A Study to Evaluate the Efficacy and Safety of PF-06882961 in Adults With Obesity
- Conditions
- Obesity
- Interventions
- Drug: PF-06882961 (Cohort 3)Drug: PF-06882961 (Cohorts 1 and 2)Drug: Placebo (Cohorts 1 and 2)Drug: Placebo (Cohort 3)
- Registration Number
- NCT04707313
- Lead Sponsor
- Pfizer
- 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 628
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description PF-06882961 140 mg BID, 4-week titration (Cohort 3) PF-06882961 (Cohort 3) The dose will be titrated with 4 weeks of dosing at each step to reach the target dose of 140 mg BID. PF-06882961 120 mg BID, 2-week titration (Cohorts 1 and 2) PF-06882961 (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. PF-06882961 120 mg BID, 1-week titration (Cohort 1) PF-06882961 (Cohorts 1 and 2) The dose will be titrated with 1 week of dosing at each step to reach the target dose of 120 mg BID. PF-06882961 40 milligrams (mg) twice daily (BID), 1-week titration (Cohort 1) PF-06882961 (Cohorts 1 and 2) The dose will be titrated with 1 week of dosing at each step to reach the target dose of 40 mg BID. Placebo (Cohorts 1 and 2) Placebo (Cohorts 1 and 2) - PF-06882961 200 mg BID, 2-week titration (Cohorts 1 and 2) PF-06882961 (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. Placebo (Cohort 3) Placebo (Cohort 3) - PF-06882961 160 mg BID, 2-week titration (Cohorts 1 and 2) PF-06882961 (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. PF-06882961 80 mg BID, 4-week titration (Cohort 3) PF-06882961 (Cohort 3) The dose will be titrated with 4 weeks of dosing at each step to reach the target dose of 80 mg BID. PF-06882961 200 mg BID, 4-week titration (Cohort 3) PF-06882961 (Cohort 3) The dose will be titrated with 4 weeks of dosing at each step to reach the target dose of 200 mg BID. PF-06882961 200 mg BID, 1-week titration (Cohort 1) PF-06882961 (Cohorts 1 and 2) The dose will be titrated with 1 week of dosing at each step to reach the target dose of 200 mg BID. PF-06882961 80 mg BID, 1-week titration (Cohort 1) PF-06882961 (Cohorts 1 and 2) The dose will be titrated with 1 week of dosing at each step to reach the target dose of 80 mg BID. PF-06882961 160 mg BID, 1-week titration (Cohort 1) PF-06882961 (Cohorts 1 and 2) The dose will be titrated with 1 week of dosing at each step to reach the target dose of 160 mg BID.
- Primary Outcome Measures
Name Time Method Cohorts 1 and 2: Percent Change From Baseline in Body Weight at End of Treatment at Week 26 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 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 Outcome Measures
Name Time Method 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) An adverse event (AE) was any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. An SAE was defined as any untoward medical occurrence that, at any dose met one or more of the criteria such as resulted in death; life threatening; required inpatient hospitalization or prolongation of existing hospitalization; persistent disability or incapacity, congenital anomaly or birth defect; suspected transmission via a Pfizer product of an infectious agent, pathogenic or non-pathogenic. An adverse event is considered treatment-emergent relative to given treatment if the event starts during the effective duration of the treatment (i.e. starting on or after the first dose but before the last dose plus follow-up period).
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) An AE was any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. An SAE was defined as any untoward medical occurrence that, at any dose met one or more of the criteria such as resulted in death; life threatening; required inpatient hospitalization or prolongation of existing hospitalization; persistent disability or incapacity, congenital anomaly or birth defect; suspected transmission via a Pfizer product of an infectious agent, pathogenic or non-pathogenic. An adverse event is considered treatment-emergent relative to given treatment if the event starts during the effective duration of the treatment (i.e. starting on or after the first dose but before the last dose plus lag time).
