<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02226172</url>
  </required_header>
  <id_info>
    <org_study_id>B1371013</org_study_id>
    <secondary_id>SMOI</secondary_id>
    <secondary_id>2014-000933-21</secondary_id>
    <secondary_id>2014-001048-40</secondary_id>
    <nct_id>NCT02226172</nct_id>
  </id_info>
  <brief_title>Single-Agent Glasdegib In Patients With Myelofibrosis Previously Treated With Ruxolitinib</brief_title>
  <official_title>A Phase 2, Double-blind, Randomized Safety And Efficacy Study Of Glasdegib (Pf-04449913) Versus Placebo In Patients With Myelofibrosis Previously Treated With Ruxolitinib</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Pfizer</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Pfizer</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      A lead-in cohort of ~20 patients with primary or secondary myelofibrosis previously treated&#xD;
      with 1 or more Janus kinase inhibitors enrolled to single-agent glasdegib to evaluate safety&#xD;
      and tolerability. Following the lead-in, a phase 2, double blind, 2-arm study, randomized 2:1&#xD;
      to oral single-agent glasdegib versus placebo in 201 patients resistant or intolerant to&#xD;
      ruxolitinib.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <start_date type="Actual">October 6, 2014</start_date>
  <completion_date type="Actual">January 31, 2018</completion_date>
  <primary_completion_date type="Actual">December 14, 2016</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>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</measure>
    <time_frame>Week 24</time_frame>
    <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.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With Treatment -Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs): Lead-in Cohort</measure>
    <time_frame>Baseline up to Week 131</time_frame>
    <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.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With Treatment Emergent Treatment -Related Adverse Events (AEs) and Serious Adverse Events (SAEs): Lead-in Cohort</measure>
    <time_frame>Baseline up to Week 131</time_frame>
    <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.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>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</measure>
    <time_frame>Baseline up to Week 131</time_frame>
    <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.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With Laboratory Abnormalities: Lead-in Cohort</measure>
    <time_frame>Baseline up to Week 131</time_frame>
    <description>Abnormality: hematology: hemoglobin less than (&lt;)0.8*lower limit of normal(LLN), platelets &lt;0.5*LLN greater than (&gt;)1.75*upper limit of normal(ULN), white blood cell count(WBC) &lt;0.6* LLN &gt;1.5* ULN,lymphocytes, total neutrophils&lt;0.8* LLN &gt;1.2* ULN, band Cells, basophils, eosinophils, monocytes &gt;1.2*ULN, blast cells &gt;1.0*ULN. Coagulation: activated partial thromboplastin time, prothrombin international ratio &gt;1.1* ULN. Liver function: bilirubin &gt;1.5*ULN, AST, ALT,lactate dehydrogenase,alkaline phosphatase &gt;3.0*ULN, protein,albumin &lt;0.8* LLN &gt;1.2* ULN. Renal:blood urea nitrogen,creatinine &gt;1.3*ULN,uric acid &gt;1.2*ULN.Electrolytes: sodium &lt;0.95*LLN &gt;1.05*ULN, potassium, chloride, calcium, magnesium &lt;0.9* LLN &gt;1.1*ULN,phosphate &lt;0.8* LLN &gt;1.2* ULN.Chemistry: glucose &lt;0.6*LLN &gt;1.5*ULN,creatine kinase &gt;2.0*ULN, amylase,lipase &gt;1.5*ULN.Urinalysis: protein, blood &gt;1.0*ULN,red blood cells,WBC &gt;=20,epithelial cells &gt;=6,casts,granular casts,hyaline &gt;1,cellular casts,crystals&gt;=1,bacteria &gt;20.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>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</measure>
    <time_frame>Baseline up to Week 131</time_frame>
    <description>Anemia (grade [g]1:&lt; LLN to 10 gram per deciliter [g/dL],g2:&lt;10 to 8g/dL,g3:&lt;8g/dL, g4:lifethreatening); platelet (g1:&lt;LLN to 75*10^3/millimeter[mm]^3, g2:&lt;75*10^3/mm^3 to 50*10^3/mm^3, g3:&lt;50*10^3/mm^3 to 25*10^3/mm^3, g4:&lt;25*10^3/mm^3); lymphopenia (g1:&lt;LLN to 8*10^2/mm^3, g2:&lt;8*10^2 to 5*10^2/mm^3, g3:&lt;5*10^2 to 2*10^2/mm^3, g4:&lt;2*10^2/mm^3);neutrophil (Absolute) (g1:&lt;LLN to 15*10^2/mm^3, g2:&lt;15*10^2 to 10*10^2/mm^3, g3:&lt;10*10^2 to 5*10^2/mm^3, g4:&lt;5*10^2/mm^3); white blood cell count(g1:&lt;LLN to 3*10^3/mm^3, g2:&lt;3*10^3 to 2*10^3/mm^3, g3:&lt;2*10^3 to 1*10^3/mm^3, g4:&lt;1*10^3/mm^3); hemoglobin (g1:increase in hemoglobin level &gt;0 to 2 g/dL above ULN or above baseline if baseline is above ULN, g2:increase in hemoglobin level&gt;2 to 4g/dL above ULN or above baseline if baseline is above ULN,g3: increase in hemoglobin level&gt;4 g/dL above ULN or above baseline if baseline is above ULN).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>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</measure>
    <time_frame>Baseline up to Week 131</time_frame>
    <description>ALT/AST g1:&gt;ULN 3*ULN, g2:&gt;3-5*ULN, g3:&gt;5 20*ULN, g4:&gt;20*ULN); Alkaline Phosphatase (g1:&gt;ULN 2.5*ULN,g2:&gt;2.5-5*ULN, g3:&gt;5 20*ULN, g4:&gt;20*ULN); Creatinine (g1:&gt;ULN-1.5*ULN,g2:&gt;1.5-3*ULN, g3:&gt;3 6*ULN, g4:&gt;6*ULN);hyperglycemia (g1:&gt;ULN-160,g2:&gt;160 250, g3:&gt;250 500, g4:&gt;500mg/dL);bilirubin(total) (g1:&gt;ULN-1.5*ULN, g2:&gt;1.5-3*ULN, g3:&gt;3 10*ULN,g4:&gt;10*ULN);hypoglycaemia (g1:&lt;LLN-55,g2:&lt;55-40, g3:&lt;40 30,g4:&lt;30mg/dL); hyperkalemia (g1:&gt;ULN-5.5,g2:&gt;5.5-6, g3:&gt;6 7,g4:&gt;7mmol/L);hypokalemia (g1:&lt;LLN-3,g2:&lt;LLN-3, g3:&lt;3 2.5, g4:&lt;2.5mmol/L);hypermagnesemia (g1:&gt;ULN-3,g3:&gt;3 8, g4:&gt;8mg/dL);hypocalcemia (g1:&lt;LLN-8,g2:&lt;8-7, g3:&lt;7-6, g4:&lt;6mg/dL); hypercalcemia (g1:&gt;ULN-11.5,g2:&gt;11.5-12.5, g3:&gt;12.5-13.5, g4:&gt;13.5mg/dL); hypomagnesemia (g1:&lt;LLN-1.2,g2:&lt;1.2-0.9,g3:&lt;0.9-0.7, g4:&lt;0.7mg/dL); hyponatremia (g1:&lt;LLN-130,g3:&lt;130-120, g4:&lt;120mmol/L);hypoalbuminemia (g1:&lt;LLN-3,g2:&lt;3 2,g3:&lt;2, g4:lifethreatening);hypophosphatemia (g1:&lt;LLN-2.5,g2:&lt;2.5-2, g3:&lt;2-1, g4:&lt;1mg/dL).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Achieving SVR ≥35% as Measured by Magnetic Resonance Imaging/Computed Tomography Scan at Week 24 in the Lead-in Cohort</measure>
    <time_frame>Week 24</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>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</measure>
    <time_frame>Week 24</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Monthly Mean Change From Baseline in Overall Total Symptom Score (TSS) in the Lead-in Cohort</measure>
    <time_frame>Weeks 12, 24, 36 and 48</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Achieving Anemia Response (Transfusion Dependent Versus Independent) in the Lead-in Cohort</measure>
    <time_frame>Baseline to end of treatment</time_frame>
    <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 &lt;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 &lt;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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>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</measure>
    <time_frame>Cycle 1, Day 15</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Glasdegib Plasma Concentration Versus Time Profile at the End of a Dosing Interval (AUCtau) in the Lead-in Cohort</measure>
    <time_frame>Cycle 1, Day 15</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Reach Cmax (Tmax) in the Lead-in Cohort</measure>
    <time_frame>Cycle 1, Day 15</time_frame>
    <description>Tmax was the time of the first occurrence of Cmax observed directly from the plasma concentration data.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Achieving SVR ≥50% as Measured by MRI/CT Scan at Week 24 in the Randomized Cohort</measure>
    <time_frame>Week 24</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Monthly Mean Change From Baseline in Overall TSS in the Randomized Cohort</measure>
    <time_frame>Weeks 12, 24, 36 and 48</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Achieving Anemia Response (Transfusion Dependent Versus Independent) in the Randomized Cohort</measure>
    <time_frame>Baseline to end of treatment</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Participant Reported Outcomes of Health Related Quality of Life and Health Status in the Randomised Cohort</measure>
    <time_frame>Baseline to end of treatment</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Median Duration of SVR in the Randomized Cohort</measure>
    <time_frame>Baseline to end of treatment</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Kaplan-Meier Estimate of Overall Survival in the Randomized Cohort</measure>
    <time_frame>Baseline to end of treatment</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Glasdegib PK Parameters in the Randomized Cohort</measure>
    <time_frame>Cycle 1, Day 15</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Psychometric Validation of the MPN-SAD in the Randomised Cohort</measure>
    <time_frame>Baseline to end of treatment</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Treatment -Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs): Randomized Cohort</measure>
