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| ID | Type | Description | Link |
|---|---|---|---|
| SMOI | Other Identifier | Alias Study Number | |
| 2014-000933-21 | EudraCT Number | ||
| 2014-001048-40 | EudraCT Number |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm A | Experimental | Oral daily dose of glasdegib (PF-04449913) 100 mg tablet in a continuous regimen of 28-day cycles. |
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| Arm B | Placebo Comparator | Oral daily dose of placebo 100 mg tablet in a continuous regimen of 28-day cycles. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Glasdegib (PF-04449913) | Drug | Oral daily dose of glasdegib (PF-04449913) 100 mg tablet in a continuous regimen of 28-day cycles. |
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| Measure | Description | Time Frame |
|---|---|---|
| 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 | 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. | Week 24 |
| Number of Participants With Treatment -Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs): Lead-in Cohort | 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. | Baseline up to Week 131 |
| Number of Participants With Treatment Emergent Treatment -Related Adverse Events (AEs) and Serious Adverse Events (SAEs): Lead-in Cohort | 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. | Baseline up to Week 131 |
| 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 | Description | Time Frame |
|---|---|---|
| Percentage of Participants Achieving SVR ≥35% as Measured by Magnetic Resonance Imaging/Computed Tomography Scan at Week 24 in the Lead-in Cohort | 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. |
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Inclusion criteria:
Diagnosis of primary MF (PMF) or secondary MF (PET-MF and PPV-MF) as per WHO 2008 criteria.
Lead-in cohort: resistant or intolerant to 1 or more Janus kinase inhibitors (licensed or experimental).
Randomized cohort: resistant or intolerant to prior ruxolitinib therapy. Documentation by the Investigator that the patient has exhausted available treatment options (eg, resistant or intolerant to hydroxyurea, etc).
Spleen 5 cm below the inferior left costal margin as measured by manual palpation.
Active symptomatic MF as defined by the screening MPN-SAD patient-reported instrument requiring a severity score of at least 5 on one symptom, or a severity score of ≥ 3 on at least two of the symptoms (on a 0 to 10 scale).
Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, 2, or 3.
Adequate organ function, demonstrated by the following laboratory values:
Recovery to Grade 1 from all clinically significant adverse events related to prior MF therapy, including transplant-related toxicities.
More than 2 months out from allogenic hematopoietic stem cell transplant prior to randomization.
Must be able to undergo MRI of abdomen (spleen and liver). Patients who are contra indicated for MRI may be enrolled and evaluated by CT scan at the discretion of the Sponsor.
18 years of age.
Male subjects able to father children and female patients of childbearing potential and at risk for pregnancy must agree to use two highly effective methods of contraception throughout the study and for 90 days after the last dose of assigned treatment.
Exclusion criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Pfizer CT.gov Call Center | Pfizer | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Mayo Clinic Building - Phoenix | Phoenix | Arizona | 85054 | United States | ||
| Mayo Clinic Hospital |
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| Label | URL |
|---|---|
| To obtain contact information for a study center near you, click here. | View source |
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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.
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| ID | Title | Description |
|---|---|---|
| FG000 | Glasdegib Lead-in | Glasdegib administered orally at a daily starting dose of 100 mg on a continuous regimen of 28-day cycles. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Placebo | Drug | Oral daily dose of placebo 100 mg tablet in a continuous regimen of 28-day cycles. |
|
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. |
| Baseline up to Week 131 |
| Number of Participants With Laboratory Abnormalities: Lead-in Cohort | 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. | Baseline up to Week 131 |
| 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 | 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). | Baseline up to Week 131 |
| 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 | 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:\ | Baseline up to Week 131 |
| Week 24 |
| 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 | 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. | Week 24 |
| Monthly Mean Change From Baseline in Overall Total Symptom Score (TSS) in the Lead-in Cohort | 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. | Weeks 12, 24, 36 and 48 |
| Percentage of Participants Achieving Anemia Response (Transfusion Dependent Versus Independent) in the Lead-in Cohort | 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. | Baseline to end of treatment |
| 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 | 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. | Cycle 1, Day 15 |
| Area Under the Glasdegib Plasma Concentration Versus Time Profile at the End of a Dosing Interval (AUCtau) in the Lead-in Cohort | 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. | Cycle 1, Day 15 |
| Time to Reach Cmax (Tmax) in the Lead-in Cohort | Tmax was the time of the first occurrence of Cmax observed directly from the plasma concentration data. | Cycle 1, Day 15 |
| Percentage of Participants Achieving SVR ≥50% as Measured by MRI/CT Scan at Week 24 in the Randomized Cohort | 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. | Week 24 |