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) Laboratory parameters:a)hematology:hemoglobin(Hg),hematocrit,erythrocytes(ery),neutrophils,ery mean corpuscular volume,platelets,leukocytes(leu),lymphocytes,basophils,eosinophils,monocytes activated partial thromboplastin time, prothrombin time,prothrombin initial normalised ratio b)chemistry:direct bilirubin(bil),indirect bil, gamma glutamyl transferase,urea nitrogen,urate,sodium,potassium,calcium(cal),cal corrected,bicarbonate,Hg a1c,creatine kinase,bile acid,calcitonin,insulin-fasting,glucose fasting,amylase,lipase,thyrotropin,thyroxine,free,cholesterol,high density lipoprotein (hdl) cholesterol,triglycerides,alanine aminotransferase c)urinalysis:urine:pH,ketone,protein, Hg, urobilinogen,nitrite,leu esterase,ery,leu,tubular epithelial cells,squamous epithelial cells,granular casts,hyaline casts,uric acid crystals,calcium oxalate crystals,amorphous crystals,mucus,microscopic exam,spermatozoa,yeast budding,transitional epithelial cells,leu cell clumps;yeast hyphae.
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) Laboratory parameters:a)hematology:hemoglobin(Hg),hematocrit,erythrocytes(ery),neutrophils,ery mean corpuscular volume,platelets,leukocytes(leu),lymphocytes,basophils,eosinophils,monocytes activated partial thromboplastin time, prothrombin time,prothrombin initial normalised ratio b)chemistry:direct bilirubin(bil),indirect bil, gamma glutamyl transferase,urea nitrogen,urate,sodium,potassium,calcium(cal),cal corrected,bicarbonate,Hg a1c,creatine kinase,bile acid,calcitonin,insulin-fasting,glucose fasting,amylase,lipase,thyrotropin,thyroxine,free,cholesterol,high density lipoprotein (hdl) cholesterol,triglycerides,alanine aminotransferase c)urinalysis:urine:pH,ketone,protein, Hg, urobilinogen,nitrite,leu esterase,ery,leu,tubular epithelial cells,squamous epithelial cells,granular casts,hyaline casts,uric acid crystals,calcium oxalate crystals,amorphous crystals,mucus,microscopic exam,spermatozoa,yeast budding,transitional epithelial cells,leu cell clumps;yeast hyphae.
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) Vital signs of systolic blood pressure, diastolic blood pressure and pulse rate and were measured using an automated device with the participant in a supine position after five minutes of rest. This reports the number of participants that met the following pre-specified criteria: systolic blood pressure (SBP) \<90 millimetres of mercury (mmHg), diastolic blood pressure (DBP) \<50 mmHg, pulse rate (PR) \<40 beats per minute, \>120 beats per minute.
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) Vital signs of systolic blood pressure, diastolic blood pressure and pulse rate and were measured using an automated device with the participant in a supine position after five minutes of rest. This reports the number of participants that met the following pre-specified criteria: systolic blood pressure (SBP) \<90 millimetres of mercury (mmHg), diastolic blood pressure (DBP) \<50 mmHg, pulse rate (PR) \<40 beats per minute, \>120 beats per minute.
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) Standard 12-lead ECGs were measured with the participant in a supine position after at least five minutes of rest. This reports the number of participants that met the following pre-specified criteria for ECG: QRS interval \>=140; PR interval \>=300; QTCF interval \>500.
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) Standard 12-lead ECGs were measured with the participant in a supine position after at least five minutes of rest. This reports the number of participants that met the following pre-specified criteria for ECG: QRS interval \>=140; PR interval \>=300; QTCF interval \>500.
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) C-SSRS is an interview-based rating scale to assess suicidal ideation and behavior. Per protocol, any participant with a pre-specified score was required to be evaluated by a mental health professional and, if meeting pre-defined criteria, discontinued from the study.
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) C-SSRS is an interview-based rating scale to assess suicidal ideation and behavior. Per protocol, any participant with a pre-specified score was required to be evaluated by a mental health professional and, if meeting pre-defined criteria, discontinued from the study.
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) PHQ-9 is a self-reported, nine-item scale for the assessment of depressive disorder. Per protocol, any participant with a pre-specified score was required to be evaluated by a mental health professional and, if meeting pre-defined criteria, discontinued from the study.