    <time_frame>Baseline up to Week 131</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Treatment Emergent Treatment -Related Adverse Events (AEs) and Serious Adverse Events (SAEs): Randomized Cohort</measure>
    <time_frame>Baseline up to Week 131</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Treatment Emergent Adverse Events (AEs) According to Maximum Severity: Randomized Cohort</measure>
    <time_frame>Baseline up to Week 131</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Laboratory Abnormalities: Randomized Cohort</measure>
    <time_frame>Baseline up to Week 131</time_frame>
    <description>Abnormality: hematology: hemoglobin less than (&lt;)0.8*lower limit of normal(LLN), platelets &lt;0.5*LLN &gt;1.75*upper limit of normal(ULN), white blood cell count(WBC) &lt;0.6* LLN greater than (&gt;)1.5* ULN,lymphocytes, total neutrophils&lt;0.8* LLN &gt;1.2* ULN, band Cells, basophils, eosinophils, monocytes &gt;1.2*ULN, blast cells &gt;1.0*ULN. Coagulation: activated partial thromboplastin time, prothrombin international ratio &gt;1.1* ULN. Liver function: bilirubin &gt;1.5*ULN, AST, ALT,lactate dehydrogenase,alkaline phosphatase &gt;3.0*ULN, protein,albumin &lt;0.8* LLN &gt;1.2* ULN. Renal:blood urea nitrogen,creatinine &gt;1.3* ULN,uric acid &gt;1.2* ULN.Electrolytes: sodium &lt;0.95*LLN &gt;1.05*ULN, potassium, chloride, calcium, magnesium &lt;0.9* LLN &gt;1.1*ULN,phosphate &lt;0.8* LLN &gt;1.2* ULN.Chemistry: glucose &lt;0.6*LLN &gt;1.5*ULN,creatine kinase &gt;2.0*ULN, amylase,lipase &gt;1.5*ULN.Urinalysis: protein, blood &gt;1.0*ULN,red blood cells,WBC &gt;=20,epithelial cells &gt;=6,casts,granular casts,hyaline &gt;1,cellular casts,crystals&gt;=1,bacteria &gt;20.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>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</measure>
    <time_frame>Baseline up to Week 131</time_frame>
    <description>Anemia g1:&lt; LLN to 10 g/dL, g2:&lt;10 to 8g/dL, g3:&lt;8g/dL, g4:lifethreatening); platelet (g1:&lt;LLN to 75*10^3/mm^3, g2:&lt;75*10^3/mm^3 to 50*10^3/mm^3, g3:&lt;50*10^3/mm^3 to 25*10^3/mm^3, g4:&lt;25*10^3/mm^3); lymphopenia (g1:&lt;LLN to 8*10^2/mm^3, g2:&lt;8*10^2 to 5*10^2/mm^3, g3:&lt;5*10^2 to 2*10^2/mm^3, g4:&lt;2*10^2/mm^3);neutrophil (absolute) (g1:&lt;LLN to 15*10^2/mm^3, g2:&lt;15*10^2 to 10*10^2/mm^3, g3:&lt;10*10^2 to 5*10^2/mm^3, g4:&lt;5*10^2/mm^3); white blood cell count (g1:&lt;LLN to 3*10^3/mm^3, g2:&lt;3*10^3 to 2*10^3/mm^3, g3: &lt;2*10^3 to 1*10^3/mm^3, g4:&lt;1*10^3/mm^3); hemoglobin(g1:increase in hemoglobin level&gt;0 to 2 g/dL above ULN or above baseline if baseline is above ULN, g2: increase in hemoglobin level&gt;2 to 4g/dL above ULN or above baseline if baseline is above ULN, g3:increase in hemoglobin level&gt;4 g/dL above ULN or above baseline if baseline is above ULN).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>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</measure>
    <time_frame>Baseline up to Week 131</time_frame>
    <description>ALT/AST g1:&gt;ULN 3*ULN, g2:&gt;3-5*ULN, g3:&gt;5 20*ULN, g4:&gt;20*ULN); Alkaline Phosphatase (g1:&gt;ULN 2.5*ULN, g2:&gt;2.5-5*ULN, g3:&gt;5 20*ULN, g4:&gt;20*ULN);Creatinine (g1:&gt;ULN-1.5*ULN, g2:&gt;1.5-3*ULN, g3:&gt;3 6*ULN, g4:&gt;6*ULN);hyperglycemia (g1:&gt;ULN-160,g2:&gt;160 250, g3:&gt;250 500,g4:&gt;500mg/dL); bilirubin(total) (g1:&gt;ULN-1.5*ULN, g2:&gt;1.5-3*ULN, g3:&gt;3 10*ULN,g4:&gt;10*ULN); hypoglycaemia (g1:&lt;LLN-55, g2:&lt;55-40, g3:&lt;40 30, g4:&lt;30mg/dL); hyperkalemia (g1:&gt;ULN-5.5,g2:&gt;5.5-6, g3:&gt;6 7,g4:&gt;7mmol/L); hypokalemia (g1:&lt;LLN-3,g2:&lt;LLN-3,g3:&lt;3 2.5, g4:&lt;2.5mmol/L); hypermagnesemia (g1:&gt;ULN-3,g3:&gt;3 8,g4:&gt;8mg/dL); hypocalcemia (g1:&lt;LLN-8,g2:&lt;8-7, g3:&lt;7-6, g4:&lt;6mg/dL); hypercalcemia (g1:&gt;ULN-11.5,g2:&gt;11.5-12.5, g3:&gt;12.5-13.5, g4:&gt;13.5mg/dL);hypomagnesemia (g1:&lt;LLN-1.2,g2:&lt;1.2-0.9, g3:&lt;0.9-0.7,g4:&lt;0.7mg/dL); hyponatremia (g1:&lt;LLN-130,g3:&lt;130-120, g4:&lt;120mmol/L);hypoalbuminemia (g1:&lt;LLN-3,g2:&lt;3-2, g3:&lt;2, g4:lifethreatening);hypophosphatemia (g1:&lt;LLN-2.5,g2:&lt;2.5-2,g3:&lt;2-1,g4:&lt;1mg/dL).</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">21</enrollment>
  <condition>Primary Myelofibrosis; Post-polycythemia Vera Myelofibrosis; Post-essential Thrombocythemia Myelofibrosis</condition>
  <arm_group>
    <arm_group_label>Arm A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Oral daily dose of glasdegib (PF-04449913) 100 mg tablet in a continuous regimen of 28-day cycles.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm B</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Oral daily dose of placebo 100 mg tablet in a continuous regimen of 28-day cycles.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Glasdegib (PF-04449913)</intervention_name>
    <description>Oral daily dose of glasdegib (PF-04449913) 100 mg tablet in a continuous regimen of 28-day cycles.</description>
    <arm_group_label>Arm A</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Oral daily dose of placebo 100 mg tablet in a continuous regimen of 28-day cycles.</description>
    <arm_group_label>Arm B</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          -  Diagnosis of primary MF (PMF) or secondary MF (PET-MF and PPV-MF) as per WHO 2008&#xD;
             criteria.&#xD;
&#xD;
          -  Lead-in cohort: resistant or intolerant to 1 or more Janus kinase inhibitors (licensed&#xD;
             or experimental).&#xD;
&#xD;
          -  Randomized cohort: resistant or intolerant to prior ruxolitinib therapy. Documentation&#xD;
             by the Investigator that the patient has exhausted available treatment options (eg,&#xD;
             resistant or intolerant to hydroxyurea, etc).&#xD;
&#xD;
          -  Spleen 5 cm below the inferior left costal margin as measured by manual palpation.&#xD;
&#xD;
          -  Active symptomatic MF as defined by the screening MPN-SAD patient-reported instrument&#xD;
             requiring a severity score of at least 5 on one symptom, or a severity score of ≥ 3 on&#xD;
             at least two of the symptoms (on a 0 to 10 scale).&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, 2, or 3.&#xD;
&#xD;
          -  Adequate organ function, demonstrated by the following laboratory values:&#xD;
&#xD;
               1. Absolute Neutrophil Count 75 x 10(9)/L;&#xD;
&#xD;
               2. Platelet count &gt;50 x 10(9)/L with no evidence of bleeding and not requiring&#xD;
                  platelet transfusions;&#xD;
&#xD;
               3. Serum creatinine &lt;1.5 x upper limit of normal (ULN) or estimated creatinine&#xD;
                  clearance 60 mL/min (as calculated using the standard method of the institution);&#xD;
&#xD;
               4. Serum amylase or lipase &lt;1.5 x ULN;&#xD;
&#xD;
               5. Aspartate aminotransferase and alanine aminotransferase values 3.0 x ULN (or 5x&#xD;
                  ULN in the case of patients with MF accompanied by hepatic extramedullary&#xD;
                  hematopoiesis, as manifested by any degree of hepatomegaly).&#xD;
&#xD;
               6. Total bilirubin values &lt;1.5 x ULN unless the bilirubin is principally&#xD;
                  unconjugated (in the context of hemolysis) or there is documented Gilbert's&#xD;
                  disease.&#xD;
&#xD;
               7. Serum electrolyte values &lt; Grade 2 (sodium, potassium, calcium, phosphorous and&#xD;
                  magnesium), per CTCAE v.4.03.&#xD;
&#xD;
          -  Recovery to Grade 1 from all clinically significant adverse events related to prior MF&#xD;
             therapy, including transplant-related toxicities.&#xD;
&#xD;
          -  More than 2 months out from allogenic hematopoietic stem cell transplant prior to&#xD;
             randomization.&#xD;
&#xD;
          -  Must be able to undergo MRI of abdomen (spleen and liver). Patients who are contra&#xD;
             indicated for MRI may be enrolled and evaluated by CT scan at the discretion of the&#xD;
             Sponsor.&#xD;
&#xD;
          -  18 years of age.&#xD;
&#xD;
          -  Male subjects able to father children and female patients of childbearing potential&#xD;
             and at risk for pregnancy must agree to use two highly effective methods of&#xD;
             contraception throughout the study and for 90 days after the last dose of assigned&#xD;
             treatment.&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  Prior treatment with a licensed or experimental smoothened inhibitor.&#xD;
&#xD;
          -  Randomized cohort only: Prior treatment with a Janus kinase inhibitor other than&#xD;
             ruxolitinib.&#xD;
&#xD;
          -  Other anti-cancer therapy up to 14 days prior to enrollment, with the exception of&#xD;
             hydroxyurea, which can be given up to 4 days prior to enrollment.&#xD;
&#xD;
          -  Splenic irradiation 3 months prior to enrollment.&#xD;
&#xD;
          -  History of congenital long QT syndrome, or a baseline &gt;470 msec QTcF abnormality&#xD;
             (average of the triplicate reading).&#xD;
&#xD;
          -  Evidence of significant cardiac disease, for example: symptomatic cardiac heart&#xD;
             failure (CHF, NYHA class 3), complete bundle branch block, significant atrial or&#xD;
             ventricular tachyarrhythmias and any unstable cardiac arrhythmias requiring&#xD;
