured at severity of symptoms and related interference at their worst level in last 24 hours by asking participants to respond to each item on an 0-10 NRS, where 0 = "not present" or "did not interfere" and 10 = "worst" or "interfered completely".
Time Frame Day 1 up to maximum of 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
The non-intensive cohort was terminated because of futility. Participants ended study intervention early and were not followed up as planned. Hence, MDASI-AML/MDS was not collected, analyzed and reported.
Arm/Group Title Non-intensive Study: Glasdegib + Azacitidine Non-intensive Study: Placebo + Azacitidine
Hide Arm/Group Description:
Participants received chemotherapy with azacitidine 75 mg/m^2 SC injection or IV infusion from Day 1 up to Day 7 of each cycle (28 day) and continued for at least 6 cycles or until unacceptable toxicity, participant refusal or death, whichever occurred first. Participants also were to receive glasdegib 100 mg PO QD from Day 1 of chemotherapy until clinical benefit or disease progression, unacceptable toxicity, consent withdrawal, or death, whichever occurred first. Eligible participants underwent HSCT per local standard of care and were to receive glasdegib unless 2 consecutive negative MRD assessments (3 year).
Participants received chemotherapy with azacitidine 75 mg/m^2 SC injection or IV infusion from Day 1 up to Day 7 of each cycle (28 day) and continued for at least 6 cycles or until unacceptable toxicity, participants refusal or death, whichever occurred first. Participants also received glasdegib 100 mg tablet matching placebo PO QD from Day 1 of chemotherapy until clinical benefit or disease progression, unacceptable toxicity, consent withdrawal, or death, whichever occurred first. Eligible participants underwent HSCT per local standard of care and were to receive glasdegib matching placebo unless 2 consecutive negative MRD assessments (2.44 year).
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
23.Secondary Outcome
Title Intensive Study: EuroQoL 5 Dimension Questionnaire 5-Level Version (EQ-5D-5L) Score
Hide Description EQ-5D-5L: brief, self-administered, validated and reliable generic health status instrument developed by the EuroQoL Group. It consists of the EQ-5D descriptive system and a visual analogue scale (VAS), the EuroQoL visual analogue scale (EQ-VAS). EQ-5D: descriptive system measures a participant's health state on 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Participant is asked to indicate his/her health state by rating each dimension on a 5-level scale (1=no problem, 5=extreme problem). This rating resulted in a 1-digit number expressing the level selected for that dimension. The digits for the 5 dimensions were combined in a 5-digit number describing the respondent's health state. The EQ-5D index scores ranges from 0 to 1, with 0=worst health state and 1=perfect health.
Time Frame Day 1 up to maximum of 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
The intensive cohort was terminated because of futility. Participants ended study intervention early and were not followed up as planned. Hence, EQ-5D-5L was not collected, analyzed and reported.
Arm/Group Title Intensive Study: Glasdegib + Cytarabine + Daunorubicin Intensive Study: Placebo + Cytarabine + Daunorubicin
Hide Arm/Group Description:
Participants received first induction therapy (28 days) (backbone chemotherapy+experimental therapy). Backbone chemotherapy: Cytarabine 100 mg/m^2 daily by IV infusion for 7 days along with daunorubicin 60 mg/m^2 daily IV for 3 days. Depending upon bone marrow blast or investigator judgement participants had second induction i.e. received either same backbone therapy or cytarabine 100 mg/m^2 IV daily for 5 days and daunorubicin 60 mg/m^2 IV daily for 2 days. Participants with <5% bone marrow blasts entered into consolation phase- treated with either or both of following: 1) cytarabine 1 to 3 gm/m^2 IV for adults >=60 to <60 years twice daily on Days 1, 3, and 5 for 4 cycle (each cycle 28 day) or cytarabine per local prescribing information. 2) Received HSCT per local standard of care. Experimental Therapy: Participants were to receive Glasdegib 100 mg tablet PO QD from Day 1 of chemotherapy up to 28 days in both induction until 2 consecutive CRMRD-negative central laboratory results, whichever came first (1.6 year).
Participants received first induction therapy (28 days) (backbone chemotherapy+experimental therapy). Backbone chemotherapy: Cytarabine 100 mg/m^2 daily by IV infusion for 7 days along with daunorubicin 60 mg/m^2 daily IV for 3 days. Depending upon bone marrow blast or investigator judgement participants had second induction i.e. received either same backbone therapy or cytarabine 100 mg/m^2 IV daily for 5 days and daunorubicin 60 mg/m^2 IV daily for 2 days. Participants with <5% bone marrow blasts entered into consolation phase- treated with either or both of following: 1) cytarabine 1 to 3 gram/m^2 IV for adults >=60 to <60 years twice daily on Days 1, 3, and 5 for 4 cycle (each cycle 28 day) or cytarabine per local prescribing information. 2) Received HSCT per local standard of care. Experimental Therapy: Participants were to receive Glasdegib 100 mg matching placebo tablet PO QD from Day 1 of chemotherapy up to 28 days in both induction until 2 consecutive CR MRD-negative central laboratory results, whichever came first (1.8 year).
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
24.Secondary Outcome
Title Non-intensive Study: EuroQoL 5 Dimension Questionnaire 5-Level Version (EQ-5D-5L) Score
Hide Description EQ-5D-5L: brief, self-administered, validated and reliable generic health status instrument developed by the EuroQoL group. It consists of the EQ-5D descriptive system and a VAS, EQ-VAS. EQ-5D: descriptive system measures a participant's health state on 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Participant is asked to indicate his/her health state by rating each dimension on a 5-level scale (1=no problem, 5=extreme problem). This rating resulted in a 1-digit number expressing the level selected for that dimension. The digits for the 5 dimensions were combined in a 5-digit number describing the respondent's health state. The EQ-5D index scores ranges from 0 to 1, with 0=worst health state and 1=perfect health.
Time Frame Day 1 up to maximum of 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
The non-intensive cohort was terminated because of futility. Participants ended study intervention early and were not followed up as planned. Hence, EQ-5D-5L was not collected, analyzed and reported.
Arm/Group Title Non-intensive Study: Glasdegib + Azacitidine Non-intensive Study: Placebo + Azacitidine
Hide Arm/Group Description:
Participants received chemotherapy with azacitidine 75 mg/m^2 SC injection or IV infusion from Day 1 up to Day 7 of each cycle (28 day) and continued for at least 6 cycles or until unacceptable toxicity, participant refusal or death, whichever occurred first. Participants also were to receive glasdegib 100 mg PO QD from Day 1 of chemotherapy until clinical benefit or disease progression, unacceptable toxicity, consent withdrawal, or death, whichever occurred first. Eligible participants underwent HSCT per local standard of care and were to receive glasdegib unless 2 consecutive negative MRD assessments (3 year).
Participants received chemotherapy with azacitidine 75 mg/m^2 SC injection or IV infusion from Day 1 up to Day 7 of each cycle (28 day) and continued for at least 6 cycles or until unacceptable toxicity, participants refusal or death, whichever occurred first. Participants also received glasdegib 100 mg tablet matching placebo PO QD from Day 1 of chemotherapy until clinical benefit or disease progression, unacceptable toxicity, consent withdrawal, or death, whichever occurred first. Eligible participants underwent HSCT per local standard of care and were to receive glasdegib matching placebo unless 2 consecutive negative MRD assessments (2.44 year).
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
25.Secondary Outcome
Title Intensive Study: EuroQoL Visual Analogue Scale (EQ-VAS)
Hide Description EQ-5D-5L: brief, self-administered, validated and reliable generic health status instrument developed by the EuroQoL group. It consists of the EQ-5D descriptive system and a VAS, EQ-VAS. EQ VAS records the respondent's self-rated health on a 20-cm vertical, VAS from 0 (worst imaginable health state) to 100 (best imaginable health state).
Time Frame Day 1 up to maximum of 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
The intensive cohort was terminated because of futility. Participants ended study intervention early and were not followed up as planned. Hence, EQ-VAS was not collected, analyzed and reported.
Arm/Group Title Intensive Study: Glasdegib + Cytarabine + Daunorubicin Intensive Study: Placebo + Cytarabine + Daunorubicin
Hide Arm/Group Description:
Participants received first induction therapy (28 days) (backbone chemotherapy+experimental therapy). Backbone chemotherapy: Cytarabine 100 mg/m^2 daily by IV infusion for 7 days along with daunorubicin 60 mg/m^2 daily IV for 3 days. Depending upon bone marrow blast or investigator judgement participants had second induction i.e. received either same backbone therapy or cytarabine 100 mg/m^2 IV daily for 5 days and daunorubicin 60 mg/m^2 IV daily for 2 days. Participants with <5% bone marrow blasts entered into consolation phase- treated with either or both of following: 1) cytarabine 1 to 3 gm/m^2 IV for adults >=60 to <60 years twice daily on Days 1, 3, and 5 for 4 cycle (each cycle 28 day) or cytarabine per local prescribing information. 2) Received HSCT per local standard of care. Experimental Therapy: Participants were to receive Glasdegib 100 mg tablet PO QD from Day 1 of chemotherapy up to 28 days in both induction until 2 consecutive CRMRD-negative central laboratory results, whichever came first (1.6 year).
Participants received first induction therapy (28 days) (backbone chemotherapy+experimental therapy). Backbone chemotherapy: Cytarabine 100 mg/m^2 daily by IV infusion for 7 days along with daunorubicin 60 mg/m^2 daily IV for 3 days. Depending upon bone marrow blast or investigator judgement participants had second induction i.e. received either same backbone therapy or cytarabine 100 mg/m^2 IV daily for 5 days and daunorubicin 60 mg/m^2 IV daily for 2 days. Participants with <5% bone marrow blasts entered into consolation phase- treated with either or both of following: 1) cytarabine 1 to 3 gram/m^2 IV for adults >=60 to <60 years twice daily on Days 1, 3, and 5 for 4 cycle (each cycle 28 day) or cytarabine per local prescribing information. 2) Received HSCT per local standard of care. Experimental Therapy: Participants were to receive Glasdegib 100 mg matching placebo tablet PO QD from Day 1 of chemotherapy up to 28 days in both induction until 2 consecutive CR MRD-negative central laboratory results, whichever came first (1.8 year).
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
26.Secondary Outcome
Title Non-intensive Study: EuroQoL Visual Analogue Scale (EQ-VAS)
Hide Description EQ-5D-5L: brief, self-administered, validated and reliable generic health status instrument developed by the EuroQoL group. It consists of the EQ-5D descriptive system and a VAS, EQ-VAS. EQ VAS records the respondent's self-rated health on a 20-cm vertical, VAS from 0 (worst imaginable health state) to 100 (best imaginable health state).
Time Frame Day 1 up to maximum of 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
The non-intensive cohort was terminated because of futility. Participants ended study intervention early and were not followed up as planned. Hence, EQ-VAS was not collected, analyzed and reported.
Arm/Group Title Non-intensive Study: Glasdegib + Azacitidine Non-intensive Study: Placebo + Azacitidine
Hide Arm/Group Description:
Participants received chemotherapy with azacitidine 75 mg/m^2 SC injection or IV infusion from Day 1 up to Day 7 of each cycle (28 day) and continued for at least 6 cycles or until unacceptable toxicity, participant refusal or death, whichever occurred first. Participants also were to receive glasdegib 100 mg PO QD from Day 1 of chemotherapy until clinical benefit or disease progression, unacceptable toxicity, consent withdrawal, or death, whichever occurred first. Eligible participants underwent HSCT per local standard of care and were to receive glasdegib unless 2 consecutive negative MRD assessments (3 year).
Participants received chemotherapy with azacitidine 75 mg/m^2 SC injection or IV infusion from Day 1 up to Day 7 of each cycle (28 day) and continued for at least 6 cycles or until unacceptable toxicity, participants refusal or death, whichever occurred first. Participants also received glasdegib 100 mg tablet matching placebo PO QD from Day 1 of chemotherapy until clinical benefit or disease progression, unacceptable toxicity, consent withdrawal, or death, whichever occurred first. Eligible participants underwent HSCT per local standard of care and were to receive glasdegib matching placebo unless 2 consecutive negative MRD assessments (2.44 year).
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
27.Secondary Outcome
Title Intensive Study: Participants Global Impression of Symptoms (PGIS)
Hide Description PGIS: is a single 1-item questionnaire designed to assess participant's overall impression of disease severity at a given point in time. It uses a 4-point Likert scale as follows: In the last 24 hours, symptoms are: 1-"absent (no symptoms)", 2-"mild", 3-" moderate", 4="severe".
Time Frame Day 1 up to maximum of 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
The intensive cohort was terminated because of futility. Participants ended study intervention early and were not followed up as planned. Hence, PGIS was not collected, analyzed and reported.
Arm/Group Title Intensive Study: Glasdegib + Cytarabine + Daunorubicin Intensive Study: Placebo + Cytarabine + Daunorubicin
Hide Arm/Group Description:
Participants received first induction therapy (28 days) (backbone chemotherapy+experimental therapy). Backbone chemotherapy: Cytarabine 100 mg/m^2 daily by IV infusion for 7 days along with daunorubicin 60 mg/m^2 daily IV for 3 days. Depending upon bone marrow blast or investigator judgement participants had second induction i.e. received either same backbone therapy or cytarabine 100 mg/m^2 IV daily for 5 days and daunorubicin 60 mg/m^2 IV daily for 2 days. Participants with <5% bone marrow blasts entered into consolation phase- treated with either or both of following: 1) cytarabine 1 to 3 gm/m^2 IV for adults >=60 to <60 years twice daily on Days 1, 3, and 5 for 4 cycle (each cycle 28 day) or cytarabine per local prescribing information. 2) Received HSCT per local standard of care. Experimental Therapy: Participants were to receive Glasdegib 100 mg tablet PO QD from Day 1 of chemotherapy up to 28 days in both induction until 2 consecutive CRMRD-negative central laboratory results, whichever came first (1.6 year).
Participants received first induction therapy (28 days) (backbone chemotherapy+experimental therapy). Backbone chemotherapy: Cytarabine 100 mg/m^2 daily by IV infusion for 7 days along with daunorubicin 60 mg/m^2 daily IV for 3 days. Depending upon bone marrow blast or investigator judgement participants had second induction i.e. received either same backbone therapy or cytarabine 100 mg/m^2 IV daily for 5 days and daunorubicin 60 mg/m^2 IV daily for 2 days. Participants with <5% bone marrow blasts entered into consolation phase- treated with either or both of following: 1) cytarabine 1 to 3 gram/m^2 IV for adults >=60 to <60 years twice daily on Days 1, 3, and 5 for 4 cycle (each cycle 28 day) or cytarabine per local prescribing information. 2) Received HSCT per local standard of care. Experimental Therapy: Participants were to receive Glasdegib 100 mg matching placebo tablet PO QD from Day 1 of chemotherapy up to 28 days in both induction until 2 consecutive CR MRD-negative central laboratory results, whichever came first (1.8 year).
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
28.Secondary Outcome
Title Non-intensive Study: Participants Global Impression of Symptoms (PGIS)
Hide Description PGIS: is a single 1-item questionnaire designed to assess participant's overall impression of disease severity at a given point in time. It uses a 4-point Likert scale as follows: In the last 24 hours, symptoms are: 1-"absent (no symptoms)", 2-"mild", 3-" moderate", 4="severe".
Time Frame Day 1 up to maximum of 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
The non-intensive cohort was terminated because of futility. Participants ended study intervention early and were not followed up as planned. Hence, PGIS was not collected, analyzed and reported.
Arm/Group Title Non-intensive Study: Glasdegib + Azacitidine Non-intensive Study: Placebo + Azacitidine
Hide Arm/Group Description:
Participants received chemotherapy with azacitidine 75 mg/m^2 SC injection or IV infusion from Day 1 up to Day 7 of each cycle (28 day) and continued for at least 6 cycles or until unacceptable toxicity, participant refusal or death, whichever occurred first. Participants also were to receive glasdegib 100 mg PO QD from Day 1 of chemotherapy until clinical benefit or disease progression, unacceptable toxicity, consent withdrawal, or death, whichever occurred first. Eligible participants underwent HSCT per local standard of care and were to receive glasdegib unless 2 consecutive negative MRD assessments (3 year).
Participants received chemotherapy with azacitidine 75 mg/m^2 SC injection or IV infusion from Day 1 up to Day 7 of each cycle (28 day) and continued for at least 6 cycles or until unacceptable toxicity, participants refusal or death, whichever occurred first. Participants also received glasdegib 100 mg tablet matching placebo PO QD from Day 1 of chemotherapy until clinical benefit or disease progression, unacceptable toxicity, consent withdrawal, or death, whichever occurred first. Eligible participants underwent HSCT per local standard of care and were to receive glasdegib matching placebo unless 2 consecutive negative MRD assessments (2.44 year).
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
29.Secondary Outcome
Title Intensive Study: Participants Global Impression of Change (PGIC)
Hide Description PGIC: a single-item questionnaire designed to assess the participant's overall sense of whether there has been a change since starting treatment as rated on a 7-point Likert scale anchored by (1) 'very much improved' to (7) 'very much worse', with (4) =' no change'. The PGIC is a measure of "participant rating of global improvement and satisfaction with treatment".
Time Frame Day 1 up to maximum of 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
The intensive cohort was terminated because of futility. Participants ended study intervention early and were not followed up as planned. Hence, PGIC was not collected, analyzed and reported.