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) PHQ-9 is a self-reported, nine-item scale for the assessment of depressive disorder. Per protocol, any participant with a pre-specified score was required to be evaluated by a mental health professional and, if meeting pre-defined criteria, discontinued from the study.
Cohorts 1 and 2: Number of Participants With >= 5% Body Weight Loss at End of Treatment Week 26 Number of participants with \>= 5% body weight loss at end of treatment were reported.
Cohort 3: Number of Participants With >=5% Body Weight Loss at End of Treatment Week 32 Number of participants with \>= 5% body weight loss at end of treatment were reported.
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 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.
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 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.
Cohorts 1 and 2: Absolute Change From Baseline in Waist Circumference at End of Treatment at Week 26 Baseline, Week 26 Absolute change from baseline in waist circumference were reported. Analysis was performed using MMRM model with treatment, time, strata (females versus males) and treatment-by-time interaction as fixed effects, baseline as a covariate and the baseline-by-time interaction with time fitted as a repeated effect and participant as a random effect. Baseline was defined as the average of the duplicate measurements collected closest prior to dosing at Day 1.
Cohort 3: Absolute Change From Baseline in Waist Circumference at End of Treatment at Week 32 Baseline, Week 32 Absolute change from baseline in waist circumference were reported. Analysis was performed using MMRM model with treatment, time, strata (females versus males) and treatment-by-time interaction as fixed effects, baseline as a covariate and the baseline-by-time interaction with time fitted as a repeated effect and participant as a random effect. Baseline was defined as the average of the duplicate measurements collected closest prior to dosing at Day 1.
Cohorts 1 and 2: Absolute Change From Baseline in Waist-to-hip Ratio at End of Treatment at Week 26 Baseline, Week 26 Absolute change from baseline in waist-to-hip ratio at end of treatment were reported. Analysis was performed using MMRM model with treatment, time, strata (females versus males) and treatment-by-time interaction as fixed effects, baseline as a covariate and the baseline-by-time interaction with time fitted as a repeated effect and participant as a random effect. Baseline was defined as the average of the duplicate measurements collected closest prior to dosing at Day 1.
Cohort 3: Absolute Change From Baseline in Waist-to-hip Ratio at End of Treatment at Week 32 Baseline, Week 32 Absolute change from baseline in waist-to-hip ratio at end of treatment were reported. Analysis was performed using MMRM model with treatment, time, strata (females versus males) and treatment-by-time interaction as fixed effects, baseline as a covariate and the baseline-by-time interaction with time fitted as a repeated effect and participant as a random effect. Baseline was defined as the average of the duplicate measurements collected closest prior to dosing at Day 1.
Cohorts 1 and 2: Absolute Change From Baseline in Percentage Hemoglobin A1c (HbA1c) at Weeks 16 and 26 Baseline, Weeks 16 and 26 Absolute change from baseline in HbA1c were reported. Analysis was performed using MMRM model with treatment, time, strata (females versus males) and treatment-by-time interaction as fixed effects, baseline as a covariate and the baseline-by-time interaction with time fitted as a repeated effect and participant as a random effect. Baseline was defined as the average of the duplicate measurements collected closest prior to dosing at Day 1.
Cohort 3: Absolute Change From Baseline in Percentage HbA1c at Weeks 16, 24 and 32 Baseline, Weeks 16, 24 and 32 Absolute change from baseline in HbA1c were reported. Analysis was performed using MMRM model with treatment, time, strata (females versus males) and treatment-by-time interaction as fixed effects, baseline as a covariate and the baseline-by-time interaction with time fitted as a repeated effect and participant as a random effect. Baseline was defined as the average of the duplicate measurements collected closest prior to dosing at Day 1.
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 Absolute change from baseline in FPG were reported. Analysis was performed using MMRM model with treatment, time, strata (females versus males) and treatment-by-time interaction as fixed effects, baseline as a covariate and the baseline-by-time interaction with time fitted as a repeated effect and participant as a random effect. Baseline was defined as the average of the duplicate measurements collected closest prior to dosing at Day 1.