             medication.&#xD;
&#xD;
          -  History of myocardial infarction or unstable angina within 6 months prior to&#xD;
             enrollment.&#xD;
&#xD;
          -  Uncontrolled inflammatory bowel disease, peptic ulcer disease or history of&#xD;
             significant gastro intestinal bleeding within 6 months of enrollment.&#xD;
&#xD;
          -  Any condition requiring chronic use of moderate/high dose steroids (equivalent to 10&#xD;
             mg QD prednisone).&#xD;
&#xD;
          -  Hematopoietic growth factor receptor agonists (eg, erythropoietin (Epo), granulocyte&#xD;
             colony stimulating factor, romiplostim, eltrombopag within 28 days of enrollment.&#xD;
&#xD;
          -  Currently active malignancy (other than MF). Prior malignancies are allowed so long as&#xD;
             there is no evidence of disease recurrence within the last 2 years (with the exception&#xD;
             of fully excised, non-complicated basal cell carcinoma which can have been active&#xD;
             within the prior 2 years, and certain localized, non-invasive fully excised skin,&#xD;
             cervical, breast, prostate or bladder tumors).&#xD;
&#xD;
          -  Prior history of chronic liver disease (eg, chronic alcoholic liver disease,&#xD;
             autoimmune hepatitis, sclerosing cholangitis, primary biliary cirrhosis,&#xD;
             hemachromatosis, non-alcoholic steatohepatitis [NASH]).&#xD;
&#xD;
          -  Active, uncontrolled bacterial, fungal or viral infection, including hepatitis B,&#xD;
             hepatitis C, known human immunodeficiency virus or acquired immunodeficiency syndrome&#xD;
             related illness.&#xD;
&#xD;
          -  Active graft versus host disease (GVHD) with other than grade 1 skin involvement or&#xD;
             GVHD requiring immunosuppressive treatment.&#xD;
&#xD;
          -  Uncontrolled disseminated intravascular coagulation.&#xD;
&#xD;
          -  Current (including their administration within 3 days prior to study entry) use or&#xD;
             anticipated need for food or drugs that are strong CYP3A4 inhibitors.&#xD;
&#xD;
          -  Current use or anticipated requirement for drugs that are known strong CYP3A4/5&#xD;
             inducers.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Pfizer CT.gov Call Center</last_name>
    <role>Study Director</role>
    <affiliation>Pfizer</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mayo Clinic Building - Phoenix</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85054</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic Hospital</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85054</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic</name>
      <address>
        <city>Scottsdale</city>
        <state>Arizona</state>
        <zip>85259</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UC San Diego Moores Cancer Center - Investigational Drug Services</name>
      <address>
        <city>La Jolla</city>
        <state>California</state>
        <zip>92037-0845</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UCSD Medical Center Clinical Laboratory - La Jolla</name>
      <address>
        <city>La Jolla</city>
        <state>California</state>
        <zip>92037</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California San Diego (UCSD) Moores Cancer Center</name>
      <address>
        <city>La Jolla</city>
        <state>California</state>
        <zip>92093-0698</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UC San Diego Medical Center- Hillcrest</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Michigan</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Weill Cornell Medical College - New York-Presbyterian Hospital</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10021</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Herbert Irving Comprehensive Cancer Center-Columbia University Medical Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Weill Cornell Medical College-New York Presbyterian Hospital</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic - Taussig Cancer Institute</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Huntsman Cancer Institute-University of Utah</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Utah, Huntsman Cancer Hospital</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Froedtert Hospital and Medical College of Wisconsin</name>
      <address>
        <city>Milwaukee</city>
        <state>Wisconsin</state>
        <zip>53226-3522</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kobe University Hospital</name>
      <address>
        <city>Kobe</city>
        <state>Hyogo</state>
        <zip>6500017</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Osaka University Hopsital</name>
      <address>
        <city>Suita-Shi</city>
        <state>Osaka</state>
        <zip>565-0871</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Juntendo University Hospital</name>
      <address>
        <city>Bunkyo-ku</city>
        <state>Tokyo</state>
        <zip>113-8431</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tokyo Medical University Hospital</name>
      <address>
        <city>Tokyo</city>
        <zip>160-0023</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Japan</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>United Kingdom</country>
  </removed_countries>
  <link>
    <url>https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=B1371013&amp;StudyName=PF-04449913%20Single-Agent%20In%20Patients%20With%20Myelofibrosis%20Previously%20Treated%20With%20a%20Janus%20Kinase%20Inhibitor</url>
    <description>To obtain contact information for a study center near you, click here.</description>
  </link>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>August 25, 2014</study_first_submitted>
  <study_first_submitted_qc>August 25, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 27, 2014</study_first_posted>
  <results_first_submitted>November 30, 2017</results_first_submitted>
  <results_first_submitted_qc>March 30, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">April 2, 2018</results_first_posted>
  <last_update_submitted>December 26, 2018</last_update_submitted>
  <last_update_submitted_qc>December 26, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">January 17, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Primary myelofibrosis</keyword>
  <keyword>Secondary myelofibrosis</keyword>
  <keyword>PMF</keyword>
  <keyword>PET-MF</keyword>
  <keyword>PPV-MF</keyword>
  <keyword>Ruxolitinib resistant or intolerant</keyword>
  <keyword>previously treated myelofibrosis</keyword>
  <keyword>smoothened inhibitor</keyword>
  <keyword>oral</keyword>
  <keyword>single agent.</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Polycythemia Vera</mesh_term>
    <mesh_term>Primary Myelofibrosis</mesh_term>
    <mesh_term>Polycythemia</mesh_term>
    <mesh_term>Thrombocytosis</mesh_term>
    <mesh_term>Thrombocythemia, Essential</mesh_term>
  </condition_browse>

  <clinical_results>

    <participant_flow>
      <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.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Glasdegib Lead-in</title>
          <description>Glasdegib administered orally at a daily starting dose of 100 mg on a continuous regimen of 28-day cycles.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="21"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="17"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Participant refused further follow-up</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Study terminated by sponsor</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Glasdegib Lead-in</title>
          <description>Glasdegib administered orally at a daily starting dose of 100 mg on a continuous regimen of 28-day cycles.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="21"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="69.3" spread="7.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <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</title>
        <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.</description>
        <time_frame>Week 24</time_frame>
        <population>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.</population>
        <group_list>
          <group group_id="O1">
            <title>Glasdegib Lead-in</title>
            <description>Glasdegib administered orally at a daily starting dose of 100 mg on a continuous regimen of 28-day cycles.</description>
          </group>
        </group_list>
        <measure>
          <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</title>
          <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.</description>
          <population>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.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Treatment -Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs): Lead-in Cohort</title>
        <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.</description>
        <time_frame>Baseline up to Week 131</time_frame>
        <population>All participants treated in the lead-in portion of the study.</population>
        <group_list>
          <group group_id="O1">
            <title>Glasdegib Lead-in</title>
