BRIGHT 1012: A Combination Study of PF-04449913 (Glasdegib) and Azacitidine In Untreated MDS, AML and CMML Patients

Sponsor
Pfizer (Industry)
Overall Status
Completed
CT.gov ID
NCT02367456
Collaborator
(none)
73
33
2
82.3
2.2
0

Study Details

Study Description

Brief Summary

This multi center open label Phase 1b study is designed to evaluate the safety, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of glasdegib (PF-04449913) when combined with azacitidine in patients with previously untreated Higher Risk Myelodysplastic Syndrome (MDS), Acute Myeloid Leukemia (AML), or Chronic Myelomonocytic Leukemia (CMML). This clinical study includes two components: (a) a safety lead in cohort (LIC) and (b) an expansion phase with an AML cohort and an MDS cohort.

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
73 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Open-label Phase 1b Study of PF-04449913 (Glasdegib) in Combination With Azacitidine in Patients With Previously Untreated Higher-Risk Myelodysplastic Syndrome, Acute Myeloid Leukemia, or Chronic Myelomonocytic Leukemia
Actual Study Start Date :
Apr 28, 2015
Actual Primary Completion Date :
Jan 29, 2020
Actual Study Completion Date :
Mar 7, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: Arm A

MDS patients: PF-04449913 (Glasdegib) 100 mg + Azacitidine 75 mg/m2

Drug: PF-04449913 (Glasdegib)
Daily dose of PF-04449913 100mg tablet in a continuous regimen of 28 day cycles

Drug: Azacitidine
75mg/m2 on Days 1-7 (+/- 3 days for each dose) of a 28 day cycle

Experimental: Arm B

AML patients: PF-04449913 (Glasdegib) 100 mg + Azacitidine 75 mg/m2

Drug: PF-04449913 (Glasdegib)
Daily dose of PF-04449913 100mg tablet in a continuous regimen of 28 day cycles

Drug: Azacitidine
75mg/m2 on Days 1-7 (+/- 3 days for each dose) of a 28 day cycle

Outcome Measures

Primary Outcome Measures

  1. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Lead-in Cohort (LIC) [Cycle 1 Day 1 up to 28 days after last dose of study drug or beginning of new anti-cancer therapy (assessed up to 16 months)]

    An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with the study treatment. TEAEs were AEs that occurred after initiation of treatment or AEs increasing in severity during treatment. Treatment-related TEAEs were determined by the investigator. Grades of AEs were defined by NCI CTCAE version 4.03.

  2. Number of Participants With Serious Adverse Events (SAEs) in the LIC [Cycle 1 Day 1 up to 28 days after last dose of study drug or beginning of new anti-cancer therapy (assessed up to 16 months)]

    An serious adverse event (SAE) was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. Treatment-related SAEs were determined by the investigator. Grades of AEs were defined by NCI CTCAE version 4.03.

  3. Number of Participants With Laboratory Abnormalities in the LIC [Cycle 1 Day 1 to last follow up visit (at least 28 days after discontinuation of treatment) (assessed up to 17 months)]

    Laboratory parameters included: hematology parameters (activated partial thromboplastin time, hemoglobin, INR, lymphocyte count, neutrophil count, platelet count, white blood cell), chemistry parameters (alanine aminotransferase, aspartate aminotransferase, alkaline aminotransferase, blood bilirubin, CPK, creatinine, calcium, blood glucose, potassium, magnesium, sodium, albumin, phosphate). Grades of laboratory abnormalities were defined by NCI CTCAE version 4.03.

  4. Percentage of Participants Achieving Complete Remission (CR) in the AML and MDS Cohorts [Cycle 1 Day 1 to End of Treatment (EoT) visit (within 14 days after last dose) (assessed up to 22 months)]

    Percentage of participants achieving CR as defined by the 2017 European Leukemia Net (ELN) Response Criteria for all participants with AML and modified International Working Group (IWG) criteria (2006) for all participants with MDS in the expansion cohorts. For AML cohort, CR was defined as neutrophils ≥ 1 x 10^9/L, platelets ≥ 1 x 10^11/L, percentage of bone marrow blasts (BMB) <5% with no peripheral blasts and no blasts with Auer rods, no extramedullary disease (EMD), and transfusion independent. For MDS cohort, CR was defined as having responses of hemoglobin ≥11 g/dL, neutrophils ≥1 x 10^9/L, platelets ≥1 x 10^11/L, percentage of blasts = 0%, percentage of BMB≤5%, and normal maturation of all cell lines (note if has persistent dysplasia), and all responses must last at least 4 weeks.

Secondary Outcome Measures

  1. Percentage of Participants Achieving Complete Remission (CR) + Partial Remission (PR) in the LIC [Cycle 1 Day 1 to last follow up visit (at least 28 days after discontinuation of treatment) (assessed up to 18 months)]

    RR (Percentage of participants achieving CR+PR among all the enrolled and treated patients as defined by modified International Working Group (IWG) criteria (2006)) in the LIC. CR was defined as having responses of hemoglobin ≥11 g/dL, neutrophils ≥1 x 10^9/L, platelets ≥1 x 10^11/L, percentage of blasts = 0%, percentage of BMB≤5%, and normal maturation of all cell lines (note if has persistent dysplasia), and all responses must last at least 4 weeks. PR was defined as meeting all CR criteria if abnormal before treatment except BMB, percentage of BMB decreased by ≥50% but still >5% for at least 4 weeks.

  2. Number of Participants With Efficacy Measures Other Than CR in the LIC [Cycle 1 Day 1 to last follow up visit (at least 28 days after discontinuation of treatment) (assessed up to 18 months)]

    Number of participants with efficacy measures other than CR as defined by modified IWG criteria (2006) in LIC, including marrow CR(mCR), stable disease(SD), hematologic improvement(HI). CR: hemoglobin≥11 g/dL, neutrophils≥1 x 10^9/L, platelets≥1 x 10^11/L, percentage of blasts=0%, percentage of BMB≤5%, normal maturation of all cell lines (note if has persistent dysplasia), all responses last at least 4 weeks. mCR: BMB≤5% & decreased by≥50%. SD: failure to achieve PR, no evidence of progression. HI: erythroid response (pretreatment<11g/dL): hemoglobin increase by≥1.5 g/dL, relevant reduction of units of red blood cell transfusions by at least 4 transfusions/8 weeks compared to pretreatment transfusion number in previous 8 weeks; platelet response (pretreatment<1x10^11/L): increase of≥30x10^9/L if starting with >20x10^9/L, and increase from <20x10^9/L to >20x10^9/L and by at least 100%; neutrophil response (pretreatment<1x10^9/L): at least a 100% increase, absolute increase >0.5x10^9/L

  3. Number of Participants With TEAEs in the AML and MDS Cohorts [Cycle 1 Day 1 to EoT visit (within 14 days after last dose) (assessed up to 24 months)]

    An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with the study treatment. TEAEs were AEs that occurred after initiation of treatment or AEs increasing in severity during treatment. Treatment-related TEAEs were determined by the investigator. AEs were graded by NCI CTCAE version 4.03.

  4. Number of Participants With SAEs in the AML and MDS Cohorts [Cycle 1 Day 1 to EoT visit (within 14 days after last dose) (assessed up to 24 months)]

    A serious adverse event (SAE) was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. Treatment-related SAEs were determined by the investigator. AEs were graded by NCI CTCAE version 4.03.

  5. Number of Participants With Laboratory Abnormalities in the AML and MDS Cohorts [Cycle 1 Day 1 to EoT visit (within 14 days after last dose) (assessed up to 24 months)]

    Laboratory parameters included: hematology parameters (activated partial thromboplastin time, hemoglobin, INR, lymphocyte count, neutrophil count, platelet count, white blood cell), chemistry parameters (alanine aminotransferase, aspartate aminotransferase, alkaline aminotransferase, blood bilirubin, CPK, creatinine, calcium, blood glucose, potassium, magnesium, sodium, albumin, phosphate). Laboratory abnormalities were graded by NCI CTCAE version 4.03.

  6. Number of Participants With Disease-Specific Efficacy Measures in the AML Cohort [Cycle 1 Day 1 to EoT visit (within 14 days after last dose) (assessed up to 20 months)]

    Number of participants with CR with partial hematologic recovery (CRh), CR with incomplete blood count recovery (CRi), partial remission (PR), stable disease (SD), and morphologic leukemia free state (MLFS). CRh: neutrophils>5x10^8/L, platelets>5x10^10/L, BMB<5%, no peripheral blasts, no blasts with Auer rods, no extramedullary disease (EMD), not qualifying for CR. CRi: neutrophils <1x10^9/L or platelets<1x10^11/L; BMB <5%, no peripheral blasts, no blasts with Auer rods; no EMD; neutrophils or platelets not recovered; not qualifying for CRh. PR: neutrophils ≥1x10^9/L; platelets ≥1x10^11/L; blasts decreased to 5-25% and ≥50% decrease from pretreatment; blasts≤5% if Auer rod positive. SD: ≥3 months of absence of CR without minimal residual disease (CRMRD-), CR, CRh, CRi, PR, and MLFS, criteria for PD not met. MLFS: neutrophils <1x10^9/L and platelets<1x10^11/L, BMB<5%, no blasts with Auer rods; no EMD; neutrophils and platelets not recovered; not qualifying for CRi

  7. Number of Participants With Disease-Specific Efficacy Measures in the MDS Cohort [Cycle 1 Day 1 to EoT visit (within 14 days after last dose) (assessed up to 22 months)]

    Number of participants with PR, marrow CR (mCR), SD, complete or partial cytogenetic response, and hematologic improvement (HI). PR: BMB >5% and decreased by ≥50% (at least 4 weeks), meeting all CR criteria if abnormal before treatment except BMB. mCR: BMB ≤5% and decreased by ≥50%. SD: failure to achieve PR, no evidence of progression. Complete or partial cytogenic response: disappearance of chromosomal abnormality without new ones, or ≥ 50% reduction of chromosomal abnormality. HI: erythroid response (pretreatment <11g/dL): hemoglobin increase by≥1.5 g/dL, relevant reduction of units of red blood cell transfusions by at least 4 transfusions/8 weeks compared to pretreatment transfusion number in previous 8 weeks; platelet response (pretreatment <1x10^11/L): increase of ≥30x10^9/L if starting with >20x10^9/L, and increase from <20x10^9/L to >20x10^9/L and by at least 100%; neutrophil response (pretreatment <1x10^9/L): at least a 100% increase, absolute increase >0.5x10^9/L.

