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Single-Agent Glasdegib In Patients With Myelofibrosis Previously Treated With Ruxolitinib

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02226172
Recruitment Status : Terminated
First Posted : August 27, 2014
Results First Posted : April 2, 2018
Last Update Posted : January 17, 2019
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Primary Myelofibrosis; Post-polycythemia Vera Myelofibrosis; Post-essential Thrombocythemia Myelofibrosis
Interventions Drug: Glasdegib (PF-04449913)
Drug: Placebo
Enrollment 21
Recruitment Details  
Pre-assignment Details In this study, 2 cohorts were involved lead-in and randomized cohort. Lead-in cohort was followed by randomized cohort. Though the drug was considered safe and tolerable in Myelofibrosis, but a key secondary efficacy outcome measure was not met. Therefore, continuation into the randomized cohort did not proceed.
Arm/Group Title Glasdegib Lead-in
Hide Arm/Group Description Glasdegib administered orally at a daily starting dose of 100 mg on a continuous regimen of 28-day cycles.
Period Title: Overall Study
Started 21
Completed 4
Not Completed 17
Reason Not Completed
Participant refused further follow-up             4
Other             5
Death             1
Study terminated by sponsor             1
Adverse Event             6
Arm/Group Title Glasdegib Lead-in
Hide Arm/Group Description Glasdegib administered orally at a daily starting dose of 100 mg on a continuous regimen of 28-day cycles.
Overall Number of Baseline Participants 21
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 21 participants
69.3  (7.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 21 participants
Female
8
  38.1%
Male
13
  61.9%
1.Primary Outcome
Title Percentage of Participants Achieving Spleen Volume Reduction (SVR) ≥35% as Measured by Magnetic Resonance Imaging (MRI)/Computed Tomography (CT) Scan at Week 24 in the Randomized Cohort
Hide Description The double blind, randomized, placebo controlled phase of the study was not enrolled after the study was terminated early so no data were collected to assess this endpoint.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all participants in the randomized Phase 2 component of the study who were randomized with study drug assignment designated according to initial randomization.
Arm/Group Title Glasdegib Lead-in
Hide Arm/Group Description:
Glasdegib administered orally at a daily starting dose of 100 mg on a continuous regimen of 28-day cycles.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
2.Primary Outcome
Title Number of Participants With Treatment -Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs): Lead-in Cohort
Hide Description An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to 28 days after last dose of study drug (up to Week 131) that were absent before treatment or that worsened relative to pretreatment state. AEs included both serious and non-serious adverse events.
Time Frame Baseline up to Week 131
Hide Outcome Measure Data
Hide Analysis Population Description
All participants treated in the lead-in portion of the study.
Arm/Group Title Glasdegib Lead-in
Hide Arm/Group Description:
Glasdegib administered orally at a daily starting dose of 100 mg on a continuous regimen of 28-day cycles.
Overall Number of Participants Analyzed 21
Measure Type: Count of Participants
Unit of Measure: Participants
AEs
21
 100.0%
SAEs
5
  23.8%
3.Primary Outcome
Title Number of Participants With Treatment Emergent Treatment -Related Adverse Events (AEs) and Serious Adverse Events (SAEs): Lead-in Cohort
Hide Description Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to 28 days after last dose of study drug (up to Week 131) that were absent before treatment or that worsened relative to pre-treatment state. Relatedness to study drug was assessed by the investigator. AEs included both serious and non-serious adverse event.
Time Frame Baseline up to Week 131
Hide Outcome Measure Data
Hide Analysis Population Description
All participants treated in the lead-in portion of the study.
Arm/Group Title Glasdegib Lead-in
Hide Arm/Group Description:
Glasdegib administered orally at a daily starting dose of 100 mg on a continuous regimen of 28-day cycles.
Overall Number of Participants Analyzed 21
Measure Type: Count of Participants
Unit of Measure: Participants
AEs
19
  90.5%
SAEs
5
  23.8%
4.Primary Outcome
Title Number of Participants With Treatment Emergent Adverse Events (AEs) According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03: Lead-in Cohort
Hide Description AE was untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. SAE was AE resulting in any outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience; persistent or significant disability; congenital anomaly.Treatment-emergent were events between first dose of study drug and up to 28 days after last dose of study drug (up to Week 131) that were absent before treatment or that worsened relative to pretreatment state.AE were assessed according to maximum severity grading based on NCI CTCAE Version 4.03.Grade 1=mild; Grade 2=moderate; within normal limits. Grade 3=severe or medically significant but not immediately life-threatening; Grade 4=life-threatening or disabling; urgent intervention indicated; Grade 5=death. Only categories with at least 1 participant with event were reported.