| Monthly Mean Change From Baseline in Overall TSS in the Randomized Cohort | 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. | Weeks 12, 24, 36 and 48 |
| Percentage of Participants Achieving Anemia Response (Transfusion Dependent Versus Independent) in the Randomized Cohort | 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. | Baseline to end of treatment |
| Participant Reported Outcomes of Health Related Quality of Life and Health Status in the Randomised Cohort | 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. | Baseline to end of treatment |
| Median Duration of SVR in the Randomized Cohort | 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. | Baseline to end of treatment |
| Kaplan-Meier Estimate of Overall Survival in the Randomized Cohort | 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. | Baseline to end of treatment |
| Glasdegib PK Parameters in the Randomized Cohort | 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. | Cycle 1, Day 15 |
| Psychometric Validation of the MPN-SAD in the Randomised Cohort | 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. | Baseline to end of treatment |
| Number of Participants With Treatment -Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs): Randomized Cohort | 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. | Baseline up to Week 131 |
| Number of Participants With Treatment Emergent Treatment -Related Adverse Events (AEs) and Serious Adverse Events (SAEs): Randomized Cohort | 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. | Baseline up to Week 131 |
| Number of Participants With Treatment Emergent Adverse Events (AEs) According to Maximum Severity: Randomized Cohort | 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. | Baseline up to Week 131 |
| Number of Participants With Laboratory Abnormalities: Randomized Cohort | 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. | Baseline up to Week 131 |
| 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 | 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). | Baseline up to Week 131 |
| 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 | 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:\ | Baseline up to Week 131 |
| Phoenix |
| Arizona |
| 85054 |
| United States |
| Mayo Clinic | Scottsdale | Arizona | 85259 | United States |
| UC San Diego Moores Cancer Center - Investigational Drug Services | La Jolla | California | 92037-0845 | United States |
| UCSD Medical Center Clinical Laboratory - La Jolla | La Jolla | California | 92037 | United States |
| University of California San Diego (UCSD) Moores Cancer Center | La Jolla | California | 92093-0698 | United States |
| UC San Diego Medical Center- Hillcrest | San Diego | California | 92103 | United States |
| University of Michigan | Ann Arbor | Michigan | 48109 | United States |
| Weill Cornell Medical College - New York-Presbyterian Hospital | New York | New York | 10021 | United States |
| Herbert Irving Comprehensive Cancer Center-Columbia University Medical Center | New York | New York | 10032 | United States |
| Weill Cornell Medical College-New York Presbyterian Hospital | New York | New York | 10065 | United States |
| Cleveland Clinic - Taussig Cancer Institute | Cleveland | Ohio | 44195 | United States |
| Huntsman Cancer Institute-University of Utah | Salt Lake City | Utah | 84112 | United States |
| University of Utah, Huntsman Cancer Hospital | Salt Lake City | Utah | 84112 | United States |
| Froedtert Hospital and Medical College of Wisconsin | Milwaukee | Wisconsin | 53226-3522 | United States |
| Kobe University Hospital | Kobe | Hyōgo | 6500017 | Japan |
| Osaka University Hopsital | Suita-Shi | Osaka | 565-0871 | Japan |
| Juntendo University Hospital | Bunkyo-ku | Tokyo | 113-8431 | Japan |
| Tokyo Medical University Hospital | Tokyo | 160-0023 | Japan |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Glasdegib Lead-in | Glasdegib administered orally at a daily starting dose of 100 mg on a continuous regimen of 28-day cycles. |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
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| Age, Continuous | Mean | Standard Deviation | Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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 | 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. | 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. | Posted | Week 24 |
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| Primary | Number of Participants With Treatment -Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs): Lead-in Cohort | 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. | All participants treated in the lead-in portion of the study. | Posted | Count of Participants | Participants | Baseline up to Week 131 |
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| Primary | Number of Participants With Treatment Emergent Treatment -Related Adverse Events (AEs) and Serious Adverse Events (SAEs): Lead-in Cohort | 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. | All participants treated in the lead-in portion of the study. | Posted | Count of Participants | Participants | Baseline up to Week 131 |
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| Primary | 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 | 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. | All participants treated in the lead-in portion of the study. | Posted | Count of Participants | Participants | Baseline up to Week 131 |
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| Primary | Number of Participants With Laboratory Abnormalities: Lead-in Cohort | 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. | All participants treated in the lead-in portion of the study. | Posted | Count of Participants | Participants | Baseline up to Week 131 |