            <description>Glasdegib administered orally at a daily starting dose of 100 mg on a continuous regimen of 28-day cycles.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Treatment -Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs): Lead-in Cohort</title>
          <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.</description>
          <population>All participants treated in the lead-in portion of the study.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>AEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Treatment Emergent Treatment -Related Adverse Events (AEs) and Serious Adverse Events (SAEs): Lead-in Cohort</title>
        <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.</description>
        <time_frame>Baseline up to Week 131</time_frame>
        <population>All participants treated in the lead-in portion of the study.</population>
        <group_list>
          <group group_id="O1">
            <title>Glasdegib Lead-in</title>
            <description>Glasdegib administered orally at a daily starting dose of 100 mg on a continuous regimen of 28-day cycles.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Treatment Emergent Treatment -Related Adverse Events (AEs) and Serious Adverse Events (SAEs): Lead-in Cohort</title>
          <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.</description>
          <population>All participants treated in the lead-in portion of the study.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>AEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <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</title>
        <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.</description>
        <time_frame>Baseline up to Week 131</time_frame>
        <population>All participants treated in the lead-in portion of the study.</population>
        <group_list>
          <group group_id="O1">
            <title>Glasdegib Lead-in</title>
            <description>Glasdegib administered orally at a daily starting dose of 100 mg on a continuous regimen of 28-day cycles.</description>
          </group>
        </group_list>
        <measure>
          <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</title>
          <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.</description>
          <population>All participants treated in the lead-in portion of the study.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Grade 3 or 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Laboratory Abnormalities: Lead-in Cohort</title>
        <description>Abnormality: hematology: hemoglobin less than (&lt;)0.8*lower limit of normal(LLN), platelets &lt;0.5*LLN greater than (&gt;)1.75*upper limit of normal(ULN), white blood cell count(WBC) &lt;0.6* LLN &gt;1.5* ULN,lymphocytes, total neutrophils&lt;0.8* LLN &gt;1.2* ULN, band Cells, basophils, eosinophils, monocytes &gt;1.2*ULN, blast cells &gt;1.0*ULN. Coagulation: activated partial thromboplastin time, prothrombin international ratio &gt;1.1* ULN. Liver function: bilirubin &gt;1.5*ULN, AST, ALT,lactate dehydrogenase,alkaline phosphatase &gt;3.0*ULN, protein,albumin &lt;0.8* LLN &gt;1.2* ULN. Renal:blood urea nitrogen,creatinine &gt;1.3*ULN,uric acid &gt;1.2*ULN.Electrolytes: sodium &lt;0.95*LLN &gt;1.05*ULN, potassium, chloride, calcium, magnesium &lt;0.9* LLN &gt;1.1*ULN,phosphate &lt;0.8* LLN &gt;1.2* ULN.Chemistry: glucose &lt;0.6*LLN &gt;1.5*ULN,creatine kinase &gt;2.0*ULN, amylase,lipase &gt;1.5*ULN.Urinalysis: protein, blood &gt;1.0*ULN,red blood cells,WBC &gt;=20,epithelial cells &gt;=6,casts,granular casts,hyaline &gt;1,cellular casts,crystals&gt;=1,bacteria &gt;20.</description>
        <time_frame>Baseline up to Week 131</time_frame>
        <population>All participants treated in the lead-in portion of the study.</population>
        <group_list>
          <group group_id="O1">
            <title>Glasdegib Lead-in</title>
            <description>Glasdegib administered orally at a daily starting dose of 100 mg on a continuous regimen of 28-day cycles.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Laboratory Abnormalities: Lead-in Cohort</title>
          <description>Abnormality: hematology: hemoglobin less than (&lt;)0.8*lower limit of normal(LLN), platelets &lt;0.5*LLN greater than (&gt;)1.75*upper limit of normal(ULN), white blood cell count(WBC) &lt;0.6* LLN &gt;1.5* ULN,lymphocytes, total neutrophils&lt;0.8* LLN &gt;1.2* ULN, band Cells, basophils, eosinophils, monocytes &gt;1.2*ULN, blast cells &gt;1.0*ULN. Coagulation: activated partial thromboplastin time, prothrombin international ratio &gt;1.1* ULN. Liver function: bilirubin &gt;1.5*ULN, AST, ALT,lactate dehydrogenase,alkaline phosphatase &gt;3.0*ULN, protein,albumin &lt;0.8* LLN &gt;1.2* ULN. Renal:blood urea nitrogen,creatinine &gt;1.3*ULN,uric acid &gt;1.2*ULN.Electrolytes: sodium &lt;0.95*LLN &gt;1.05*ULN, potassium, chloride, calcium, magnesium &lt;0.9* LLN &gt;1.1*ULN,phosphate &lt;0.8* LLN &gt;1.2* ULN.Chemistry: glucose &lt;0.6*LLN &gt;1.5*ULN,creatine kinase &gt;2.0*ULN, amylase,lipase &gt;1.5*ULN.Urinalysis: protein, blood &gt;1.0*ULN,red blood cells,WBC &gt;=20,epithelial cells &gt;=6,casts,granular casts,hyaline &gt;1,cellular casts,crystals&gt;=1,bacteria &gt;20.</description>
          <population>All participants treated in the lead-in portion of the study.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <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</title>
        <description>Anemia (grade [g]1:&lt; LLN to 10 gram per deciliter [g/dL],g2:&lt;10 to 8g/dL,g3:&lt;8g/dL, g4:lifethreatening); platelet (g1:&lt;LLN to 75*10^3/millimeter[mm]^3, g2:&lt;75*10^3/mm^3 to 50*10^3/mm^3, g3:&lt;50*10^3/mm^3 to 25*10^3/mm^3, g4:&lt;25*10^3/mm^3); lymphopenia (g1:&lt;LLN to 8*10^2/mm^3, g2:&lt;8*10^2 to 5*10^2/mm^3, g3:&lt;5*10^2 to 2*10^2/mm^3, g4:&lt;2*10^2/mm^3);neutrophil (Absolute) (g1:&lt;LLN to 15*10^2/mm^3, g2:&lt;15*10^2 to 10*10^2/mm^3, g3:&lt;10*10^2 to 5*10^2/mm^3, g4:&lt;5*10^2/mm^3); white blood cell count(g1:&lt;LLN to 3*10^3/mm^3, g2:&lt;3*10^3 to 2*10^3/mm^3, g3:&lt;2*10^3 to 1*10^3/mm^3, g4:&lt;1*10^3/mm^3); hemoglobin (g1:increase in hemoglobin level &gt;0 to 2 g/dL above ULN or above baseline if baseline is above ULN, g2:increase in hemoglobin level&gt;2 to 4g/dL above ULN or above baseline if baseline is above ULN,g3: increase in hemoglobin level&gt;4 g/dL above ULN or above baseline if baseline is above ULN).</description>
        <time_frame>Baseline up to Week 131</time_frame>
        <population>All participants treated in the lead-in portion of the study.</population>
        <group_list>
          <group group_id="O1">
            <title>Glasdegib Lead-in</title>
            <description>Glasdegib administered orally at a daily starting dose of 100 mg on a continuous regimen of 28-day cycles.</description>
          </group>
        </group_list>
        <measure>
          <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</title>
          <description>Anemia (grade [g]1:&lt; LLN to 10 gram per deciliter [g/dL],g2:&lt;10 to 8g/dL,g3:&lt;8g/dL, g4:lifethreatening); platelet (g1:&lt;LLN to 75*10^3/millimeter[mm]^3, g2:&lt;75*10^3/mm^3 to 50*10^3/mm^3, g3:&lt;50*10^3/mm^3 to 25*10^3/mm^3, g4:&lt;25*10^3/mm^3); lymphopenia (g1:&lt;LLN to 8*10^2/mm^3, g2:&lt;8*10^2 to 5*10^2/mm^3, g3:&lt;5*10^2 to 2*10^2/mm^3, g4:&lt;2*10^2/mm^3);neutrophil (Absolute) (g1:&lt;LLN to 15*10^2/mm^3, g2:&lt;15*10^2 to 10*10^2/mm^3, g3:&lt;10*10^2 to 5*10^2/mm^3, g4:&lt;5*10^2/mm^3); white blood cell count(g1:&lt;LLN to 3*10^3/mm^3, g2:&lt;3*10^3 to 2*10^3/mm^3, g3:&lt;2*10^3 to 1*10^3/mm^3, g4:&lt;1*10^3/mm^3); hemoglobin (g1:increase in hemoglobin level &gt;0 to 2 g/dL above ULN or above baseline if baseline is above ULN, g2:increase in hemoglobin level&gt;2 to 4g/dL above ULN or above baseline if baseline is above ULN,g3: increase in hemoglobin level&gt;4 g/dL above ULN or above baseline if baseline is above ULN).</description>
          <population>All participants treated in the lead-in portion of the study.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Grade 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Achieving SVR ≥35% as Measured by Magnetic Resonance Imaging/Computed Tomography Scan at Week 24 in the Lead-in Cohort</title>
        <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.</description>
        <time_frame>Week 24</time_frame>
        <population>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.</population>
        <group_list>
          <group group_id="O1">
            <title>Glasdegib Lead-in</title>
            <description>Glasdegib administered orally at a daily starting dose of 100 mg on a continuous regimen of 28-day cycles.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Achieving SVR ≥35% as Measured by Magnetic Resonance Imaging/Computed Tomography Scan at Week 24 in the Lead-in Cohort</title>
          <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.</description>
          <population>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.</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <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</title>
        <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.</description>
        <time_frame>Week 24</time_frame>
        <population>Lead-in Analysis Set</population>
        <group_list>