Arm/Group Title Intensive Study: Glasdegib + Cytarabine + Daunorubicin Intensive Study: Placebo + Cytarabine + Daunorubicin
Hide Arm/Group Description:
Participants received first induction therapy (28 days) (backbone chemotherapy+experimental therapy). Backbone chemotherapy: Cytarabine 100 mg/m^2 daily by IV infusion for 7 days along with daunorubicin 60 mg/m^2 daily IV for 3 days. Depending upon bone marrow blast or investigator judgement participants had second induction i.e. received either same backbone therapy or cytarabine 100 mg/m^2 IV daily for 5 days and daunorubicin 60 mg/m^2 IV daily for 2 days. Participants with <5% bone marrow blasts entered into consolation phase- treated with either or both of following: 1) cytarabine 1 to 3 gm/m^2 IV for adults >=60 to <60 years twice daily on Days 1, 3, and 5 for 4 cycle (each cycle 28 day) or cytarabine per local prescribing information. 2) Received HSCT per local standard of care. Experimental Therapy: Participants were to receive Glasdegib 100 mg tablet PO QD from Day 1 of chemotherapy up to 28 days in both induction until 2 consecutive CRMRD-negative central laboratory results, whichever came first (1.6 year).
Participants received first induction therapy (28 days) (backbone chemotherapy+experimental therapy). Backbone chemotherapy: Cytarabine 100 mg/m^2 daily by IV infusion for 7 days along with daunorubicin 60 mg/m^2 daily IV for 3 days. Depending upon bone marrow blast or investigator judgement participants had second induction i.e. received either same backbone therapy or cytarabine 100 mg/m^2 IV daily for 5 days and daunorubicin 60 mg/m^2 IV daily for 2 days. Participants with <5% bone marrow blasts entered into consolation phase- treated with either or both of following: 1) cytarabine 1 to 3 gram/m^2 IV for adults >=60 to <60 years twice daily on Days 1, 3, and 5 for 4 cycle (each cycle 28 day) or cytarabine per local prescribing information. 2) Received HSCT per local standard of care. Experimental Therapy: Participants were to receive Glasdegib 100 mg matching placebo tablet PO QD from Day 1 of chemotherapy up to 28 days in both induction until 2 consecutive CR MRD-negative central laboratory results, whichever came first (1.8 year).
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
30.Secondary Outcome
Title Non-intensive Study: Participants Global Impression of Change (PGIC)
Hide Description PGIC: a single-item questionnaire designed to assess the participant's overall sense of whether there has been a change since starting treatment as rated on a 7-point Likert scale anchored by (1) 'very much improved' to (7) 'very much worse', with (4) =' no change'. The PGIC is a measure of "participant rating of global improvement and satisfaction with treatment".
Time Frame Day 1 up to maximum of 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
The non-intensive cohort was terminated because of futility. Participants ended study intervention early and were not followed up as planned. Hence, PGIC was not collected, analyzed and reported.
Arm/Group Title Non-intensive Study: Glasdegib + Azacitidine Non-intensive Study: Placebo + Azacitidine
Hide Arm/Group Description:
Participants received chemotherapy with azacitidine 75 mg/m^2 SC injection or IV infusion from Day 1 up to Day 7 of each cycle (28 day) and continued for at least 6 cycles or until unacceptable toxicity, participant refusal or death, whichever occurred first. Participants also were to receive glasdegib 100 mg PO QD from Day 1 of chemotherapy until clinical benefit or disease progression, unacceptable toxicity, consent withdrawal, or death, whichever occurred first. Eligible participants underwent HSCT per local standard of care and were to receive glasdegib unless 2 consecutive negative MRD assessments (3 year).
Participants received chemotherapy with azacitidine 75 mg/m^2 SC injection or IV infusion from Day 1 up to Day 7 of each cycle (28 day) and continued for at least 6 cycles or until unacceptable toxicity, participants refusal or death, whichever occurred first. Participants also received glasdegib 100 mg tablet matching placebo PO QD from Day 1 of chemotherapy until clinical benefit or disease progression, unacceptable toxicity, consent withdrawal, or death, whichever occurred first. Eligible participants underwent HSCT per local standard of care and were to receive glasdegib matching placebo unless 2 consecutive negative MRD assessments (2.44 year).
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
31.Secondary Outcome
Title Intensive Study: Number of Participants With Adverse Events (AEs),Serious Adverse Events (SAEs) and According to Severity AEs Graded by NCI CTCAE v.4.03
Hide Description AE: any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. SAE: any AE, regardless of dose, that led to death; was life-threatening; required hospitalization or prolonged hospitalization; led to persistent or significant incapacity or led to congenital anomaly or birth defect. AEs included SAEs and all non-SAEs. NCI CTCAE v.4.03, Grade 3=severe adverse event, Grade 4= life threatening consequences; urgent intervention indicated, Grade 5= death related to adverse event.
Time Frame Day 1 up to maximum of 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis (SA) set included all participants who received at least one dose of study drug.
Arm/Group Title Intensive Study: Glasdegib + Cytarabine + Daunorubicin Intensive Study: Placebo + Cytarabine + Daunorubicin
Hide Arm/Group Description:
Participants received first induction therapy (28 days) (backbone chemotherapy+experimental therapy). Backbone chemotherapy: Cytarabine 100 mg/m^2 daily by IV infusion for 7 days along with daunorubicin 60 mg/m^2 daily IV for 3 days. Depending upon bone marrow blast or investigator judgement participants had second induction i.e. received either same backbone therapy or cytarabine 100 mg/m^2 IV daily for 5 days and daunorubicin 60 mg/m^2 IV daily for 2 days. Participants with <5% bone marrow blasts entered into consolation phase- treated with either or both of following: 1) cytarabine 1 to 3 gm/m^2 IV for adults >=60 to <60 years twice daily on Days 1, 3, and 5 for 4 cycle (each cycle 28 day) or cytarabine per local prescribing information. 2) Received HSCT per local standard of care. Experimental Therapy: Participants were to receive Glasdegib 100 mg tablet PO QD from Day 1 of chemotherapy up to 28 days in both induction until 2 consecutive CRMRD-negative central laboratory results, whichever came first (1.6 year).
Participants received first induction therapy (28 days) (backbone chemotherapy+experimental therapy). Backbone chemotherapy: Cytarabine 100 mg/m^2 daily by IV infusion for 7 days along with daunorubicin 60 mg/m^2 daily IV for 3 days. Depending upon bone marrow blast or investigator judgement participants had second induction i.e. received either same backbone therapy or cytarabine 100 mg/m^2 IV daily for 5 days and daunorubicin 60 mg/m^2 IV daily for 2 days. Participants with <5% bone marrow blasts entered into consolation phase- treated with either or both of following: 1) cytarabine 1 to 3 gram/m^2 IV for adults >=60 to <60 years twice daily on Days 1, 3, and 5 for 4 cycle (each cycle 28 day) or cytarabine per local prescribing information. 2) Received HSCT per local standard of care. Experimental Therapy: Participants were to receive Glasdegib 100 mg matching placebo tablet PO QD from Day 1 of chemotherapy up to 28 days in both induction until 2 consecutive CR MRD-negative central laboratory results, whichever came first (1.8 year).
Overall Number of Participants Analyzed 198 201
Measure Type: Count of Participants
Unit of Measure: Participants
AEs
196
  99.0%
198
  98.5%
SAEs
86
  43.4%
92
  45.8%
Grade 3 or 4 AE
173
  87.4%
169
  84.1%
Grade 5 AE
16
   8.1%
20
  10.0%
32.Secondary Outcome
Title Non-intensive Study: Number of Participants With Adverse Events (AEs),Serious Adverse Events (SAEs) and According to Severity AEs Graded by NCI CTCAE v.4.03
Hide Description AE: any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. SAE: any AE, regardless of dose, that led to death; was life-threatening; required hospitalization or prolonged hospitalization; led to persistent or significant incapacity or led to congenital anomaly or birth defect. AEs included SAEs and all non-SAEs. NCI CTCAE v.4.03, Grade 3=severe adverse event, Grade 4= life threatening consequences; urgent intervention indicated, Grade 5= death related to adverse event.
Time Frame Day 1 up to maximum of 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
SA set included all participants who received at least one dose of study drug.
Arm/Group Title Non-intensive Study: Glasdegib + Azacitidine Non-intensive Study: Placebo + Azacitidine
Hide Arm/Group Description:
Participants received chemotherapy with azacitidine 75 mg/m^2 SC injection or IV infusion from Day 1 up to Day 7 of each cycle (28 day) and continued for at least 6 cycles or until unacceptable toxicity, participant refusal or death, whichever occurred first. Participants also were to receive glasdegib 100 mg PO QD from Day 1 of chemotherapy until clinical benefit or disease progression, unacceptable toxicity, consent withdrawal, or death, whichever occurred first. Eligible participants underwent HSCT per local standard of care and were to receive glasdegib unless 2 consecutive negative MRD assessments (3 year).
Participants received chemotherapy with azacitidine 75 mg/m^2 SC injection or IV infusion from Day 1 up to Day 7 of each cycle (28 day) and continued for at least 6 cycles or until unacceptable toxicity, participants refusal or death, whichever occurred first. Participants also received glasdegib 100 mg tablet matching placebo PO QD from Day 1 of chemotherapy until clinical benefit or disease progression, unacceptable toxicity, consent withdrawal, or death, whichever occurred first. Eligible participants underwent HSCT per local standard of care and were to receive glasdegib matching placebo unless 2 consecutive negative MRD assessments (2.44 year).
Overall Number of Participants Analyzed 162 160
Measure Type: Count of Participants
Unit of Measure: Participants
AEs
161
  99.4%
158
  98.8%
SAEs
117
  72.2%
124
  77.5%
Grade 3 or 4 AE
106
  65.4%
100
  62.5%
Grade 5 AE
50
  30.9%
52
  32.5%
33.Secondary Outcome
Title Intensive Study: Number of Participants With Treatment Related Adverse Events (AEs) and Serious Adverse Events (SAEs) Graded by NCI CTCAE v.4.03
Hide Description A treatment-related AE was any untoward medical occurrence attributed to the study drug in a participant who received study drug. SAE: any AE, regardless of dose, that led to death; was life-threatening; required hospitalization or prolonged hospitalization; led to persistent or significant incapacity or led to congenital anomaly or birth defect. NCI CTCAE v.4.03, Grade 3=severe adverse event, Grade 4= life threatening consequences; urgent intervention indicated, Grade 5= death related to adverse event.
Time Frame Day 1 up to maximum of 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
SA set included all participants who received at least one dose of study drug.
Arm/Group Title Intensive Study: Glasdegib + Cytarabine + Daunorubicin Intensive Study: Placebo + Cytarabine + Daunorubicin
Hide Arm/Group Description:
Participants received first induction therapy (28 days) (backbone chemotherapy+experimental therapy). Backbone chemotherapy: Cytarabine 100 mg/m^2 daily by IV infusion for 7 days along with daunorubicin 60 mg/m^2 daily IV for 3 days. Depending upon bone marrow blast or investigator judgement participants had second induction i.e. received either same backbone therapy or cytarabine 100 mg/m^2 IV daily for 5 days and daunorubicin 60 mg/m^2 IV daily for 2 days. Participants with <5% bone marrow blasts entered into consolation phase- treated with either or both of following: 1) cytarabine 1 to 3 gm/m^2 IV for adults >=60 to <60 years twice daily on Days 1, 3, and 5 for 4 cycle (each cycle 28 day) or cytarabine per local prescribing information. 2) Received HSCT per local standard of care. Experimental Therapy: Participants were to receive Glasdegib 100 mg tablet PO QD from Day 1 of chemotherapy up to 28 days in both induction until 2 consecutive CRMRD-negative central laboratory results, whichever came first (1.6 year).
Participants received first induction therapy (28 days) (backbone chemotherapy+experimental therapy). Backbone chemotherapy: Cytarabine 100 mg/m^2 daily by IV infusion for 7 days along with daunorubicin 60 mg/m^2 daily IV for 3 days. Depending upon bone marrow blast or investigator judgement participants had second induction i.e. received either same backbone therapy or cytarabine 100 mg/m^2 IV daily for 5 days and daunorubicin 60 mg/m^2 IV daily for 2 days. Participants with <5% bone marrow blasts entered into consolation phase- treated with either or both of following: 1) cytarabine 1 to 3 gram/m^2 IV for adults >=60 to <60 years twice daily on Days 1, 3, and 5 for 4 cycle (each cycle 28 day) or cytarabine per local prescribing information. 2) Received HSCT per local standard of care. Experimental Therapy: Participants were to receive Glasdegib 100 mg matching placebo tablet PO QD from Day 1 of chemotherapy up to 28 days in both induction until 2 consecutive CR MRD-negative central laboratory results, whichever came first (1.8 year).
Overall Number of Participants Analyzed 198 201
Measure Type: Count of Participants
Unit of Measure: Participants
Treatment related AEs
181
  91.4%
188
  93.5%
Treatment related SAEs
48
  24.2%
60
  29.9%
Grade 3 or 4 AE
161
  81.3%
149
  74.1%
Grade 5 AE
5
   2.5%
8
   4.0%
34.Secondary Outcome
Title Non-intensive Study: Number of Participants With Treatment Related Adverse Events (AEs) and Serious Adverse Events (SAEs) Graded by NCI CTCAE v.4.03
Hide Description A treatment-related AE was any untoward medical occurrence attributed to the study drug in a participant who received study drug. SAE: any AE, regardless of dose, that led to death; was life-threatening; required hospitalization or prolonged hospitalization; led to persistent or significant incapacity or led to congenital anomaly or birth defect. NCI CTCAE v4.03, Grade 3=severe adverse event, Grade 4= life threatening consequences; urgent intervention indicated, Grade 5= death related to adverse event.
Time Frame Day 1 up to maximum of 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
SA set included all participants who received at least one dose of study drug.
Arm/Group Title Non-intensive Study: Glasdegib + Azacitidine Non-intensive Study: Placebo + Azacitidine
Hide Arm/Group Description:
Participants received chemotherapy with azacitidine 75 mg/m^2 SC injection or IV infusion from Day 1 up to Day 7 of each cycle (28 day) and continued for at least 6 cycles or until unacceptable toxicity, participant refusal or death, whichever occurred first. Participants also were to receive glasdegib 100 mg PO QD from Day 1 of chemotherapy until clinical benefit or disease progression, unacceptable toxicity, consent withdrawal, or death, whichever occurred first. Eligible participants underwent HSCT per local standard of care and were to receive glasdegib unless 2 consecutive negative MRD assessments (3 year).
Participants received chemotherapy with azacitidine 75 mg/m^2 SC injection or IV infusion from Day 1 up to Day 7 of each cycle (28 day) and continued for at least 6 cycles or until unacceptable toxicity, participants refusal or death, whichever occurred first. Participants also received glasdegib 100 mg tablet matching placebo PO QD from Day 1 of chemotherapy until clinical benefit or disease progression, unacceptable toxicity, consent withdrawal, or death, whichever occurred first. Eligible participants underwent HSCT per local standard of care and were to receive glasdegib matching placebo unless 2 consecutive negative MRD assessments (2.44 year).
Overall Number of Participants Analyzed 162 160
Measure Type: Count of Participants
Unit of Measure: Participants
Treatment related AEs
133
  82.1%
123
  76.9%
Treatment related SAEs
45
  27.8%
37
  23.1%
Grade 3 or 4 AE
97
  59.9%
72
  45.0%
Grade 5 AE
4
   2.5%
4
   2.5%
35.Secondary Outcome
Title Intensive Study: Number of Participants With Shift From Baseline in Hematological Laboratory Abnormalities Graded by NCI CTCAE v.4.03
Hide Description Hematology laboratory test included: anemia, hemoglobin increased, international normalized ratio (INR) increased, lymphocyte count decreased, lymphocyte count increased, neutrophil count decreased, platelet count decreased, and white blood cell decreased. Laboratory results were categorically summarized according to the NCI-CTCAE criteria v4.03. Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling. Number of participants with shift from baseline for hematology laboratory test were assessed. Only those laboratory test parameters in which at least 1 participant had data were reported.
Time Frame Day 1 up to maximum of 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
SA set included all participants who received at least one dose of study drug. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure and "Number Analyzed" signifies participants evaluable for specified rows.
Arm/Group Title Intensive Study: Glasdegib + Cytarabine + Daunorubicin Intensive Study: Placebo + Cytarabine + Daunorubicin
Hide Arm/Group Description:
Participants received first induction therapy (28 days) (backbone chemotherapy+experimental therapy). Backbone chemotherapy: Cytarabine 100 mg/m^2 daily by IV infusion for 7 days along with daunorubicin 60 mg/m^2 daily IV for 3 days. Depending upon bone marrow blast or investigator judgement participants had second induction i.e. received either same backbone therapy or cytarabine 100 mg/m^2 IV daily for 5 days and daunorubicin 60 mg/m^2 IV daily for 2 days. Participants with <5% bone marrow blasts entered into consolation phase- treated with either or both of following: 1) cytarabine 1 to 3 gm/m^2 IV for adults >=60 to <60 years twice daily on Days 1, 3, and 5 for 4 cycle (each cycle 28 day) or cytarabine per local prescribing information. 2) Received HSCT per local standard of care. Experimental Therapy: Participants were to receive Glasdegib 100 mg tablet PO QD from Day 1 of chemotherapy up to 28 days in both induction until 2 consecutive CRMRD-negative central laboratory results, whichever came first (1.6 year).
Participants received first induction therapy (28 days) (backbone chemotherapy+experimental therapy). Backbone chemotherapy: Cytarabine 100 mg/m^2 daily by IV infusion for 7 days along with daunorubicin 60 mg/m^2 daily IV for 3 days. Depending upon bone marrow blast or investigator judgement participants had second induction i.e. received either same backbone therapy or cytarabine 100 mg/m^2 IV daily for 5 days and daunorubicin 60 mg/m^2 IV daily for 2 days. Participants with <5% bone marrow blasts entered into consolation phase- treated with either or both of following: 1) cytarabine 1 to 3 gram/m^2 IV for adults >=60 to <60 years twice daily on Days 1, 3, and 5 for 4 cycle (each cycle 28 day) or cytarabine per local prescribing information. 2) Received HSCT per local standard of care. Experimental Therapy: Participants were to receive Glasdegib 100 mg matching placebo tablet PO QD from Day 1 of chemotherapy up to 28 days in both induction until 2 consecutive CR MRD-negative central laboratory results, whichever came first (1.8 year).