  8. Kaplan-Meier Estimate of Median Overall Survival (OS) in the AML and MDS Cohorts [Cycle 1 Day 1 to date of death from any cause (assessed up to 24 months)]

    Overall survival (OS) was defined as the time from date of first study treatment to date of death from any cause. Patients last known to be alive were to be censored at the date of last contact. OS was analyzed and displayed graphically for each expansion cohort separately using the Kaplan-Meier method. The median event time and corresponding two-sided 95%CI were provided for each cohort. OS was first analyzed when the primary endpoint of CR was analyzed in the respective expansion cohort.

  9. Duration of CR in the AML and MDS Cohorts [Cycle 1 Day 1 to EoT visit (within 14 days after last dose) (assessed up to 24 months)]

    Duration of CR was defined as the duration from date of first achieving CR to the date of disease progression (relapse) after CR, or death due to any cause. Participants last known to be alive who were free from disease progression or relapse after CR were censored at the date of the last assessment that verified their disease status. Duration of CR was analyzed using the Kaplan-Meier method. Disease progression was defined as: percentage of bone marrow blasts increased by ≥50% to >5% (for participants with <5% blasts at screening), >10% (for participants with 5-10% blasts at screening), >20% (for participants with 11-20% blasts at screening) or >30% (for participants with 21-30% blasts at screening), and with any of the following condition: at least 50% decrease from maximum remission/response in granulocytes or platelets; reduction in hemoglobin by ≥2 g/dL; transfusion dependence.

  10. Time to CR in the AML and MDS Cohorts [Cycle 1 Day 1 to EoT visit (within 14 days after last dose) (assessed up to 24 months)]

    Time to CR was defined for participants in the expansion cohorts who had achieved response on study as the time from date of the first dose of study drug to date of the first documentation of response. Time to CR was analyzed using the Kaplan-Meier method.

  11. Maximum Plasma Concentration (Cmax) of Glasdegib Dosed in Combination With Azacitidine (C1D7) and When Dosed Alone (C1D15) in the Lead-in Cohort [Pre-dose and 0.25, 1, 4, 6, 24 hours post-dose on Cycle 1 Day 7 and Day 15]

    Maximum plasma concentration of glasdegib dosed in combination with azacitidine (C1D7) and when dosed alone (C1D15) in the Lead-in Cohort was estimated using non-compartmental analysis.

  12. Area Under the Plasma Concentration Curve From Time Zero to End of Dosing Interval (AUCtau) of Glasdegib Dosed in Combination With Azacitidine (C1D7) and When Dosed Alone (C1D15) in the Lead-in Cohort [Pre-dose and 0.25, 1, 4, 6, 24 hours post-dose on Cycle 1 Day 7 and Day 15]

    Area under the plasma concentration curve from time zero to end of dosing interval (AUCtau) of glasdegib dosed in combination with azacitidine (C1D7) and when dosed alone (C1D15) in the Lead-in Cohort was estimated using non-compartmental analysis.

  13. Time to First Occurrence of Maximum Plasma Concentration (Tmax) of Glasdegib Dosed in Combination With Azacitidine (C1D7) and When Dosed Alone (C1D15) in the Lead-in Cohort [Pre-dose and 0.25, 1, 4, 6, 24 hours post-dose on Cycle 1 Day 7 and Day 15]

    Time to first occurrence of maximum plasma concentration of glasdegib dosed in combination with azacitidine (C1D7) and when dosed alone (C1D15) in the Lead-in Cohort was estimated using non-compartmental analysis.

  14. Maximum Plasma Concentration (Cmax) of Azacitidine Dosed in Combination With Glasdegib (C1D7) and When Dosed Alone (C1D1) in the Lead-in Cohort [0.25, 0.5, 1, 2, 6 hours post-dose on Cycle 1 Day 1; pre-dose and 0.25, 0.5, 1, 2, 6 hours post-dose on Cycle 1 Day 7.]

    Maximum plasma concentration of azacitidine dosed in combination with glasdegib (C1D7) and when dosed alone (C1D1) in the Lead-in Cohort was estimated using non-compartmental analysis.

  15. Area Under the Plasma Concentration Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of Azacitidine Dosed in Combination With Glasdegib (C1D7) and When Dosed Alone (C1D1) in the Lead-in Cohort [0.25, 0.5, 1, 2, 6 hours post-dose on Cycle 1 Day 1; pre-dose and 0.25, 0.5, 1, 2, 6 hours post-dose on Cycle 1 Day 7.]

    Area under the plasma concentration curve from time zero to extrapolated infinite time (AUCinf) of azacitidine dosed in combination with glasdegib (C1D7) and when dosed alone (C1D1) in the Lead-in Cohort was estimated using non-compartmental analysis.

  16. Tmax of Azacitidine Dosed in Combination With Glasdegib (C1D7) and When Dosed Alone (C1D1) in the Lead-in Cohort [0.25, 0.5, 1, 2, 6 hours post-dose on Cycle 1 Day 1; pre-dose and 0.25, 0.5, 1, 2, 6 hours post-dose on Cycle 1 Day 7.]

    Time to first occurrence of maximum plasma concentration of azacitidine dosed in combination with glasdegib (C1D7) and when dosed alone (C1D1) in the Lead-in Cohort was estimated using non-compartmental analysis.

  17. Trough Plasma Concentration (Ctrough) of Glasdegib on C1D15 and C2D1 in the AML and MDS Cohorts [Pre-dose and 1 and 4 hours post-dose on Cycle 1 Day 15 and Cycle 2 Day 1.]

    Trough plasma concentration was defined as the estimated lowest concentration before next dose administration.

  18. Number of Participants Meeting Categorical Criteria of QTcF Values in LIC, AML and MDS Cohorts [Cycle 1 Day 1 to EoT visit (assessed up to 16 months in the LIC cohort and 24 months in the AML and MDS cohorts)]

    Number of participants that met categorical criteria of QTcF values in LIC, AML and MDS cohorts

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion criteria:
  • Patients must have previously untreated MDS, AML, or CMML according to the WHO 2016 classification.

  • MDS patients must have Intermediate (>3 to 4.5 points), High Risk (>4.5 - 6) or Very High Risk (>6 points) disease according to the Revised International Prognostic Scoring System 2012 (IPSS-R).

  • Clinical indication for treatment with azacitidine for MDS or AML.

Exclusion criteria:
  • Patients with AML who are candidates for standard induction chemotherapy as first line treatment.

  • Patients with known active CNS leukemia.

  • Prior treatment with a smoothened inhibitor (SMOi) and/or hypomethylating agent.

Contacts and Locations

Locations

Site City State Country Postal Code
1 University of Alabama at Birmingham the Kirklin Clinic Birmingham Alabama United States 35233
2 University of Alabama at Birmingham Birmingham Alabama United States 35249
3 UC San Diego Moores Cancer Center La Jolla California United States 92093
4 Smilow Cancer Center at Yale New Haven Hospital New Haven Connecticut United States 06510
5 The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore Maryland United States 21287
6 Montefiore Einstein Center for Cancer Bronx New York United States 10461
7 Montefiore Medical Center Bronx New York United States 10467
8 Roswell Park Cancer Institute Buffalo New York United States 14263
9 Stony Brook University Hospital Cancer Center Stony Brook New York United States 11794
10 Stony Brook University Stony Brook New York United States 11794
11 Duke University Health System: Adult Bone Marrow Transplant Clinic Durham North Carolina United States 27705
12 Duke University Health System, Duke University Hospital Durham North Carolina United States 27710
13 Duke University Health System Durham North Carolina United States 27710
14 Investigational Chemotherapy Service Durham North Carolina United States 27710
15 Cleveland Clinic Taussig Cancer Center Cleveland Ohio United States 44195
16 Henry-Joyce Cancer Center Nashville Tennessee United States 37232
17 Vanderbilt - Ingram Cancer Center Nashville Tennessee United States 37232
18 Huntsman Cancer Hospital Salt Lake City Utah United States 84112
19 Huntsman Cancer Institute Salt Lake City Utah United States 84112
20 Seattle Cancer Care Alliance (SCCA) Seattle Washington United States 98109
21 University of Washington Medical Center (UWMC) Seattle Washington United States 98195
22 Ziekenhuis Netwerk Antwerpen - Campus Stuivenberg Antwerpen Belgium 2060
23 UZ Leuven Leuven Belgium 3000
24 Tom Baker Cancer Center Calgary Alberta Canada T2N 4N2
25 University Of Alberta Hospital Edmonton Alberta Canada T6G 2B7
26 CHU d'Amiens-Picardie - Hopital SUD Amiens cedex 01 France 80054
27 Hopital Saint-Louis (AP-HP) - Service Hematologie Senior Paris CEDEX 10 France 75475
28 Hospices Civils de Lyon - Hopital Lyon Sud- Hematologie Pierre Benite Cedex France 69495
29 CHU de Tours-Hopital Bretonneau-Centre Regional de cancerologie Henry Kaplan Tours Cedex 01 France 37044
30 Staedtisches Klinikum Braunschweig gGmbH Braunschweig Germany 38114
31 King's College Hospital London United Kingdom SE5 9RS
32 The Newcastle Hospitals NHS Foundation Trust Newcastle upon Tyne United Kingdom NE7 7DN
33 Oxford University Hospitals NHS Foundation Trust Oxford United Kingdom OX3 9DU