          <group group_id="O1">
            <title>Glasdegib Lead-in</title>
            <description>Glasdegib administered orally at a daily starting dose of 100 mg on a continuous regimen of 28-day cycles.</description>
          </group>
        </group_list>
        <measure>
          <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</title>
          <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.</description>
          <population>Lead-in Analysis Set</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.8" lower_limit="1.2" upper_limit="30.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Monthly Mean Change From Baseline in Overall Total Symptom Score (TSS) in the Lead-in Cohort</title>
        <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.</description>
        <time_frame>Weeks 12, 24, 36 and 48</time_frame>
        <population>Lead-in Analysis Set</population>
        <group_list>
          <group group_id="O1">
            <title>Glasdegib Lead-in</title>
            <description>Glasdegib administered orally at a daily starting dose of 100 mg on a continuous regimen of 28-day cycles.</description>
          </group>
        </group_list>
        <measure>
          <title>Monthly Mean Change From Baseline in Overall Total Symptom Score (TSS) in the Lead-in Cohort</title>
          <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.</description>
          <population>Lead-in Analysis Set</population>
          <units>Score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Monthly mean change at Week 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="13"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.74" spread="14.07"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Monthly mean change at Week 24</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.95" spread="5.78"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Monthly mean change at Week 36</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.11" spread="NA">No standard deviation was calculable since n=1.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Monthly mean change at Week 48</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-8.39" spread="11.52"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Achieving Anemia Response (Transfusion Dependent Versus Independent) in the Lead-in Cohort</title>
        <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 &lt;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 &lt;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.</description>
        <time_frame>Baseline to end of treatment</time_frame>
        <population>Lead-in Analysis Set</population>
        <group_list>
          <group group_id="O1">
            <title>Glasdegib Lead-in</title>
            <description>Glasdegib administered orally at a daily starting dose of 100 mg on a continuous regimen of 28-day cycles.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Achieving Anemia Response (Transfusion Dependent Versus Independent) in the Lead-in Cohort</title>
          <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 &lt;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 &lt;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.</description>
          <population>Lead-in Analysis Set</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Transfusion independent ≥20 g/L Hb increase</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="17"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Transfusion dependent</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <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</title>
        <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.</description>
        <time_frame>Cycle 1, Day 15</time_frame>
        <population>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 ).</population>
        <group_list>
          <group group_id="O1">
            <title>Glasdegib Lead-in</title>
            <description>Glasdegib administered orally at a daily starting dose of 100 mg on a continuous regimen of 28-day cycles.</description>
          </group>
        </group_list>
        <measure>
          <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</title>
          <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.</description>
          <population>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 ).</population>
          <units>nanograms per milliliter (ng/mL)</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cmax</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="996.8" spread="45"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cmin</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="191.9" spread="68"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cav</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="17"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="548.0" spread="50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Area Under the Glasdegib Plasma Concentration Versus Time Profile at the End of a Dosing Interval (AUCtau) in the Lead-in Cohort</title>
        <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.</description>
        <time_frame>Cycle 1, Day 15</time_frame>
        <population>PK Parameter Analysis Population</population>
        <group_list>
          <group group_id="O1">
            <title>Glasdegib Lead-in</title>
            <description>Glasdegib administered orally at a daily starting dose of 100 mg on a continuous regimen of 28-day cycles.</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Glasdegib Plasma Concentration Versus Time Profile at the End of a Dosing Interval (AUCtau) in the Lead-in Cohort</title>
          <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.</description>
          <population>PK Parameter Analysis Population</population>
          <units>ng·hr/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13150" spread="50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Reach Cmax (Tmax) in the Lead-in Cohort</title>
        <description>Tmax was the time of the first occurrence of Cmax observed directly from the plasma concentration data.</description>
        <time_frame>Cycle 1, Day 15</time_frame>
        <population>PK Parameter Analysis Population</population>
        <group_list>
          <group group_id="O1">
            <title>Glasdegib Lead-in</title>
            <description>Glasdegib administered orally at a daily starting dose of 100 mg on a continuous regimen of 28-day cycles.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Reach Cmax (Tmax) in the Lead-in Cohort</title>
          <description>Tmax was the time of the first occurrence of Cmax observed directly from the plasma concentration data.</description>
          <population>PK Parameter Analysis Population</population>
          <units>Hours</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.02" lower_limit="0.483" upper_limit="4.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Achieving SVR ≥50% as Measured by MRI/CT Scan at Week 24 in the Randomized Cohort</title>
        <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.</description>
        <time_frame>Week 24</time_frame>
        <population>FAS</population>
        <group_list>
          <group group_id="O1">
            <title>Glasdegib Lead-in</title>
            <description>Glasdegib administered orally at a daily starting dose of 100 mg on a continuous regimen of 28-day cycles.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Achieving SVR ≥50% as Measured by MRI/CT Scan at Week 24 in the Randomized Cohort</title>
          <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.</description>
          <population>FAS</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Monthly Mean Change From Baseline in Overall TSS in the Randomized Cohort</title>
        <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.</description>
        <time_frame>Weeks 12, 24, 36 and 48</time_frame>
        <population>FAS</population>
        <group_list>
          <group group_id="O1">
            <title>Glasdegib Lead-in</title>
            <description>Glasdegib administered orally at a daily starting dose of 100 mg on a continuous regimen of 28-day cycles.</description>
          </group>
        </group_list>
        <measure>
          <title>Monthly Mean Change From Baseline in Overall TSS in the Randomized Cohort</title>
          <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.</description>
          <population>FAS</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Achieving Anemia Response (Transfusion Dependent Versus Independent) in the Randomized Cohort</title>
        <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.</description>
        <time_frame>Baseline to end of treatment</time_frame>
        <population>FAS</population>
        <group_list>
          <group group_id="O1">
            <title>Glasdegib Lead-in</title>
            <description>Glasdegib administered orally at a daily starting dose of 100 mg on a continuous regimen of 28-day cycles.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Achieving Anemia Response (Transfusion Dependent Versus Independent) in the Randomized Cohort</title>
          <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.</description>