Overall Number of Participants Analyzed 196 197
Measure Type: Count of Participants
Unit of Measure: Participants
Anemia: Missing (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 196 participants 197 participants
0
   0.0%
2
   1.0%
Anemia: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 196 participants 197 participants
27
  13.8%
14
   7.1%
Anemia: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 196 participants 197 participants
113
  57.7%
103
  52.3%
Anemia: Grade 3/4 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 196 participants 197 participants
4
   2.0%
5
   2.5%
Anemia: Grade 3/4 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 196 participants 197 participants
52
  26.5%
73
  37.1%
Hemoglobin increased: Missing (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 196 participants 197 participants
0
   0.0%
2
   1.0%
Hemoglobin increased: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 196 participants 197 participants
194
  99.0%
194
  98.5%
Hemoglobin increased: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 196 participants 197 participants
2
   1.0%
1
   0.5%
INR increased: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 3 participants 1 participants
3
 100.0%
1
 100.0%
Lymphocyte count decreased: Missing (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 193 participants 193 participants
0
   0.0%
2
   1.0%
Lymphocyte count decreased: Missing (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 193 participants 193 participants
0
   0.0%
4
   2.1%
Lymphocyte count decreased: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 193 participants 193 participants
21
  10.9%
26
  13.5%
Lymphocyte count decreased: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 193 participants 193 participants
160
  82.9%
152
  78.8%
Lymphocyte count decreased: Grade 3/4 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 193 participants 193 participants
1
   0.5%
0
   0.0%
Lymphocyte count decreased: Grade 3/4 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 193 participants 193 participants
11
   5.7%
9
   4.7%
Lymphocyte count increased: Missing (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 193 participants 193 participants
0
   0.0%
6
   3.1%
Lymphocyte count increased: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 193 participants 193 participants
185
  95.9%
180
  93.3%
Lymphocyte count increased: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 193 participants 193 participants
6
   3.1%
4
   2.1%
Lymphocyte count increased: Grade 3/4 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 193 participants 193 participants
1
   0.5%
3
   1.6%
Lymphocyte count increased: Grade 3/4 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 193 participants 193 participants
1
   0.5%
0
   0.0%
Neutrophil count decreased: Missing (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 194 participants 193 participants
0
   0.0%
4
   2.1%
Neutrophil count decreased: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 194 participants 193 participants
4
   2.1%
2
   1.0%
Neutrophil count decreased: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 194 participants 193 participants
85
  43.8%
79
  40.9%
Neutrophil count decreased: Grade 3/4 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 194 participants 193 participants
0
   0.0%
2
   1.0%
Neutrophil count decreased: Grade 3/4 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 194 participants 193 participants
105
  54.1%
106
  54.9%
Platelet count decreased: Missing (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 196 participants 197 participants
1
   0.5%
2
   1.0%
Platelet count decreased: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 196 participants 197 participants
98
  50.0%
100
  50.8%
Platelet count decreased: Grade 3/4 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 196 participants 197 participants
97
  49.5%
95
  48.2%
White blood cell decreased: Missing (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 196 participants 197 participants
1
   0.5%
4
   2.0%
White blood cell decreased: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 196 participants 197 participants
3
   1.5%
2
   1.0%
White blood cell decreased: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 196 participants 197 participants
155
  79.1%
156
  79.2%
White blood cell decreased: Grade 3/4 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 196 participants 197 participants
37
  18.9%
35
  17.8%
36.Secondary Outcome
Title Non-intensive Study: Number of Participants With Shift From Baseline in Hematological Laboratory Abnormalities Graded by NCI CTCAE v.4.03
Hide Description Hematology laboratory test included: anemia, hemoglobin increased, INR increased, lymphocyte count decreased, lymphocyte count increased, neutrophil count decreased, platelet count decreased, and white blood cell decreased. Laboratory results were categorically summarized according to the NCI-CTCAE criteria v4.03. Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling. Number of participants with shift from baseline for hematology laboratory test were assessed. Only those laboratory test parameters in which at least 1 participant had data were reported.
Time Frame Day 1 up to maximum of 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
SA set included all participants who received at least one dose of study drug. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure and "Number Analyzed" signifies participants evaluable for specified rows.
Arm/Group Title Non-intensive Study: Glasdegib + Azacitidine Non-intensive Study: Placebo + Azacitidine
Hide Arm/Group Description:
Participants received chemotherapy with azacitidine 75 mg/m^2 SC injection or IV infusion from Day 1 up to Day 7 of each cycle (28 day) and continued for at least 6 cycles or until unacceptable toxicity, participant refusal or death, whichever occurred first. Participants also were to receive glasdegib 100 mg PO QD from Day 1 of chemotherapy until clinical benefit or disease progression, unacceptable toxicity, consent withdrawal, or death, whichever occurred first. Eligible participants underwent HSCT per local standard of care and were to receive glasdegib unless 2 consecutive negative MRD assessments (3 year).
Participants received chemotherapy with azacitidine 75 mg/m^2 SC injection or IV infusion from Day 1 up to Day 7 of each cycle (28 day) and continued for at least 6 cycles or until unacceptable toxicity, participants refusal or death, whichever occurred first. Participants also received glasdegib 100 mg tablet matching placebo PO QD from Day 1 of chemotherapy until clinical benefit or disease progression, unacceptable toxicity, consent withdrawal, or death, whichever occurred first. Eligible participants underwent HSCT per local standard of care and were to receive glasdegib matching placebo unless 2 consecutive negative MRD assessments (2.44 year).
Overall Number of Participants Analyzed 162 160
Measure Type: Count of Participants
Unit of Measure: Participants
Anemia: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 160 participants 160 participants
29
  18.1%
41
  25.6%
Anemia: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 160 participants 160 participants
97
  60.6%
87
  54.4%
Anemia: Grade 3/4 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 160 participants 160 participants
5
   3.1%
1
   0.6%
Anemia: Grade 3/4 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 160 participants 160 participants
29
  18.1%
31
  19.4%
Hemoglobin increased: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 160 participants 160 participants
160
 100.0%
159
  99.4%
Hemoglobin increased: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 160 participants 160 participants
0
   0.0%
1
   0.6%
Lymphocyte count decreased: Missing (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 159 participants 160 participants
2
   1.3%
0
   0.0%
Lymphocyte count decreased: Missing (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 159 participants 160 participants
1
   0.6%
0
   0.0%
Lymphocyte count decreased: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 159 participants 160 participants
96
  60.4%
89
  55.6%
Lymphocyte count decreased: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 159 participants 160 participants
51
  32.1%
54
  33.8%
Lymphocyte count decreased: Grade 3/4 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 159 participants 160 participants
2
   1.3%
4
   2.5%
Lymphocyte count decreased: Grade 3/4 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 159 participants 160 participants
7
   4.4%
13
   8.1%
Lymphocyte count increased: Missing (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 159 participants 160 participants
3
   1.9%
0
   0.0%
Lymphocyte count increased: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 159 participants 160 participants
147
  92.5%
157
  98.1%
Lymphocyte count increased: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 159 participants 160 participants
7
   4.4%
3
   1.9%
Lymphocyte count increased: Grade 3/4 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 159 participants 160 participants
2
   1.3%
0
   0.0%
Neutrophil count decreased: Missing (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 159 participants 160 participants
4
   2.5%
0
   0.0%
Neutrophil count decreased: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 159 participants 160 participants
13
   8.2%
22
  13.8%
Neutrophil count decreased: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 159 participants 160 participants
48
  30.2%
40
  25.0%
Neutrophil count decreased: Grade 3/4 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 159 participants 160 participants
2
   1.3%
1
   0.6%
Neutrophil count decreased: Grade 3/4 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 159 participants 160 participants
92
  57.9%
97
  60.6%
Platelet count decreased: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 160 participants 160 participants
21
  13.1%
28
  17.5%
Platelet count decreased: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 160 participants 160 participants
55
  34.4%
64
  40.0%
Platelet count decreased: Grade 3/4 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 160 participants 160 participants
1
   0.6%
0
   0.0%
Platelet count decreased: Grade 3/4 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 160 participants 160 participants
83
  51.9%
68
  42.5%
White blood cell decreased: Missing (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 160 participants 159 participants
1
   0.6%
0
   0.0%
White blood cell decreased: Missing (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 160 participants 159 participants
1
   0.6%
0
   0.0%
White blood cell decreased: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 160 participants 159 participants
43
  26.9%
48
  30.2%
White blood cell decreased: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 160 participants 159 participants
70
  43.8%
62
  39.0%
White blood cell decreased: Grade 3/4 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 160 participants 159 participants
0
   0.0%
1
   0.6%
White blood cell decreased: Grade 3/4 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 160 participants 159 participants
45
  28.1%
48
  30.2%
37.Secondary Outcome
Title Intensive Study: Number of Participants With Shift From Baseline in Chemistry Laboratory Abnormalities Graded by NCI CTCAE v.4.03
Hide Description Chemistry laboratory test included: alanine aminotransferase increased, alkaline phosphatase increased, aspartate aminotransferase increased, blood bilirubin increased, chronic kidney disease, creatine phosphokinase (CPK) increased, creatinine increased, gamma glutamyl transferase (GGT) increased, hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, and hypophosphatemia. Laboratory results were categorically summarized according to the NCI-CTCAE criteria v4.03. Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling. Number of participants with shift from baseline for chemistry laboratory test were assessed. Only those laboratory test parameters in which at least 1 participant had data were reported.
Time Frame Day 1 up to maximum of 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
SA set included all participants who received at least one dose of study drug. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure and "Number Analyzed" signifies participants evaluable for specific rows.
Arm/Group Title Intensive Study: Glasdegib + Cytarabine + Daunorubicin Intensive Study: Placebo + Cytarabine + Daunorubicin
Hide Arm/Group Description:
Participants received first induction therapy (28 days) (backbone chemotherapy+experimental therapy). Backbone chemotherapy: Cytarabine 100 mg/m^2 daily by IV infusion for 7 days along with daunorubicin 60 mg/m^2 daily IV for 3 days. Depending upon bone marrow blast or investigator judgement participants had second induction i.e. received either same backbone therapy or cytarabine 100 mg/m^2 IV daily for 5 days and daunorubicin 60 mg/m^2 IV daily for 2 days. Participants with <5% bone marrow blasts entered into consolation phase- treated with either or both of following: 1) cytarabine 1 to 3 gm/m^2 IV for adults >=60 to <60 years twice daily on Days 1, 3, and 5 for 4 cycle (each cycle 28 day) or cytarabine per local prescribing information. 2) Received HSCT per local standard of care. Experimental Therapy: Participants were to receive Glasdegib 100 mg tablet PO QD from Day 1 of chemotherapy up to 28 days in both induction until 2 consecutive CRMRD-negative central laboratory results, whichever came first (1.6 year).
Participants received first induction therapy (28 days) (backbone chemotherapy+experimental therapy). Backbone chemotherapy: Cytarabine 100 mg/m^2 daily by IV infusion for 7 days along with daunorubicin 60 mg/m^2 daily IV for 3 days. Depending upon bone marrow blast or investigator judgement participants had second induction i.e. received either same backbone therapy or cytarabine 100 mg/m^2 IV daily for 5 days and daunorubicin 60 mg/m^2 IV daily for 2 days. Participants with <5% bone marrow blasts entered into consolation phase- treated with either or both of following: 1) cytarabine 1 to 3 gram/m^2 IV for adults >=60 to <60 years twice daily on Days 1, 3, and 5 for 4 cycle (each cycle 28 day) or cytarabine per local prescribing information. 2) Received HSCT per local standard of care. Experimental Therapy: Participants were to receive Glasdegib 100 mg matching placebo tablet PO QD from Day 1 of chemotherapy up to 28 days in both induction until 2 consecutive CR MRD-negative central laboratory results, whichever came first (1.8 year).
Overall Number of Participants Analyzed 196 198
Measure Type: Count of Participants
Unit of Measure: Participants
Alanine aminotransferase increased: Missing (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 193 participants 198 participants
1
   0.5%
1
   0.5%
Alanine aminotransferase increased: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 193 participants 198 participants
175
  90.7%
184
  92.9%
Alanine aminotransferase increased: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 193 participants 198 participants
16
   8.3%
13
   6.6%
Alanine aminotransferase increased: Grade 3/4 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 193 participants 198 participants
1
   0.5%
0
   0.0%
Alkaline phosphatase increased: Missing (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 191 participants 198 participants
2
   1.0%
3
   1.5%
Alkaline phosphatase increased: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 191 participants 198 participants
187
  97.9%
192
  97.0%
Alkaline phosphatase increased: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 191 participants 198 participants
2
   1.0%
3
   1.5%
Aspartate aminotransferase increased: Missing (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 193 participants 198 participants
5
   2.6%
2
   1.0%
Aspartate aminotransferase increased: Missing (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 193 participants 198 participants
0
   0.0%
1
   0.5%
Aspartate aminotransferase increased: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 193 participants 198 participants
173
  89.6%
186
  93.9%
Aspartate aminotransferase increased: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 193 participants 198 participants
15
   7.8%
9
   4.5%
Blood bilirubin increased: Missing (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 192 participants 198 participants
0
   0.0%
3
   1.5%
Blood bilirubin increased: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 192 participants 198 participants
184
  95.8%
189
  95.5%
Blood bilirubin increased: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 192 participants 198 participants
8
   4.2%
5
   2.5%
Blood bilirubin increased: Grade 3/4 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 192 participants 198 participants
0
   0.0%
1
   0.5%
Chronic kidney disease: Missing (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 195 participants 198 participants
4
   2.1%
5
   2.5%
Chronic kidney disease: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 195 participants 198 participants
182
  93.3%
188
  94.9%
Chronic kidney disease: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 195 participants 198 participants
8
   4.1%
4
   2.0%
Chronic kidney disease: Grade 3/4 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 195 participants 198 participants
1
   0.5%
0
   0.0%
Chronic kidney disease: Grade 3/4 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 195 participants 198 participants
0
   0.0%
1
   0.5%
CPK increased: Missing (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 183 participants 185 participants
20
  10.9%
19
  10.3%
CPK increased: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 183 participants 185 participants
161
  88.0%
166
  89.7%
CPK increased: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 183 participants 185 participants
2
   1.1%
0
   0.0%
Creatinine increased: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 195 participants 198 participants
188
  96.4%
192
  97.0%
Creatinine increased: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 195 participants 198 participants
7
   3.6%
6
   3.0%
GGT increased: Missing (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 13 participants 20 participants
5
  38.5%
7
  35.0%
GGT increased: Missing (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 13 participants 20 participants
8
  61.5%
11
  55.0%
GGT increased: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 13 participants 20 participants
0
   0.0%
2
  10.0%
Hypercalcemia: Missing (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 192 participants 197 participants
1
   0.5%
5
   2.5%
Hypercalcemia: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 192 participants 197 participants
191
  99.5%
192
  97.5%
Hyperglycemia: Missing (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 194 participants 198 participants
1
   0.5%
3
   1.5%
Hyperglycemia: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 194 participants 198 participants
174
  89.7%
183
  92.4%
Hyperglycemia: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 194 participants 198 participants
15
   7.7%
10
   5.1%
Hyperglycemia: Grade 3/4 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 194 participants 198 participants
2
   1.0%
1
   0.5%
Hyperglycemia: Grade 3/4 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 194 participants 198 participants
2
   1.0%
1
   0.5%
Hyperkalemia: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 196 participants 198 participants
194
  99.0%
194
  98.0%
Hyperkalemia: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 196 participants 198 participants
2
   1.0%
3
   1.5%
Hyperkalemia: Grade 3/4 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 196 participants 198 participants
0
   0.0%
1
   0.5%
Hypermagnesemia: Missing (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 193 participants 192 participants
2
   1.0%
4
   2.1%
Hypermagnesemia: Missing (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 193 participants 192 participants
0
   0.0%
1
   0.5%
Hypermagnesemia: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 193 participants 192 participants
190
  98.4%
184
  95.8%
Hypermagnesemia: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 193 participants 192 participants
1
   0.5%
2
   1.0%
Hypermagnesemia: Grade 3/4 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 193 participants 192 participants
0
   0.0%
1
   0.5%
Hypernatremia: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 196 participants 198 participants
196
 100.0%
196
  99.0%
Hypernatremia: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 196 participants 198 participants
0
   0.0%
1
   0.5%
Hypernatremia: Grade 3/4 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 196 participants 198 participants
0
   0.0%
1
   0.5%
Hypoalbuminemia: Missing (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 192 participants 198 participants
0
   0.0%
3
   1.5%
Hypoalbuminemia: Missing (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 192 participants 198 participants
1
   0.5%
1
   0.5%
Hypoalbuminemia: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 192 participants 198 participants
185
  96.4%
185
  93.4%
Hypoalbuminemia: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 192 participants 198 participants
5
   2.6%
8
   4.0%
Hypoalbuminemia: Grade 3/4 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 192 participants 198 participants
1
   0.5%
1
   0.5%
Hypocalcemia: Missing (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 192 participants 197 participants
1
   0.5%
5
   2.5%
Hypocalcemia: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 192 participants 197 participants
190
  99.0%
189
  95.9%
Hypocalcemia: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 192 participants 197 participants
1
   0.5%
3
   1.5%
Hypoglycemia: Missing (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 194 participants 198 participants
1
   0.5%
3
   1.5%
Hypoglycemia: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 194 participants 198 participants
193
  99.5%
194
  98.0%
Hypoglycemia: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 194 participants 198 participants
0
   0.0%
1
   0.5%
Hypokalemia: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 196 participants 198 participants
155
  79.1%
159
  80.3%
Hypokalemia: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 196 participants 198 participants
41
  20.9%
37
  18.7%
Hypokalemia: Grade 3/4 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 196 participants 198 participants
0
   0.0%
2
   1.0%
Hypomagnesemia: Missing (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 193 participants 192 participants
2
   1.0%
5
   2.6%
Hypomagnesemia: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 193 participants 192 participants
190
  98.4%
187
  97.4%
Hypomagnesemia: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 193 participants 192 participants
1
   0.5%
0
   0.0%
Hyponatremia: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 196 participants 198 participants
177
  90.3%
188
  94.9%
Hyponatremia: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 196 participants 198 participants
17
   8.7%
8
   4.0%
Hyponatremia: Grade 3/4 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 196 participants 198 participants
1
   0.5%
1
   0.5%
Hyponatremia: Grade 3/4 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 196 participants 198 participants
1
   0.5%
1
   0.5%
Hypophosphatemia: Missing (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 193 participants 193 participants
3
   1.6%
3
   1.6%
Hypophosphatemia: Missing (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 193 participants 193 participants
1
   0.5%
1
   0.5%
Hypophosphatemia: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 193 participants 193 participants
153
  79.3%
153
  79.3%
Hypophosphatemia: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade Number Analyzed 193 participants 193 participants
33
  17.1%
33
  17.1%
Hypophosphatemia: Grade 3/4 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 193 participants 193 participants
0
   0.0%
2
   1.0%
Hypophosphatemia: Grade 3/4 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 193 participants 193 participants
3
   1.6%
1
   0.5%
38.Secondary Outcome
Title Non-intensive Study: Number of Participants With Shift From Baseline in Chemistry Laboratory Abnormalities Graded by NCI CTCAE v.4.03
Hide Description Chemistry laboratory test included: alanine aminotransferase increased, alkaline phosphatase increased, aspartate aminotransferase increased, blood bilirubin increased, chronic kidney disease, CPK increased, creatinine increased, GGT increased, hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, and hypophosphatemia. Laboratory results were categorically summarized according to the NCI-CTCAE criteria v4.03. Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling. Number of participants with shift from baseline for chemistry laboratory test were assessed. Only those laboratory test parameters in which at least 1 participant had data were reported.