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| Primary | 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 | 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). | All participants treated in the lead-in portion of the study. | Posted | Count of Participants | Participants | Baseline up to Week 131 |
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| Secondary | Percentage of Participants Achieving SVR ≥35% as Measured by Magnetic Resonance Imaging/Computed Tomography Scan at Week 24 in the Lead-in Cohort | 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. | 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. | Posted | Number | Percentage of participants | Week 24 |
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| Secondary | 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 | 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. | Lead-in Analysis Set | Posted | Number | Percentage of participants | Week 24 |
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| Secondary | Monthly Mean Change From Baseline in Overall Total Symptom Score (TSS) in the Lead-in Cohort | 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. | Lead-in Analysis Set | Posted | Mean | Standard Deviation | Score on a scale | Weeks 12, 24, 36 and 48 |
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| Secondary | Percentage of Participants Achieving Anemia Response (Transfusion Dependent Versus Independent) in the Lead-in Cohort | 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. | Lead-in Analysis Set | Posted | Number | Percentage of participants | Baseline to end of treatment |
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| Secondary | 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 | 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. | 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 ). | Posted | Geometric Mean | Geometric Coefficient of Variation | nanograms per milliliter (ng/mL) | Cycle 1, Day 15 |
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| Secondary | Area Under the Glasdegib Plasma Concentration Versus Time Profile at the End of a Dosing Interval (AUCtau) in the Lead-in Cohort | 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. | PK Parameter Analysis Population | Posted | Geometric Mean | Geometric Coefficient of Variation | ng·hr/mL | Cycle 1, Day 15 |
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| Secondary | Time to Reach Cmax (Tmax) in the Lead-in Cohort | Tmax was the time of the first occurrence of Cmax observed directly from the plasma concentration data. | PK Parameter Analysis Population | Posted | Median | Full Range | Hours | Cycle 1, Day 15 |
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| Secondary | Percentage of Participants Achieving SVR ≥50% as Measured by MRI/CT Scan at Week 24 in the Randomized Cohort | 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. | FAS | Posted | Week 24 |
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| Secondary | Monthly Mean Change From Baseline in Overall TSS in the Randomized Cohort | 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. | FAS | Posted | Weeks 12, 24, 36 and 48 |
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| Secondary | Percentage of Participants Achieving Anemia Response (Transfusion Dependent Versus Independent) in the Randomized Cohort | 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. | FAS | Posted | Baseline to end of treatment |
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| Secondary | Participant Reported Outcomes of Health Related Quality of Life and Health Status in the Randomised Cohort | 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. | FAS | Posted | Baseline to end of treatment |
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| Secondary | Median Duration of SVR in the Randomized Cohort | 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. | FAS | Posted | Baseline to end of treatment |
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| Secondary | Kaplan-Meier Estimate of Overall Survival in the Randomized Cohort | 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. | FAS | Posted | Baseline to end of treatment |
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| Secondary | Glasdegib PK Parameters in the Randomized Cohort | 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. | PK Parameter Analysis Population | Posted | Cycle 1, Day 15 |
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| Secondary | Psychometric Validation of the MPN-SAD in the Randomised Cohort | 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. | FAS | Posted | Baseline to end of treatment |
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| Secondary | Number of Participants With Treatment -Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs): Randomized Cohort | 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. | 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. | Posted | Baseline up to Week 131 |
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| Secondary | Number of Participants With Treatment Emergent Treatment -Related Adverse Events (AEs) and Serious Adverse Events (SAEs): Randomized Cohort | 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. | 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. | Posted | Baseline up to Week 131 |
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| Secondary | Number of Participants With Treatment Emergent Adverse Events (AEs) According to Maximum Severity: Randomized Cohort | 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. | 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. | Posted | Baseline up to Week 131 |
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| Secondary | Number of Participants With Laboratory Abnormalities: Randomized Cohort | 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. | 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. | Posted | Baseline up to Week 131 |
