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).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
628
4 matching placebo tablets taken twice daily
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
2 matching placebo tablets taken twice daily
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.
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
Cohorts 1 and 2: Percent Change From Baseline in Body Weight at End of Treatment at 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.
Time frame: Baseline, Week 26
Cohort 3: Percent Change From Baseline in Body Weight at End of Treatment at 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.
Time frame: Baseline, Week 32
Cohorts 1 and 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious AEs (TESAEs)
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).
Time frame: 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
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).
Time frame: 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
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.
Time frame: 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
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.
Time frame: 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
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.
Time frame: 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
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.
Time frame: 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
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.
Time frame: 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
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.
Time frame: 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
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.
Time frame: 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
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.
Time frame: 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
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.
Time frame: 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
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.
Time frame: 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
Number of participants with \>= 5% body weight loss at end of treatment were reported.
Time frame: Week 26
Cohort 3: Number of Participants With >=5% Body Weight Loss at End of Treatment
Number of participants with \>= 5% body weight loss at end of treatment were reported.
Time frame: Week 32
Cohorts 1 and 2: Percent Change From Baseline in Body Weight at 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.
Time frame: 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
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.
Time frame: 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
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.
Time frame: Baseline, Week 26
Cohort 3: Absolute Change From Baseline in Waist Circumference at End of Treatment at 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.
Time frame: Baseline, Week 32
Cohorts 1 and 2: Absolute Change From Baseline in Waist-to-hip Ratio at End of Treatment at 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.
Time frame: Baseline, Week 26
Cohort 3: Absolute Change From Baseline in Waist-to-hip Ratio at End of Treatment at 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.
Time frame: Baseline, Week 32
Cohorts 1 and 2: Absolute Change From Baseline in Percentage Hemoglobin A1c (HbA1c) at 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.
Time frame: Baseline, Weeks 16 and 26
Cohort 3: Absolute Change From Baseline in Percentage HbA1c at 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.
Time frame: 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
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.
Time frame: 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
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.
Time frame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32
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