Time Frame Day 1 up to maximum of 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
SA set included all participants who received at least one dose of study drug. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure and "Number Analyzed" signifies participants evaluable for specific rows.
Arm/Group Title Non-intensive Study: Glasdegib + Azacitidine Non-intensive Study: Placebo + Azacitidine
Hide Arm/Group Description:
Participants received chemotherapy with azacitidine 75 mg/m^2 SC injection or IV infusion from Day 1 up to Day 7 of each cycle (28 day) and continued for at least 6 cycles or until unacceptable toxicity, participant refusal or death, whichever occurred first. Participants also were to receive glasdegib 100 mg PO QD from Day 1 of chemotherapy until clinical benefit or disease progression, unacceptable toxicity, consent withdrawal, or death, whichever occurred first. Eligible participants underwent HSCT per local standard of care and were to receive glasdegib unless 2 consecutive negative MRD assessments (3 year).
Participants received chemotherapy with azacitidine 75 mg/m^2 SC injection or IV infusion from Day 1 up to Day 7 of each cycle (28 day) and continued for at least 6 cycles or until unacceptable toxicity, participants refusal or death, whichever occurred first. Participants also received glasdegib 100 mg tablet matching placebo PO QD from Day 1 of chemotherapy until clinical benefit or disease progression, unacceptable toxicity, consent withdrawal, or death, whichever occurred first. Eligible participants underwent HSCT per local standard of care and were to receive glasdegib matching placebo unless 2 consecutive negative MRD assessments (2.44 year).
Overall Number of Participants Analyzed 160 160
Measure Type: Count of Participants
Unit of Measure: Participants
Alanine aminotransferase increased: Missing (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 160 participants 160 participants
2
   1.3%
0
   0.0%
Alanine aminotransferase increased: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 160 participants 160 participants
152
  95.0%
154
  96.3%
Alanine aminotransferase increased: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 160 participants 160 participants
6
   3.8%
6
   3.8%
Alanine aminotransferase increased: Grade 3/4 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 160 participants 160 participants
0
   0.0%
0
   0.0%
Alkaline phosphatase increased: Missing (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 159 participants 159 participants
0
   0.0%
1
   0.6%
Alkaline phosphatase increased: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 159 participants 159 participants
159
 100.0%
157
  98.7%
Alkaline phosphatase increased: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 159 participants 159 participants
0
   0.0%
1
   0.6%
Aspartate aminotransferase increased: Missing (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 159 participants 160 participants
3
   1.9%
0
   0.0%
Aspartate aminotransferase increased: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 159 participants 160 participants
152
  95.6%
156
  97.5%
Aspartate aminotransferase increased: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 159 participants 160 participants
4
   2.5%
4
   2.5%
Blood bilirubin increased: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 160 participants 160 participants
157
  98.1%
159
  99.4%
Blood bilirubin increased: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 160 participants 160 participants
3
   1.9%
1
   0.6%
Chronic kidney disease: Missing (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 160 participants 160 participants
2
   1.3%
1
   0.6%
Chronic kidney disease: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 160 participants 160 participants
130
  81.3%
134
  83.8%
Chronic kidney disease: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 160 participants 160 participants
28
  17.5%
23
  14.4%
Chronic kidney disease: Grade 3/4 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 160 participants 160 participants
0
   0.0%
2
   1.3%
CPK increased: Missing (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 157 participants 157 participants
9
   5.7%
8
   5.1%
CPK increased: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 157 participants 157 participants
147
  93.6%
147
  93.6%
CPK increased: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 157 participants 157 participants
1
   0.6%
2
   1.3%
Creatinine increased: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 160 participants 160 participants
153
  95.6%
155
  96.9%
Creatinine increased: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 160 participants 160 participants
7
   4.4%
5
   3.1%
GGT increased: Missing (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 8 participants 8 participants
3
  37.5%
5
  62.5%
GGT increased: Missing (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 8 participants 8 participants
4
  50.0%
3
  37.5%
GGT increased: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 8 participants 8 participants
1
  12.5%
0
   0.0%
Hypercalcemia: Missing (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 158 participants 160 participants
2
   1.3%
2
   1.3%
Hypercalcemia: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 158 participants 160 participants
156
  98.7%
158
  98.8%
Hyperglycemia: Missing (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 160 participants 160 participants
2
   1.3%
4
   2.5%
Hyperglycemia: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 160 participants 160 participants
147
  91.9%
136
  85.0%
Hyperglycemia: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 160 participants 160 participants
8
   5.0%
14
   8.8%
Hyperglycemia: Grade 3/4 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 160 participants 160 participants
2
   1.3%
2
   1.3%
Hyperkalemia: Missing (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 159 participants 160 participants
2
   1.3%
0
   0.0%
Hyperkalemia: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 159 participants 160 participants
155
  97.5%
157
  98.1%
Hyperkalemia: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 159 participants 160 participants
2
   1.3%
3
   1.9%
Hyperkalemia: Grade 3/4 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 159 participants 160 participants
0
   0.0%
0
   0.0%
Hyperkalemia: Grade 3/4 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 159 participants 160 participants
0
   0.0%
0
   0.0%
Hypermagnesemia: Missing (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 159 participants 160 participants
2
   1.3%
4
   2.5%
Hypermagnesemia: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 159 participants 160 participants
155
  97.5%
154
  96.3%
Hypermagnesemia: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 159 participants 160 participants
2
   1.3%
2
   1.3%
Hypernatremia: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 160 participants 160 participants
158
  98.8%
159
  99.4%
Hypernatremia: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 160 participants 160 participants
2
   1.3%
1
   0.6%
Hypoalbuminemia: Missing (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 159 participants 160 participants
2
   1.3%
0
   0.0%
Hypoalbuminemia: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 159 participants 160 participants
151
  95.0%
157
  98.1%
Hypoalbuminemia: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 159 participants 160 participants
6
   3.8%
3
   1.9%
Hypocalcemia: Missing (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 158 participants 160 participants
2
   1.3%
2
   1.3%
Hypocalcemia: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 158 participants 160 participants
154
  97.5%
155
  96.9%
Hypocalcemia: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 158 participants 160 participants
1
   0.6%
3
   1.9%
Hypocalcemia: Grade 3/4 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 158 participants 160 participants
0
   0.0%
0
   0.0%
Hypoglycemia: Missing (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 160 participants 160 participants
2
   1.3%
4
   2.5%
Hypoglycemia: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 160 participants 160 participants
155
  96.9%
156
  97.5%
Hypoglycemia: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 160 participants 160 participants
3
   1.9%
0
   0.0%
Hypokalemia: Missing (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 159 participants 160 participants
2
   1.3%
0
   0.0%
Hypokalemia: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 159 participants 160 participants
129
  81.1%
139
  86.9%
Hypokalemia: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 159 participants 160 participants
23
  14.5%
15
   9.4%
Hypokalemia: Grade 3/4 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 159 participants 160 participants
1
   0.6%
2
   1.3%
Hypokalemia: Grade 3/4 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 159 participants 160 participants
4
   2.5%
4
   2.5%
Hypomagnesemia: Missing (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 159 participants 160 participants
2
   1.3%
4
   2.5%
Hypomagnesemia: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 159 participants 160 participants
151
  95.0%
153
  95.6%
Hypomagnesemia: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 159 participants 160 participants
6
   3.8%
2
   1.3%
Hypomagnesemia: Grade 3/4 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 159 participants 160 participants
0
   0.0%
1
   0.6%
Hyponatremia: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 160 participants 160 participants
135
  84.4%
142
  88.8%
Hyponatremia: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 160 participants 160 participants
24
  15.0%
15
   9.4%
Hyponatremia: Grade 3/4 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 160 participants 160 participants
0
   0.0%
1
   0.6%
Hyponatremia: Grade 3/4 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 160 participants 160 participants
1
   0.6%
2
   1.3%
Hypophosphatemia: Missing (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 158 participants 160 participants
3
   1.9%
2
   1.3%
Hypophosphatemia: Missing (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 158 participants 160 participants
1
   0.6%
0
   0.0%
Hypophosphatemia: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 158 participants 160 participants
141
  89.2%
138
  86.3%
Hypophosphatemia: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade Number Analyzed 158 participants 160 participants
12
   7.6%
17
  10.6%
Hypophosphatemia: Grade 3/4 (baseline grade) to Grade <=2 (CTCAE grade) Number Analyzed 158 participants 160 participants
0
   0.0%
1
   0.6%
Hypophosphatemia: Grade 3/4 (baseline grade) to Grade 3/4 (CTCAE grade) Number Analyzed 158 participants 160 participants
1
   0.6%
2
   1.3%
39.Secondary Outcome
Title Intensive Study: Number of Participants With Shift From Baseline in Coagulation Laboratory Abnormalities Graded by NCI CTCAE v.4.03
Hide Description Coagulation laboratory test included: activated partial thromboplastin time prolonged, and INR increased. Laboratory results were categorically summarized according to the NCI-CTCAE criteria v4.03. Grade 0= no abnormality; Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling. Number of participants with shift from baseline for coagulation were assessed. Only those laboratory test parameters in which at least 1 participant had data were reported.
Time Frame Day 1 up to maximum of 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
SA set included all participants who received at least one dose of study drug. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure and "Number Analyzed" signifies participants evaluable for specific rows.
Arm/Group Title Intensive Study: Glasdegib + Cytarabine + Daunorubicin Intensive Study: Placebo + Cytarabine + Daunorubicin
Hide Arm/Group Description:
Participants received first induction therapy (28 days) (backbone chemotherapy+experimental therapy). Backbone chemotherapy: Cytarabine 100 mg/m^2 daily by IV infusion for 7 days along with daunorubicin 60 mg/m^2 daily IV for 3 days. Depending upon bone marrow blast or investigator judgement participants had second induction i.e. received either same backbone therapy or cytarabine 100 mg/m^2 IV daily for 5 days and daunorubicin 60 mg/m^2 IV daily for 2 days. Participants with <5% bone marrow blasts entered into consolation phase- treated with either or both of following: 1) cytarabine 1 to 3 gm/m^2 IV for adults >=60 to <60 years twice daily on Days 1, 3, and 5 for 4 cycle (each cycle 28 day) or cytarabine per local prescribing information. 2) Received HSCT per local standard of care. Experimental Therapy: Participants were to receive Glasdegib 100 mg tablet PO QD from Day 1 of chemotherapy up to 28 days in both induction until 2 consecutive CRMRD-negative central laboratory results, whichever came first (1.6 year).
Participants received first induction therapy (28 days) (backbone chemotherapy+experimental therapy). Backbone chemotherapy: Cytarabine 100 mg/m^2 daily by IV infusion for 7 days along with daunorubicin 60 mg/m^2 daily IV for 3 days. Depending upon bone marrow blast or investigator judgement participants had second induction i.e. received either same backbone therapy or cytarabine 100 mg/m^2 IV daily for 5 days and daunorubicin 60 mg/m^2 IV daily for 2 days. Participants with <5% bone marrow blasts entered into consolation phase- treated with either or both of following: 1) cytarabine 1 to 3 gram/m^2 IV for adults >=60 to <60 years twice daily on Days 1, 3, and 5 for 4 cycle (each cycle 28 day) or cytarabine per local prescribing information. 2) Received HSCT per local standard of care. Experimental Therapy: Participants were to receive Glasdegib 100 mg matching placebo tablet PO QD from Day 1 of chemotherapy up to 28 days in both induction until 2 consecutive CR MRD-negative central laboratory results, whichever came first (1.8 year).
Overall Number of Participants Analyzed 6 11
Measure Type: Count of Participants
Unit of Measure: Participants
Activated partial thromboplastin time prolonged: Missing (baseline grade) to Grade 0 (CTCAE grade) Number Analyzed 4 participants 9 participants
1
  25.0%
0
   0.0%
Activated partial thromboplastin time prolonged: Missing (baseline grade) to Grade 1 (CTCAE grade) Number Analyzed 4 participants 9 participants
0
   0.0%
1
  11.1%
Activated partial thromboplastin time prolonged: Grade 0 (baseline grade) to Grade 0 (CTCAE grade) Number Analyzed 4 participants 9 participants
0
   0.0%
4
  44.4%
Activated partial thromboplastin time prolonged: Grade 0 (baseline grade) to Grade 1 (CTCAE grade) Number Analyzed 4 participants 9 participants
1
  25.0%
2
  22.2%
Activated partial thromboplastin time prolonged: Grade 0 (baseline grade) to Grade 2 (CTCAE grade) Number Analyzed 4 participants 9 participants
0
   0.0%
1
  11.1%
Activated partial thromboplastin time prolonged: Grade 0 (baseline grade) to Grade 3 (CTCAE grade) Number Analyzed 4 participants 9 participants
1
  25.0%
0
   0.0%
Activated partial thromboplastin time prolonged: Grade 1 (baseline grade) to Grade 1 (CTCAE grade) Number Analyzed 4 participants 9 participants
1
  25.0%
1
  11.1%
INR increased: Missing (baseline grade) to Grade 0 (CTCAE grade) Number Analyzed 6 participants 11 participants
1
  16.7%
1
   9.1%
INR increased: Missing (baseline grade) to Grade 1 (CTCAE grade) Number Analyzed 6 participants 11 participants
0
   0.0%
1
   9.1%
INR increased: Missing (baseline grade) to Grade 2 (CTCAE grade) Number Analyzed 6 participants 11 participants
1
  16.7%
0
   0.0%
INR increased: Grade 0 (baseline grade) to Grade 0 (CTCAE grade) Number Analyzed 6 participants 11 participants
0
   0.0%
2
  18.2%
INR increased: Grade 0 (baseline grade) to Grade 1 (CTCAE grade) Number Analyzed 6 participants 11 participants
1
  16.7%
0
   0.0%
INR increased: Grade 0 (baseline grade) to Grade 2 (CTCAE grade) Number Analyzed 6 participants 11 participants
1
  16.7%
1
   9.1%
INR increased: Grade 0 (baseline grade) to Grade 3 (CTCAE grade) Number Analyzed 6 participants 11 participants
0
   0.0%
1
   9.1%
INR increased: Grade 1 (baseline grade) to Grade 0 (CTCAE grade) Number Analyzed 6 participants 11 participants
0
   0.0%
1
   9.1%
INR increased: Grade 1 (baseline grade) to Grade 1 (CTCAE grade) Number Analyzed 6 participants 11 participants
0
   0.0%
3
  27.3%
INR increased: Grade 1 (baseline grade) to Grade 2 (CTCAE grade) Number Analyzed 6 participants 11 participants
1
  16.7%
1
   9.1%
INR increased: Grade 1 (baseline grade) to Grade 3 (CTCAE grade) Number Analyzed 6 participants 11 participants
1
  16.7%
0
   0.0%
40.Secondary Outcome
Title Non-intensive Study: Number of Participants With Shift From Baseline in Coagulation Laboratory Abnormalities Graded by NCI CTCAE v.4.03
Hide Description Coagulation laboratory test included: activated partial thromboplastin time prolonged, and INR increased. Laboratory results were categorically summarized according to the NCI-CTCAE criteria v4.03. Grade 0= no abnormality; Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling. Number of participants with shift from baseline for coagulation were assessed. Only those laboratory test parameters in which at least 1 participant had data were reported.
Time Frame Day 1 up to maximum of 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
SA set included all participants who received at least one dose of study drug. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure and "Number Analyzed" signifies participants evaluable for specific rows.
Arm/Group Title Non-intensive Study: Glasdegib + Azacitidine Non-intensive Study: Placebo + Azacitidine
Hide Arm/Group Description:
Participants received chemotherapy with azacitidine 75 mg/m^2 SC injection or IV infusion from Day 1 up to Day 7 of each cycle (28 day) and continued for at least 6 cycles or until unacceptable toxicity, participant refusal or death, whichever occurred first. Participants also were to receive glasdegib 100 mg PO QD from Day 1 of chemotherapy until clinical benefit or disease progression, unacceptable toxicity, consent withdrawal, or death, whichever occurred first. Eligible participants underwent HSCT per local standard of care and were to receive glasdegib unless 2 consecutive negative MRD assessments (3 year).