Time Frame Baseline up to Week 131
Hide Outcome Measure Data
Hide Analysis Population Description
All participants treated in the lead-in portion of the study.
Arm/Group Title Glasdegib Lead-in
Hide Arm/Group Description:
Glasdegib administered orally at a daily starting dose of 100 mg on a continuous regimen of 28-day cycles.
Overall Number of Participants Analyzed 21
Measure Type: Count of Participants
Unit of Measure: Participants
Grade 3 or 4
14
  66.7%
Grade 5
1
   4.8%
5.Primary Outcome
Title Number of Participants With Laboratory Abnormalities: Lead-in Cohort
Hide Description Abnormality: hematology: hemoglobin less than (<)0.8*lower limit of normal(LLN), platelets <0.5*LLN greater than (>)1.75*upper limit of normal(ULN), white blood cell count(WBC) <0.6* LLN >1.5* ULN,lymphocytes, total neutrophils<0.8* LLN >1.2* ULN, band Cells, basophils, eosinophils, monocytes >1.2*ULN, blast cells >1.0*ULN. Coagulation: activated partial thromboplastin time, prothrombin international ratio >1.1* ULN. Liver function: bilirubin >1.5*ULN, AST, ALT,lactate dehydrogenase,alkaline phosphatase >3.0*ULN, protein,albumin <0.8* LLN >1.2* ULN. Renal:blood urea nitrogen,creatinine >1.3*ULN,uric acid >1.2*ULN.Electrolytes: sodium <0.95*LLN >1.05*ULN, potassium, chloride, calcium, magnesium <0.9* LLN >1.1*ULN,phosphate <0.8* LLN >1.2* ULN.Chemistry: glucose <0.6*LLN >1.5*ULN,creatine kinase >2.0*ULN, amylase,lipase >1.5*ULN.Urinalysis: protein, blood >1.0*ULN,red blood cells,WBC >=20,epithelial cells >=6,casts,granular casts,hyaline >1,cellular casts,crystals>=1,bacteria >20.
Time Frame Baseline up to Week 131
Hide Outcome Measure Data
Hide Analysis Population Description
All participants treated in the lead-in portion of the study.
Arm/Group Title Glasdegib Lead-in
Hide Arm/Group Description:
Glasdegib administered orally at a daily starting dose of 100 mg on a continuous regimen of 28-day cycles.
Overall Number of Participants Analyzed 21
Measure Type: Count of Participants
Unit of Measure: Participants
21
 100.0%
6.Primary Outcome
Title Number of Participants With Laboratory Test Abnormalities According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03 Grade 3 and Above Hematological Test Abnormalities: Lead-in Cohort
Hide Description Anemia (grade [g]1:< LLN to 10 gram per deciliter [g/dL],g2:<10 to 8g/dL,g3:<8g/dL, g4:lifethreatening); platelet (g1:<LLN to 75*10^3/millimeter[mm]^3, g2:<75*10^3/mm^3 to 50*10^3/mm^3, g3:<50*10^3/mm^3 to 25*10^3/mm^3, g4:<25*10^3/mm^3); lymphopenia (g1:<LLN to 8*10^2/mm^3, g2:<8*10^2 to 5*10^2/mm^3, g3:<5*10^2 to 2*10^2/mm^3, g4:<2*10^2/mm^3);neutrophil (Absolute) (g1:<LLN to 15*10^2/mm^3, g2:<15*10^2 to 10*10^2/mm^3, g3:<10*10^2 to 5*10^2/mm^3, g4:<5*10^2/mm^3); white blood cell count(g1:<LLN to 3*10^3/mm^3, g2:<3*10^3 to 2*10^3/mm^3, g3:<2*10^3 to 1*10^3/mm^3, g4:<1*10^3/mm^3); hemoglobin (g1:increase in hemoglobin level >0 to 2 g/dL above ULN or above baseline if baseline is above ULN, g2:increase in hemoglobin level>2 to 4g/dL above ULN or above baseline if baseline is above ULN,g3: increase in hemoglobin level>4 g/dL above ULN or above baseline if baseline is above ULN).
Time Frame Baseline up to Week 131
Hide Outcome Measure Data
Hide Analysis Population Description
All participants treated in the lead-in portion of the study.
Arm/Group Title Glasdegib Lead-in
Hide Arm/Group Description:
Glasdegib administered orally at a daily starting dose of 100 mg on a continuous regimen of 28-day cycles.