Sponsors and Collaborators

  • Pfizer

Investigators

  • Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

More Information

Additional Information:

Publications

None provided.
Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT02367456
Other Study ID Numbers:
  • B1371012
  • 2014-001345-24
  • BRIGHT MDS&AML1012
First Posted:
Feb 20, 2015
Last Update Posted:
May 31, 2022
Last Verified:
May 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Keywords provided by Pfizer
Additional relevant MeSH terms:

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail 12 participants were enrolled and received the combination treatment of glasdegib and azacitidine in the Lead-in Cohort (LIC). 31 participants were enrolled in the acute myeloid leukemia (AML) cohort. 1 participant withdrew consent before receiving treatment. 30 participants received the combination treatment of glasdegib and azacitidine. 30 participants were enrolled in the myelodysplastic syndrome (MDS) cohort and received the combination treatment of glasdegib and azacitidine.
Arm/Group Title Lead-in Cohort AML Cohort MDS Cohort
Arm/Group Description Participants received SC administration of azacitidine daily at a dose of 75 mg/m2/day on Days 1-7 of every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD. In Cycle 1 only, administration of glasdegib commenced on Day 2 of the cycle (C1D2) to permit drug-drug interaction (DDI) evaluation. Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD. Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD.
Period Title: Overall Study
STARTED 12 30 30
COMPLETED 0 0 0
NOT COMPLETED 12 30 30

Baseline Characteristics

Arm/Group Title Lead-in Cohort AML Cohort MDS Cohort Total
Arm/Group Description Participants received SC administration of azacitidine daily at a dose of 75 mg/m2/day on Days 1-7 of every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD. In Cycle 1 only, administration of glasdegib commenced on Day 2 of the cycle (C1D2) to permit DDI evaluation. Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD. Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD. Total of all reporting groups
Overall Participants 12 30 30 72
Age, Customized (Count of Participants)
<18 years
0
0%
0
0%
0
0%
0
0%
18-44 years
0
0%
0
0%
0
0%
0
0%
45-64 years
3
25%
3
10%
7
23.3%
13
18.1%
>=65 years
9
75%
27
90%
23
76.7%
59
81.9%
Age, Customized (Count of Participants)
<75 years
7
58.3%
16
53.3%
22
73.3%
45
62.5%
>=75 years
5
41.7%
14
46.7%
8
26.7%
27
37.5%
Sex: Female, Male (Count of Participants)
Female
5
41.7%
12
40%
6
20%
23
31.9%
Male
7
58.3%
18
60%
24
80%
49
68.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino
0
0%
1
3.3%
2
6.7%
3
4.2%
Not Hispanic or Latino
12
100%
23
76.7%
23
76.7%
58
80.6%
Unknown or Not Reported
0
0%
6
20%
5
16.7%
11
15.3%
Race/Ethnicity, Customized (Count of Participants)
White
11
91.7%
22
73.3%
24
80%
57
79.2%
Black or African American
0
0%
1
3.3%
0
0%
1
1.4%
Asian
1
8.3%
1
3.3%
0
0%
2
2.8%
Other
0
0%
0
0%
1
3.3%
1
1.4%
Unknown
0
0%
6
20%
5
16.7%
11
15.3%
Not reported
0
0%
0
0%
0
0%
0
0%

Outcome Measures

1. Primary Outcome
Title Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Lead-in Cohort (LIC)
Description An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with the study treatment. TEAEs were AEs that occurred after initiation of treatment or AEs increasing in severity during treatment. Treatment-related TEAEs were determined by the investigator. Grades of AEs were defined by NCI CTCAE version 4.03.
Time Frame Cycle 1 Day 1 up to 28 days after last dose of study drug or beginning of new anti-cancer therapy (assessed up to 16 months)

Outcome Measure Data

Analysis Population Description
The safety analysis population included all participants who received at least 1 dose of any study treatment.
Arm/Group Title Lead-in Cohort
Arm/Group Description Participants received SC administration of azacitidine daily at a dose of 75 mg/m2/day on Days 1-7 of every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD. In Cycle 1 only, administration of glasdegib commenced on Day 2 of the cycle (C1D2) to permit DDI evaluation.
Measure Participants 12
All-causality TEAEs
12
100%
Treatment-related TEAEs
12
100%
Maximum Grade 3 or 4 TEAEs
8
66.7%
2. Primary Outcome
Title Number of Participants With Serious Adverse Events (SAEs) in the LIC
Description An serious adverse event (SAE) was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. Treatment-related SAEs were determined by the investigator. Grades of AEs were defined by NCI CTCAE version 4.03.
Time Frame Cycle 1 Day 1 up to 28 days after last dose of study drug or beginning of new anti-cancer therapy (assessed up to 16 months)

Outcome Measure Data

Analysis Population Description
The safety analysis population included all participants who received at least 1 dose of any study treatment.
Arm/Group Title Lead-in Cohort
Arm/Group Description Participants received SC administration of azacitidine daily at a dose of 75 mg/m2/day on Days 1-7 of every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD. In Cycle 1 only, administration of glasdegib commenced on Day 2 of the cycle (C1D2) to permit DDI evaluation.
Measure Participants 12
All-causality SAEs
9
75%
Treatment-related SAEs
7
58.3%
3. Primary Outcome
Title Number of Participants With Laboratory Abnormalities in the LIC
Description Laboratory parameters included: hematology parameters (activated partial thromboplastin time, hemoglobin, INR, lymphocyte count, neutrophil count, platelet count, white blood cell), chemistry parameters (alanine aminotransferase, aspartate aminotransferase, alkaline aminotransferase, blood bilirubin, CPK, creatinine, calcium, blood glucose, potassium, magnesium, sodium, albumin, phosphate). Grades of laboratory abnormalities were defined by NCI CTCAE version 4.03.
Time Frame Cycle 1 Day 1 to last follow up visit (at least 28 days after discontinuation of treatment) (assessed up to 17 months)

Outcome Measure Data

Analysis Population Description
The safety analysis population included all participants who received at least 1 dose of any study treatment.
Arm/Group Title Lead-in Cohort
Arm/Group Description Participants received SC administration of azacitidine daily at a dose of 75 mg/m2/day on Days 1-7 of every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD. In Cycle 1 only, administration of glasdegib commenced on Day 2 of the cycle (C1D2) to permit DDI evaluation.
Measure Participants 12
Activated partial thromboplastin time prolonged
5
41.7%
Anemia
12
100%
Hemoglobin increased
0
0%
INR increased
8
66.7%
Lymphocyte count decreased
9
75%
Lymphocyte count increased
3
25%
Neutrophil count decreased
10
83.3%
Platelet count decreased
12
100%
White blood cell decreased
11
91.7%
Alanine aminotransferase increased
4
33.3%
Alkaline phosphatase increase
0
0%
Aspartate aminotransferase increased
2
16.7%
Blood bilirubin increased
6
50%
CPK increased
0
0%
Creatinine increased
11
91.7%
Hypercalcemia
1
8.3%
Hyperglycemia
1
8.3%
Hyperkalemia
3
25%
Hypermagnesemia
2
16.7%
Hypernatremia
1
8.3%
Hypoalbuminemia
5
41.7%
Hypocalcemia
3
25%
Hypoglycemia
1
8.3%
Hypokalemia
3
25%
Hypomagnesemia
2
16.7%
Hyponatremia
6
50%
Hypophosphatemia
4
33.3%
4. Primary Outcome
Title Percentage of Participants Achieving Complete Remission (CR) in the AML and MDS Cohorts
Description Percentage of participants achieving CR as defined by the 2017 European Leukemia Net (ELN) Response Criteria for all participants with AML and modified International Working Group (IWG) criteria (2006) for all participants with MDS in the expansion cohorts. For AML cohort, CR was defined as neutrophils ≥ 1 x 10^9/L, platelets ≥ 1 x 10^11/L, percentage of bone marrow blasts (BMB) <5% with no peripheral blasts and no blasts with Auer rods, no extramedullary disease (EMD), and transfusion independent. For MDS cohort, CR was defined as having responses of hemoglobin ≥11 g/dL, neutrophils ≥1 x 10^9/L, platelets ≥1 x 10^11/L, percentage of blasts = 0%, percentage of BMB≤5%, and normal maturation of all cell lines (note if has persistent dysplasia), and all responses must last at least 4 weeks.
Time Frame Cycle 1 Day 1 to End of Treatment (EoT) visit (within 14 days after last dose) (assessed up to 22 months)