Participants received chemotherapy with azacitidine 75 mg/m^2 SC injection or IV infusion from Day 1 up to Day 7 of each cycle (28 day) and continued for at least 6 cycles or until unacceptable toxicity, participants refusal or death, whichever occurred first. Participants also received glasdegib 100 mg tablet matching placebo PO QD from Day 1 of chemotherapy until clinical benefit or disease progression, unacceptable toxicity, consent withdrawal, or death, whichever occurred first. Eligible participants underwent HSCT per local standard of care and were to receive glasdegib matching placebo unless 2 consecutive negative MRD assessments (2.44 year).
Overall Number of Participants Analyzed 17 13
Measure Type: Count of Participants
Unit of Measure: Participants
Activated partial thromboplastin time prolonged: Missing (baseline grade) to Grade 0 (CTCAE grade) Number Analyzed 17 participants 12 participants
1
   5.9%
0
   0.0%
Activated partial thromboplastin time prolonged: Grade 0 (baseline grade) to Grade 0 (CTCAE grade) Number Analyzed 17 participants 12 participants
8
  47.1%
5
  41.7%
Activated partial thromboplastin time prolonged: Grade 0 (baseline grade) to Grade 1 (CTCAE grade) Number Analyzed 17 participants 12 participants
5
  29.4%
7
  58.3%
Activated partial thromboplastin time prolonged: Grade 1 (baseline grade) to Grade 0 (CTCAE grade) Number Analyzed 17 participants 12 participants
1
   5.9%
0
   0.0%
Activated partial thromboplastin time prolonged: Grade 1 (baseline grade) to Grade 1 (CTCAE grade) Number Analyzed 17 participants 12 participants
1
   5.9%
0
   0.0%
Activated partial thromboplastin time prolonged: Grade 2 (baseline grade) to Grade 1 (CTCAE grade) Number Analyzed 17 participants 12 participants
1
   5.9%
0
   0.0%
INR increased: Missing (baseline grade) to Grade 0 (CTCAE grade) Number Analyzed 17 participants 13 participants
1
   5.9%
0
   0.0%
INR increased: Grade 0 (baseline grade) to Grade 0 (CTCAE grade) Number Analyzed 17 participants 13 participants
4
  23.5%
5
  38.5%
INR increased: Grade 0 (baseline grade) to Grade 1 (CTCAE grade) Number Analyzed 17 participants 13 participants
6
  35.3%
4
  30.8%
INR increased: Grade 0 (baseline grade) to Grade 2 (CTCAE grade) Number Analyzed 17 participants 13 participants
1
   5.9%
2
  15.4%
INR increased: Grade 0 (baseline grade) to Grade 3 (CTCAE grade) Number Analyzed 17 participants 13 participants
1
   5.9%
0
   0.0%
INR increased: Grade 1 (baseline grade) to Grade 1 (CTCAE grade) Number Analyzed 17 participants 13 participants
1
   5.9%
1
   7.7%
INR increased: Grade 1 (baseline grade) to Grade 2 (CTCAE grade) Number Analyzed 17 participants 13 participants
2
  11.8%
0
   0.0%
INR increased: Grade 3 (baseline grade) to Grade 1 (CTCAE grade) Number Analyzed 17 participants 13 participants
1
   5.9%
1
   7.7%
41.Secondary Outcome
Title Intensive Study: Plasma Trough Concentration (Ctrough) of Glasdegib
Hide Description Ctrough of Glasdegib was measured in nanogram per milliliter (ng/mL).
Time Frame Induction, Day 10+/-1: pre-dose, 1, 4 hour (hr); Consolidation phase, Day 1: pre-dose, 1, 4 hr
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population included all participants who were treated and who had at least 1 value of analyte concentration of Glasdegib available. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure and "Number Analyzed" signifies participants evaluable for specific time points.
Arm/Group Title Intensive Study: Glasdegib + Cytarabine + Daunorubicin
Hide Arm/Group Description:
Participants received first induction therapy (28 days) (backbone chemotherapy+experimental therapy). Backbone chemotherapy: Cytarabine 100 mg/m^2 daily by IV infusion for 7 days along with daunorubicin 60 mg/m^2 daily IV for 3 days. Depending upon bone marrow blast or investigator judgement participants had second induction i.e. received either same backbone therapy or cytarabine 100 mg/m^2 IV daily for 5 days and daunorubicin 60 mg/m^2 IV daily for 2 days. Participants with <5% bone marrow blasts entered into consolation phase- treated with either or both of following: 1) cytarabine 1 to 3 gm/m^2 IV for adults >=60 to <60 years twice daily on Days 1, 3, and 5 for 4 cycle (each cycle 28 day) or cytarabine per local prescribing information. 2) Received HSCT per local standard of care. Experimental Therapy: Participants were to receive Glasdegib 100 mg tablet PO QD from Day 1 of chemotherapy up to 28 days in both induction until 2 consecutive CRMRD-negative central laboratory results, whichever came first (1.6 year).
Overall Number of Participants Analyzed 123
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/ml
Induction Day 10 Number Analyzed 81 participants
413.54
(125%)
Consolidation 1, Day 1 Number Analyzed 33 participants
245.48
(80%)
Consolidation 2, Day 1 Number Analyzed 41 participants
259.79
(122%)
42.Secondary Outcome
Title Non-intensive Study: Plasma Trough Concentration (Ctrough) of Glasdegib
Hide Description Ctrough of Glasdegib was measured in ng/mL.
Time Frame Pre-dose: Cycle 1 Day 15 and Cycle 2 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population included all participants who were treated and who had at least 1 value of analyte concentration of Glasdegib available. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure and "Number Analyzed" signifies participants evaluable for specific time points.
Arm/Group Title Non-intensive Study: Glasdegib + Azacitidine
Hide Arm/Group Description:
Participants received chemotherapy with azacitidine 75 mg/m^2 SC injection or IV infusion from Day 1 up to Day 7 of each cycle (28 day) and continued for at least 6 cycles or until unacceptable toxicity, participant refusal or death, whichever occurred first. Participants also were to receive glasdegib 100 mg PO QD from Day 1 of chemotherapy until clinical benefit or disease progression, unacceptable toxicity, consent withdrawal, or death, whichever occurred first. Eligible participants underwent HSCT per local standard of care and were to receive glasdegib unless 2 consecutive negative MRD assessments (3 year).
Overall Number of Participants Analyzed 53
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/ml
Cycle 1 Day 15 Number Analyzed 34 participants
565.44
(126%)
Cycle 2 Day 1 Number Analyzed 37 participants
472.42
(122%)
43.Secondary Outcome
Title Intensive Study: Number of Participants With Shift From Baseline in Corrected QT (QTc) Interval
Hide Description Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. The time corresponding to beginning of depolarization to repolarization of the ventricles (QT interval) was adjusted for RR interval using QT and RR from each ECG by Fridericia's formula (QTcF = QT divided by cube root of RR) and by Bazette's formula (QTcB = QT divided by square root of RR). Participants with maximum increase from baseline of <=450 to >500 msec (post-baseline) were summarized. Number of participants with shift from baseline for QTc were assessed. Only those QTc parameters in which at least 1 participant had data were reported.
Time Frame Day 1 up to maximum of 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
SA set included all participants who received at least one dose of study drug. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure and "Number Analyzed" signifies participants evaluable for specific time points.
Arm/Group Title Intensive Study: Glasdegib + Cytarabine + Daunorubicin Intensive Study: Placebo + Cytarabine + Daunorubicin
Hide Arm/Group Description:
Participants received first induction therapy (28 days) (backbone chemotherapy+experimental therapy). Backbone chemotherapy: Cytarabine 100 mg/m^2 daily by IV infusion for 7 days along with daunorubicin 60 mg/m^2 daily IV for 3 days. Depending upon bone marrow blast or investigator judgement participants had second induction i.e. received either same backbone therapy or cytarabine 100 mg/m^2 IV daily for 5 days and daunorubicin 60 mg/m^2 IV daily for 2 days. Participants with <5% bone marrow blasts entered into consolation phase- treated with either or both of following: 1) cytarabine 1 to 3 gm/m^2 IV for adults >=60 to <60 years twice daily on Days 1, 3, and 5 for 4 cycle (each cycle 28 day) or cytarabine per local prescribing information. 2) Received HSCT per local standard of care. Experimental Therapy: Participants were to receive Glasdegib 100 mg tablet PO QD from Day 1 of chemotherapy up to 28 days in both induction until 2 consecutive CRMRD-negative central laboratory results, whichever came first (1.6 year).
Participants received first induction therapy (28 days) (backbone chemotherapy+experimental therapy). Backbone chemotherapy: Cytarabine 100 mg/m^2 daily by IV infusion for 7 days along with daunorubicin 60 mg/m^2 daily IV for 3 days. Depending upon bone marrow blast or investigator judgement participants had second induction i.e. received either same backbone therapy or cytarabine 100 mg/m^2 IV daily for 5 days and daunorubicin 60 mg/m^2 IV daily for 2 days. Participants with <5% bone marrow blasts entered into consolation phase- treated with either or both of following: 1) cytarabine 1 to 3 gram/m^2 IV for adults >=60 to <60 years twice daily on Days 1, 3, and 5 for 4 cycle (each cycle 28 day) or cytarabine per local prescribing information. 2) Received HSCT per local standard of care. Experimental Therapy: Participants were to receive Glasdegib 100 mg matching placebo tablet PO QD from Day 1 of chemotherapy up to 28 days in both induction until 2 consecutive CR MRD-negative central laboratory results, whichever came first (1.8 year).
Overall Number of Participants Analyzed 188 189
Measure Type: Count of Participants
Unit of Measure: Participants
QTcB: <=450 msec (baseline) to <=450 msec (post-baseline) Number Analyzed 188 participants 188 participants
51
  27.1%
71
  37.8%
QTcB: <=450 msec (baseline) to >450-<=480 msec (post-baseline) Number Analyzed 188 participants 188 participants
64
  34.0%
63
  33.5%
QTcB: <=450 msec (baseline) to >480-<=500 msec (post-baseline) Number Analyzed 188 participants 188 participants
18
   9.6%
11
   5.9%
QTcB: <=450 msec (baseline) to >500 msec (post-baseline) Number Analyzed 188 participants 188 participants
11
   5.9%
6
   3.2%
QTcB: >450-<=480 msec (baseline) to <=450 msec (post-baseline) Number Analyzed 188 participants 188 participants
2
   1.1%
3
   1.6%
QTcB: >450-<=480 msec (baseline) to >450-<=480 msec (post-baseline) Number Analyzed 188 participants 188 participants
20
  10.6%
17
   9.0%
QTcB: >450-<=480 msec (baseline) to >480-<=500 msec (post-baseline) Number Analyzed 188 participants 188 participants
16
   8.5%
10
   5.3%
QTcB: >450-<=480 msec (baseline) to >500 msec (post-baseline) Number Analyzed 188 participants 188 participants
1
   0.5%
5
   2.7%
QTcB: >480-<=500 msec (baseline) to >450-<=480 msec (post-baseline) Number Analyzed 188 participants 188 participants
1
   0.5%
0
   0.0%
QTcB: >480-<=500 msec (baseline) to >480-<=500 msec (post-baseline) Number Analyzed 188 participants 188 participants
2
   1.1%
1
   0.5%
QTcB: >480-<=500 msec (baseline) to >500 msec (post-baseline) Number Analyzed 188 participants 188 participants
1
   0.5%
0
   0.0%
QTcB: >500 msec (baseline) to >500 msec (post-baseline) Number Analyzed 188 participants 188 participants
1
   0.5%
1
   0.5%
QTcF: <=450 msec (baseline) to <=450 msec (post-baseline) Number Analyzed 187 participants 189 participants
116
  62.0%
132
  69.8%
QTcF: <=450 msec (baseline) to >450-<=480 msec (post-baseline) Number Analyzed 187 participants 189 participants
50
  26.7%
39
  20.6%
QTcF: <=450 msec (baseline) to >480-<=500 msec (post-baseline) Number Analyzed 187 participants 189 participants
8
   4.3%
10
   5.3%
QTcF: <=450 msec (baseline) to >500 msec (post-baseline) Number Analyzed 187 participants 189 participants
5
   2.7%
0
   0.0%
QTcF: >450-<=480 msec (baseline) to <=450 msec (post-baseline) Number Analyzed 187 participants 189 participants
2
   1.1%
1
   0.5%
QTcF: >450-<=480 msec (baseline) to >450-<=480 msec (post-baseline) Number Analyzed 187 participants 189 participants
5
   2.7%
5
   2.6%
QTcF: >450-<=480 msec (baseline) to >500 msec (post-baseline) Number Analyzed 187 participants 189 participants
1
   0.5%
1
   0.5%
QTcF: >480-<=500 msec (baseline) to >480-<=500 msec (post-baseline) Number Analyzed 187 participants 189 participants
0
   0.0%
1
   0.5%
44.Secondary Outcome
Title Non-intensive Study: Number of Participants With Shift From Baseline in Corrected QT (QTc) Interval
Hide Description Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. The time corresponding to beginning of depolarization to repolarization of the ventricles (QT interval) was adjusted for RR interval using QT and RR from each ECG by Fridericia's formula (QTcF = QT divided by cube root of RR) and by Bazette's formula (QTcB = QT divided by square root of RR). Participants with maximum increase from baseline of <=450 to >500 msec (post-baseline) were summarized. Number of participants with shift from baseline for QTc were assessed. Only those QTc parameters in which at least 1 participant had data were reported.
Time Frame Day 1 up to maximum of 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
SA set included all participants who received at least one dose of study drug. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure and "Number Analyzed" signifies participants evaluable for specific time points.
Arm/Group Title Non-intensive Study: Glasdegib + Azacitidine Non-intensive Study: Placebo + Azacitidine
Hide Arm/Group Description:
Participants received chemotherapy with azacitidine 75 mg/m^2 SC injection or IV infusion from Day 1 up to Day 7 of each cycle (28 day) and continued for at least 6 cycles or until unacceptable toxicity, participant refusal or death, whichever occurred first. Participants also were to receive glasdegib 100 mg PO QD from Day 1 of chemotherapy until clinical benefit or disease progression, unacceptable toxicity, consent withdrawal, or death, whichever occurred first. Eligible participants underwent HSCT per local standard of care and were to receive glasdegib unless 2 consecutive negative MRD assessments (3 year).
Participants received chemotherapy with azacitidine 75 mg/m^2 SC injection or IV infusion from Day 1 up to Day 7 of each cycle (28 day) and continued for at least 6 cycles or until unacceptable toxicity, participants refusal or death, whichever occurred first. Participants also received glasdegib 100 mg tablet matching placebo PO QD from Day 1 of chemotherapy until clinical benefit or disease progression, unacceptable toxicity, consent withdrawal, or death, whichever occurred first. Eligible participants underwent HSCT per local standard of care and were to receive glasdegib matching placebo unless 2 consecutive negative MRD assessments (2.44 year).
Overall Number of Participants Analyzed 158 155
Measure Type: Count of Participants
Unit of Measure: Participants
QTcB: <=450 msec (baseline) to <=450 msec (post-baseline) Number Analyzed 158 participants 155 participants
48
  30.4%
58
  37.4%
QTcB: <=450 msec (baseline) to >450-<=480 msec (post-baseline) Number Analyzed 158 participants 155 participants
53
  33.5%
43
  27.7%
QTcB: <=450 msec (baseline) to >480-<=500 msec (post-baseline) Number Analyzed 158 participants 155 participants
6
   3.8%
11
   7.1%
QTcB: <=450 msec (baseline) to >500 msec (post-baseline) Number Analyzed 158 participants 155 participants
7
   4.4%
3
   1.9%
QTcB: >450-<=480 msec (baseline) to <=450 msec (post-baseline) Number Analyzed 158 participants 155 participants
0
   0.0%
1
   0.6%
QTcB: >450-<=480 msec (baseline) to >450-<=480 msec (post-baseline) Number Analyzed 158 participants 155 participants
20
  12.7%
22
  14.2%
QTcB: >450-<=480 msec (baseline) to >480-<=500 msec (post-baseline) Number Analyzed 158 participants 155 participants
13
   8.2%
8
   5.2%
QTcB: >450-<=480 msec (baseline) to >500 msec (post-baseline) Number Analyzed 158 participants 155 participants
5
   3.2%
3
   1.9%
QTcB: >480-<=500 msec (baseline) to >450-<=480 msec (post-baseline) Number Analyzed 158 participants 155 participants
1
   0.6%
2
   1.3%
QTcB: >480-<=500 msec (baseline) to >480-<=500 msec (post-baseline) Number Analyzed 158 participants 155 participants
3
   1.9%
1
   0.6%
QTcB: >480-<=500 msec (baseline) to >500 msec (post-baseline) Number Analyzed 158 participants 155 participants
2
   1.3%
3
   1.9%
QTcF: <=450 msec (baseline) to <=450 msec (post-baseline) Number Analyzed 155 participants 155 participants
100
  64.5%
104
  67.1%
QTcF: <=450 msec (baseline) to >450-<=480 msec (post-baseline) Number Analyzed 155 participants 155 participants
39
  25.2%
36
  23.2%
QTcF: <=450 msec (baseline) to >480-<=500 msec (post-baseline) Number Analyzed 155 participants 155 participants
7
   4.5%
0
   0.0%
QTcF: >450 - <=480 (baseline) to <=450msec (post-baseline) Number Analyzed 155 participants 155 participants
1
   0.6%
1
   0.6%
QTcF: >450 - <=480 msec (baseline) to >450 - <=480msec(post baseline) Number Analyzed 158 participants 155 participants
0
   0.0%
1
   0.6%
QTcF: >450 - <=480 msec (baseline) to >480 - <=500 msec (post baseline) Number Analyzed 158 participants 155 participants
5
   3.2%
8
   5.2%
QTcF: >480 msec (baseline) to <=500 msec (post baseline) Number Analyzed 158 participants 155 participants
1
   0.6%
4
   2.6%
QTcF: >450 - <=480 (baseline) to >500 msec (post baseline) Number Analyzed 158 participants 155 participants
1
   0.6%
1
   0.6%
QTcF: >480 - <=500msec (baseline) to >480 - <=500 msec (post baseline) Number Analyzed 158 participants 155 participants
1
   0.6%
0
   0.0%
Time Frame Intensive study: Day 1 up to maximum of 2 years; non-intensive study: Day 1 up to maximum of 3 years
Adverse Event Reporting Description Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. All-Cause Mortality was assessed for all randomized participants whereas serious and other adverse events were assessed for safety population.