Overall Number of Participants Analyzed 21
Measure Type: Count of Participants
Unit of Measure: Participants
Grade 3
3
  14.3%
Grade 4
2
   9.5%
7.Primary Outcome
Title Number of Participants With Laboratory Test Abnormalities According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03 Grade 3 and Above Chemistry Test Abnormalities: Lead-in Cohort
Hide Description ALT/AST g1:>ULN 3*ULN, g2:>3-5*ULN, g3:>5 20*ULN, g4:>20*ULN); Alkaline Phosphatase (g1:>ULN 2.5*ULN,g2:>2.5-5*ULN, g3:>5 20*ULN, g4:>20*ULN); Creatinine (g1:>ULN-1.5*ULN,g2:>1.5-3*ULN, g3:>3 6*ULN, g4:>6*ULN);hyperglycemia (g1:>ULN-160,g2:>160 250, g3:>250 500, g4:>500mg/dL);bilirubin(total) (g1:>ULN-1.5*ULN, g2:>1.5-3*ULN, g3:>3 10*ULN,g4:>10*ULN);hypoglycaemia (g1:<LLN-55,g2:<55-40, g3:<40 30,g4:<30mg/dL); hyperkalemia (g1:>ULN-5.5,g2:>5.5-6, g3:>6 7,g4:>7mmol/L);hypokalemia (g1:<LLN-3,g2:<LLN-3, g3:<3 2.5, g4:<2.5mmol/L);hypermagnesemia (g1:>ULN-3,g3:>3 8, g4:>8mg/dL);hypocalcemia (g1:<LLN-8,g2:<8-7, g3:<7-6, g4:<6mg/dL); hypercalcemia (g1:>ULN-11.5,g2:>11.5-12.5, g3:>12.5-13.5, g4:>13.5mg/dL); hypomagnesemia (g1:<LLN-1.2,g2:<1.2-0.9,g3:<0.9-0.7, g4:<0.7mg/dL); hyponatremia (g1:<LLN-130,g3:<130-120, g4:<120mmol/L);hypoalbuminemia (g1:<LLN-3,g2:<3 2,g3:<2, g4:lifethreatening);hypophosphatemia (g1:<LLN-2.5,g2:<2.5-2, g3:<2-1, g4:<1mg/dL).
Time Frame Baseline up to Week 131
Hide Outcome Measure Data
Hide Analysis Population Description
All participants treated in the lead-in portion of the study.
Arm/Group Title Glasdegib Lead-in
Hide Arm/Group Description:
Glasdegib administered orally at a daily starting dose of 100 mg on a continuous regimen of 28-day cycles.
Overall Number of Participants Analyzed 21
Measure Type: Count of Participants
Unit of Measure: Participants
Grade 3
5
  23.8%
Grade 4
1
   4.8%
8.Secondary Outcome
Title Percentage of Participants Achieving SVR ≥35% as Measured by Magnetic Resonance Imaging/Computed Tomography Scan at Week 24 in the Lead-in Cohort
Hide Description MRI (CT scan may have been permitted if MRI was contraindicated) of the spleen and the liver was performed at baseline, then every 12 weeks while the participant was on treatment. The same method of assessment used at baseline was used for the duration of the trial to ensure consistency. Spleen volume was assessed by a central, independent blinded reader.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Lead-in Analysis Set - included all participants treated in the lead-in portion of the study. Only participants who remained on treatment at Week 24 underwent MRI/CT scan.
Arm/Group Title Glasdegib Lead-in
Hide Arm/Group Description:
Glasdegib administered orally at a daily starting dose of 100 mg on a continuous regimen of 28-day cycles.
Overall Number of Participants Analyzed 6
Measure Type: Number
Unit of Measure: Percentage of participants
0
9.Secondary Outcome
Title Percentage of Participants Achieving ≥50% Reduction From Baseline in Total Symptom Score (TSS) as Measured by the Myeloproliferative Neoplasm-Symptom Assessment Diary (MPN-SAD) at Week 24 in the Lead-in Cohort
Hide Description The MPN-SAD assessed the impact of 9 myelofibrosis symptoms, at their worst, over the past 7 days and over the past 24 hours on a scale of 0 (absent) to 10 (worst imaginable). The 9 symptoms are early satiety, abdominal discomfort, inactivity, night sweats, pruritus, bone pain, pain below the ribs on the left-hand side, fatigue and shortness of breath. The TSS is the sum of the individual scores, excluding inactivity and shortness of breath. The TSS at Week 24 is the average of the daily total scores from the last 28 days of symptom scores immediately prior to Week 24. A higher score indicates worse symptoms.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Lead-in Analysis Set
Arm/Group Title Glasdegib Lead-in
Hide Arm/Group Description:
Glasdegib administered orally at a daily starting dose of 100 mg on a continuous regimen of 28-day cycles.