          <population>FAS</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Participant Reported Outcomes of Health Related Quality of Life and Health Status in the Randomised Cohort</title>
        <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.</description>
        <time_frame>Baseline to end of treatment</time_frame>
        <population>FAS</population>
        <group_list>
          <group group_id="O1">
            <title>Glasdegib Lead-in</title>
            <description>Glasdegib administered orally at a daily starting dose of 100 mg on a continuous regimen of 28-day cycles.</description>
          </group>
        </group_list>
        <measure>
          <title>Participant Reported Outcomes of Health Related Quality of Life and Health Status in the Randomised Cohort</title>
          <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.</description>
          <population>FAS</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Median Duration of SVR in the Randomized Cohort</title>
        <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.</description>
        <time_frame>Baseline to end of treatment</time_frame>
        <population>FAS</population>
        <group_list>
          <group group_id="O1">
            <title>Glasdegib Lead-in</title>
            <description>Glasdegib administered orally at a daily starting dose of 100 mg on a continuous regimen of 28-day cycles.</description>
          </group>
        </group_list>
        <measure>
          <title>Median Duration of SVR in the Randomized Cohort</title>
          <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.</description>
          <population>FAS</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Kaplan-Meier Estimate of Overall Survival in the Randomized Cohort</title>
        <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.</description>
        <time_frame>Baseline to end of treatment</time_frame>
        <population>FAS</population>
        <group_list>
          <group group_id="O1">
            <title>Glasdegib Lead-in</title>
            <description>Glasdegib administered orally at a daily starting dose of 100 mg on a continuous regimen of 28-day cycles.</description>
          </group>
        </group_list>
        <measure>
          <title>Kaplan-Meier Estimate of Overall Survival in the Randomized Cohort</title>
          <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.</description>
          <population>FAS</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Glasdegib PK Parameters in the Randomized Cohort</title>
        <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.</description>
        <time_frame>Cycle 1, Day 15</time_frame>
        <population>PK Parameter Analysis Population</population>
        <group_list>
          <group group_id="O1">
            <title>Glasdegib Lead-in</title>
            <description>Glasdegib administered orally at a daily starting dose of 100 mg on a continuous regimen of 28-day cycles.</description>
          </group>
        </group_list>
        <measure>
          <title>Glasdegib PK Parameters in the Randomized Cohort</title>
          <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.</description>
          <population>PK Parameter Analysis Population</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Psychometric Validation of the MPN-SAD in the Randomised Cohort</title>
        <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.</description>
        <time_frame>Baseline to end of treatment</time_frame>
        <population>FAS</population>
        <group_list>
          <group group_id="O1">
            <title>Glasdegib Lead-in</title>
            <description>Glasdegib administered orally at a daily starting dose of 100 mg on a continuous regimen of 28-day cycles.</description>
          </group>
        </group_list>
        <measure>
          <title>Psychometric Validation of the MPN-SAD in the Randomised Cohort</title>
          <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.</description>
          <population>FAS</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Treatment -Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs): Randomized Cohort</title>
        <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.</description>
        <time_frame>Baseline up to Week 131</time_frame>
        <population>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.</population>
        <group_list>
          <group group_id="O1">
            <title>Glasdegib Lead-in</title>
            <description>Glasdegib administered orally at a daily starting dose of 100 mg on a continuous regimen of 28-day cycles.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Treatment -Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs): Randomized Cohort</title>
          <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.</description>
          <population>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.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Treatment Emergent Treatment -Related Adverse Events (AEs) and Serious Adverse Events (SAEs): Randomized Cohort</title>
        <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.</description>
        <time_frame>Baseline up to Week 131</time_frame>
        <population>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.</population>
        <group_list>
          <group group_id="O1">
            <title>Glasdegib Lead-in</title>
            <description>Glasdegib administered orally at a daily starting dose of 100 mg on a continuous regimen of 28-day cycles.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Treatment Emergent Treatment -Related Adverse Events (AEs) and Serious Adverse Events (SAEs): Randomized Cohort</title>
          <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.</description>
          <population>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.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Treatment Emergent Adverse Events (AEs) According to Maximum Severity: Randomized Cohort</title>
        <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.</description>
        <time_frame>Baseline up to Week 131</time_frame>
        <population>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.</population>
        <group_list>
          <group group_id="O1">
            <title>Glasdegib Lead-in</title>
            <description>Glasdegib administered orally at a daily starting dose of 100 mg on a continuous regimen of 28-day cycles.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Treatment Emergent Adverse Events (AEs) According to Maximum Severity: Randomized Cohort</title>
          <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.</description>
          <population>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.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Laboratory Abnormalities: Randomized Cohort</title>
        <description>Abnormality: hematology: hemoglobin less than (&lt;)0.8*lower limit of normal(LLN), platelets &lt;0.5*LLN &gt;1.75*upper limit of normal(ULN), white blood cell count(WBC) &lt;0.6* LLN greater than (&gt;)1.5* ULN,lymphocytes, total neutrophils&lt;0.8* LLN &gt;1.2* ULN, band Cells, basophils, eosinophils, monocytes &gt;1.2*ULN, blast cells &gt;1.0*ULN. Coagulation: activated partial thromboplastin time, prothrombin international ratio &gt;1.1* ULN. Liver function: bilirubin &gt;1.5*ULN, AST, ALT,lactate dehydrogenase,alkaline phosphatase &gt;3.0*ULN, protein,albumin &lt;0.8* LLN &gt;1.2* ULN. Renal:blood urea nitrogen,creatinine &gt;1.3* ULN,uric acid &gt;1.2* ULN.Electrolytes: sodium &lt;0.95*LLN &gt;1.05*ULN, potassium, chloride, calcium, magnesium &lt;0.9* LLN &gt;1.1*ULN,phosphate &lt;0.8* LLN &gt;1.2* ULN.Chemistry: glucose &lt;0.6*LLN &gt;1.5*ULN,creatine kinase &gt;2.0*ULN, amylase,lipase &gt;1.5*ULN.Urinalysis: protein, blood &gt;1.0*ULN,red blood cells,WBC &gt;=20,epithelial cells &gt;=6,casts,granular casts,hyaline &gt;1,cellular casts,crystals&gt;=1,bacteria &gt;20.</description>
        <time_frame>Baseline up to Week 131</time_frame>
        <population>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.</population>
        <group_list>
          <group group_id="O1">
            <title>Glasdegib Lead-in</title>
            <description>Glasdegib administered orally at a daily starting dose of 100 mg on a continuous regimen of 28-day cycles.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Laboratory Abnormalities: Randomized Cohort</title>
          <description>Abnormality: hematology: hemoglobin less than (&lt;)0.8*lower limit of normal(LLN), platelets &lt;0.5*LLN &gt;1.75*upper limit of normal(ULN), white blood cell count(WBC) &lt;0.6* LLN greater than (&gt;)1.5* ULN,lymphocytes, total neutrophils&lt;0.8* LLN &gt;1.2* ULN, band Cells, basophils, eosinophils, monocytes &gt;1.2*ULN, blast cells &gt;1.0*ULN. Coagulation: activated partial thromboplastin time, prothrombin international ratio &gt;1.1* ULN. Liver function: bilirubin &gt;1.5*ULN, AST, ALT,lactate dehydrogenase,alkaline phosphatase &gt;3.0*ULN, protein,albumin &lt;0.8* LLN &gt;1.2* ULN. Renal:blood urea nitrogen,creatinine &gt;1.3* ULN,uric acid &gt;1.2* ULN.Electrolytes: sodium &lt;0.95*LLN &gt;1.05*ULN, potassium, chloride, calcium, magnesium &lt;0.9* LLN &gt;1.1*ULN,phosphate &lt;0.8* LLN &gt;1.2* ULN.Chemistry: glucose &lt;0.6*LLN &gt;1.5*ULN,creatine kinase &gt;2.0*ULN, amylase,lipase &gt;1.5*ULN.Urinalysis: protein, blood &gt;1.0*ULN,red blood cells,WBC &gt;=20,epithelial cells &gt;=6,casts,granular casts,hyaline &gt;1,cellular casts,crystals&gt;=1,bacteria &gt;20.</description>