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| Primary | 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 | 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:\ | All participants treated in the lead-in portion of the study. | Posted | Count of Participants | Participants | Baseline up to Week 131 |
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| Secondary | 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 | 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). | 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. | Posted | Baseline up to Week 131 |
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| Secondary | 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 | 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:\ | 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. | Posted | Baseline up to Week 131 |
|
Baseline up to Week 131
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.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Glasdegib Lead-in | Glasdegib administered orally at a daily starting dose of 100 mg on a continuous regimen of 28-day cycles. | 1 | 21 | 5 | 21 | 20 | 21 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Gastric varices haemorrhage | Gastrointestinal disorders | MedDRA v20.1 | Non-systematic Assessment |
| |
| Varices oesophageal | Gastrointestinal disorders | MedDRA v20.1 | Non-systematic Assessment |
| |
| Disease progression | General disorders | MedDRA v20.1 | Non-systematic Assessment |
| |
| Fatigue | General disorders | MedDRA v20.1 | Non-systematic Assessment |
| |
| Portal hypertension | Hepatobiliary disorders | MedDRA v20.1 | Non-systematic Assessment |
| |
| Failure to thrive | Metabolism and nutrition disorders | MedDRA v20.1 | Non-systematic Assessment |
| |
| Memory impairment | Nervous system disorders | MedDRA v20.1 | Non-systematic Assessment |
| |
| Mental status changes | Psychiatric disorders | MedDRA v20.1 | Non-systematic Assessment |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA v20.1 | Non-systematic Assessment |
| |
| Confusional state | Psychiatric disorders | MedDRA v20.1 | Non-systematic Assessment |
| |
| Sinus tachycardia | Cardiac disorders | MedDRA v20.1 | Non-systematic Assessment |
| |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA v20.1 | Non-systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA v20.1 | Non-systematic Assessment |
| |
| Postoperative ileus | Injury, poisoning and procedural complications | MedDRA v20.1 | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA v20.1 | Non-systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA v20.1 | Non-systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA v20.1 | Non-systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA v20.1 | Non-systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA v20.1 | Non-systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA v20.1 | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA v20.1 | Non-systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | MedDRA v20.1 | Non-systematic Assessment |
| |
| Asthenia | General disorders | MedDRA v20.1 | Non-systematic Assessment |
| |
| Fatigue | General disorders | MedDRA v20.1 | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA v20.1 | Non-systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA v20.1 | Non-systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA v20.1 | Non-systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA v20.1 | Non-systematic Assessment |
| |
| Electrocardiogram QT prolonged | Investigations | MedDRA v20.1 | Non-systematic Assessment |
| |
| Lipase increased | Investigations | MedDRA v20.1 | Non-systematic Assessment |
| |
| Lymphocyte count decreased | Investigations | MedDRA v20.1 | Non-systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA v20.1 | Non-systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA v20.1 | Non-systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA v20.1 | Non-systematic Assessment |
| |
| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA v20.1 | Non-systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA v20.1 | Non-systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA v20.1 | Non-systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA v20.1 | Non-systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA v20.1 | Non-systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA v20.1 | Non-systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | MedDRA v20.1 | Non-systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA v20.1 | Non-systematic Assessment |
| |
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA v20.1 | Non-systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA v20.1 | Non-systematic Assessment |
| |
| Night sweats | Skin and subcutaneous tissue disorders | MedDRA v20.1 | Non-systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA v20.1 | Non-systematic Assessment |
| |
| Pruritus generalised | Skin and subcutaneous tissue disorders | MedDRA v20.1 | Non-systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA v20.1 | Non-systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA v20.1 | Non-systematic Assessment |
|
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Pfizer ClinicalTrials.gov Call Center | Pfizer, Inc. | 1-800-718-1021 | ClinicalTrials.gov_Inquiries@pfizer.com |
| ID | Term |
|---|---|
| D055728 | Primary Myelofibrosis |
| ID | Term |
|---|---|
| D009196 | Myeloproliferative Disorders |
| D001855 | Bone Marrow Diseases |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C000592580 | glasdegib |
Not provided
Not provided
Not provided
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| Title | Denominators | Categories | ||||
|---|---|---|---|---|---|---|
|
| Participants |
|
| Units |
|---|
| Counts |
|---|
| Participants |
|
| Units | Counts |
|---|---|
| Participants |
|
|
| Units | Counts |
|---|
| Participants |
|
| Units | Counts |
|---|---|
| Participants |
|