Overall Number of Participants Analyzed 21
Measure Type: Number
Unit of Measure: Percentage of participants
4.8
10.Secondary Outcome
Title Monthly Mean Change From Baseline in Overall Total Symptom Score (TSS) in the Lead-in Cohort
Hide Description The MPN-SAD assessed the impact of 9 myelofibrosis symptoms, at their worst, over the past 7 days and over the past 24 hours on a scale of 0 (absent) to 10 (worst imaginable). The 9 symptoms are early satiety, abdominal discomfort, inactivity, night sweats, pruritus, bone pain, pain below the ribs on the left-hand side, fatigue and shortness of breath. The TSS is the sum of the individual scores, excluding inactivity and shortness of breath. The TSS at Week 24 is the average of the daily total scores from the last 28 days of symptom scores immediately prior to Week 24. A higher score indicates worse symptoms.
Time Frame Weeks 12, 24, 36 and 48
Hide Outcome Measure Data
Hide Analysis Population Description
Lead-in Analysis Set
Arm/Group Title Glasdegib Lead-in
Hide Arm/Group Description:
Glasdegib administered orally at a daily starting dose of 100 mg on a continuous regimen of 28-day cycles.
Overall Number of Participants Analyzed 21
Mean (Standard Deviation)
Unit of Measure: Score on a scale
Monthly mean change at Week 12 Number Analyzed 13 participants
-2.74  (14.07)
Monthly mean change at Week 24 Number Analyzed 6 participants
-4.95  (5.78)
Monthly mean change at Week 36 Number Analyzed 1 participants
-4.11 [1]   (NA)
Monthly mean change at Week 48 Number Analyzed 2 participants
-8.39  (11.52)
[1]
No standard deviation was calculable since n=1.
11.Secondary Outcome
Title Percentage of Participants Achieving Anemia Response (Transfusion Dependent Versus Independent) in the Lead-in Cohort
Hide Description Anemia response was defined as transfusion-independent participants with a ≥20 gram per liter (g/L) increase in hemoglobin (Hb) level where baseline Hb level was <100 g/L, or baseline transfusion-dependent patients becoming transfusion-independent post-baseline. Transfusion dependency before the start of study treatment was defined as transfusions of ≥6 units of packed red blood cells in the 12 weeks prior to start of study treatment, for a final pre-treatment Hb of <85 g/L. In addition, the most recent transfusion episode must have occurred in the 28 days prior to study enrollment. Response in transfusion-dependent patients required absence of any packed red blood cell transfusions during any consecutive rolling 12-week interval during the treatment phase, capped by a Hb level of ≥85 g/L.
Time Frame Baseline to end of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
Lead-in Analysis Set
Arm/Group Title Glasdegib Lead-in
Hide Arm/Group Description:
Glasdegib administered orally at a daily starting dose of 100 mg on a continuous regimen of 28-day cycles.
Overall Number of Participants Analyzed 21
Measure Type: Number
Unit of Measure: Percentage of participants
Transfusion independent ≥20 g/L Hb increase Number Analyzed 17 participants
5.9
Transfusion dependent Number Analyzed 4 participants
0
12.Secondary Outcome
Title Maximum Observed Glasdegib Plasma Concentration (Cmax), Minimum Glasdegib Plasma Concentration Observed Prior to the Next Dose (Cmin), and Average Observed Glasdegib Plasma Concentration (Cavg) in the Lead-in Cohort
Hide Description Cmax was the highest plasma concentration of glasdegib observed directly from the plasma concentration data. Cmin was the lowest plasma concentration of glasdegib observed directly from the plasma concentration data. Cavg was the average concentration at steady state estimated using non-compartmental pharmacokinetic (PK) analysis.
Time Frame Cycle 1, Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
PK Parameter Analysis Population - included all enrolled participants treated who had at least 1 of the PK parameters of interest and were dose compliant (at steady state for glasdegib ).
Arm/Group Title Glasdegib Lead-in
Hide Arm/Group Description:
Glasdegib administered orally at a daily starting dose of 100 mg on a continuous regimen of 28-day cycles.
Overall Number of Participants Analyzed 19
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanograms per milliliter (ng/mL)
Cmax Number Analyzed 19 participants
996.8
(45%)
Cmin Number Analyzed 19 participants
191.9
(68%)
Cav Number Analyzed 17 participants
548.0
(50%)
13.Secondary Outcome
Title Area Under the Glasdegib Plasma Concentration Versus Time Profile at the End of a Dosing Interval (AUCtau) in the Lead-in Cohort
Hide Description AUCtau was the area under the glasdegib plasma concentration-time profile from time zero to the end of the dosing interval (24 hours) estimated by non-compartmental PK analysis using the linear/log trapezoidal method.