          <population>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.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <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</title>
        <description>ALT/AST g1:&gt;ULN 3*ULN, g2:&gt;3-5*ULN, g3:&gt;5 20*ULN, g4:&gt;20*ULN); Alkaline Phosphatase (g1:&gt;ULN 2.5*ULN,g2:&gt;2.5-5*ULN, g3:&gt;5 20*ULN, g4:&gt;20*ULN); Creatinine (g1:&gt;ULN-1.5*ULN,g2:&gt;1.5-3*ULN, g3:&gt;3 6*ULN, g4:&gt;6*ULN);hyperglycemia (g1:&gt;ULN-160,g2:&gt;160 250, g3:&gt;250 500, g4:&gt;500mg/dL);bilirubin(total) (g1:&gt;ULN-1.5*ULN, g2:&gt;1.5-3*ULN, g3:&gt;3 10*ULN,g4:&gt;10*ULN);hypoglycaemia (g1:&lt;LLN-55,g2:&lt;55-40, g3:&lt;40 30,g4:&lt;30mg/dL); hyperkalemia (g1:&gt;ULN-5.5,g2:&gt;5.5-6, g3:&gt;6 7,g4:&gt;7mmol/L);hypokalemia (g1:&lt;LLN-3,g2:&lt;LLN-3, g3:&lt;3 2.5, g4:&lt;2.5mmol/L);hypermagnesemia (g1:&gt;ULN-3,g3:&gt;3 8, g4:&gt;8mg/dL);hypocalcemia (g1:&lt;LLN-8,g2:&lt;8-7, g3:&lt;7-6, g4:&lt;6mg/dL); hypercalcemia (g1:&gt;ULN-11.5,g2:&gt;11.5-12.5, g3:&gt;12.5-13.5, g4:&gt;13.5mg/dL); hypomagnesemia (g1:&lt;LLN-1.2,g2:&lt;1.2-0.9,g3:&lt;0.9-0.7, g4:&lt;0.7mg/dL); hyponatremia (g1:&lt;LLN-130,g3:&lt;130-120, g4:&lt;120mmol/L);hypoalbuminemia (g1:&lt;LLN-3,g2:&lt;3 2,g3:&lt;2, g4:lifethreatening);hypophosphatemia (g1:&lt;LLN-2.5,g2:&lt;2.5-2, g3:&lt;2-1, g4:&lt;1mg/dL).</description>
        <time_frame>Baseline up to Week 131</time_frame>
        <population>All participants treated in the lead-in portion of the study.</population>
        <group_list>
          <group group_id="O1">
            <title>Glasdegib Lead-in</title>
            <description>Glasdegib administered orally at a daily starting dose of 100 mg on a continuous regimen of 28-day cycles.</description>
          </group>
        </group_list>
        <measure>
          <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</title>
          <description>ALT/AST g1:&gt;ULN 3*ULN, g2:&gt;3-5*ULN, g3:&gt;5 20*ULN, g4:&gt;20*ULN); Alkaline Phosphatase (g1:&gt;ULN 2.5*ULN,g2:&gt;2.5-5*ULN, g3:&gt;5 20*ULN, g4:&gt;20*ULN); Creatinine (g1:&gt;ULN-1.5*ULN,g2:&gt;1.5-3*ULN, g3:&gt;3 6*ULN, g4:&gt;6*ULN);hyperglycemia (g1:&gt;ULN-160,g2:&gt;160 250, g3:&gt;250 500, g4:&gt;500mg/dL);bilirubin(total) (g1:&gt;ULN-1.5*ULN, g2:&gt;1.5-3*ULN, g3:&gt;3 10*ULN,g4:&gt;10*ULN);hypoglycaemia (g1:&lt;LLN-55,g2:&lt;55-40, g3:&lt;40 30,g4:&lt;30mg/dL); hyperkalemia (g1:&gt;ULN-5.5,g2:&gt;5.5-6, g3:&gt;6 7,g4:&gt;7mmol/L);hypokalemia (g1:&lt;LLN-3,g2:&lt;LLN-3, g3:&lt;3 2.5, g4:&lt;2.5mmol/L);hypermagnesemia (g1:&gt;ULN-3,g3:&gt;3 8, g4:&gt;8mg/dL);hypocalcemia (g1:&lt;LLN-8,g2:&lt;8-7, g3:&lt;7-6, g4:&lt;6mg/dL); hypercalcemia (g1:&gt;ULN-11.5,g2:&gt;11.5-12.5, g3:&gt;12.5-13.5, g4:&gt;13.5mg/dL); hypomagnesemia (g1:&lt;LLN-1.2,g2:&lt;1.2-0.9,g3:&lt;0.9-0.7, g4:&lt;0.7mg/dL); hyponatremia (g1:&lt;LLN-130,g3:&lt;130-120, g4:&lt;120mmol/L);hypoalbuminemia (g1:&lt;LLN-3,g2:&lt;3 2,g3:&lt;2, g4:lifethreatening);hypophosphatemia (g1:&lt;LLN-2.5,g2:&lt;2.5-2, g3:&lt;2-1, g4:&lt;1mg/dL).</description>
          <population>All participants treated in the lead-in portion of the study.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Grade 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <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</title>
        <description>Anemia g1:&lt; LLN to 10 g/dL, g2:&lt;10 to 8g/dL, g3:&lt;8g/dL, g4:lifethreatening); platelet (g1:&lt;LLN to 75*10^3/mm^3, g2:&lt;75*10^3/mm^3 to 50*10^3/mm^3, g3:&lt;50*10^3/mm^3 to 25*10^3/mm^3, g4:&lt;25*10^3/mm^3); lymphopenia (g1:&lt;LLN to 8*10^2/mm^3, g2:&lt;8*10^2 to 5*10^2/mm^3, g3:&lt;5*10^2 to 2*10^2/mm^3, g4:&lt;2*10^2/mm^3);neutrophil (absolute) (g1:&lt;LLN to 15*10^2/mm^3, g2:&lt;15*10^2 to 10*10^2/mm^3, g3:&lt;10*10^2 to 5*10^2/mm^3, g4:&lt;5*10^2/mm^3); white blood cell count (g1:&lt;LLN to 3*10^3/mm^3, g2:&lt;3*10^3 to 2*10^3/mm^3, g3: &lt;2*10^3 to 1*10^3/mm^3, g4:&lt;1*10^3/mm^3); hemoglobin(g1:increase in hemoglobin level&gt;0 to 2 g/dL above ULN or above baseline if baseline is above ULN, g2: increase in hemoglobin level&gt;2 to 4g/dL above ULN or above baseline if baseline is above ULN, g3:increase in hemoglobin level&gt;4 g/dL above ULN or above baseline if baseline is above ULN).</description>
        <time_frame>Baseline up to Week 131</time_frame>
        <population>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.</population>
        <group_list>
          <group group_id="O1">
            <title>Glasdegib Lead-in</title>
            <description>Glasdegib administered orally at a daily starting dose of 100 mg on a continuous regimen of 28-day cycles.</description>
          </group>
        </group_list>
        <measure>
          <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</title>
          <description>Anemia g1:&lt; LLN to 10 g/dL, g2:&lt;10 to 8g/dL, g3:&lt;8g/dL, g4:lifethreatening); platelet (g1:&lt;LLN to 75*10^3/mm^3, g2:&lt;75*10^3/mm^3 to 50*10^3/mm^3, g3:&lt;50*10^3/mm^3 to 25*10^3/mm^3, g4:&lt;25*10^3/mm^3); lymphopenia (g1:&lt;LLN to 8*10^2/mm^3, g2:&lt;8*10^2 to 5*10^2/mm^3, g3:&lt;5*10^2 to 2*10^2/mm^3, g4:&lt;2*10^2/mm^3);neutrophil (absolute) (g1:&lt;LLN to 15*10^2/mm^3, g2:&lt;15*10^2 to 10*10^2/mm^3, g3:&lt;10*10^2 to 5*10^2/mm^3, g4:&lt;5*10^2/mm^3); white blood cell count (g1:&lt;LLN to 3*10^3/mm^3, g2:&lt;3*10^3 to 2*10^3/mm^3, g3: &lt;2*10^3 to 1*10^3/mm^3, g4:&lt;1*10^3/mm^3); hemoglobin(g1:increase in hemoglobin level&gt;0 to 2 g/dL above ULN or above baseline if baseline is above ULN, g2: increase in hemoglobin level&gt;2 to 4g/dL above ULN or above baseline if baseline is above ULN, g3:increase in hemoglobin level&gt;4 g/dL above ULN or above baseline if baseline is above ULN).</description>
          <population>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.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <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</title>
        <description>ALT/AST g1:&gt;ULN 3*ULN, g2:&gt;3-5*ULN, g3:&gt;5 20*ULN, g4:&gt;20*ULN); Alkaline Phosphatase (g1:&gt;ULN 2.5*ULN, g2:&gt;2.5-5*ULN, g3:&gt;5 20*ULN, g4:&gt;20*ULN);Creatinine (g1:&gt;ULN-1.5*ULN, g2:&gt;1.5-3*ULN, g3:&gt;3 6*ULN, g4:&gt;6*ULN);hyperglycemia (g1:&gt;ULN-160,g2:&gt;160 250, g3:&gt;250 500,g4:&gt;500mg/dL); bilirubin(total) (g1:&gt;ULN-1.5*ULN, g2:&gt;1.5-3*ULN, g3:&gt;3 10*ULN,g4:&gt;10*ULN); hypoglycaemia (g1:&lt;LLN-55, g2:&lt;55-40, g3:&lt;40 30, g4:&lt;30mg/dL); hyperkalemia (g1:&gt;ULN-5.5,g2:&gt;5.5-6, g3:&gt;6 7,g4:&gt;7mmol/L); hypokalemia (g1:&lt;LLN-3,g2:&lt;LLN-3,g3:&lt;3 2.5, g4:&lt;2.5mmol/L); hypermagnesemia (g1:&gt;ULN-3,g3:&gt;3 8,g4:&gt;8mg/dL); hypocalcemia (g1:&lt;LLN-8,g2:&lt;8-7, g3:&lt;7-6, g4:&lt;6mg/dL); hypercalcemia (g1:&gt;ULN-11.5,g2:&gt;11.5-12.5, g3:&gt;12.5-13.5, g4:&gt;13.5mg/dL);hypomagnesemia (g1:&lt;LLN-1.2,g2:&lt;1.2-0.9, g3:&lt;0.9-0.7,g4:&lt;0.7mg/dL); hyponatremia (g1:&lt;LLN-130,g3:&lt;130-120, g4:&lt;120mmol/L);hypoalbuminemia (g1:&lt;LLN-3,g2:&lt;3-2, g3:&lt;2, g4:lifethreatening);hypophosphatemia (g1:&lt;LLN-2.5,g2:&lt;2.5-2,g3:&lt;2-1,g4:&lt;1mg/dL).</description>
        <time_frame>Baseline up to Week 131</time_frame>
        <population>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.</population>
        <group_list>
          <group group_id="O1">
            <title>Glasdegib Lead-in</title>
            <description>Glasdegib administered orally at a daily starting dose of 100 mg on a continuous regimen of 28-day cycles.</description>
          </group>
        </group_list>
        <measure>
          <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</title>
          <description>ALT/AST g1:&gt;ULN 3*ULN, g2:&gt;3-5*ULN, g3:&gt;5 20*ULN, g4:&gt;20*ULN); Alkaline Phosphatase (g1:&gt;ULN 2.5*ULN, g2:&gt;2.5-5*ULN, g3:&gt;5 20*ULN, g4:&gt;20*ULN);Creatinine (g1:&gt;ULN-1.5*ULN, g2:&gt;1.5-3*ULN, g3:&gt;3 6*ULN, g4:&gt;6*ULN);hyperglycemia (g1:&gt;ULN-160,g2:&gt;160 250, g3:&gt;250 500,g4:&gt;500mg/dL); bilirubin(total) (g1:&gt;ULN-1.5*ULN, g2:&gt;1.5-3*ULN, g3:&gt;3 10*ULN,g4:&gt;10*ULN); hypoglycaemia (g1:&lt;LLN-55, g2:&lt;55-40, g3:&lt;40 30, g4:&lt;30mg/dL); hyperkalemia (g1:&gt;ULN-5.5,g2:&gt;5.5-6, g3:&gt;6 7,g4:&gt;7mmol/L); hypokalemia (g1:&lt;LLN-3,g2:&lt;LLN-3,g3:&lt;3 2.5, g4:&lt;2.5mmol/L); hypermagnesemia (g1:&gt;ULN-3,g3:&gt;3 8,g4:&gt;8mg/dL); hypocalcemia (g1:&lt;LLN-8,g2:&lt;8-7, g3:&lt;7-6, g4:&lt;6mg/dL); hypercalcemia (g1:&gt;ULN-11.5,g2:&gt;11.5-12.5, g3:&gt;12.5-13.5, g4:&gt;13.5mg/dL);hypomagnesemia (g1:&lt;LLN-1.2,g2:&lt;1.2-0.9, g3:&lt;0.9-0.7,g4:&lt;0.7mg/dL); hyponatremia (g1:&lt;LLN-130,g3:&lt;130-120, g4:&lt;120mmol/L);hypoalbuminemia (g1:&lt;LLN-3,g2:&lt;3-2, g3:&lt;2, g4:lifethreatening);hypophosphatemia (g1:&lt;LLN-2.5,g2:&lt;2.5-2,g3:&lt;2-1,g4:&lt;1mg/dL).</description>
          <population>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.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Baseline up to Week 131</time_frame>
      <desc>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.</desc>
      <group_list>
        <group group_id="E1">