Outcome Measure Data

Analysis Population Description
The full analysis population included all participants who received at least 1 dose of any study treatment.
Arm/Group Title AML Cohort MDS Cohort
Arm/Group Description Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD. Participants received SC or IV administration of azacitidine with a starting dose of 75 mg/m2/day for 7 days every 28 days, and received daily oral administration of glasdegib at home with a starting dose of 100 mg QD.
Measure Participants 30 30
Number (95% Confidence Interval) [Percentage of participants]
20.0
166.7%
13.3
44.3%
5. Secondary Outcome
Title Percentage of Participants Achieving Complete Remission (CR) + Partial Remission (PR) in the LIC
Description RR (Percentage of participants achieving CR+PR among all the enrolled and treated patients as defined by modified International Working Group (IWG) criteria (2006)) in the LIC. CR was defined as having responses of hemoglobin ≥11 g/dL, neutrophils ≥1 x 10^9/L, platelets ≥1 x 10^11/L, percentage of blasts = 0%, percentage of BMB≤5%, and normal maturation of all cell lines (note if has persistent dysplasia), and all responses must last at least 4 weeks. PR was defined as meeting all CR criteria if abnormal before treatment except BMB, percentage of BMB decreased by ≥50% but still >5% for at least 4 weeks.
Time Frame Cycle 1 Day 1 to last follow up visit (at least 28 days after discontinuation of treatment) (assessed up to 18 months)

Outcome Measure Data

Analysis Population Description
The safety analysis population included all participants who received at least 1 dose of study treatment.
Arm/Group Title Lead-in Cohort
Arm/Group Description Participants received SC administration of azacitidine daily at a dose of 75 mg/m2/day on Days 1-7 of every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD. In Cycle 1 only, administration of glasdegib commenced on Day 2 of the cycle (C1D2) to permit DDI evaluation.
Measure Participants 12
Number [Percentage of participants]
25.0
208.3%
6. Secondary Outcome
Title Number of Participants With Efficacy Measures Other Than CR in the LIC
Description Number of participants with efficacy measures other than CR as defined by modified IWG criteria (2006) in LIC, including marrow CR(mCR), stable disease(SD), hematologic improvement(HI). CR: hemoglobin≥11 g/dL, neutrophils≥1 x 10^9/L, platelets≥1 x 10^11/L, percentage of blasts=0%, percentage of BMB≤5%, normal maturation of all cell lines (note if has persistent dysplasia), all responses last at least 4 weeks. mCR: BMB≤5% & decreased by≥50%. SD: failure to achieve PR, no evidence of progression. HI: erythroid response (pretreatment<11g/dL): hemoglobin increase by≥1.5 g/dL, relevant reduction of units of red blood cell transfusions by at least 4 transfusions/8 weeks compared to pretreatment transfusion number in previous 8 weeks; platelet response (pretreatment<1x10^11/L): increase of≥30x10^9/L if starting with >20x10^9/L, and increase from <20x10^9/L to >20x10^9/L and by at least 100%; neutrophil response (pretreatment<1x10^9/L): at least a 100% increase, absolute increase >0.5x10^9/L
Time Frame Cycle 1 Day 1 to last follow up visit (at least 28 days after discontinuation of treatment) (assessed up to 18 months)

Outcome Measure Data

Analysis Population Description
The full analysis set was defined as all participants who received at least 1 dose of any study treatment.
Arm/Group Title Lead-in Cohort
Arm/Group Description Participants received SC administration of azacitidine daily at a dose of 75 mg/m2/day on Days 1-7 of every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD. In Cycle 1 only, administration of glasdegib commenced on Day 2 of the cycle (C1D2) to permit DDI evaluation.
Measure Participants 12
Marrow CR (mCR)
2
16.7%
Stable disease (SD)
4
33.3%
Hematologic improvement (HI) of at least 1 lineage
6
50%
7. Secondary Outcome
Title Number of Participants With TEAEs in the AML and MDS Cohorts
Description An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with the study treatment. TEAEs were AEs that occurred after initiation of treatment or AEs increasing in severity during treatment. Treatment-related TEAEs were determined by the investigator. AEs were graded by NCI CTCAE version 4.03.
Time Frame Cycle 1 Day 1 to EoT visit (within 14 days after last dose) (assessed up to 24 months)

Outcome Measure Data

Analysis Population Description
The safety analysis population included all participants who received at least 1 dose of any study treatment.
Arm/Group Title AML Cohort MDS Cohort
Arm/Group Description Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD. Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD.
Measure Participants 30 30
All-causality TEAEs
30
250%
30
100%
Treatment-related TEAEs
29
241.7%
29
96.7%
8. Secondary Outcome
Title Number of Participants With SAEs in the AML and MDS Cohorts
Description A serious adverse event (SAE) was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. Treatment-related SAEs were determined by the investigator. AEs were graded by NCI CTCAE version 4.03.
Time Frame Cycle 1 Day 1 to EoT visit (within 14 days after last dose) (assessed up to 24 months)

Outcome Measure Data

Analysis Population Description
The safety analysis population included all participants who received at least 1 dose of study treatment
Arm/Group Title AML Cohort MDS Cohort
Arm/Group Description Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD. Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD.
Measure Participants 30 30
All-causality SAEs
24
200%
18
60%
Treatment-related SAEs
8
66.7%
8
26.7%
9. Secondary Outcome
Title Number of Participants With Laboratory Abnormalities in the AML and MDS Cohorts
Description Laboratory parameters included: hematology parameters (activated partial thromboplastin time, hemoglobin, INR, lymphocyte count, neutrophil count, platelet count, white blood cell), chemistry parameters (alanine aminotransferase, aspartate aminotransferase, alkaline aminotransferase, blood bilirubin, CPK, creatinine, calcium, blood glucose, potassium, magnesium, sodium, albumin, phosphate). Laboratory abnormalities were graded by NCI CTCAE version 4.03.
Time Frame Cycle 1 Day 1 to EoT visit (within 14 days after last dose) (assessed up to 24 months)

Outcome Measure Data

Analysis Population Description
The safety analysis population included all participants who received at least 1 dose of any study treatment.
Arm/Group Title AML Cohort MDS Cohort
Arm/Group Description Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD. Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD.
Measure Participants 30 30
Activated partial thromboplastin time prolonged
0
0%
0
0%
Anemia
30
250%
29
96.7%
Hemoglobin increased
0
0%
0
0%
INR increased
0
0%
1
3.3%
Lymphocyte count decreased
23
191.7%
23
76.7%
Lymphocyte count increased
6
50%
1
3.3%
Neutrophil count decreased
25
208.3%
25
83.3%
Platelet count decreased
29
241.7%
26
86.7%
White blood cell decreased
22
183.3%
27
90%
Alanine aminotransferase increased
13
108.3%
12
40%
Alkaline phosphatase increased
7
58.3%
7
23.3%
Aspartate aminotransferase increased
11
91.7%
8
26.7%
Blood bilirubin increased
3
25%
10
33.3%
CPK increased
5
41.7%
4
13.3%
Creatinine increased
29
241.7%
28
93.3%
Hypercalcemia
3
25%
0
0%
Hyperglycemia
3
25%
4
13.3%
Hyperkalemia
6
50%
6
20%
Hypermagnesemia
1
8.3%
2
6.7%
Hypernatremia
2
16.7%
1
3.3%
Hypoalbuminemia
22
183.3%
17
56.7%
Hypocalcemia
3
25%
11
36.7%
Hypoglycemia
4
33.3%
2
6.7%
Hypokalemia
8
66.7%
3
10%
Hypomagnesemia
12
100%
9
30%
Hyponatremia
18
150%
12
40%
Hypophosphatemia
13
108.3%
7
23.3%
10. Secondary Outcome
Title Number of Participants With Disease-Specific Efficacy Measures in the AML Cohort
Description Number of participants with CR with partial hematologic recovery (CRh), CR with incomplete blood count recovery (CRi), partial remission (PR), stable disease (SD), and morphologic leukemia free state (MLFS). CRh: neutrophils>5x10^8/L, platelets>5x10^10/L, BMB<5%, no peripheral blasts, no blasts with Auer rods, no extramedullary disease (EMD), not qualifying for CR. CRi: neutrophils <1x10^9/L or platelets<1x10^11/L; BMB <5%, no peripheral blasts, no blasts with Auer rods; no EMD; neutrophils or platelets not recovered; not qualifying for CRh. PR: neutrophils ≥1x10^9/L; platelets ≥1x10^11/L; blasts decreased to 5-25% and ≥50% decrease from pretreatment; blasts≤5% if Auer rod positive. SD: ≥3 months of absence of CR without minimal residual disease (CRMRD-), CR, CRh, CRi, PR, and MLFS, criteria for PD not met. MLFS: neutrophils <1x10^9/L and platelets<1x10^11/L, BMB<5%, no blasts with Auer rods; no EMD; neutrophils and platelets not recovered; not qualifying for CRi
Time Frame Cycle 1 Day 1 to EoT visit (within 14 days after last dose) (assessed up to 20 months)