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 Absolute change from baseline in FPG were reported. Analysis was performed using MMRM model with treatment, time, strata (females versus males) and treatment-by-time interaction as fixed effects, baseline as a covariate and the baseline-by-time interaction with time fitted as a repeated effect and participant as a random effect. Baseline was defined as the average of the duplicate measurements collected closest prior to dosing at Day 1.
Trial Locations
- Locations (40)
PMG Research, Inc. d/b/a PMG Research of Knoxville
🇺🇸Knoxville, Tennessee, United States
Rivergrove Medical Clinic
🇨🇦Winnipeg, Manitoba, Canada
Aggarwal and Associates Limited
🇨🇦Brampton, Ontario, Canada
Milestone Research , Inc
🇨🇦London, Ontario, Canada
Manna Research Toronto
🇨🇦Toronto, Ontario, Canada
Ecogene-21
🇨🇦Chicoutimi, Quebec, Canada
Diex Recherche Sherbrooke Inc.
🇨🇦Sherbrooke, Quebec, Canada
Centre de Recherche Saint-Louis
🇨🇦Quebec, Canada
Alpha Recherche Clinique
🇨🇦Quebec, Canada
Medical Corporation Heishinkai OCROM Clinic
🇯🇵Suita-shi, Osaka, Japan
Tokyo Center Clinic
🇯🇵Chuo-ku, Tokyo, Japan
Fukuwa Clinic
🇯🇵Chuo-ku, Tokyo, Japan
Medical Corporation Heishinkai ToCROM Clinic
🇯🇵Shinjuku-ku, Tokyo, Japan
China Medical University Hospital
🇨🇳Taichung City, Taiwan
National Cheng Kung University Hospital
🇨🇳Tainan, Taiwan
Accellacare - Wilmington
🇺🇸Wilmington, North Carolina, United States
Pinnacle Research Group, LLC
🇺🇸Anniston, Alabama, United States
Anaheim Clinical Trials, LLC
🇺🇸Anaheim, California, United States
Velocity Clinical Research - Westlake
🇺🇸Los Angeles, California, United States
Alliance for Multispecialty Research, LLC
🇺🇸Coral Gables, Florida, United States
Optimus U Corporation
🇺🇸Miami, Florida, United States
Clinical Neuroscience Solutions, Inc.
🇺🇸Memphis, Tennessee, United States
ForCare Clinical Research
🇺🇸Tampa, Florida, United States
Clinical Investigation Specialists
🇺🇸Gurnee, Illinois, United States
MediSphere Medical Research Center, LLC
🇺🇸Evansville, Indiana, United States
Velocity Clinical Research, Valparaiso
🇺🇸Valparaiso, Indiana, United States
Cotton O'Neil Clinical Research Center
🇺🇸Topeka, Kansas, United States
L-MARC Research Center
🇺🇸Louisville, Kentucky, United States
ActivMed Practices & Research, LLC
🇺🇸Methuen, Massachusetts, United States
Velocity Clinical Research, Omaha
🇺🇸Omaha, Nebraska, United States
PMG Research of Hickory, LLC
🇺🇸Hickory, North Carolina, United States
PMG Research of Raleigh, LLC
🇺🇸Raleigh, North Carolina, United States
PMG Research of Salisbury, LLC
🇺🇸Salisbury, North Carolina, United States
Lillestol Research LLC
🇺🇸Fargo, North Dakota, United States
Velocity Clinical Research, Inc.
🇺🇸Cleveland, Ohio, United States
Clinical Trials of South Carolina
🇺🇸Moncks Corner, South Carolina, United States
Coastal Carolina Research Center
🇺🇸North Charleston, South Carolina, United States
Palmetto Primary Care Physicians (Sub-I physicals only)
🇺🇸Summerville, South Carolina, United States
Palmetto Clinical Research
🇺🇸Summerville, South Carolina, United States
Internal Medicine and Pediatric Associates of Bristol, PC
🇺🇸Bristol, Tennessee, United States