          <title>Glasdegib Lead-in</title>
          <description>Glasdegib administered orally at a daily starting dose of 100 mg on a continuous regimen of 28-day cycles.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA v20.1</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Sinus tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Gastric varices haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Varices oesophageal</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Disease progression</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Portal hypertension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Postoperative ileus</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Failure to thrive</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Memory impairment</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Mental status changes</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Confusional state</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Respiratory failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA v20.1</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="20" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Electrocardiogram QT prolonged</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Lipase increased</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Hyperuricaemia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Hyperglycaemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Dyspnoea exertional</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Night sweats</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Pruritus generalised</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>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.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Pfizer ClinicalTrials.gov Call Center</name_or_title>
      <organization>Pfizer, Inc.</organization>
      <phone>1-800-718-1021</phone>
      <email>ClinicalTrials.gov_Inquiries@pfizer.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02226172
org study id: B1371013
secondary id: SMOI
secondary id: 2014-000933-21
secondary id: 2014-001048-40
nct id: NCT02226172
lead sponsor: 
has dmc: Yes
A lead-in cohort of ~20 patients with primary or secondary myelofibrosis previously treated
      with 1 or more Janus kinase inhibitors enrolled to single-agent glasdegib to evaluate safety
      and tolerability. Following the lead-in, a phase 2, double blind, 2-arm study, randomized 2:1
      to oral single-agent glasdegib versus placebo in 201 patients resistant or intolerant to
      ruxolitinib.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: 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
time frame: Week 24
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.
measure: Number of Participants With Treatment -Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs): Lead-in Cohort
time frame: Baseline up to Week 131
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.
measure: Number of Participants With Treatment Emergent Treatment -Related Adverse Events (AEs) and Serious Adverse Events (SAEs): Lead-in Cohort
time frame: Baseline up to Week 131
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.
measure: 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
time frame: Baseline up to Week 131
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.
measure: Number of Participants With Laboratory Abnormalities: Lead-in Cohort
time frame: Baseline up to Week 131
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.
measure: 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
time frame: Baseline up to Week 131
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).
measure: 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
time frame: Baseline up to Week 131
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).
measure: Percentage of Participants Achieving SVR ≥35% as Measured by Magnetic Resonance Imaging/Computed Tomography Scan at Week 24 in the Lead-in Cohort
time frame: Week 24
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.
measure: 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
time frame: Week 24
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.
measure: Monthly Mean Change From Baseline in Overall Total Symptom Score (TSS) in the Lead-in Cohort
time frame: Weeks 12, 24, 36 and 48
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.
measure: Percentage of Participants Achieving Anemia Response (Transfusion Dependent Versus Independent) in the Lead-in Cohort
time frame: Baseline to end of treatment
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.
measure: 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
time frame: Cycle 1, Day 15
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.
measure: Area Under the Glasdegib Plasma Concentration Versus Time Profile at the End of a Dosing Interval (AUCtau) in the Lead-in Cohort
time frame: Cycle 1, Day 15
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.
measure: Time to Reach Cmax (Tmax) in the Lead-in Cohort
time frame: Cycle 1, Day 15
description: Tmax was the time of the first occurrence of Cmax observed directly from the plasma concentration data.
measure: Percentage of Participants Achieving SVR ≥50% as Measured by MRI/CT Scan at Week 24 in the Randomized Cohort
time frame: Week 24
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.
measure: Monthly Mean Change From Baseline in Overall TSS in the Randomized Cohort
time frame: Weeks 12, 24, 36 and 48
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.
measure: Percentage of Participants Achieving Anemia Response (Transfusion Dependent Versus Independent) in the Randomized Cohort
time frame: Baseline to end of treatment
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.
measure: Participant Reported Outcomes of Health Related Quality of Life and Health Status in the Randomised Cohort
time frame: Baseline to end of treatment
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.
measure: Median Duration of SVR in the Randomized Cohort
time frame: Baseline to end of treatment
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.
measure: Kaplan-Meier Estimate of Overall Survival in the Randomized Cohort
time frame: Baseline to end of treatment
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.
measure: Glasdegib PK Parameters in the Randomized Cohort
time frame: Cycle 1, Day 15
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.
measure: Psychometric Validation of the MPN-SAD in the Randomised Cohort
time frame: Baseline to end of treatment
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.
measure: Number of Participants With Treatment -Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs): Randomized Cohort
time frame: Baseline up to Week 131
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.
measure: Number of Participants With Treatment Emergent Treatment -Related Adverse Events (AEs) and Serious Adverse Events (SAEs): Randomized Cohort
time frame: Baseline up to Week 131
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.
measure: Number of Participants With Treatment Emergent Adverse Events (AEs) According to Maximum Severity: Randomized Cohort
time frame: Baseline up to Week 131
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.
measure: Number of Participants With Laboratory Abnormalities: Randomized Cohort
time frame: Baseline up to Week 131
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.
measure: 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
time frame: Baseline up to Week 131
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).
measure: 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
time frame: Baseline up to Week 131
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).
arm group label: Arm A
arm group type: Experimental
description: Oral daily dose of glasdegib (PF-04449913) 100 mg tablet in a continuous regimen of 28-day cycles.
arm group label: Arm B
arm group type: Placebo Comparator
description: Oral daily dose of placebo 100 mg tablet in a continuous regimen of 28-day cycles.
intervention type: Drug
intervention name: Glasdegib (PF-04449913)
description: Oral daily dose of glasdegib (PF-04449913) 100 mg tablet in a continuous regimen of 28-day cycles.
arm group label: Arm A
intervention type: Drug
intervention name: Placebo
description: Oral daily dose of placebo 100 mg tablet in a continuous regimen of 28-day cycles.
arm group label: Arm B
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Pfizer CT.gov Call Center
role: Study Director
affiliation: Pfizer
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country: Japan
country: United States
country: United Kingdom
url: https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=B1371013&StudyName=PF-04449913%20Single-Agent%20In%20Patients%20With%20Myelofibrosis%20Previously%20Treated%20With%20a%20Janus%20Kinase%20Inhibitor
description: To obtain contact information for a study center near you, click here.
responsible party type: Sponsor
mesh term: Polycythemia Vera
mesh term: Primary Myelofibrosis
mesh term: Polycythemia
mesh term: Thrombocytosis
mesh term: Thrombocythemia, Essential
participant flow: 
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reported events: 
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point of contact: 