Outcome Measure Data

Analysis Population Description
The full analysis population included all participants who received at least 1 dose of any study treatment.
Arm/Group Title AML Cohort
Arm/Group Description Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD.
Measure Participants 30
CRh
0
0%
CRi
1
8.3%
PR
2
16.7%
MLFS
1
8.3%
SD
6
50%
11. Secondary Outcome
Title Number of Participants With Disease-Specific Efficacy Measures in the MDS Cohort
Description Number of participants with PR, marrow CR (mCR), SD, complete or partial cytogenetic response, and hematologic improvement (HI). PR: BMB >5% and decreased by ≥50% (at least 4 weeks), meeting all CR criteria if abnormal before treatment except BMB. mCR: BMB ≤5% and decreased by ≥50%. SD: failure to achieve PR, no evidence of progression. Complete or partial cytogenic response: disappearance of chromosomal abnormality without new ones, or ≥ 50% reduction of chromosomal abnormality. HI: erythroid response (pretreatment <11g/dL): hemoglobin increase by≥1.5 g/dL, relevant reduction of units of red blood cell transfusions by at least 4 transfusions/8 weeks compared to pretreatment transfusion number in previous 8 weeks; platelet response (pretreatment <1x10^11/L): increase of ≥30x10^9/L if starting with >20x10^9/L, and increase from <20x10^9/L to >20x10^9/L and by at least 100%; neutrophil response (pretreatment <1x10^9/L): at least a 100% increase, absolute increase >0.5x10^9/L.
Time Frame Cycle 1 Day 1 to EoT visit (within 14 days after last dose) (assessed up to 22 months)

Outcome Measure Data

Analysis Population Description
The safety analysis population included all participants who received at least 1 dose of any study treatment.
Arm/Group Title MDS Cohort
Arm/Group Description Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD.
Measure Participants 30
PR
3
25%
mCR
5
41.7%
SD
8
66.7%
Complete cytogenetic response
3
25%
Partial cytogenetic response
1
8.3%
HI of at least 1 lineage
9
75%
HI of at least 1 lineage without CR or PR
3
25%
12. Secondary Outcome
Title Kaplan-Meier Estimate of Median Overall Survival (OS) in the AML and MDS Cohorts
Description Overall survival (OS) was defined as the time from date of first study treatment to date of death from any cause. Patients last known to be alive were to be censored at the date of last contact. OS was analyzed and displayed graphically for each expansion cohort separately using the Kaplan-Meier method. The median event time and corresponding two-sided 95%CI were provided for each cohort. OS was first analyzed when the primary endpoint of CR was analyzed in the respective expansion cohort.
Time Frame Cycle 1 Day 1 to date of death from any cause (assessed up to 24 months)

Outcome Measure Data

Analysis Population Description
The full analysis population included all participants who received at least 1 dose of any study treatment.
Arm/Group Title AML Cohort MDS Cohort
Arm/Group Description Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD. Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD.
Measure Participants 30 30
Median (95% Confidence Interval) [Months]
9.2
15.8
13. Secondary Outcome
Title Duration of CR in the AML and MDS Cohorts
Description Duration of CR was defined as the duration from date of first achieving CR to the date of disease progression (relapse) after CR, or death due to any cause. Participants last known to be alive who were free from disease progression or relapse after CR were censored at the date of the last assessment that verified their disease status. Duration of CR was analyzed using the Kaplan-Meier method. Disease progression was defined as: percentage of bone marrow blasts increased by ≥50% to >5% (for participants with <5% blasts at screening), >10% (for participants with 5-10% blasts at screening), >20% (for participants with 11-20% blasts at screening) or >30% (for participants with 21-30% blasts at screening), and with any of the following condition: at least 50% decrease from maximum remission/response in granulocytes or platelets; reduction in hemoglobin by ≥2 g/dL; transfusion dependence.
Time Frame Cycle 1 Day 1 to EoT visit (within 14 days after last dose) (assessed up to 24 months)

Outcome Measure Data

Analysis Population Description
The full analysis population included all participants who received at least 1 dose of any study treatment.
Arm/Group Title AML Cohort MDS Cohort
Arm/Group Description Participants received SC or IV administration of azacitidine with a starting dose of 75 mg/m2/day for 7 days every 28 days, and received daily oral administration of glasdegib at home with a starting dose of 100 mg QD. Participants received SC or IV administration of azacitidine with a starting dose of 75 mg/m2/day for 7 days every 28 days, and received daily oral administration of glasdegib at home with a starting dose of 100 mg QD.
Measure Participants 30 30
Median (Full Range) [Months]
4.73
3.71
14. Secondary Outcome
Title Time to CR in the AML and MDS Cohorts
Description Time to CR was defined for participants in the expansion cohorts who had achieved response on study as the time from date of the first dose of study drug to date of the first documentation of response. Time to CR was analyzed using the Kaplan-Meier method.
Time Frame Cycle 1 Day 1 to EoT visit (within 14 days after last dose) (assessed up to 24 months)

Outcome Measure Data

Analysis Population Description
The full analysis population included all participants who received at least 1 dose of any study treatment.
Arm/Group Title AML Cohort MDS Cohort
Arm/Group Description Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD. Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD.
Measure Participants 30 30
Median (Full Range) [Months]
5.54
4.39
15. Secondary Outcome
Title Maximum Plasma Concentration (Cmax) of Glasdegib Dosed in Combination With Azacitidine (C1D7) and When Dosed Alone (C1D15) in the Lead-in Cohort
Description Maximum plasma concentration of glasdegib dosed in combination with azacitidine (C1D7) and when dosed alone (C1D15) in the Lead-in Cohort was estimated using non-compartmental analysis.
Time Frame Pre-dose and 0.25, 1, 4, 6, 24 hours post-dose on Cycle 1 Day 7 and Day 15

Outcome Measure Data

Analysis Population Description
The PK concentration analysis set included all participants who received treatment and had at least 1 value of analyte concentration of glasdegib or azacitidine available.
Arm/Group Title Lead-in Cohort
Arm/Group Description Participants received SC administration of azacitidine daily at a dose of 75 mg/m2/day on Days 1-7 of every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD. In Cycle 1 only, administration of glasdegib commenced on Day 2 of the cycle (C1D2) to permit DDI evaluation.
Measure Participants 12
C1D7
1013
(58)
C1D15
991.4
(57)
16. Secondary Outcome
Title Area Under the Plasma Concentration Curve From Time Zero to End of Dosing Interval (AUCtau) of Glasdegib Dosed in Combination With Azacitidine (C1D7) and When Dosed Alone (C1D15) in the Lead-in Cohort
Description Area under the plasma concentration curve from time zero to end of dosing interval (AUCtau) of glasdegib dosed in combination with azacitidine (C1D7) and when dosed alone (C1D15) in the Lead-in Cohort was estimated using non-compartmental analysis.
Time Frame Pre-dose and 0.25, 1, 4, 6, 24 hours post-dose on Cycle 1 Day 7 and Day 15

Outcome Measure Data

Analysis Population Description
The PK parameter analysis set included all participants who received study treatment and had at least 1 of the PK parameters of interest.
Arm/Group Title Lead-in Cohort
Arm/Group Description Participants received SC administration of azacitidine daily at a dose of 75 mg/m2/day on Days 1-7 of every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD. In Cycle 1 only, administration of glasdegib commenced on Day 2 of the cycle (C1D2) to permit DDI evaluation.
Measure Participants 12
C1D7
13230
(49)
C1D15
14350
(61)
17. Secondary Outcome
Title Time to First Occurrence of Maximum Plasma Concentration (Tmax) of Glasdegib Dosed in Combination With Azacitidine (C1D7) and When Dosed Alone (C1D15) in the Lead-in Cohort
Description Time to first occurrence of maximum plasma concentration of glasdegib dosed in combination with azacitidine (C1D7) and when dosed alone (C1D15) in the Lead-in Cohort was estimated using non-compartmental analysis.
Time Frame Pre-dose and 0.25, 1, 4, 6, 24 hours post-dose on Cycle 1 Day 7 and Day 15

Outcome Measure Data

Analysis Population Description
The PK parameter analysis set included all participants who received study treatment and had at least 1 of the PK parameters of interest.
Arm/Group Title Lead-in Cohort
Arm/Group Description Participants received SC administration of azacitidine daily at a dose of 75 mg/m2/day on Days 1-7 of every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD. In Cycle 1 only, administration of glasdegib commenced on Day 2 of the cycle (C1D2) to permit DDI evaluation.
Measure Participants 12
C1D7
1.050
C1D15
1.500
18. Secondary Outcome
Title Maximum Plasma Concentration (Cmax) of Azacitidine Dosed in Combination With Glasdegib (C1D7) and When Dosed Alone (C1D1) in the Lead-in Cohort
Description Maximum plasma concentration of azacitidine dosed in combination with glasdegib (C1D7) and when dosed alone (C1D1) in the Lead-in Cohort was estimated using non-compartmental analysis.
Time Frame 0.25, 0.5, 1, 2, 6 hours post-dose on Cycle 1 Day 1; pre-dose and 0.25, 0.5, 1, 2, 6 hours post-dose on Cycle 1 Day 7.

