A PHASE 2B, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL GROUP, DOSE-RANGING STUDY TO EVALUATE THE EFFICACY AND SAFETY OF PF-06882961 ADMINISTRATION IN ADULTS WITH OBESITY
Overview
- Phase
- Phase 2
- Intervention
- Placebo (Cohorts 1 and 2)
- Conditions
- Obesity
- Sponsor
- Pfizer
- Enrollment
- 628
- Locations
- 40
- Primary Endpoint
- Cohorts 1 and 2: Percent Change From Baseline in Body Weight at End of Treatment at Week 26
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
The purpose of this clinical trial is to learn about the safety and effects of the study medicine (called PF-06882961) for the potential treatment of obesity. The study will compare the experiences of participants taking the study medicine (PF-06882961) to those of participants who take placebo (a look- alike substance that contains no active study medicine). The aim is to measure the body's response to the study medicine, including any changes in participants' body weight, waist and hip measurements, how well they tolerate the study medicine, and to measure levels of the study medicine in participants' blood.
This study is seeking participants who have obesity, who do not have diabetes and who have had a stable body weight and not participated in a formal weight loss program in the 90 days before the study. The study medicine or placebo will be taken as tablets by mouth 2 times a day (1 time in the morning and 1 time in the evening).
There are 3 groups of participants (called cohorts) in this study. For participants in Cohorts 1 and 2, total study participation will be about 9 months, with 15 planned study visits (14 visits to the study clinic and 1 telephone call). For participants in Cohort 3, total study participation will be about 10 months, with 21 planned study visits (12 visits to the study clinic and 9 telephone calls).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Participants with obesity, defined as a Body Mass Index greater than or equal to 30.0 kg/m2
- •Stable body weight, defined as \<5 kg change (per participant report) for 90 days before visit 1
Exclusion Criteria
- •Any condition possibly affecting drug absorption
- •Current or prior diagnosis of Type 1 or Type 2 diabetes mellitus or secondary forms of diabetes
- •History of myocardial infarction, unstable angina, arterial revascularization, stroke, heart failure, or transient ischemic attack within 6 months prior to visit 1
- •Any malignancy not considered cured
- •Personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 or suspected MTC
- •History of acute pancreatitis within 180 days (6 months) prior to visit 1 or any history of chronic pancreatitis
- •Symptomatic gallbladder disease
- •Medical history or characteristics suggestive of genetic or syndromic obesity or obesity induced by other endocrinological disorders
- •History of major depressive disorder or other severe psychiatric disorders within the last 2 years
- •Any lifetime history of a suicide attempt
Arms & Interventions
Placebo (Cohorts 1 and 2)
Intervention: Placebo (Cohorts 1 and 2)
PF-06882961 40 milligrams (mg) twice daily (BID), 1-week titration (Cohort 1)
The dose will be titrated with 1 week of dosing at each step to reach the target dose of 40 mg BID.
Intervention: PF-06882961 (Cohorts 1 and 2)
PF-06882961 80 mg BID, 1-week titration (Cohort 1)
The dose will be titrated with 1 week of dosing at each step to reach the target dose of 80 mg BID.
Intervention: PF-06882961 (Cohorts 1 and 2)
PF-06882961 120 mg BID, 1-week titration (Cohort 1)
The dose will be titrated with 1 week of dosing at each step to reach the target dose of 120 mg BID.
Intervention: PF-06882961 (Cohorts 1 and 2)
PF-06882961 160 mg BID, 1-week titration (Cohort 1)
The dose will be titrated with 1 week of dosing at each step to reach the target dose of 160 mg BID.
Intervention: PF-06882961 (Cohorts 1 and 2)
PF-06882961 200 mg BID, 1-week titration (Cohort 1)
The dose will be titrated with 1 week of dosing at each step to reach the target dose of 200 mg BID.
Intervention: PF-06882961 (Cohorts 1 and 2)
PF-06882961 120 mg BID, 2-week titration (Cohorts 1 and 2)
The dose will be titrated with 2 weeks of dosing at each step to reach the target dose of 120 mg BID.
Intervention: PF-06882961 (Cohorts 1 and 2)
PF-06882961 160 mg BID, 2-week titration (Cohorts 1 and 2)
The dose will be titrated with 2 weeks of dosing at each step to reach the target dose of 160 mg BID.
Intervention: PF-06882961 (Cohorts 1 and 2)
PF-06882961 200 mg BID, 2-week titration (Cohorts 1 and 2)
The dose will be titrated with 2 weeks of dosing at each step to reach the target dose of 200 mg BID.
Intervention: PF-06882961 (Cohorts 1 and 2)
Placebo (Cohort 3)
Intervention: Placebo (Cohort 3)
PF-06882961 80 mg BID, 4-week titration (Cohort 3)
The dose will be titrated with 4 weeks of dosing at each step to reach the target dose of 80 mg BID.
Intervention: PF-06882961 (Cohort 3)
PF-06882961 140 mg BID, 4-week titration (Cohort 3)
The dose will be titrated with 4 weeks of dosing at each step to reach the target dose of 140 mg BID.
Intervention: PF-06882961 (Cohort 3)
PF-06882961 200 mg BID, 4-week titration (Cohort 3)
The dose will be titrated with 4 weeks of dosing at each step to reach the target dose of 200 mg BID.
