A Study to Evaluate the Efficacy and Safety of PF-06882961 in Adults With Obesity

Study Overview
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Brief Summary
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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).

Official Title
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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

Conditions
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Obesity

Intervention / Treatment
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* Drug: Placebo (Cohorts 1 and 2)
* Drug: PF-06882961 (Cohorts 1 and 2)
* Drug: Placebo (Cohort 3)
* Drug: PF-06882961 (Cohort 3)


Participation Criteria
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Eligibility Criteria
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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 Known medical history of active liver disease, including chronic active hepatitis B or C, or primary biliary cirrhosis Known history of HIV Supine blood pressure greater than or equal to 160 mmHg (systolic) or greater than or equal to 100 mmHg (diastolic) Clinically relevant ECG abnormalities Positive urine drug screen Participation in a formal weight reduction program within 90 days prior to visit 1

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo (Cohorts 1 and 2)<br> | Drug: Placebo (Cohorts 1 and 2)<br>* 4 matching placebo tablets taken twice daily<br>|
| Experimental: PF-06882961 40 milligrams (mg) twice daily (BID), 1-week titration (Cohort 1)<br>The dose will be titrated with 1 week of dosing at each step to reach the target dose of 40 mg BID. | Drug: PF-06882961 (Cohorts 1 and 2)<br>* Participants will be randomized to one of 5 active target dose levels (40, 80, 120, 160 or 200 mg BID) achieved through 1-week titration steps, or 3 active target dose levels (120, 160 or 200 mg BID) achieved through 2-week titration steps, taking 4 tablets twice daily<br>|
| Experimental: PF-06882961 80 mg BID, 1-week titration (Cohort 1)<br>The dose will be titrated with 1 week of dosing at each step to reach the target dose of 80 mg BID. | Drug: PF-06882961 (Cohorts 1 and 2)<br>* Participants will be randomized to one of 5 active target dose levels (40, 80, 120, 160 or 200 mg BID) achieved through 1-week titration steps, or 3 active target dose levels (120, 160 or 200 mg BID) achieved through 2-week titration steps, taking 4 tablets twice daily<br>|
| Experimental: PF-06882961 120 mg BID, 1-week titration (Cohort 1)<br>The dose will be titrated with 1 week of dosing at each step to reach the target dose of 120 mg BID. | Drug: PF-06882961 (Cohorts 1 and 2)<br>* Participants will be randomized to one of 5 active target dose levels (40, 80, 120, 160 or 200 mg BID) achieved through 1-week titration steps, or 3 active target dose levels (120, 160 or 200 mg BID) achieved through 2-week titration steps, taking 4 tablets twice daily<br>|
| Experimental: PF-06882961 160 mg BID, 1-week titration (Cohort 1)<br>The dose will be titrated with 1 week of dosing at each step to reach the target dose of 160 mg BID. | Drug: PF-06882961 (Cohorts 1 and 2)<br>* Participants will be randomized to one of 5 active target dose levels (40, 80, 120, 160 or 200 mg BID) achieved through 1-week titration steps, or 3 active target dose levels (120, 160 or 200 mg BID) achieved through 2-week titration steps, taking 4 tablets twice daily<br>|
| Experimental: PF-06882961 200 mg BID, 1-week titration (Cohort 1)<br>The dose will be titrated with 1 week of dosing at each step to reach the target dose of 200 mg BID. | Drug: PF-06882961 (Cohorts 1 and 2)<br>* Participants will be randomized to one of 5 active target dose levels (40, 80, 120, 160 or 200 mg BID) achieved through 1-week titration steps, or 3 active target dose levels (120, 160 or 200 mg BID) achieved through 2-week titration steps, taking 4 tablets twice daily<br>|
| Experimental: PF-06882961 120 mg BID, 2-week titration (Cohorts 1 and 2)<br>The dose will be titrated with 2 weeks of dosing at each step to reach the target dose of 120 mg BID. | Drug: PF-06882961 (Cohorts 1 and 2)<br>* Participants will be randomized to one of 5 active target dose levels (40, 80, 120, 160 or 200 mg BID) achieved through 1-week titration steps, or 3 active target dose levels (120, 160 or 200 mg BID) achieved through 2-week titration steps, taking 4 tablets twice daily<br>|