Time Frame Cycle 1, Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
PK Parameter Analysis Population
Arm/Group Title Glasdegib Lead-in
Hide Arm/Group Description:
Glasdegib administered orally at a daily starting dose of 100 mg on a continuous regimen of 28-day cycles.
Overall Number of Participants Analyzed 17
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng·hr/mL
13150
(50%)
14.Secondary Outcome
Title Time to Reach Cmax (Tmax) in the Lead-in Cohort
Hide Description Tmax was the time of the first occurrence of Cmax observed directly from the plasma concentration data.
Time Frame Cycle 1, Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
PK Parameter Analysis Population
Arm/Group Title Glasdegib Lead-in
Hide Arm/Group Description:
Glasdegib administered orally at a daily starting dose of 100 mg on a continuous regimen of 28-day cycles.
Overall Number of Participants Analyzed 19
Median (Full Range)
Unit of Measure: Hours
1.02
(0.483 to 4.00)
15.Secondary Outcome
Title Percentage of Participants Achieving SVR ≥50% as Measured by MRI/CT Scan at Week 24 in the Randomized Cohort
Hide Description The double blind, randomized, placebo controlled phase of the study was not enrolled after the study was terminated early so no data were collected to assess this endpoint.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Glasdegib Lead-in
Hide Arm/Group Description:
Glasdegib administered orally at a daily starting dose of 100 mg on a continuous regimen of 28-day cycles.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
16.Secondary Outcome
Title Monthly Mean Change From Baseline in Overall TSS in the Randomized Cohort
Hide Description The double blind, randomized, placebo controlled phase of the study was not enrolled after the study was terminated early so no data were collected to assess this endpoint.
Time Frame Weeks 12, 24, 36 and 48
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Glasdegib Lead-in
Hide Arm/Group Description:
Glasdegib administered orally at a daily starting dose of 100 mg on a continuous regimen of 28-day cycles.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
17.Secondary Outcome
Title Percentage of Participants Achieving Anemia Response (Transfusion Dependent Versus Independent) in the Randomized Cohort
Hide Description The double blind, randomized, placebo controlled phase of the study was not enrolled after the study was terminated early so no data were collected to assess this endpoint.
Time Frame Baseline to end of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Glasdegib Lead-in
Hide Arm/Group Description:
Glasdegib administered orally at a daily starting dose of 100 mg on a continuous regimen of 28-day cycles.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
18.Secondary Outcome
Title Participant Reported Outcomes of Health Related Quality of Life and Health Status in the Randomised Cohort
Hide Description The double blind, randomized, placebo controlled phase of the study was not enrolled after the study was terminated early so no data were collected to assess this endpoint.
Time Frame Baseline to end of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Glasdegib Lead-in
Hide Arm/Group Description:
Glasdegib administered orally at a daily starting dose of 100 mg on a continuous regimen of 28-day cycles.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
19.Secondary Outcome
Title Median Duration of SVR in the Randomized Cohort
Hide Description The double blind, randomized, placebo controlled phase of the study was not enrolled after the study was terminated early so no data were collected to assess this endpoint.
Time Frame Baseline to end of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Glasdegib Lead-in
Hide Arm/Group Description:
Glasdegib administered orally at a daily starting dose of 100 mg on a continuous regimen of 28-day cycles.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
20.Secondary Outcome
Title Kaplan-Meier Estimate of Overall Survival in the Randomized Cohort
Hide Description The double blind, randomized, placebo controlled phase of the study was not enrolled after the study was terminated early so no data were collected to assess this endpoint.
Time Frame Baseline to end of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Glasdegib Lead-in
Hide Arm/Group Description:
Glasdegib administered orally at a daily starting dose of 100 mg on a continuous regimen of 28-day cycles.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
21.Secondary Outcome
Title Glasdegib PK Parameters in the Randomized Cohort
Hide Description The double blind, randomized, placebo controlled phase of the study was not enrolled after the study was terminated early so no data were collected to assess this endpoint.
Time Frame Cycle 1, Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
PK Parameter Analysis Population
Arm/Group Title Glasdegib Lead-in
Hide Arm/Group Description:
Glasdegib administered orally at a daily starting dose of 100 mg on a continuous regimen of 28-day cycles.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
22.Secondary Outcome
Title Psychometric Validation of the MPN-SAD in the Randomised Cohort
Hide Description The double blind, randomized, placebo controlled phase of the study was not enrolled after the study was terminated early so no data were collected to assess this endpoint.
Time Frame Baseline to end of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Glasdegib Lead-in
Hide Arm/Group Description:
Glasdegib administered orally at a daily starting dose of 100 mg on a continuous regimen of 28-day cycles.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
23.Secondary Outcome
Title Number of Participants With Treatment -Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs): Randomized Cohort
Hide Description An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. A treatment emergent AE was defined as an event that emerged during the treatment period that was absent before treatment, or worsened during the treatment period relative to the pretreatment state.