Intervention: PF-06882961 (Cohort 3)
Outcomes
Primary Outcomes
Cohorts 1 and 2: Percent Change From Baseline in Body Weight at End of Treatment at Week 26
Time Frame: Baseline, Week 26
Percent change from baseline in body weight at end of treatment was reported in this outcome measure. Analysis was performed using MMRM with treatment, time, strata (females versus males) and treatment-by-time interaction as fixed effects, natural log-transformed baseline as a covariate and the (natural log-transformed baseline)-by-time interaction with time fitted as a repeated effect and participant as a random effect. Values were back-transformed from the log scale. Percent change = 100 multiply by \[\*\](back-transformed LS Mean minus \[-\] 1). Baseline was defined as the average of the duplicate measurements collected closest prior to dosing at Day 1.
Cohort 3: Percent Change From Baseline in Body Weight at End of Treatment at Week 32
Time Frame: Baseline, Week 32
Percent change from baseline in body weight at end of treatment was reported in this outcome measure. Analysis was performed using MMRM with treatment, time, strata (females versus males) and treatment-by-time interaction as fixed effects, natural log-transformed baseline as a covariate and the (natural log-transformed baseline)-by-time interaction with time fitted as a repeated effect and participant as a random effect. Values were back-transformed from the log scale. Percent change = 100\*(back-transformed LS Mean - 1). Baseline was defined as the average of the duplicate measurements collected closest prior to dosing at Day 1.
Secondary Outcomes
- Cohorts 1 and 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious AEs (TESAEs)(From first dose of study intervention on Day 1 up to 28-35 days after last dose of study treatment (maximum up to 31 weeks))
- Cohort 3: Number of Participants With TEAEs and TESAEs(From first dose of study intervention on Day 1 up to 28-35 days after last dose of study treatment (maximum up to 37 weeks))
- Cohorts 1 and 2: Number of Participants With Laboratory Abnormalities, Without Regard to Baseline Abnormality(From first dose of study intervention on Day 1 up to 28-35 days after last dose of study treatment (up to 31 weeks))
- Cohort 3: Number of Participants With Laboratory Abnormalities, Without Regard to Baseline Abnormality(From first dose of study intervention on Day 1 up to 28-35 days after last dose of study treatment (up to 37 weeks))
- Cohorts 1 and 2: Number of Participants According to Categorization of Vital Signs Data(From first dose of study intervention on Day 1 up to 28-35 days after last dose of study treatment (up to 31 weeks))
- Cohort 3: Number of Participants According to Categorization of Vital Signs Data(From first dose of study intervention on Day 1 up to 28-35 days after last dose of study treatment (up to 37 weeks))
- Cohorts 1 and 2: Number of Participants According to Categorization of Electrocardiogram (ECG) Parameters(From first dose of study intervention on Day 1 up to 28-35 days after last dose of study treatment (up to 31 weeks))
- Cohort 3: Number of Participants According to Categorization of ECG Parameters(From first dose of study intervention on Day 1 up to 28-35 days after last dose of study treatment (up to 37 weeks))
- Cohorts 1 and 2: Number of Participants With Categorical Scores on Columbia-Suicide Severity Rating Scale (C-SSRS) Leading to Study Discontinuation(Week 0 (Baseline), 2, 4, 6, 8, 10, 12, 16, 18, 22, 26, Follow-up (Week 31))
- Cohort 3: Number of Participants With Categorical Scores on C-SSRS Leading to Study Discontinuation(Week 0 (Baseline), 4, 8, 12, 16, 20, 24, 28, 32, Follow-up (Week 37))
- Cohort 1 and 2: Number of Participants With Scores on the Patient Health Questionnaire-9 (PHQ-9) Leading to Study Discontinuation(Week 0 (Baseline) , 2, 4, 6, 8, 10, 12, 16, 18, 22, 26, Follow-up (Week 31))
- Cohort 3: Number of Participants With Scores on the PHQ-9 Leading to Study Discontinuation(Week 0 (Baseline), 4, 8, 12, 16, 20, 24, 28, 32, Follow-up (Week 37))
- Cohorts 1 and 2: Number of Participants With >= 5% Body Weight Loss at End of Treatment(Week 26)
- Cohort 3: Number of Participants With >=5% Body Weight Loss at End of Treatment(Week 32)
- Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22(Baseline, Weeks 2, 4, 6, 8, 10, 12,16, 18, 22)
- Cohort 3: Percent Change From Baseline in Body Weight at Weeks 4, 8, 12, 16, 20, 24 and 28(Baseline, Weeks 4, 8, 12, 16, 20, 24 and 28)
- Cohorts 1 and 2: Absolute Change From Baseline in Waist Circumference at End of Treatment at Week 26(Baseline, Week 26)
- Cohort 3: Absolute Change From Baseline in Waist Circumference at End of Treatment at Week 32(Baseline, Week 32)
- Cohorts 1 and 2: Absolute Change From Baseline in Waist-to-hip Ratio at End of Treatment at Week 26(Baseline, Week 26)
- Cohort 3: Absolute Change From Baseline in Waist-to-hip Ratio at End of Treatment at Week 32(Baseline, Week 32)
- Cohorts 1 and 2: Absolute Change From Baseline in Percentage Hemoglobin A1c (HbA1c) at Weeks 16 and 26(Baseline, Weeks 16 and 26)
- Cohort 3: Absolute Change From Baseline in Percentage HbA1c at Weeks 16, 24 and 32(Baseline, Weeks 16, 24 and 32)
- Cohorts 1 and 2: Absolute Change From Baseline in Fasting Plasma Glucose (FPG) at Weeks 2, 4, 6, 8, 10, 12, 16, 18, 22, 26(Baseline, Weeks 2, 4, 6, 8, 10, 12, 16, 18, 22, 26)
- Cohort 3: Absolute Change From Baseline in FPG at Weeks 4, 8, 12, 16, 20, 24, 28, 32(Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32)