 
Arm/Group Title Intensive Study: Glasdegib + Cytarabine + Daunorubicin Intensive Study: Placebo + Cytarabine + Daunorubicin Non-intensive Study: Glasdegib + Azacitidine Non-intensive Study: Placebo + Azacitidine
Hide Arm/Group Description Participants received first induction therapy (28 days) (backbone chemotherapy+experimental therapy). Backbone chemotherapy: Cytarabine 100 mg/m^2 daily by IV infusion for 7 days along with daunorubicin 60 mg/m^2 daily IV for 3 days. Depending upon bone marrow blast or investigator judgement participants had second induction i.e. received either same backbone therapy or cytarabine 100 mg/m^2 IV daily for 5 days and daunorubicin 60 mg/m^2 IV daily for 2 days. Participants with <5% bone marrow blasts entered into consolation phase- treated with either or both of following: 1) cytarabine 1 to 3 gm/m^2 IV for adults >=60 to <60 years twice daily on Days 1, 3, and 5 for 4 cycle (each cycle 28 day) or cytarabine per local prescribing information. 2) Received HSCT per local standard of care. Experimental Therapy: Participants were to receive Glasdegib 100 mg tablet PO QD from Day 1 of chemotherapy up to 28 days in both induction until 2 consecutive CRMRD-negative central laboratory results, whichever came first (1.6 year). Participants received first induction therapy (28 days) (backbone chemotherapy+experimental therapy). Backbone chemotherapy: Cytarabine 100 mg/m^2 daily by IV infusion for 7 days along with daunorubicin 60 mg/m^2 daily IV for 3 days. Depending upon bone marrow blast or investigator judgement participants had second induction i.e. received either same backbone therapy or cytarabine 100 mg/m^2 IV daily for 5 days and daunorubicin 60 mg/m^2 IV daily for 2 days. Participants with <5% bone marrow blasts entered into consolation phase- treated with either or both of following: 1) cytarabine 1 to 3 gram/m^2 IV for adults >=60 to <60 years twice daily on Days 1, 3, and 5 for 4 cycle (each cycle 28 day) or cytarabine per local prescribing information. 2) Received HSCT per local standard of care. Experimental Therapy: Participants were to receive Glasdegib 100 mg matching placebo tablet PO QD from Day 1 of chemotherapy up to 28 days in both induction until 2 consecutive CR MRD-negative central laboratory results, whichever came first (1.8 year). Participants received chemotherapy with azacitidine 75 mg/m^2 SC injection or IV infusion from Day 1 up to Day 7 of each cycle (28 day) and continued for at least 6 cycles or until unacceptable toxicity, participant refusal or death, whichever occurred first. Participants also were to receive glasdegib 100 mg PO QD from Day 1 of chemotherapy until clinical benefit or disease progression, unacceptable toxicity, consent withdrawal, or death, whichever occurred first. Eligible participants underwent HSCT per local standard of care and were to receive glasdegib unless 2 consecutive negative MRD assessments (3 year). Participants received chemotherapy with azacitidine 75 mg/m^2 SC injection or IV infusion from Day 1 up to Day 7 of each cycle (28 day) and continued for at least 6 cycles or until unacceptable toxicity, participants refusal or death, whichever occurred first. Participants also received glasdegib 100 mg tablet matching placebo PO QD from Day 1 of chemotherapy until clinical benefit or disease progression, unacceptable toxicity, consent withdrawal, or death, whichever occurred first. Eligible participants underwent HSCT per local standard of care and were to receive glasdegib matching placebo unless 2 consecutive negative MRD assessments (2.44 year).
All-Cause Mortality
Intensive Study: Glasdegib + Cytarabine + Daunorubicin Intensive Study: Placebo + Cytarabine + Daunorubicin Non-intensive Study: Glasdegib + Azacitidine Non-intensive Study: Placebo + Azacitidine
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   90/201 (44.78%)   88/203 (43.35%)   117/163 (71.78%)   113/162 (69.75%) 
Hide Serious Adverse Events
Intensive Study: Glasdegib + Cytarabine + Daunorubicin Intensive Study: Placebo + Cytarabine + Daunorubicin Non-intensive Study: Glasdegib + Azacitidine Non-intensive Study: Placebo + Azacitidine
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   86/198 (43.43%)   92/201 (45.77%)   117/162 (72.22%)   124/160 (77.50%) 
Blood and lymphatic system disorders         
Anaemia * 1  2/198 (1.01%)  1/201 (0.50%)  6/162 (3.70%)  5/160 (3.13%) 
Febrile neutropenia * 1  18/198 (9.09%)  17/201 (8.46%)  24/162 (14.81%)  20/160 (12.50%) 
Neutropenia * 1  0/198 (0.00%)  1/201 (0.50%)  0/162 (0.00%)  1/160 (0.63%) 
Thrombocytopenia * 1  1/198 (0.51%)  3/201 (1.49%)  2/162 (1.23%)  1/160 (0.63%) 
Leukocytosis * 1  2/198 (1.01%)  0/201 (0.00%)  0/162 (0.00%)  0/160 (0.00%) 
Splenic necrosis * 1  1/198 (0.51%)  0/201 (0.00%)  0/162 (0.00%)  0/160 (0.00%) 
Cardiac disorders         
Atrial fibrillation * 1  3/198 (1.52%)  1/201 (0.50%)  1/162 (0.62%)  2/160 (1.25%) 
Cardiac arrest * 1  1/198 (0.51%)  0/201 (0.00%)  0/162 (0.00%)  2/160 (1.25%) 
Cardiac failure * 1  0/198 (0.00%)  1/201 (0.50%)  0/162 (0.00%)  3/160 (1.88%) 
Cardiac failure acute * 1  1/198 (0.51%)  0/201 (0.00%)  1/162 (0.62%)  0/160 (0.00%) 
Myocarditis * 1  1/198 (0.51%)  0/201 (0.00%)  1/162 (0.62%)  0/160 (0.00%) 
Acute myocardial infarction * 1  1/198 (0.51%)  0/201 (0.00%)  0/162 (0.00%)  0/160 (0.00%) 
Cardiac failure congestive * 1  0/198 (0.00%)  1/201 (0.50%)  0/162 (0.00%)  0/160 (0.00%) 
Cardiomyopathy * 1  0/198 (0.00%)  1/201 (0.50%)  0/162 (0.00%)  0/160 (0.00%) 
Intracardiac mass * 1  0/198 (0.00%)  1/201 (0.50%)  0/162 (0.00%)  0/160 (0.00%) 
Left ventricular dysfunction * 1  0/198 (0.00%)  1/201 (0.50%)  0/162 (0.00%)  0/160 (0.00%) 
Myocardial infarction * 1  0/198 (0.00%)  1/201 (0.50%)  0/162 (0.00%)  0/160 (0.00%) 
Myocardial ischaemia * 1  0/198 (0.00%)  1/201 (0.50%)  0/162 (0.00%)  0/160 (0.00%) 
Atrial flutter * 2  0/198 (0.00%)  0/201 (0.00%)  1/162 (0.62%)  0/160 (0.00%) 
Bradycardia * 2  0/198 (0.00%)  0/201 (0.00%)  0/162 (0.00%)  1/160 (0.63%) 
Cardiorenal syndrome * 2  0/198 (0.00%)  0/201 (0.00%)  1/162 (0.62%)  0/160 (0.00%) 
Ventricular fibrillation * 2  0/198 (0.00%)  0/201 (0.00%)  0/162 (0.00%)  1/160 (0.63%) 
Eye disorders         
Vision blurred * 1  0/198 (0.00%)  1/201 (0.50%)  0/162 (0.00%)  0/160 (0.00%) 
Gastrointestinal disorders         
Colitis * 1  0/198 (0.00%)  1/201 (0.50%)  4/162 (2.47%)  1/160 (0.63%) 
Constipation * 1  1/198 (0.51%)  0/201 (0.00%)  2/162 (1.23%)  0/160 (0.00%) 
Diarrhoea * 1  1/198 (0.51%)  0/201 (0.00%)  3/162 (1.85%)  2/160 (1.25%) 
Diverticulum intestinal haemorrhagic * 1  0/198 (0.00%)  1/201 (0.50%)  0/162 (0.00%)  1/160 (0.63%) 
Gastrointestinal haemorrhage * 1  3/198 (1.52%)  0/201 (0.00%)  2/162 (1.23%)  1/160 (0.63%) 
Haematemesis * 1  0/198 (0.00%)  1/201 (0.50%)  0/162 (0.00%)  1/160 (0.63%) 
Intestinal haemorrhage * 1  0/198 (0.00%)  1/201 (0.50%)  0/162 (0.00%)  1/160 (0.63%) 
Large intestine perforation * 1  0/198 (0.00%)  1/201 (0.50%)  1/162 (0.62%)  0/160 (0.00%) 
Lower gastrointestinal haemorrhage * 1  1/198 (0.51%)  1/201 (0.50%)  1/162 (0.62%)  0/160 (0.00%) 
Neutropenic colitis * 1  0/198 (0.00%)  1/201 (0.50%)  0/162 (0.00%)  1/160 (0.63%) 
Rectal haemorrhage * 1  0/198 (0.00%)  1/201 (0.50%)  0/162 (0.00%)  1/160 (0.63%) 
Upper gastrointestinal haemorrhage * 1  2/198 (1.01%)  0/201 (0.00%)  1/162 (0.62%)  0/160 (0.00%) 
Anal fistula * 1  1/198 (0.51%)  1/201 (0.50%)  0/162 (0.00%)  0/160 (0.00%) 
Enteritis * 1  0/198 (0.00%)  1/201 (0.50%)  0/162 (0.00%)  0/160 (0.00%) 
Enterocolitis * 1  1/198 (0.51%)  1/201 (0.50%)  0/162 (0.00%)  0/160 (0.00%) 
Gastric ulcer * 1  1/198 (0.51%)  0/201 (0.00%)  0/162 (0.00%)  0/160 (0.00%) 
Intussusception * 1  1/198 (0.51%)  0/201 (0.00%)  0/162 (0.00%)  0/160 (0.00%) 
Proctalgia * 1  1/198 (0.51%)  0/201 (0.00%)  0/162 (0.00%)  0/160 (0.00%) 
Small intestinal haemorrhage * 1  1/198 (0.51%)  0/201 (0.00%)  0/162 (0.00%)  0/160 (0.00%) 
Abdominal pain * 2  0/198 (0.00%)  0/201 (0.00%)  2/162 (1.23%)  0/160 (0.00%) 
Abdominal distension * 2  0/198 (0.00%)  0/201 (0.00%)  1/162 (0.62%)  0/160 (0.00%) 
Anal fissure * 2  0/198 (0.00%)  0/201 (0.00%)  1/162 (0.62%)  0/160 (0.00%) 
Intra-abdominal haematoma * 2  0/198 (0.00%)  0/201 (0.00%)  0/162 (0.00%)  1/160 (0.63%) 
Mechanical ileus * 2  0/198 (0.00%)  0/201 (0.00%)  1/162 (0.62%)  0/160 (0.00%) 
Nausea * 2  0/198 (0.00%)  0/201 (0.00%)  1/162 (0.62%)  0/160 (0.00%) 
Pancreatitis * 2  0/198 (0.00%)  0/201 (0.00%)  2/162 (1.23%)  0/160 (0.00%) 
Stomatitis * 2  0/198 (0.00%)  0/201 (0.00%)  0/162 (0.00%)  1/160 (0.63%) 
Vomiting * 2  0/198 (0.00%)  0/201 (0.00%)  1/162 (0.62%)  2/160 (1.25%) 
Gastritis * 2  0/198 (0.00%)  0/201 (0.00%)  2/162 (1.23%)  0/160 (0.00%) 
Gastrointestinal perforation * 2  0/198 (0.00%)  0/201 (0.00%)  0/162 (0.00%)  1/160 (0.63%) 
Glossitis * 2  0/198 (0.00%)  0/201 (0.00%)  0/162 (0.00%)  1/160 (0.63%) 
Haemorrhoidal haemorrhage * 2  0/198 (0.00%)  0/201 (0.00%)  0/162 (0.00%)  1/160 (0.63%) 
Haemorrhoids thrombosed * 2  0/198 (0.00%)  0/201 (0.00%)  0/162 (0.00%)  1/160 (0.63%) 
Ileus * 2  0/198 (0.00%)  0/201 (0.00%)  2/162 (1.23%)  0/160 (0.00%) 
Inguinal hernia * 2  0/198 (0.00%)  0/201 (0.00%)  1/162 (0.62%)  0/160 (0.00%) 
General disorders         
Disease progression * 1  2/198 (1.01%)  5/201 (2.49%)  14/162 (8.64%)  22/160 (13.75%) 
Multiple organ dysfunction syndrome * 1  0/198 (0.00%)  1/201 (0.50%)  2/162 (1.23%)  0/160 (0.00%) 
Pyrexia * 1  4/198 (2.02%)  6/201 (2.99%)  11/162 (6.79%)  11/160 (6.88%) 
Chills * 1  0/198 (0.00%)  1/201 (0.50%)  0/162 (0.00%)  0/160 (0.00%) 
Malaise * 1  1/198 (0.51%)  0/201 (0.00%)  0/162 (0.00%)  0/160 (0.00%) 
Mucosal inflammation * 1  0/198 (0.00%)  1/201 (0.50%)  0/162 (0.00%)  0/160 (0.00%) 
Non-cardiac chest pain * 1  1/198 (0.51%)  0/201 (0.00%)  0/162 (0.00%)  0/160 (0.00%) 
Asthenia * 2  0/198 (0.00%)  0/201 (0.00%)  0/162 (0.00%)  2/160 (1.25%) 
Death * 2  0/198 (0.00%)  0/201 (0.00%)  4/162 (2.47%)  2/160 (1.25%) 
Sudden death * 2  0/198 (0.00%)  0/201 (0.00%)  1/162 (0.62%)  1/160 (0.63%) 
Fatigue * 2  0/198 (0.00%)  0/201 (0.00%)  1/162 (0.62%)  1/160 (0.63%) 
General physical health deterioration * 2  0/198 (0.00%)  0/201 (0.00%)  0/162 (0.00%)  3/160 (1.88%) 
Soft tissue inflammation * 2  0/198 (0.00%)  0/201 (0.00%)  0/162 (0.00%)  1/160 (0.63%) 
Hepatobiliary disorders         
Cholecystitis acute * 1  0/198 (0.00%)  1/201 (0.50%)  0/162 (0.00%)  1/160 (0.63%) 
Hyperbilirubinaemia * 1  2/198 (1.01%)  0/201 (0.00%)  0/162 (0.00%)  1/160 (0.63%) 
Cholecystitis * 1  0/198 (0.00%)  1/201 (0.50%)  0/162 (0.00%)  0/160 (0.00%) 
Cholelithiasis * 1  1/198 (0.51%)  0/201 (0.00%)  0/162 (0.00%)  0/160 (0.00%) 
Drug-induced liver injury * 1  0/198 (0.00%)  1/201 (0.50%)  0/162 (0.00%)  0/160 (0.00%) 
Hepatitis * 1  0/198 (0.00%)  1/201 (0.50%)  0/162 (0.00%)  0/160 (0.00%) 
Bile duct stone * 2  0/198 (0.00%)  0/201 (0.00%)  1/162 (0.62%)  0/160 (0.00%) 
Cholangitis acute * 2  0/198 (0.00%)  0/201 (0.00%)  0/162 (0.00%)  1/160 (0.63%) 
Immune system disorders         
Graft versus host disease * 1  0/198 (0.00%)  1/201 (0.50%)  0/162 (0.00%)  0/160 (0.00%) 
Graft versus host disease in gastrointestinal tract * 1  1/198 (0.51%)  0/201 (0.00%)  0/162 (0.00%)  0/160 (0.00%) 
Graft versus host disease in skin * 1  1/198 (0.51%)  1/201 (0.50%)  0/162 (0.00%)  0/160 (0.00%) 
Hypersensitivity * 1  0/198 (0.00%)  1/201 (0.50%)  0/162 (0.00%)  0/160 (0.00%) 
Cytokine release syndrome * 2  0/198 (0.00%)  0/201 (0.00%)  1/162 (0.62%)  0/160 (0.00%) 
Infections and infestations         
Arthritis infective * 1  1/198 (0.51%)  0/201 (0.00%)  1/162 (0.62%)  0/160 (0.00%) 
Bacteraemia * 1  4/198 (2.02%)  2/201 (1.00%)  3/162 (1.85%)  4/160 (2.50%) 