Outcome Measure Data

Analysis Population Description
The PK concentration analysis set included all participants who received treatment and had at least 1 value of analyte concentration of glasdegib or azacitidine available.
Arm/Group Title Lead-in Cohort
Arm/Group Description Participants received SC administration of azacitidine daily at a dose of 75 mg/m2/day on Days 1-7 of every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD. In Cycle 1 only, administration of glasdegib commenced on Day 2 of the cycle (C1D2) to permit DDI evaluation.
Measure Participants 12
C1D1
778.5
(23)
C1D7
716.9
(32)
19. Secondary Outcome
Title Area Under the Plasma Concentration Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of Azacitidine Dosed in Combination With Glasdegib (C1D7) and When Dosed Alone (C1D1) in the Lead-in Cohort
Description Area under the plasma concentration curve from time zero to extrapolated infinite time (AUCinf) of azacitidine dosed in combination with glasdegib (C1D7) and when dosed alone (C1D1) in the Lead-in Cohort was estimated using non-compartmental analysis.
Time Frame 0.25, 0.5, 1, 2, 6 hours post-dose on Cycle 1 Day 1; pre-dose and 0.25, 0.5, 1, 2, 6 hours post-dose on Cycle 1 Day 7.

Outcome Measure Data

Analysis Population Description
The PK parameter analysis set included all participants who received study treatment and had at least 1 of the PK parameters of interest.
Arm/Group Title Lead-in Cohort
Arm/Group Description Participants received SC administration of azacitidine daily at a dose of 75 mg/m2/day on Days 1-7 of every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD. In Cycle 1 only, administration of glasdegib commenced on Day 2 of the cycle (C1D2) to permit DDI evaluation.
Measure Participants 12
C1D1
1319
(19)
C1D7
1260
(21)
20. Secondary Outcome
Title Tmax of Azacitidine Dosed in Combination With Glasdegib (C1D7) and When Dosed Alone (C1D1) in the Lead-in Cohort
Description Time to first occurrence of maximum plasma concentration of azacitidine dosed in combination with glasdegib (C1D7) and when dosed alone (C1D1) in the Lead-in Cohort was estimated using non-compartmental analysis.
Time Frame 0.25, 0.5, 1, 2, 6 hours post-dose on Cycle 1 Day 1; pre-dose and 0.25, 0.5, 1, 2, 6 hours post-dose on Cycle 1 Day 7.

Outcome Measure Data

Analysis Population Description
The PK parameter analysis set included all participants who received study treatment and had at least 1 of the PK parameters of interest.
Arm/Group Title Lead-in Cohort
Arm/Group Description Participants received SC administration of azacitidine daily at a dose of 75 mg/m2/day on Days 1-7 of every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD. In Cycle 1 only, administration of glasdegib commenced on Day 2 of the cycle (C1D2) to permit DDI evaluation.
Measure Participants 12
C1D1
0.5000
C1D7
0.5000
21. Secondary Outcome
Title Trough Plasma Concentration (Ctrough) of Glasdegib on C1D15 and C2D1 in the AML and MDS Cohorts
Description Trough plasma concentration was defined as the estimated lowest concentration before next dose administration.
Time Frame Pre-dose and 1 and 4 hours post-dose on Cycle 1 Day 15 and Cycle 2 Day 1.

Outcome Measure Data

Analysis Population Description
The PK concentration analysis set included all participants who received treatment and had at least 1 value of analyte concentration of glasdegib or azacitidine available.
Arm/Group Title AML Cohort MDS Cohort
Arm/Group Description Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD. Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD.
Measure Participants 30 30
C1D15
468.440
(88)
308.144
(95)
C2D1
462.806
(110)
167.483
(52)
22. Secondary Outcome
Title Number of Participants Meeting Categorical Criteria of QTcF Values in LIC, AML and MDS Cohorts
Description Number of participants that met categorical criteria of QTcF values in LIC, AML and MDS cohorts
Time Frame Cycle 1 Day 1 to EoT visit (assessed up to 16 months in the LIC cohort and 24 months in the AML and MDS cohorts)

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Lead-in Cohort AML Cohort MDS Cohort
Arm/Group Description Participants received SC administration of azacitidine daily at a dose of 75 mg/m2/day on Days 1-7 of every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD. In Cycle 1 only, administration of glasdegib commenced on Day 2 of the cycle (C1D2) to permit DDI evaluation. Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD. Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD.
Measure Participants 12 30 30
Maximum QTcF interval <450 ms
5
41.7%
16
53.3%
18
60%
450 ms <=Maximum QTcF interval <480 ms
2
16.7%
6
20%
6
20%
480 ms <=Maximum QTcF interval <500 ms
4
33.3%
5
16.7%
4
13.3%
Maximum QTcF interval ≥500 ms
1
8.3%
3
10%
2
6.7%
QTcF maximum increase from baseline <30 ms
3
25%
18
60%
23
76.7%
30 ms <= QTcF maximum increase <60 ms
7
58.3%
10
33.3%
5
16.7%
QTcF maximum increase from baseline >=60 ms
2
16.7%
2
6.7%
2
6.7%