Time Frame Baseline up to Week 131
Hide Outcome Measure Data
Hide Analysis Population Description
The double blind, randomized, placebo controlled phase of the study was not enrolled as the study was terminated early so, no data were collected to assess this outcome measure.
Arm/Group Title Glasdegib Lead-in
Hide Arm/Group Description:
Glasdegib administered orally at a daily starting dose of 100 mg on a continuous regimen of 28-day cycles.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
24.Secondary Outcome
Title Number of Participants With Treatment Emergent Treatment -Related Adverse Events (AEs) and Serious Adverse Events (SAEs): Randomized Cohort
Hide Description Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. A treatment emergent AE was defined as an event that emerged during the treatment period that was absent before treatment, or worsened during the treatment period relative to the pretreatment state. Relatedness to study drug was assessed by the investigator.
Time Frame Baseline up to Week 131
Hide Outcome Measure Data
Hide Analysis Population Description
The double blind, randomized, placebo controlled phase of the study was not enrolled as the study was terminated early so, no data were collected to assess this outcome measure.
Arm/Group Title Glasdegib Lead-in
Hide Arm/Group Description:
Glasdegib administered orally at a daily starting dose of 100 mg on a continuous regimen of 28-day cycles.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
25.Secondary Outcome
Title Number of Participants With Treatment Emergent Adverse Events (AEs) According to Maximum Severity: Randomized Cohort
Hide Description AE was untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. SAE was AE resulting in any of following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. A treatment emergent AE was defined as an event that emerged during the treatment period that was absent before treatment, or worsened during the treatment period relative to the pretreatment state. AE were assessed according to maximum severity grading based on NCI CTCAE Version 4.03.Grade 1=mild; Grade 2=moderate; within normal limits. Grade 3=severe or medically significant but not immediately life-threatening; Grade 4=life-threatening or disabling; urgent intervention indicated; Grade 5=death.
Time Frame Baseline up to Week 131
Hide Outcome Measure Data
Hide Analysis Population Description
The double blind, randomized, placebo controlled phase of the study was not enrolled as the study was terminated early so, no data were collected to assess this outcome measure.
Arm/Group Title Glasdegib Lead-in
Hide Arm/Group Description:
Glasdegib administered orally at a daily starting dose of 100 mg on a continuous regimen of 28-day cycles.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
26.Secondary Outcome
Title Number of Participants With Laboratory Abnormalities: Randomized Cohort
Hide Description Abnormality: hematology: hemoglobin less than (<)0.8*lower limit of normal(LLN), platelets <0.5*LLN >1.75*upper limit of normal(ULN), white blood cell count(WBC) <0.6* LLN greater than (>)1.5* ULN,lymphocytes, total neutrophils<0.8* LLN >1.2* ULN, band Cells, basophils, eosinophils, monocytes >1.2*ULN, blast cells >1.0*ULN. Coagulation: activated partial thromboplastin time, prothrombin international ratio >1.1* ULN. Liver function: bilirubin >1.5*ULN, AST, ALT,lactate dehydrogenase,alkaline phosphatase >3.0*ULN, protein,albumin <0.8* LLN >1.2* ULN. Renal:blood urea nitrogen,creatinine >1.3* ULN,uric acid >1.2* ULN.Electrolytes: sodium <0.95*LLN >1.05*ULN, potassium, chloride, calcium, magnesium <0.9* LLN >1.1*ULN,phosphate <0.8* LLN >1.2* ULN.Chemistry: glucose <0.6*LLN >1.5*ULN,creatine kinase >2.0*ULN, amylase,lipase >1.5*ULN.Urinalysis: protein, blood >1.0*ULN,red blood cells,WBC >=20,epithelial cells >=6,casts,granular casts,hyaline >1,cellular casts,crystals>=1,bacteria >20.
Time Frame Baseline up to Week 131
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Hide Analysis Population Description
The double blind, randomized, placebo controlled phase of the study was not enrolled as the study was terminated early so, no data were collected to assess this outcome measure.