Bronchopulmonary aspergillosis * 1  1/198 (0.51%)  1/201 (0.50%)  1/162 (0.62%)  0/160 (0.00%) 
Cellulitis * 1  1/198 (0.51%)  0/201 (0.00%)  2/162 (1.23%)  7/160 (4.38%) 
Clostridium difficile colitis * 1  1/198 (0.51%)  1/201 (0.50%)  1/162 (0.62%)  0/160 (0.00%) 
Enterobacter bacteraemia * 1  0/198 (0.00%)  1/201 (0.50%)  1/162 (0.62%)  0/160 (0.00%) 
Escherichia bacteraemia * 1  1/198 (0.51%)  1/201 (0.50%)  1/162 (0.62%)  1/160 (0.63%) 
Infection * 1  3/198 (1.52%)  0/201 (0.00%)  1/162 (0.62%)  5/160 (3.13%) 
Neutropenic sepsis * 1  1/198 (0.51%)  2/201 (1.00%)  3/162 (1.85%)  5/160 (3.13%) 
Perirectal abscess * 1  0/198 (0.00%)  1/201 (0.50%)  1/162 (0.62%)  0/160 (0.00%) 
Pneumonia * 1  15/198 (7.58%)  11/201 (5.47%)  29/162 (17.90%)  36/160 (22.50%) 
Pneumonia fungal * 1  2/198 (1.01%)  2/201 (1.00%)  2/162 (1.23%)  0/160 (0.00%) 
Pseudomembranous colitis * 1  1/198 (0.51%)  0/201 (0.00%)  0/162 (0.00%)  1/160 (0.63%) 
Sepsis * 1  15/198 (7.58%)  13/201 (6.47%)  14/162 (8.64%)  10/160 (6.25%) 
Septic shock * 1  2/198 (1.01%)  4/201 (1.99%)  4/162 (2.47%)  7/160 (4.38%) 
Soft tissue infection * 1  1/198 (0.51%)  0/201 (0.00%)  0/162 (0.00%)  3/160 (1.88%) 
Upper respiratory tract infection * 1  1/198 (0.51%)  0/201 (0.00%)  2/162 (1.23%)  0/160 (0.00%) 
Urinary tract infection * 1  0/198 (0.00%)  1/201 (0.50%)  9/162 (5.56%)  4/160 (2.50%) 
Anorectal infection * 1  0/198 (0.00%)  1/201 (0.50%)  0/162 (0.00%)  0/160 (0.00%) 
Atypical pneumonia * 1  0/198 (0.00%)  1/201 (0.50%)  0/162 (0.00%)  0/160 (0.00%) 
Bacterial sepsis * 1  0/198 (0.00%)  1/201 (0.50%)  0/162 (0.00%)  0/160 (0.00%) 
Brain abscess * 1  0/198 (0.00%)  1/201 (0.50%)  0/162 (0.00%)  0/160 (0.00%) 
Candida pneumonia * 1  0/198 (0.00%)  1/201 (0.50%)  0/162 (0.00%)  0/160 (0.00%) 
Clostridial sepsis * 1  1/198 (0.51%)  0/201 (0.00%)  0/162 (0.00%)  1/160 (0.63%) 
Clostridium bacteraemia * 1  0/198 (0.00%)  1/201 (0.50%)  0/162 (0.00%)  0/160 (0.00%) 
Clostridium colitis * 1  1/198 (0.51%)  0/201 (0.00%)  0/162 (0.00%)  0/160 (0.00%) 
Device related bacteraemia * 1  0/198 (0.00%)  1/201 (0.50%)  0/162 (0.00%)  0/160 (0.00%) 
Diarrhoea infectious * 1  0/198 (0.00%)  1/201 (0.50%)  0/162 (0.00%)  0/160 (0.00%) 
Disseminated varicella zoster virus infection * 1  0/198 (0.00%)  1/201 (0.50%)  0/162 (0.00%)  0/160 (0.00%) 
Enterococcal bacteraemia * 1  2/198 (1.01%)  0/201 (0.00%)  1/162 (0.62%)  1/160 (0.63%) 
Escherichia sepsis * 1  1/198 (0.51%)  1/201 (0.50%)  0/162 (0.00%)  0/160 (0.00%) 
Febrile infection * 1  0/198 (0.00%)  1/201 (0.50%)  0/162 (0.00%)  0/160 (0.00%) 
Fungal infection * 1  1/198 (0.51%)  0/201 (0.00%)  0/162 (0.00%)  0/160 (0.00%) 
Fungal sepsis * 1  0/198 (0.00%)  1/201 (0.50%)  0/162 (0.00%)  0/160 (0.00%) 
Groin abscess * 1  1/198 (0.51%)  0/201 (0.00%)  0/162 (0.00%)  0/160 (0.00%) 
Herpes ophthalmic * 1  1/198 (0.51%)  0/201 (0.00%)  0/162 (0.00%)  0/160 (0.00%) 
Herpes zoster * 1  0/198 (0.00%)  1/201 (0.50%)  0/162 (0.00%)  0/160 (0.00%) 
Peritonitis * 1  1/198 (0.51%)  0/201 (0.00%)  0/162 (0.00%)  0/160 (0.00%) 
Pseudomonal bacteraemia * 1  3/198 (1.52%)  0/201 (0.00%)  0/162 (0.00%)  0/160 (0.00%) 
Pseudomonal sepsis * 1  0/198 (0.00%)  1/201 (0.50%)  0/162 (0.00%)  0/160 (0.00%) 
Pulmonary tuberculosis * 1  1/198 (0.51%)  0/201 (0.00%)  0/162 (0.00%)  0/160 (0.00%) 
Streptococcal sepsis * 1  0/198 (0.00%)  1/201 (0.50%)  0/162 (0.00%)  0/160 (0.00%) 
Urethritis * 1  1/198 (0.51%)  0/201 (0.00%)  0/162 (0.00%)  1/160 (0.63%) 
Abscess * 2  0/198 (0.00%)  0/201 (0.00%)  0/162 (0.00%)  1/160 (0.63%) 
Anal abscess * 2  0/198 (0.00%)  0/201 (0.00%)  1/162 (0.62%)  0/160 (0.00%) 
Bronchitis * 2  0/198 (0.00%)  0/201 (0.00%)  1/162 (0.62%)  1/160 (0.63%) 
COVID-19 * 2  0/198 (0.00%)  0/201 (0.00%)  2/162 (1.23%)  4/160 (2.50%) 
COVID-19 pneumonia * 2  0/198 (0.00%)  0/201 (0.00%)  2/162 (1.23%)  4/160 (2.50%) 
Candida sepsis * 2  0/198 (0.00%)  0/201 (0.00%)  0/162 (0.00%)  1/160 (0.63%) 
Catheter site infection * 2  0/198 (0.00%)  0/201 (0.00%)  1/162 (0.62%)  0/160 (0.00%) 
Device related infection * 2  0/198 (0.00%)  0/201 (0.00%)  0/162 (0.00%)  1/160 (0.63%) 
Diverticulitis * 2  0/198 (0.00%)  0/201 (0.00%)  0/162 (0.00%)  1/160 (0.63%) 
Herpes dermatitis * 2  0/198 (0.00%)  0/201 (0.00%)  0/162 (0.00%)  1/160 (0.63%) 
Infected skin ulcer * 2  0/198 (0.00%)  0/201 (0.00%)  1/162 (0.62%)  0/160 (0.00%) 
Influenza * 2  0/198 (0.00%)  0/201 (0.00%)  1/162 (0.62%)  0/160 (0.00%) 
Klebsiella bacteraemia * 2  0/198 (0.00%)  0/201 (0.00%)  0/162 (0.00%)  2/160 (1.25%) 
Liver abscess * 2  0/198 (0.00%)  0/201 (0.00%)  1/162 (0.62%)  0/160 (0.00%) 
Lower respiratory tract infection * 2  0/198 (0.00%)  0/201 (0.00%)  1/162 (0.62%)  0/160 (0.00%) 
Lower respiratory tract infection bacterial * 2  0/198 (0.00%)  0/201 (0.00%)  0/162 (0.00%)  1/160 (0.63%) 
Otitis media acute * 2  0/198 (0.00%)  0/201 (0.00%)  0/162 (0.00%)  1/160 (0.63%) 
Periodontitis * 2  0/198 (0.00%)  0/201 (0.00%)  0/162 (0.00%)  2/160 (1.25%) 
Pharyngitis * 2  0/198 (0.00%)  0/201 (0.00%)  0/162 (0.00%)  1/160 (0.63%) 
Pneumonia staphylococcal * 2  0/198 (0.00%)  0/201 (0.00%)  0/162 (0.00%)  1/160 (0.63%) 
Post procedural infection * 2  0/198 (0.00%)  0/201 (0.00%)  0/162 (0.00%)  1/160 (0.63%) 
Pyelonephritis acute * 2  0/198 (0.00%)  0/201 (0.00%)  1/162 (0.62%)  2/160 (1.25%) 
Rectal abscess * 2  0/198 (0.00%)  0/201 (0.00%)  0/162 (0.00%)  1/160 (0.63%) 
Skin infection * 2  0/198 (0.00%)  0/201 (0.00%)  0/162 (0.00%)  1/160 (0.63%) 
Staphylococcal sepsis * 2  0/198 (0.00%)  0/201 (0.00%)  1/162 (0.62%)  0/160 (0.00%) 
Subdiaphragmatic abscess * 2  0/198 (0.00%)  0/201 (0.00%)  1/162 (0.62%)  0/160 (0.00%) 
Suspected COVID-19 * 2  0/198 (0.00%)  0/201 (0.00%)  0/162 (0.00%)  1/160 (0.63%) 
Systemic infection * 2  0/198 (0.00%)  0/201 (0.00%)  0/162 (0.00%)  1/160 (0.63%) 
Systemic mycosis * 2  0/198 (0.00%)  0/201 (0.00%)  1/162 (0.62%)  0/160 (0.00%) 
Wound infection * 2  0/198 (0.00%)  0/201 (0.00%)  1/162 (0.62%)  0/160 (0.00%) 
Oral infection * 2  0/198 (0.00%)  0/201 (0.00%)  1/162 (0.62%)  0/160 (0.00%) 
Enteritis infectious * 2  0/198 (0.00%)  0/201 (0.00%)  0/162 (0.00%)  1/160 (0.63%) 
Epididymitis * 2  0/198 (0.00%)  0/201 (0.00%)  0/162 (0.00%)  1/160 (0.63%) 
Superinfection bacterial * 2  0/198 (0.00%)  0/201 (0.00%)  0/162 (0.00%)  1/160 (0.63%) 
Injury, poisoning and procedural complications         
Fall * 1  1/198 (0.51%)  0/201 (0.00%)  0/162 (0.00%)  2/160 (1.25%) 
Spinal fracture * 1  0/198 (0.00%)  1/201 (0.50%)  0/162 (0.00%)  0/160 (0.00%) 
Splenic rupture * 1  0/198 (0.00%)  1/201 (0.50%)  0/162 (0.00%)  0/160 (0.00%) 
Femoral neck fracture * 2  0/198 (0.00%)  0/201 (0.00%)  0/162 (0.00%)  1/160 (0.63%) 
Hip fracture * 2  0/198 (0.00%)  0/201 (0.00%)  1/162 (0.62%)  0/160 (0.00%) 
Lumbar vertebral fracture * 2  0/198 (0.00%)  0/201 (0.00%)  0/162 (0.00%)  1/160 (0.63%) 
Post procedural complication * 2  0/198 (0.00%)  0/201 (0.00%)  0/162 (0.00%)  1/160 (0.63%) 
Subdural haematoma * 2  0/198 (0.00%)  0/201 (0.00%)  1/162 (0.62%)  0/160 (0.00%) 
Subdural haemorrhage * 2  0/198 (0.00%)  0/201 (0.00%)  0/162 (0.00%)  1/160 (0.63%) 
Tooth fracture * 2  0/198 (0.00%)  0/201 (0.00%)  0/162 (0.00%)  1/160 (0.63%) 
Transfusion reaction * 2  0/198 (0.00%)  0/201 (0.00%)  1/162 (0.62%)  0/160 (0.00%) 
Investigations         
Blood creatinine increased * 1  3/198 (1.52%)  1/201 (0.50%)  2/162 (1.23%)  2/160 (1.25%) 
Electrocardiogram QT prolonged * 1  13/198 (6.57%)  8/201 (3.98%)  5/162 (3.09%)  3/160 (1.88%) 
Platelet count decreased * 1  1/198 (0.51%)  0/201 (0.00%)  1/162 (0.62%)  0/160 (0.00%) 
Alanine aminotransferase increased * 1  1/198 (0.51%)  2/201 (1.00%)  1/162 (0.62%)  0/160 (0.00%) 
Aspartate aminotransferase increased * 1  1/198 (0.51%)  2/201 (1.00%)  1/162 (0.62%)  0/160 (0.00%) 
Blood alkaline phosphatase increased * 1  1/198 (0.51%)  1/201 (0.50%)  0/162 (0.00%)  0/160 (0.00%) 
Blood bilirubin increased * 1  2/198 (1.01%)  3/201 (1.49%)  0/162 (0.00%)  0/160 (0.00%) 
Blood lactate dehydrogenase increased * 1  0/198 (0.00%)  1/201 (0.50%)  0/162 (0.00%)  0/160 (0.00%) 
Gamma-glutamyltransferase increased * 1  0/198 (0.00%)  1/201 (0.50%)  0/162 (0.00%)  0/160 (0.00%) 
Neutrophil count decreased * 1  0/198 (0.00%)  1/201 (0.50%)  0/162 (0.00%)  0/160 (0.00%) 
C-reactive protein increased * 2  0/198 (0.00%)  0/201 (0.00%)  0/162 (0.00%)  2/160 (1.25%) 
Creatinine renal clearance decreased * 2  0/198 (0.00%)  0/201 (0.00%)  1/162 (0.62%)  0/160 (0.00%) 
Electroencephalogram abnormal * 2  0/198 (0.00%)  0/201 (0.00%)  1/162 (0.62%)  0/160 (0.00%) 
SARS-CoV-2 test positive * 2  0/198 (0.00%)  0/201 (0.00%)  0/162 (0.00%)  1/160 (0.63%) 
Weight decreased * 2  0/198 (0.00%)  0/201 (0.00%)  1/162 (0.62%)  0/160 (0.00%) 
Metabolism and nutrition disorders         
Decreased appetite * 1  0/198 (0.00%)  1/201 (0.50%)  3/162 (1.85%)  1/160 (0.63%) 
Hyperglycaemia * 1  0/198 (0.00%)  1/201 (0.50%)  0/162 (0.00%)  0/160 (0.00%) 
Hypokalaemia * 1  0/198 (0.00%)  1/201 (0.50%)  0/162 (0.00%)  0/160 (0.00%) 
Failure to thrive * 2  0/198 (0.00%)  0/201 (0.00%)  0/162 (0.00%)  1/160 (0.63%) 
Hyperkalaemia * 2  0/198 (0.00%)  0/201 (0.00%)  0/162 (0.00%)  3/160 (1.88%) 
Hyperuricaemia * 2  0/198 (0.00%)  0/201 (0.00%)  2/162 (1.23%)  0/160 (0.00%) 
Hyponatraemia * 2  1/198 (0.51%)  0/201 (0.00%)  2/162 (1.23%)  1/160 (0.63%) 
Hypophosphataemia * 2  0/198 (0.00%)  0/201 (0.00%)  1/162 (0.62%)  1/160 (0.63%) 
Musculoskeletal and connective tissue disorders         
Myalgia * 1  0/198 (0.00%)  1/201 (0.50%)  0/162 (0.00%)  1/160 (0.63%) 
Back pain * 2  0/198 (0.00%)  0/201 (0.00%)  1/162 (0.62%)  0/160 (0.00%) 
Osteoarthritis * 2  0/198 (0.00%)  0/201 (0.00%)  0/162 (0.00%)  1/160 (0.63%) 
Soft tissue necrosis * 2  0/198 (0.00%)  0/201 (0.00%)  1/162 (0.62%)  0/160 (0.00%) 
Synovitis * 2  0/198 (0.00%)  0/201 (0.00%)  0/162 (0.00%)  1/160 (0.63%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Differentiation syndrome * 2  0/198 (0.00%)  0/201 (0.00%)  0/162 (0.00%)  2/160 (1.25%) 
Gastrointestinal neoplasm * 2  0/198 (0.00%)  0/201 (0.00%)  0/162 (0.00%)  1/160 (0.63%) 
Neoplasm progression * 2  0/198 (0.00%)  0/201 (0.00%)  0/162 (0.00%)  2/160 (1.25%) 
Neoplasm prostate * 2  0/198 (0.00%)  0/201 (0.00%)  1/162 (0.62%)  0/160 (0.00%) 
Nervous system disorders         
Epilepsy * 1  0/198 (0.00%)  1/201 (0.50%)  1/162 (0.62%)  0/160 (0.00%) 
Haemorrhage intracranial * 1  2/198 (1.01%)  2/201 (1.00%)  1/162 (0.62%)  1/160 (0.63%) 
Syncope * 1  1/198 (0.51%)  0/201 (0.00%)  1/162 (0.62%)  1/160 (0.63%) 
Carotid artery stenosis * 1  0/198 (0.00%)  1/201 (0.50%)  0/162 (0.00%)  0/160 (0.00%) 
Cerebral haemorrhage * 1  1/198 (0.51%)  1/201 (0.50%)  0/162 (0.00%)  0/160 (0.00%) 
Seizure * 1  0/198 (0.00%)  1/201 (0.50%)  0/162 (0.00%)  1/160 (0.63%) 
Central nervous system lesion * 2  0/198 (0.00%)  0/201 (0.00%)  0/162 (0.00%)  1/160 (0.63%) 
Cerebral infarction * 2  0/198 (0.00%)  0/201 (0.00%)  2/162 (1.23%)  2/160 (1.25%) 
Cerebrovascular accident * 2  0/198 (0.00%)  0/201 (0.00%)  2/162 (1.23%)  2/160 (1.25%) 
Encephalopathy * 2  0/198 (0.00%)  0/201 (0.00%)  0/162 (0.00%)  1/160 (0.63%) 
Intracranial aneurysm * 2  0/198 (0.00%)  0/201 (0.00%)  0/162 (0.00%)  1/160 (0.63%) 
Metabolic encephalopathy * 2  0/198 (0.00%)  0/201 (0.00%)  1/162 (0.62%)  0/160 (0.00%) 
Partial seizures * 2  0/198 (0.00%)  0/201 (0.00%)  1/162 (0.62%)  0/160 (0.00%) 
Somnolence * 2  0/198 (0.00%)  0/201 (0.00%)  1/162 (0.62%)  0/160 (0.00%) 
Psychiatric disorders         
Confusional state * 1  0/198 (0.00%)  1/201 (0.50%)  1/162 (0.62%)  0/160 (0.00%) 
Adjustment disorder with depressed mood * 1  1/198 (0.51%)  0/201 (0.00%)  0/162 (0.00%)  0/160 (0.00%) 