| Experimental: PF-06882961 160 mg BID, 2-week titration (Cohorts 1 and 2)<br>The dose will be titrated with 2 weeks of dosing at each step to reach the target dose of 160 mg BID. | Drug: PF-06882961 (Cohorts 1 and 2)<br>* Participants will be randomized to one of 5 active target dose levels (40, 80, 120, 160 or 200 mg BID) achieved through 1-week titration steps, or 3 active target dose levels (120, 160 or 200 mg BID) achieved through 2-week titration steps, taking 4 tablets twice daily<br>|
| Experimental: PF-06882961 200 mg BID, 2-week titration (Cohorts 1 and 2)<br>The dose will be titrated with 2 weeks of dosing at each step to reach the target dose of 200 mg BID. | Drug: PF-06882961 (Cohorts 1 and 2)<br>* Participants will be randomized to one of 5 active target dose levels (40, 80, 120, 160 or 200 mg BID) achieved through 1-week titration steps, or 3 active target dose levels (120, 160 or 200 mg BID) achieved through 2-week titration steps, taking 4 tablets twice daily<br>|
| Placebo Comparator: Placebo (Cohort 3)<br> | Drug: Placebo (Cohort 3)<br>* 2 matching placebo tablets taken twice daily<br>|
| Experimental: PF-06882961 80 mg BID, 4-week titration (Cohort 3)<br>The dose will be titrated with 4 weeks of dosing at each step to reach the target dose of 80 mg BID. | Drug: PF-06882961 (Cohort 3)<br>* Participants will be randomized to one of 3 active target dose levels (80, 140 or 200 mg BID) achieved through 4-week titration steps, taking 2 tablets twice daily.<br>|
| Experimental: PF-06882961 140 mg BID, 4-week titration (Cohort 3)<br>The dose will be titrated with 4 weeks of dosing at each step to reach the target dose of 140 mg BID. | Drug: PF-06882961 (Cohort 3)<br>* Participants will be randomized to one of 3 active target dose levels (80, 140 or 200 mg BID) achieved through 4-week titration steps, taking 2 tablets twice daily.<br>|
| Experimental: PF-06882961 200 mg BID, 4-week titration (Cohort 3)<br>The dose will be titrated with 4 weeks of dosing at each step to reach the target dose of 200 mg BID. | Drug: PF-06882961 (Cohort 3)<br>* Participants will be randomized to one of 3 active target dose levels (80, 140 or 200 mg BID) achieved through 4-week titration steps, taking 2 tablets twice daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent change from baseline in body weight |  | Cohorts 1 and 2: Baseline and Week 26; Cohort 3: Baseline and Week 32 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body weight loss of greater than or equal to 5% |  | Cohorts 1 and 2: Baseline and Week 26; Cohort 3: Baseline and Week 32 | 
| Percent change from baseline in body weight |  | Cohorts 1 and 2: Baseline, Week 2, 4, 6, 8, 10, 12, 16, 18 and 22; Cohort 3: Baseline, Week 4, 8, 12, 16, 20, 24 and 28 | 
| Absolute change from baseline in waist circumference |  | Cohorts 1 and 2: Baseline and Week 26; Cohort 3: Baseline and Week 32 | 
| Absolute change from baseline in waist-to-hip ratio |  | Cohorts 1 and 2: Baseline and Week 26; Cohort 3: Baseline and Week 32 | 
| Absolute change from baseline in hemoglobin A1c |  | Cohorts 1 and 2: Baseline, Week 16 and 26; Cohort 3: Baseline, Week 16, 24 and 32 | 
| Absolute change from baseline in fasting plasma glucose |  | Cohorts 1 and 2: Baseline, Week 2, 4, 6, 8, 10, 12, 16, 18, 22 and 26; Cohort 3: Baseline, Week 4, 8, 12, 16, 20, 24, 28 and 32 | 
| Incidence of treatment emergent adverse events (AEs and SAEs) |  | Cohorts 1 and 2: Baseline up to Week 31; Cohort 3: Baseline up to Week 37 | 
| Incidence of treatment emergent clinically significant laboratory abnormalities |  | Cohorts 1 and 2: Baseline up to Week 28; Cohort 3: Baseline up to Week 34 | 
| Incidence of treatment emergent clinically significant vital sign abnormalities |  | Cohorts 1 and 2: Baseline up to Week 28; Cohort 3: Baseline up to Week 34 | 
| Incidence of treatment emergent clinically significant electrocardiogram (ECG) abnormalities |  | Cohorts 1 and 2: Baseline up to Week 28; Cohort 3: Baseline up to Week 34 | 
| Number of participants with categorical scores on the Columbia-Suicide Severity Rating Scale (C-SSRS) |  | Cohorts 1 and 2: Baseline up to Week 28; Cohort 3: Baseline up to Week 34 | 
| Number of participants with categorical scores on the Patient Health Questionniare-9 (PHQ-9) |  | Cohorts 1 and 2: Baseline up to Week 28; Cohort 3: Baseline up to Week 34 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Weight loss