Arm/Group Title Glasdegib Lead-in
Hide Arm/Group Description:
Glasdegib administered orally at a daily starting dose of 100 mg on a continuous regimen of 28-day cycles.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
27.Secondary Outcome
Title Number of Participants With Laboratory Test Abnormalities By Maximum Severity: National Cancer Institute Common Terminology Criteria for Adverse Event (Version 4.0) Grade 3 and Above Hematological Test Abnormalities: Randomized Cohort
Hide Description Anemia g1:< LLN to 10 g/dL, g2:<10 to 8g/dL, g3:<8g/dL, g4:lifethreatening); platelet (g1:<LLN to 75*10^3/mm^3, g2:<75*10^3/mm^3 to 50*10^3/mm^3, g3:<50*10^3/mm^3 to 25*10^3/mm^3, g4:<25*10^3/mm^3); lymphopenia (g1:<LLN to 8*10^2/mm^3, g2:<8*10^2 to 5*10^2/mm^3, g3:<5*10^2 to 2*10^2/mm^3, g4:<2*10^2/mm^3);neutrophil (absolute) (g1:<LLN to 15*10^2/mm^3, g2:<15*10^2 to 10*10^2/mm^3, g3:<10*10^2 to 5*10^2/mm^3, g4:<5*10^2/mm^3); white blood cell count (g1:<LLN to 3*10^3/mm^3, g2:<3*10^3 to 2*10^3/mm^3, g3: <2*10^3 to 1*10^3/mm^3, g4:<1*10^3/mm^3); hemoglobin(g1:increase in hemoglobin level>0 to 2 g/dL above ULN or above baseline if baseline is above ULN, g2: increase in hemoglobin level>2 to 4g/dL above ULN or above baseline if baseline is above ULN, g3:increase in hemoglobin level>4 g/dL above ULN or above baseline if baseline is above ULN).
Time Frame Baseline up to Week 131
Hide Outcome Measure Data
Hide Analysis Population Description
The double blind, randomized, placebo controlled phase of the study was not enrolled as the study was terminated early so, no data were collected to assess this outcome measure.
Arm/Group Title Glasdegib Lead-in
Hide Arm/Group Description:
Glasdegib administered orally at a daily starting dose of 100 mg on a continuous regimen of 28-day cycles.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
28.Secondary Outcome
Title Number of Participants With Laboratory Test Abnormalities By Maximum Severity: National Cancer Institute Common Terminology Criteria for Adverse Event (Version 4.0) Grade 3 and Above Chemistry Test Abnormalities: Randomized Cohort
Hide Description ALT/AST g1:>ULN 3*ULN, g2:>3-5*ULN, g3:>5 20*ULN, g4:>20*ULN); Alkaline Phosphatase (g1:>ULN 2.5*ULN, g2:>2.5-5*ULN, g3:>5 20*ULN, g4:>20*ULN);Creatinine (g1:>ULN-1.5*ULN, g2:>1.5-3*ULN, g3:>3 6*ULN, g4:>6*ULN);hyperglycemia (g1:>ULN-160,g2:>160 250, g3:>250 500,g4:>500mg/dL); bilirubin(total) (g1:>ULN-1.5*ULN, g2:>1.5-3*ULN, g3:>3 10*ULN,g4:>10*ULN); hypoglycaemia (g1:<LLN-55, g2:<55-40, g3:<40 30, g4:<30mg/dL); hyperkalemia (g1:>ULN-5.5,g2:>5.5-6, g3:>6 7,g4:>7mmol/L); hypokalemia (g1:<LLN-3,g2:<LLN-3,g3:<3 2.5, g4:<2.5mmol/L); hypermagnesemia (g1:>ULN-3,g3:>3 8,g4:>8mg/dL); hypocalcemia (g1:<LLN-8,g2:<8-7, g3:<7-6, g4:<6mg/dL); hypercalcemia (g1:>ULN-11.5,g2:>11.5-12.5, g3:>12.5-13.5, g4:>13.5mg/dL);hypomagnesemia (g1:<LLN-1.2,g2:<1.2-0.9, g3:<0.9-0.7,g4:<0.7mg/dL); hyponatremia (g1:<LLN-130,g3:<130-120, g4:<120mmol/L);hypoalbuminemia (g1:<LLN-3,g2:<3-2, g3:<2, g4:lifethreatening);hypophosphatemia (g1:<LLN-2.5,g2:<2.5-2,g3:<2-1,g4:<1mg/dL).
Time Frame Baseline up to Week 131
Hide Outcome Measure Data
Hide Analysis Population Description
The double blind, randomized, placebo controlled phase of the study was not enrolled as the study was terminated early so, no data were collected to assess this outcome measure.
Arm/Group Title Glasdegib Lead-in
Hide Arm/Group Description:
Glasdegib administered orally at a daily starting dose of 100 mg on a continuous regimen of 28-day cycles.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame Baseline up to Week 131
Adverse Event Reporting Description An event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in another participant, or 1 participant may have experienced both a serious and non-serious event. All participants treated in the lead-in portion of the study. It was the analysis population for all analyses on the lead-in portion of the study.