Adverse Events

Time Frame From Cycle 1 Day 1 till up to 28 days after last dose of study drug or beginning of new anti-cancer therapy (assessed up to 16 months in the LIC cohort and 24 months in the AML and MDS cohorts)
Adverse Event Reporting Description The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Arm/Group Title Lead-in Cohort AML Cohort MDS Cohort
Arm/Group Description Participants received SC administration of azacitidine daily at a dose of 75 mg/m2/day on Days 1-7 of every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD. In Cycle 1 only, administration of glasdegib commenced on Day 2 of the cycle (C1D2) to permit DDI evaluation. Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD. Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD.
All Cause Mortality
Lead-in Cohort AML Cohort MDS Cohort
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 9/12 (75%) 22/30 (73.3%) 15/30 (50%)
Serious Adverse Events
Lead-in Cohort AML Cohort MDS Cohort
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 9/12 (75%) 24/30 (80%) 18/30 (60%)
Blood and lymphatic system disorders
Anaemia 0/12 (0%) 1/30 (3.3%) 1/30 (3.3%)
Febrile neutropenia 4/12 (33.3%) 6/30 (20%) 5/30 (16.7%)
Thrombocytopenia 0/12 (0%) 1/30 (3.3%) 1/30 (3.3%)
Cardiac disorders
Acute myocardial infarction 1/12 (8.3%) 0/30 (0%) 0/30 (0%)
Angina pectoris 0/12 (0%) 1/30 (3.3%) 0/30 (0%)
Atrial fibrillation 0/12 (0%) 0/30 (0%) 1/30 (3.3%)
Cardiac failure 0/12 (0%) 0/30 (0%) 1/30 (3.3%)
Right ventricular failure 0/12 (0%) 1/30 (3.3%) 0/30 (0%)
Gastrointestinal disorders
Abdominal pain 0/12 (0%) 1/30 (3.3%) 0/30 (0%)
Ascites 0/12 (0%) 1/30 (3.3%) 1/30 (3.3%)
Constipation 1/12 (8.3%) 1/30 (3.3%) 0/30 (0%)
Gastrointestinal haemorrhage 0/12 (0%) 1/30 (3.3%) 0/30 (0%)
Nausea 0/12 (0%) 0/30 (0%) 1/30 (3.3%)
Upper gastrointestinal haemorrhage 0/12 (0%) 1/30 (3.3%) 0/30 (0%)
Vomiting 0/12 (0%) 1/30 (3.3%) 0/30 (0%)
General disorders
Disease progression 0/12 (0%) 3/30 (10%) 1/30 (3.3%)
General physical health deterioration 0/12 (0%) 1/30 (3.3%) 0/30 (0%)
Multiple organ dysfunction syndrome 1/12 (8.3%) 0/30 (0%) 0/30 (0%)
Pyrexia 2/12 (16.7%) 4/30 (13.3%) 2/30 (6.7%)
Infections and infestations
Bacteraemia 0/12 (0%) 0/30 (0%) 1/30 (3.3%)
Bronchopulmonary aspergillosis 0/12 (0%) 0/30 (0%) 1/30 (3.3%)
Catheter site cellulitis 0/12 (0%) 0/30 (0%) 1/30 (3.3%)
Cellulitis 2/12 (16.7%) 0/30 (0%) 1/30 (3.3%)
Cystitis 0/12 (0%) 1/30 (3.3%) 0/30 (0%)
Lower respiratory tract infection 0/12 (0%) 1/30 (3.3%) 0/30 (0%)
Neutropenic sepsis 1/12 (8.3%) 0/30 (0%) 0/30 (0%)
Osteomyelitis 1/12 (8.3%) 0/30 (0%) 0/30 (0%)
Pneumonia 0/12 (0%) 1/30 (3.3%) 1/30 (3.3%)
Pseudomonal sepsis 0/12 (0%) 1/30 (3.3%) 0/30 (0%)
Pyelonephritis 0/12 (0%) 1/30 (3.3%) 0/30 (0%)
Respiratory tract infection 1/12 (8.3%) 0/30 (0%) 0/30 (0%)
Sepsis 0/12 (0%) 1/30 (3.3%) 5/30 (16.7%)
Septic shock 1/12 (8.3%) 1/30 (3.3%) 0/30 (0%)
Streptococcal infection 0/12 (0%) 0/30 (0%) 1/30 (3.3%)
Urinary tract infection 0/12 (0%) 2/30 (6.7%) 0/30 (0%)
Urosepsis 0/12 (0%) 1/30 (3.3%) 0/30 (0%)
Injury, poisoning and procedural complications
Fall 0/12 (0%) 1/30 (3.3%) 1/30 (3.3%)
Femur fracture 0/12 (0%) 0/30 (0%) 1/30 (3.3%)
Lumbar vertebral fracture 1/12 (8.3%) 0/30 (0%) 0/30 (0%)
Post procedural haemorrhage 0/12 (0%) 0/30 (0%) 1/30 (3.3%)
Sternal fracture 1/12 (8.3%) 0/30 (0%) 0/30 (0%)
Subdural haematoma 0/12 (0%) 1/30 (3.3%) 0/30 (0%)
Investigations
Electrocardiogram QT prolonged 1/12 (8.3%) 2/30 (6.7%) 0/30 (0%)
Metabolism and nutrition disorders
Gout 1/12 (8.3%) 0/30 (0%) 1/30 (3.3%)
Hyponatraemia 0/12 (0%) 1/30 (3.3%) 0/30 (0%)
Tumor lysis syndrome 0/12 (0%) 1/30 (3.3%) 0/30 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia 0/12 (0%) 1/30 (3.3%) 0/30 (0%)
Musculoskeletal chest pain 1/12 (8.3%) 0/30 (0%) 0/30 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastrointestinal lymphoma 0/12 (0%) 1/30 (3.3%) 0/30 (0%)
Lung neoplasm malignant 1/12 (8.3%) 0/30 (0%) 0/30 (0%)
Metastases to liver 0/12 (0%) 0/30 (0%) 1/30 (3.3%)
Myelodysplastic syndrome 0/12 (0%) 0/30 (0%) 1/30 (3.3%)
Nervous system disorders
Cerebral haemorrhage 0/12 (0%) 1/30 (3.3%) 0/30 (0%)
Cerebrovascular accident 0/12 (0%) 1/30 (3.3%) 0/30 (0%)
Subarachnoid haemorrhage 0/12 (0%) 1/30 (3.3%) 0/30 (0%)
Syncope 0/12 (0%) 1/30 (3.3%) 0/30 (0%)
Psychiatric disorders
Depression 0/12 (0%) 1/30 (3.3%) 0/30 (0%)
Renal and urinary disorders
Acute kidney injury 0/12 (0%) 0/30 (0%) 1/30 (3.3%)
Renal failure 0/12 (0%) 1/30 (3.3%) 0/30 (0%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndome 1/12 (8.3%) 0/30 (0%) 0/30 (0%)
Epistaxis 0/12 (0%) 0/30 (0%) 1/30 (3.3%)
Hypoxia 0/12 (0%) 1/30 (3.3%) 0/30 (0%)
Pneumonitis 0/12 (0%) 1/30 (3.3%) 0/30 (0%)
Pulmonary arterial hypertension 0/12 (0%) 0/30 (0%) 1/30 (3.3%)
Respiratory failure 0/12 (0%) 1/30 (3.3%) 0/30 (0%)
Vascular disorders
Haematoma 1/12 (8.3%) 0/30 (0%) 0/30 (0%)
Hypotension 0/12 (0%) 1/30 (3.3%) 1/30 (3.3%)
Orthostatic hypotension 0/12 (0%) 1/30 (3.3%) 0/30 (0%)
Other (Not Including Serious) Adverse Events
Lead-in Cohort AML Cohort MDS Cohort
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 12/12 (100%) 29/30 (96.7%) 29/30 (96.7%)
Blood and lymphatic system disorders
Anaemia 9/12 (75%) 6/30 (20%) 11/30 (36.7%)
Febrile neutropenia 0/12 (0%) 3/30 (10%) 2/30 (6.7%)
Leukopenia 0/12 (0%) 2/30 (6.7%) 0/30 (0%)
Neutropenia 6/12 (50%) 0/30 (0%) 3/30 (10%)
Thrombocytopenia 3/12 (25%) 0/30 (0%) 3/30 (10%)
Cardiac disorders
Atrial fibrillation 0/12 (0%) 2/30 (6.7%) 3/30 (10%)
Tachycardia 1/12 (8.3%) 0/30 (0%) 0/30 (0%)
Ear and labyrinth disorders
Ear pain 1/12 (8.3%) 0/30 (0%) 0/30 (0%)
Tinnitus 0/12 (0%) 0/30 (0%) 2/30 (6.7%)
Eye disorders
Vision blurred 0/12 (0%) 2/30 (6.7%) 0/30 (0%)
Gastrointestinal disorders
Abdominal pain 2/12 (16.7%) 6/30 (20%) 4/30 (13.3%)
Abdominal pain upper 0/12 (0%) 2/30 (6.7%) 0/30 (0%)
Ascites 0/12 (0%) 2/30 (6.7%) 0/30 (0%)
Constipation 9/12 (75%) 18/30 (60%) 15/30 (50%)
Dental caries 1/12 (8.3%) 0/30 (0%) 0/30 (0%)
Diarrhoea 6/12 (50%) 16/30 (53.3%) 14/30 (46.7%)
Dry mouth 2/12 (16.7%) 4/30 (13.3%) 4/30 (13.3%)
Dysepsia 2/12 (16.7%) 0/30 (0%) 2/30 (6.7%)
Dysphagia 0/12 (0%) 0/30 (0%) 3/30 (10%)
Enterocolitis 1/12 (8.3%) 0/30 (0%) 0/30 (0%)
Gastrooesophageal reflux disease 1/12 (8.3%) 0/30 (0%) 0/30 (0%)
Gingival bleeding 1/12 (8.3%) 0/30 (0%) 2/30 (6.7%)
Haematochezia 1/12 (8.3%) 0/30 (0%) 0/30 (0%)
Haemorrhoids 1/12 (8.3%) 4/30 (13.3%) 2/30 (6.7%)
Nausea 8/12 (66.7%) 19/30 (63.3%) 20/30 (66.7%)
Oesophagitis 1/12 (8.3%) 0/30 (0%) 0/30 (0%)
Oral dysaethesia 1/12 (8.3%) 0/30 (0%) 0/30 (0%)
Proctalgia 1/12 (8.3%) 0/30 (0%) 0/30 (0%)
Rectal haemorrhage 0/12 (0%) 2/30 (6.7%) 0/30 (0%)
Stomatitis 1/12 (8.3%) 2/30 (6.7%) 4/30 (13.3%)
Vomiting 4/12 (33.3%) 13/30 (43.3%) 10/30 (33.3%)
General disorders
Asthenia 2/12 (16.7%) 3/30 (10%) 0/30 (0%)
Chest pain 0/12 (0%) 2/30 (6.7%) 0/30 (0%)
Chills 1/12 (8.3%) 2/30 (6.7%) 0/30 (0%)