Hallucination * 2  0/198 (0.00%)  0/201 (0.00%)  1/162 (0.62%)  0/160 (0.00%) 
Renal and urinary disorders         
Acute kidney injury * 1  2/198 (1.01%)  3/201 (1.49%)  1/162 (0.62%)  1/160 (0.63%) 
Chronic kidney disease * 2  0/198 (0.00%)  0/201 (0.00%)  1/162 (0.62%)  0/160 (0.00%) 
Haematuria * 2  0/198 (0.00%)  0/201 (0.00%)  2/162 (1.23%)  1/160 (0.63%) 
Renal failure * 2  0/198 (0.00%)  0/201 (0.00%)  1/162 (0.62%)  0/160 (0.00%) 
Urinary retention * 2  0/198 (0.00%)  0/201 (0.00%)  0/162 (0.00%)  1/160 (0.63%) 
Respiratory, thoracic and mediastinal disorders         
Dyspnoea * 1  0/198 (0.00%)  1/201 (0.50%)  3/162 (1.85%)  1/160 (0.63%) 
Epistaxis * 1  2/198 (1.01%)  0/201 (0.00%)  1/162 (0.62%)  0/160 (0.00%) 
Respiratory failure * 1  1/198 (0.51%)  3/201 (1.49%)  1/162 (0.62%)  1/160 (0.63%) 
Acute respiratory distress syndrome * 1  1/198 (0.51%)  0/201 (0.00%)  0/162 (0.00%)  0/160 (0.00%) 
Acute respiratory failure * 1  1/198 (0.51%)  4/201 (1.99%)  0/162 (0.00%)  0/160 (0.00%) 
Hypoxia * 1  1/198 (0.51%)  2/201 (1.00%)  0/162 (0.00%)  0/160 (0.00%) 
Lung infiltration * 1  0/198 (0.00%)  1/201 (0.50%)  0/162 (0.00%)  0/160 (0.00%) 
Pulmonary alveolar haemorrhage * 1  0/198 (0.00%)  1/201 (0.50%)  0/162 (0.00%)  0/160 (0.00%) 
Pulmonary haemorrhage * 1  1/198 (0.51%)  0/201 (0.00%)  0/162 (0.00%)  0/160 (0.00%) 
Oropharyngeal pain * 2  0/198 (0.00%)  0/201 (0.00%)  1/162 (0.62%)  0/160 (0.00%) 
Pneumonia aspiration * 2  0/198 (0.00%)  0/201 (0.00%)  1/162 (0.62%)  0/160 (0.00%) 
Pneumonitis * 2  0/198 (0.00%)  0/201 (0.00%)  0/162 (0.00%)  3/160 (1.88%) 
Pneumothorax * 2  0/198 (0.00%)  0/201 (0.00%)  0/162 (0.00%)  1/160 (0.63%) 
Pulmonary oedema * 2  0/198 (0.00%)  0/201 (0.00%)  0/162 (0.00%)  1/160 (0.63%) 
Skin and subcutaneous tissue disorders         
Erythema * 1  1/198 (0.51%)  0/201 (0.00%)  0/162 (0.00%)  0/160 (0.00%) 
Rash * 1  1/198 (0.51%)  0/201 (0.00%)  0/162 (0.00%)  0/160 (0.00%) 
Rash maculo-papular * 1  0/198 (0.00%)  1/201 (0.50%)  0/162 (0.00%)  0/160 (0.00%) 
Dermatitis exfoliative generalised * 2  0/198 (0.00%)  0/201 (0.00%)  1/162 (0.62%)  0/160 (0.00%) 
Drug eruption * 2  0/198 (0.00%)  0/201 (0.00%)  0/162 (0.00%)  1/160 (0.63%) 
Vascular disorders         
Deep vein thrombosis * 1  0/198 (0.00%)  1/201 (0.50%)  0/162 (0.00%)  1/160 (0.63%) 
Hypotension * 1  1/198 (0.51%)  1/201 (0.50%)  1/162 (0.62%)  1/160 (0.63%) 
Embolism * 1  0/198 (0.00%)  1/201 (0.50%)  0/162 (0.00%)  0/160 (0.00%) 
Orthostatic hypotension * 1  1/198 (0.51%)  0/201 (0.00%)  0/162 (0.00%)  0/160 (0.00%) 
Aneurysm ruptured * 2  0/198 (0.00%)  0/201 (0.00%)  0/162 (0.00%)  1/160 (0.63%) 
Axillary vein thrombosis * 2  0/198 (0.00%)  0/201 (0.00%)  0/162 (0.00%)  1/160 (0.63%) 
Circulatory collapse * 2  0/198 (0.00%)  0/201 (0.00%)  1/162 (0.62%)  0/160 (0.00%) 
Hypovolaemic shock * 2  0/198 (0.00%)  0/201 (0.00%)  0/162 (0.00%)  1/160 (0.63%) 
Peripheral ischaemia * 2  0/198 (0.00%)  0/201 (0.00%)  0/162 (0.00%)  1/160 (0.63%) 
Thrombophlebitis superficial * 2  0/198 (0.00%)  0/201 (0.00%)  1/162 (0.62%)  0/160 (0.00%) 
Thrombosis * 2  0/198 (0.00%)  0/201 (0.00%)  0/162 (0.00%)  1/160 (0.63%) 
Venous thrombosis * 2  0/198 (0.00%)  0/201 (0.00%)  1/162 (0.62%)  0/160 (0.00%) 
Superficial vein thrombosis * 2  0/198 (0.00%)  0/201 (0.00%)  1/162 (0.62%)  0/160 (0.00%) 
1
Term from vocabulary, MedDRA v23.1
2
Term from vocabulary, MedDRA v24.1
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Intensive Study: Glasdegib + Cytarabine + Daunorubicin Intensive Study: Placebo + Cytarabine + Daunorubicin Non-intensive Study: Glasdegib + Azacitidine Non-intensive Study: Placebo + Azacitidine
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   194/198 (97.98%)   195/201 (97.01%)   154/162 (95.06%)   148/160 (92.50%) 
Blood and lymphatic system disorders         
Anaemia * 1  101/198 (51.01%)  97/201 (48.26%)  73/162 (45.06%)  71/160 (44.38%) 
Febrile neutropenia * 1  97/198 (48.99%)  96/201 (47.76%)  23/162 (14.20%)  22/160 (13.75%) 
Leukopenia * 1  10/198 (5.05%)  13/201 (6.47%)  13/162 (8.02%)  4/160 (2.50%) 
Neutropenia * 1  41/198 (20.71%)  43/201 (21.39%)  38/162 (23.46%)  30/160 (18.75%) 
Thrombocytopenia * 1  52/198 (26.26%)  52/201 (25.87%)  38/162 (23.46%)  35/160 (21.88%) 
Cardiac disorders         
Sinus tachycardia * 1  11/198 (5.56%)  7/201 (3.48%)  0/162 (0.00%)  0/160 (0.00%) 
Gastrointestinal disorders         
Abdominal pain * 1  31/198 (15.66%)  29/201 (14.43%)  12/162 (7.41%)  10/160 (6.25%) 
Constipation * 1  71/198 (35.86%)  61/201 (30.35%)  58/162 (35.80%)  52/160 (32.50%) 
Diarrhoea * 1  96/198 (48.48%)  88/201 (43.78%)  39/162 (24.07%)  32/160 (20.00%) 
Haemorrhoids * 1  13/198 (6.57%)  19/201 (9.45%)  9/162 (5.56%)  11/160 (6.88%) 
Nausea * 1  110/198 (55.56%)  106/201 (52.74%)  58/162 (35.80%)  44/160 (27.50%) 
Vomiting * 1  57/198 (28.79%)  40/201 (19.90%)  35/162 (21.60%)  32/160 (20.00%) 
Abdominal pain upper * 1  12/198 (6.06%)  9/201 (4.48%)  0/162 (0.00%)  0/160 (0.00%) 
Dyspepsia * 1  12/198 (6.06%)  5/201 (2.49%)  0/162 (0.00%)  0/160 (0.00%) 
Proctalgia * 1  14/198 (7.07%)  6/201 (2.99%)  0/162 (0.00%)  0/160 (0.00%) 
Stomatitis * 1  29/198 (14.65%)  41/201 (20.40%)  0/162 (0.00%)  0/160 (0.00%) 
General disorders         
Asthenia * 1  15/198 (7.58%)  11/201 (5.47%)  16/162 (9.88%)  18/160 (11.25%) 
Fatigue * 1  31/198 (15.66%)  32/201 (15.92%)  14/162 (8.64%)  23/160 (14.37%) 
Oedema peripheral * 1  25/198 (12.63%)  32/201 (15.92%)  11/162 (6.79%)  19/160 (11.88%) 
Pyrexia * 1  84/198 (42.42%)  84/201 (41.79%)  42/162 (25.93%)  38/160 (23.75%) 
Chills * 1  20/198 (10.10%)  11/201 (5.47%)  0/162 (0.00%)  0/160 (0.00%) 
Mucosal inflammation * 1  12/198 (6.06%)  7/201 (3.48%)  0/162 (0.00%)  0/160 (0.00%) 
Non-cardiac chest pain * 1  13/198 (6.57%)  8/201 (3.98%)  0/162 (0.00%)  0/160 (0.00%) 
Oedema * 1  9/198 (4.55%)  19/201 (9.45%)  0/162 (0.00%)  0/160 (0.00%) 
Injection site reaction * 2  0/198 (0.00%)  0/201 (0.00%)  12/162 (7.41%)  7/160 (4.38%) 
Hepatobiliary disorders         
Hyperbilirubinaemia * 2  0/198 (0.00%)  0/201 (0.00%)  11/162 (6.79%)  1/160 (0.63%) 
Infections and infestations         
Pneumonia * 1  32/198 (16.16%)  33/201 (16.42%)  19/162 (11.73%)  16/160 (10.00%) 
Upper respiratory tract infection * 1  9/198 (4.55%)  11/201 (5.47%)  12/162 (7.41%)  11/160 (6.88%) 
Urinary tract infection * 1  5/198 (2.53%)  11/201 (5.47%)  17/162 (10.49%)  10/160 (6.25%) 
Bacteraemia * 1  16/198 (8.08%)  11/201 (5.47%)  0/162 (0.00%)  0/160 (0.00%) 
Injury, poisoning and procedural complications         
Fall * 2  0/198 (0.00%)  0/201 (0.00%)  11/162 (6.79%)  10/160 (6.25%) 
Investigations         
Alanine aminotransferase increased * 1  39/198 (19.70%)  53/201 (26.37%)  14/162 (8.64%)  12/160 (7.50%) 
Aspartate aminotransferase increased * 1  30/198 (15.15%)  41/201 (20.40%)  11/162 (6.79%)  9/160 (5.63%) 
Blood creatinine increased * 1  18/198 (9.09%)  13/201 (6.47%)  20/162 (12.35%)  13/160 (8.13%) 
Electrocardiogram QT prolonged * 1  21/198 (10.61%)  20/201 (9.95%)  20/162 (12.35%)  19/160 (11.88%) 
Gamma-glutamyltransferase increased * 1  12/198 (6.06%)  22/201 (10.95%)  10/162 (6.17%)  8/160 (5.00%) 
Neutrophil count decreased * 1  56/198 (28.28%)  49/201 (24.38%)  22/162 (13.58%)  23/160 (14.37%) 
Platelet count decreased * 1  77/198 (38.89%)  73/201 (36.32%)  30/162 (18.52%)  26/160 (16.25%) 
Weight decreased * 1  21/198 (10.61%)  22/201 (10.95%)  36/162 (22.22%)  19/160 (11.88%) 
White blood cell count decreased * 1  63/198 (31.82%)  53/201 (26.37%)  17/162 (10.49%)  18/160 (11.25%) 
Blood alkaline phosphatase increased * 1  14/198 (7.07%)  13/201 (6.47%)  0/162 (0.00%)  0/160 (0.00%) 
Blood bilirubin increased * 1  25/198 (12.63%)  13/201 (6.47%)  0/162 (0.00%)  0/160 (0.00%) 
Lymphocyte count decreased * 1  19/198 (9.60%)  21/201 (10.45%)  0/162 (0.00%)  0/160 (0.00%) 
C-reactive protein increased * 2  0/198 (0.00%)  0/201 (0.00%)  7/162 (4.32%)  9/160 (5.63%) 
White blood cell count increased * 2  0/198 (0.00%)  0/201 (0.00%)  9/162 (5.56%)  8/160 (5.00%) 
Metabolism and nutrition disorders         
Decreased appetite * 1  52/198 (26.26%)  41/201 (20.40%)  45/162 (27.78%)  21/160 (13.13%) 
Hyperglycaemia * 1  10/198 (5.05%)  10/201 (4.98%)  6/162 (3.70%)  9/160 (5.63%) 
Hypoalbuminaemia * 1  32/198 (16.16%)  30/201 (14.93%)  11/162 (6.79%)  13/160 (8.13%) 
Hypocalcaemia * 1  25/198 (12.63%)  17/201 (8.46%)  10/162 (6.17%)  13/160 (8.13%) 
Hypokalaemia * 1  76/198 (38.38%)  83/201 (41.29%)  35/162 (21.60%)  22/160 (13.75%) 
Hypomagnesaemia * 1  29/198 (14.65%)  24/201 (11.94%)  11/162 (6.79%)  5/160 (3.13%) 
Hyponatraemia * 1  24/198 (12.12%)  15/201 (7.46%)  17/162 (10.49%)  9/160 (5.63%) 
Hypophosphataemia * 1  42/198 (21.21%)  44/201 (21.89%)  10/162 (6.17%)  15/160 (9.38%) 
Hyperuricaemia * 1  13/198 (6.57%)  9/201 (4.48%)  0/162 (0.00%)  0/160 (0.00%) 
Musculoskeletal and connective tissue disorders         
Arthralgia * 1  17/198 (8.59%)  14/201 (6.97%)  11/162 (6.79%)  12/160 (7.50%) 
Back pain * 1  22/198 (11.11%)  17/201 (8.46%)  8/162 (4.94%)  12/160 (7.50%) 
Muscle spasms * 1  20/198 (10.10%)  3/201 (1.49%)  31/162 (19.14%)  4/160 (2.50%) 
Myalgia * 1  15/198 (7.58%)  11/201 (5.47%)  0/162 (0.00%)  0/160 (0.00%) 
Nervous system disorders         
Dizziness * 1  23/198 (11.62%)  18/201 (8.96%)  9/162 (5.56%)  14/160 (8.75%) 
Dysgeusia * 1  39/198 (19.70%)  20/201 (9.95%)  38/162 (23.46%)  8/160 (5.00%) 
Headache * 1  39/198 (19.70%)  47/201 (23.38%)  4/162 (2.47%)  9/160 (5.63%) 
Paraesthesia * 1  11/198 (5.56%)  0/201 (0.00%)  0/162 (0.00%)  0/160 (0.00%) 
Psychiatric disorders         
Insomnia * 1  27/198 (13.64%)  30/201 (14.93%)  12/162 (7.41%)  8/160 (5.00%) 
Respiratory, thoracic and mediastinal disorders         
Cough * 1  23/198 (11.62%)  23/201 (11.44%)  10/162 (6.17%)  20/160 (12.50%) 
Dyspnoea * 1  15/198 (7.58%)  23/201 (11.44%)  12/162 (7.41%)  18/160 (11.25%) 
Epistaxis * 1  19/198 (9.60%)  20/201 (9.95%)  8/162 (4.94%)  11/160 (6.88%) 
Oropharyngeal pain * 1  19/198 (9.60%)  19/201 (9.45%)  0/162 (0.00%)  0/160 (0.00%) 
Skin and subcutaneous tissue disorders         
Alopecia * 1  22/198 (11.11%)  26/201 (12.94%)  20/162 (12.35%)  3/160 (1.88%) 
Pruritus * 1  12/198 (6.06%)  11/201 (5.47%)  8/162 (4.94%)  9/160 (5.63%) 
Rash * 1  46/198 (23.23%)  51/201 (25.37%)  10/162 (6.17%)  13/160 (8.13%) 
Dry skin * 1  13/198 (6.57%)  10/201 (4.98%)  0/162 (0.00%)  0/160 (0.00%) 
Petechiae * 1  8/198 (4.04%)  11/201 (5.47%)  0/162 (0.00%)  0/160 (0.00%) 
Rash maculo-papular * 1  21/198 (10.61%)  21/201 (10.45%)  0/162 (0.00%)  0/160 (0.00%) 
Purpura * 2  0/198 (0.00%)  0/201 (0.00%)  9/162 (5.56%)  5/160 (3.13%) 
Vascular disorders         
Hypertension * 1  10/198 (5.05%)  25/201 (12.44%)  0/162 (0.00%)  0/160 (0.00%) 
Hypotension * 1  18/198 (9.09%)  17/201 (8.46%)  0/162 (0.00%)  0/160 (0.00%) 
1
Term from vocabulary, MedDRA v23.1
2
Term from vocabulary, MedDRA v24.1
*
Indicates events were collected by non-systematic assessment
In this study, inadvertently a participant was counted twice for an non-SAE "Pyrexia" at PCD, at SCD update this duplicity has been rectified. Due to this reason total number of participants affected by non-SAE in non-intensive placebo arm was updated to "148".
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: NCT03416179    
Other Study ID Numbers: B1371019
2017-002822-19 ( EudraCT Number )
BRIGHT ( Other Identifier: Alias Study Number )
BRIGHT AML1019 ( Other Identifier: Alias Study Number )
First Submitted: December 21, 2017
First Posted: January 31, 2018
Results First Submitted: June 2, 2021
Results First Posted: June 25, 2021
Last Update Posted: April 21, 2023