 
Arm/Group Title Glasdegib Lead-in
Hide Arm/Group Description Glasdegib administered orally at a daily starting dose of 100 mg on a continuous regimen of 28-day cycles.
All-Cause Mortality
Glasdegib Lead-in
Affected / at Risk (%)
Total   1/21 (4.76%) 
Hide Serious Adverse Events
Glasdegib Lead-in
Affected / at Risk (%)
Total   5/21 (23.81%) 
Cardiac disorders   
Sinus tachycardia * 1  1/21 (4.76%) 
Gastrointestinal disorders   
Gastric varices haemorrhage * 1  1/21 (4.76%) 
Varices oesophageal * 1  1/21 (4.76%) 
General disorders   
Disease progression * 1  1/21 (4.76%) 
Fatigue * 1  1/21 (4.76%) 
Hepatobiliary disorders   
Portal hypertension * 1  1/21 (4.76%) 
Infections and infestations   
Bronchitis * 1  1/21 (4.76%) 
Injury, poisoning and procedural complications   
Postoperative ileus * 1  1/21 (4.76%) 
Metabolism and nutrition disorders   
Failure to thrive * 1  1/21 (4.76%) 
Nervous system disorders   
Memory impairment * 1  1/21 (4.76%) 
Psychiatric disorders   
Mental status changes * 1  1/21 (4.76%) 
Confusional state * 1  1/21 (4.76%) 
Respiratory, thoracic and mediastinal disorders   
Respiratory failure * 1  1/21 (4.76%) 
Hypoxia * 1  1/21 (4.76%) 
1
Term from vocabulary, MedDRA v20.1
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Glasdegib Lead-in
Affected / at Risk (%)
Total   20/21 (95.24%) 
Blood and lymphatic system disorders   
Anaemia * 1  5/21 (23.81%) 
Neutropenia * 1  2/21 (9.52%) 
Thrombocytopenia * 1  3/21 (14.29%) 
Gastrointestinal disorders   
Abdominal pain * 1  2/21 (9.52%) 
Abdominal pain upper * 1  2/21 (9.52%) 
Constipation * 1  3/21 (14.29%) 
Diarrhoea * 1  2/21 (9.52%) 
Dry mouth * 1  2/21 (9.52%) 
Nausea * 1  4/21 (19.05%) 
General disorders   
Asthenia * 1  3/21 (14.29%) 
Fatigue * 1  7/21 (33.33%) 
Pyrexia * 1  4/21 (19.05%) 
Infections and infestations   
Upper respiratory tract infection * 1  3/21 (14.29%) 
Injury, poisoning and procedural complications   
Fall * 1  2/21 (9.52%) 
Investigations   
Electrocardiogram QT prolonged * 1  3/21 (14.29%) 
Lipase increased * 1  5/21 (23.81%) 
Lymphocyte count decreased * 1  3/21 (14.29%) 
Weight decreased * 1  6/21 (28.57%) 
Metabolism and nutrition disorders   
Decreased appetite * 1  7/21 (33.33%) 
Dehydration * 1  3/21 (14.29%) 
Hyperuricaemia * 1  4/21 (19.05%) 
Hyperglycaemia * 1  2/21 (9.52%) 
Musculoskeletal and connective tissue disorders   
Back pain * 1  2/21 (9.52%) 
Muscle spasms * 1  12/21 (57.14%) 
Myalgia * 1  3/21 (14.29%) 
Pain in extremity * 1  3/21 (14.29%) 
Nervous system disorders   
Dizziness * 1  3/21 (14.29%) 
Dysgeusia * 1  13/21 (61.90%) 
Respiratory, thoracic and mediastinal disorders   
Cough * 1  3/21 (14.29%) 
Dyspnoea exertional * 1  2/21 (9.52%) 
Skin and subcutaneous tissue disorders   
Alopecia * 1  8/21 (38.10%) 
Night sweats * 1  2/21 (9.52%) 
Pruritus * 1  2/21 (9.52%) 
Pruritus generalised * 1  2/21 (9.52%) 
Rash * 1  3/21 (14.29%) 
1
Term from vocabulary, MedDRA v20.1
*
Indicates events were collected by non-systematic assessment
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days from the time submitted to the sponsor for review. Investigators will, on request, remove any previously undisclosed Confidential Information (other than the Study results themselves) before disclosure.
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
Layout table for additonal information
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT02226172    
Other Study ID Numbers: B1371013
SMOI ( Other Identifier: Alias Study Number )
2014-000933-21 ( EudraCT Number )
2014-001048-40 ( EudraCT Number )
First Submitted: August 25, 2014
First Posted: August 27, 2014
Results First Submitted: November 30, 2017
Results First Posted: April 2, 2018
Last Update Posted: January 17, 2019