Fatigue 6/12 (50%) 8/30 (26.7%) 9/30 (30%)
General physical health deterioration 0/12 (0%) 2/30 (6.7%) 0/30 (0%)
Injection site erythema 3/12 (25%) 2/30 (6.7%) 0/30 (0%)
Injection site irritation 1/12 (8.3%) 0/30 (0%) 0/30 (0%)
Injection site nodule 1/12 (8.3%) 0/30 (0%) 0/30 (0%)
Injection site pain 0/12 (0%) 3/30 (10%) 0/30 (0%)
Injection site reaction 2/12 (16.7%) 2/30 (6.7%) 5/30 (16.7%)
Oedema peripheral 3/12 (25%) 4/30 (13.3%) 8/30 (26.7%)
Pain 1/12 (8.3%) 5/30 (16.7%) 2/30 (6.7%)
Pyrexia 2/12 (16.7%) 8/30 (26.7%) 3/30 (10%)
Hepatobiliary disorders
Ischaemic hepatitis 1/12 (8.3%) 0/30 (0%) 0/30 (0%)
Jaundice 1/12 (8.3%) 0/30 (0%) 0/30 (0%)
Infections and infestations
Bacteraemia 1/12 (8.3%) 0/30 (0%) 0/30 (0%)
Cellulitis 2/12 (16.7%) 0/30 (0%) 0/30 (0%)
Device related infection 0/12 (0%) 0/30 (0%) 2/30 (6.7%)
Diverticulitis 1/12 (8.3%) 0/30 (0%) 0/30 (0%)
Folliculitis 3/12 (25%) 0/30 (0%) 0/30 (0%)
Oral candidiasis 0/12 (0%) 4/30 (13.3%) 0/30 (0%)
Pneumonia 3/12 (25%) 0/30 (0%) 2/30 (6.7%)
Sepsis 2/12 (16.7%) 0/30 (0%) 0/30 (0%)
Sinusitis 1/12 (8.3%) 0/30 (0%) 0/30 (0%)
Upper respiratory tract infection 1/12 (8.3%) 0/30 (0%) 0/30 (0%)
Urinary tract infection 3/12 (25%) 2/30 (6.7%) 2/30 (6.7%)
Injury, poisoning and procedural complications
Contusion 2/12 (16.7%) 0/30 (0%) 5/30 (16.7%)
Fall 0/12 (0%) 8/30 (26.7%) 7/30 (23.3%)
Postoperative hypotension 1/12 (8.3%) 0/30 (0%) 0/30 (0%)
Investigations
Alanine transferase increased 0/12 (0%) 3/30 (10%) 4/30 (13.3%)
Aspartate aminotransferase increase 0/12 (0%) 4/30 (13.3%) 5/30 (16.7%)
Blood alkaline phosphatase increased 0/12 (0%) 3/30 (10%) 2/30 (6.7%)
Blood bilirubin increased 2/12 (16.7%) 3/30 (10%) 4/30 (13.3%)
Blood creatine phosphokinase increased 0/12 (0%) 0/30 (0%) 2/30 (6.7%)
Blood creatinine increased 0/12 (0%) 4/30 (13.3%) 4/30 (13.3%)
Blood lactate dehydrogenase increased 1/12 (8.3%) 0/30 (0%) 0/30 (0%)
C-reactive protein increased 0/12 (0%) 3/30 (10%) 0/30 (0%)
Electrocardiogram QT prolonged 5/12 (41.7%) 5/30 (16.7%) 3/30 (10%)
Heart rate irregular 1/12 (8.3%) 0/30 (0%) 0/30 (0%)
International normalised ratio increased 0/12 (0%) 3/30 (10%) 2/30 (6.7%)
Lymphocyte count decreased 0/12 (0%) 4/30 (13.3%) 4/30 (13.3%)
Neutrophil count decreased 0/12 (0%) 2/30 (6.7%) 11/30 (36.7%)
Platelet count decreased 0/12 (0%) 5/30 (16.7%) 11/30 (36.7%)
Weight decreased 5/12 (41.7%) 4/30 (13.3%) 5/30 (16.7%)
White blood cell count decreased 1/12 (8.3%) 7/30 (23.3%) 8/30 (26.7%)
Metabolism and nutrition disorders
Decreased appetite 2/12 (16.7%) 16/30 (53.3%) 9/30 (30%)
Hyperglycaemia 0/12 (0%) 4/30 (13.3%) 6/30 (20%)
Hyperkalaemia 0/12 (0%) 0/30 (0%) 2/30 (6.7%)
Hypernatraemia 0/12 (0%) 2/30 (6.7%) 0/30 (0%)
Hyperuricaemia 1/12 (8.3%) 0/30 (0%) 0/30 (0%)
Hypoalbuminaemia 0/12 (0%) 5/30 (16.7%) 4/30 (13.3%)
Hypocalcaemia 1/12 (8.3%) 2/30 (6.7%) 0/30 (0%)
Hypokalaemia 1/12 (8.3%) 8/30 (26.7%) 2/30 (6.7%)
Hypomagnesaemia 2/12 (16.7%) 6/30 (20%) 6/30 (20%)
Hyponatraemia 3/12 (25%) 7/30 (23.3%) 6/30 (20%)
Hypophosphataemia 2/12 (16.7%) 2/30 (6.7%) 2/30 (6.7%)
Musculoskeletal and connective tissue disorders
Arthralgia 0/12 (0%) 2/30 (6.7%) 3/30 (10%)
Arthritis 1/12 (8.3%) 0/30 (0%) 0/30 (0%)
Back pain 0/12 (0%) 6/30 (20%) 0/30 (0%)
Flank pain 0/12 (0%) 3/30 (10%) 2/30 (6.7%)
Haemarthrosis 1/12 (8.3%) 0/30 (0%) 0/30 (0%)
Muscle spasms 4/12 (33.3%) 9/30 (30%) 15/30 (50%)
Muscular weakness 0/12 (0%) 4/30 (13.3%) 4/30 (13.3%)
Myalgia 1/12 (8.3%) 2/30 (6.7%) 5/30 (16.7%)
Neck pain 0/12 (0%) 0/30 (0%) 2/30 (6.7%)
Pain in extremity 2/12 (16.7%) 0/30 (0%) 0/30 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Melanocytic naevus 1/12 (8.3%) 0/30 (0%) 0/30 (0%)
Nervous system disorders
Ageusia 0/12 (0%) 2/30 (6.7%) 2/30 (6.7%)
Amnesia 0/12 (0%) 0/30 (0%) 2/30 (6.7%)
Dizziness 2/12 (16.7%) 3/30 (10%) 7/30 (23.3%)
Dizziness postural 0/12 (0%) 2/30 (6.7%) 0/30 (0%)
Dysgeusia 5/12 (41.7%) 4/30 (13.3%) 13/30 (43.3%)
Headache 0/12 (0%) 3/30 (10%) 7/30 (23.3%)
Hypoaesthesia 1/12 (8.3%) 0/30 (0%) 3/30 (10%)
Hypogeusia 1/12 (8.3%) 0/30 (0%) 0/30 (0%)
Paraesthesia 0/12 (0%) 4/30 (13.3%) 0/30 (0%)
Presyncope 0/12 (0%) 2/30 (6.7%) 0/30 (0%)
Taste disorder 1/12 (8.3%) 3/30 (10%) 0/30 (0%)
Psychiatric disorders
Anxiety 1/12 (8.3%) 4/30 (13.3%) 0/30 (0%)
Delirium 1/12 (8.3%) 0/30 (0%) 0/30 (0%)
Depression 1/12 (8.3%) 0/30 (0%) 2/30 (6.7%)
Insomnia 2/12 (16.7%) 6/30 (20%) 5/30 (16.7%)
Mental status change 1/12 (8.3%) 0/30 (0%) 0/30 (0%)
Sleep disorder 0/12 (0%) 3/30 (10%) 3/30 (10%)
Renal and urinary disorders
Acute kidney injury 1/12 (8.3%) 0/30 (0%) 0/30 (0%)
Dysuria 0/12 (0%) 2/30 (6.7%) 0/30 (0%)
Haematuria 2/12 (16.7%) 2/30 (6.7%) 0/30 (0%)
Pollakiuria 3/12 (25%) 0/30 (0%) 2/30 (6.7%)
Renal failure 1/12 (8.3%) 0/30 (0%) 0/30 (0%)
Urinary incontinence 1/12 (8.3%) 0/30 (0%) 0/30 (0%)
Urinary retention 2/12 (16.7%) 0/30 (0%) 0/30 (0%)
Urinary tract pain 1/12 (8.3%) 0/30 (0%) 0/30 (0%)
Respiratory, thoracic and mediastinal disorders
Atelectasis 1/12 (8.3%) 0/30 (0%) 0/30 (0%)
Cough 3/12 (25%) 7/30 (23.3%) 5/30 (16.7%)
Dysphonia 0/12 (0%) 0/30 (0%) 2/30 (6.7%)
Dyspnoea 4/12 (33.3%) 8/30 (26.7%) 6/30 (20%)
Dyspnoea exertional 1/12 (8.3%) 0/30 (0%) 0/30 (0%)
Epistaxis 1/12 (8.3%) 4/30 (13.3%) 4/30 (13.3%)
Hiccups 1/12 (8.3%) 0/30 (0%) 0/30 (0%)
Hypoxia 2/12 (16.7%) 0/30 (0%) 0/30 (0%)
Nasal congestion 0/12 (0%) 2/30 (6.7%) 0/30 (0%)
Oropharyngeal pain 2/12 (16.7%) 4/30 (13.3%) 0/30 (0%)
Pleural effusion 1/12 (8.3%) 3/30 (10%) 0/30 (0%)
Respiratory distress 1/12 (8.3%) 0/30 (0%) 0/30 (0%)
Rhinorrhoea 4/12 (33.3%) 2/30 (6.7%) 2/30 (6.7%)
Tachypnoea 1/12 (8.3%) 0/30 (0%) 0/30 (0%)
Skin and subcutaneous tissue disorders
Acne 0/12 (0%) 0/30 (0%) 2/30 (6.7%)
Alopecia 4/12 (33.3%) 2/30 (6.7%) 7/30 (23.3%)
Dermatitis acneiform 1/12 (8.3%) 0/30 (0%) 0/30 (0%)
Ecchymosis 2/12 (16.7%) 0/30 (0%) 0/30 (0%)
Erythema 1/12 (8.3%) 0/30 (0%) 0/30 (0%)
Night sweats 0/12 (0%) 2/30 (6.7%) 0/30 (0%)
Pruitus 1/12 (8.3%) 0/30 (0%) 2/30 (6.7%)
Purpura 0/12 (0%) 0/30 (0%) 3/30 (10%)
Rash 3/12 (25%) 3/30 (10%) 3/30 (10%)
Rash maculo-papular 0/12 (0%) 0/30 (0%) 2/30 (6.7%)
Skin disorder 0/12 (0%) 2/30 (6.7%) 0/30 (0%)
Skin ulcer 1/12 (8.3%) 0/30 (0%) 0/30 (0%)
Vascular disorders
Deep vein thrombosis 0/12 (0%) 3/30 (10%) 0/30 (0%)
Haematoma 2/12 (16.7%) 3/30 (10%) 0/30 (0%)
Haemorrhage 1/12 (8.3%) 0/30 (0%) 0/30 (0%)
Hypertension 0/12 (0%) 3/30 (10%) 0/30 (0%)
Hypotension 2/12 (16.7%) 3/30 (10%) 8/30 (26.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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

Name/Title Pfizer ClinicalTrials.gov Call Center
Organization Pfizer, Inc.
Phone 8007181021
Email ClinicalTrials.gov_Inquiries@pfizer.com
Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT02367456
Other Study ID Numbers:
  • B1371012
  • 2014-001345-24
  • BRIGHT MDS&AML1012
First Posted:
Feb 20, 2015
Last Update Posted:
May 31, 2022
Last Verified:
May 1, 2022