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

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

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04707313

Enrollment

628

Registered

2021-01-13

Start date

2021-01-29

Completion date

2023-10-11

Last updated

2024-11-05

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Obesity

Keywords

Weight loss

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).

Interventions

DRUGPlacebo (Cohorts 1 and 2)

4 matching placebo tablets taken twice daily

DRUGPF-06882961 (Cohorts 1 and 2)

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

DRUGPlacebo (Cohort 3)

2 matching placebo tablets taken twice daily

DRUGPF-06882961 (Cohort 3)

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.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to 75 Years

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
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.
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).
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.
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.
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).

Countries

Canada, Japan, Taiwan, United States

Participant flow

Pre-assignment details

A total of 1220 participants were screened (Cohorts 1 and 2: 926 and Cohort 3: 294), of which 592 failed screening and 628 were randomized (Cohorts 1 and 2: 499 and Cohort 3: 129) in the study. Data for participants with the same dose and dosing frequency from Cohorts 1 and 2 were combined as pre-specified in the statistical analysis plan.

Participants by arm

Arm	Count
Cohorts 1 and 2: Placebo Participants received placebo matched to PF-06882961 twice daily (BID), orally for a total of 26 weeks.	71
Cohort 1: PF-06882961 40 mg BID (1-week Titration) Participants received oral daily doses of PF-06882961, titrated with 1-week at each step to a target dose of 40 mg BID, for a total of 26 weeks.	62
Cohort 1: PF-06882961 80mg BID (1-week Titration) Participants received oral daily doses of PF-06882961, titrated with 1-week at each step to a target dose of 80 mg BID, for a total of 26 weeks.	63
Cohort 1: PF-06882961 120mg BID (1-week Titration) Participants received oral daily doses of PF-06882961, titrated with 1-week at each step to a target dose of 120 mg BID, for a total of 26 weeks.	64
Cohorts 1 and 2: PF-06882961 120 mg BID (2-week Titration) Participants received oral daily doses of PF-06882961, titrated with 2-week at each step to a target dose of 120 mg BID, for a total of 26 weeks.	38
Cohort 1: PF-06882961 160 mg BID (1-week Titration) Participants received oral daily doses of PF-06882961, titrated with 1-week at each step to a target dose of 160 mg BID, for a total of 26 weeks.	63
Cohorts 1 and 2: PF-06882961 160 mg BID (2-week Titration) Participants received oral daily doses of PF-06882961, titrated with 2-week at each step to a target dose of 160 mg BID, for a total of 26 weeks.	37
Cohort 1: PF-06882961 200 mg BID (1-week Titration) Participants received oral daily doses of PF-06882961, titrated with 1-week at each step to a target dose of 200 mg BID, for a total of 26 weeks.	63
Cohorts 1 and 2: PF-06882961 200 mg BID (2-week Titration) Participants received oral daily doses of PF-06882961, titrated with 2-week at each step to a target dose of 200 mg BID, for a total of 26 weeks.	36
Cohort 3: Placebo Participants received placebo matched to PF-06882961 BID, orally for 32 weeks.	19
Cohort 3: PF-06882961 80mg BID (4-week Titration) Participants received oral daily doses of PF-06882961, titrated with 4-week at each step to a target dose of 80 mg BID, for 32 weeks.	37
Cohort 3: PF-06882961 140mg BID (4-week Titration) Participants received oral daily doses of PF-06882961, titrated with 4-week at each step to a target dose of 140 mg BID, for 32 weeks.	37
Cohort 3: PF-06882961 200mg BID (4-week Titration) Participants received oral daily doses of PF-06882961, titrated with 4-week at each step to a target dose of 200 mg BID, for 32 weeks.	36
Total	626

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004	FG005	FG006	FG007	FG008	FG009	FG010	FG011	FG012
Cohort 3 (Week 0 to Week 32)	Adverse Event	0	0	0	0	0	0	0	0	0	0	9	16	18
Cohort 3 (Week 0 to Week 32)	Lack of Efficacy	0	0	0	0	0	0	0	0	0	3	1	1	0
Cohort 3 (Week 0 to Week 32)	Lost to Follow-up	0	0	0	0	0	0	0	0	0	3	5	2	3
Cohort 3 (Week 0 to Week 32)	Other	0	0	0	0	0	0	0	0	0	0	1	0	1
Cohort 3 (Week 0 to Week 32)	Protocol Violation	0	0	0	0	0	0	0	0	0	1	1	0	0
Cohort 3 (Week 0 to Week 32)	Withdrawal by Subject	0	0	0	0	0	0	0	0	0	1	7	3	3
Cohorts 1 and 2(Week 1 - Week 26)	Adverse Event	4	20	23	25	15	38	15	42	16	0	0	0	0
Cohorts 1 and 2(Week 1 - Week 26)	Lack of Efficacy	5	1	0	0	1	0	0	0	0	0	0	0	0
Cohorts 1 and 2(Week 1 - Week 26)	Lost to Follow-up	5	4	4	5	3	2	3	2	2	0	0	0	0
Cohorts 1 and 2(Week 1 - Week 26)	Non-compliance with study drug	0	1	2	0	1	0	0	0	0	0	0	0	0
Cohorts 1 and 2(Week 1 - Week 26)	Other	1	4	1	1	2	0	0	0	1	0	0	0	0
Cohorts 1 and 2(Week 1 - Week 26)	Protocol Violation	1	0	0	0	0	1	2	1	0	0	0	0	0
Cohorts 1 and 2(Week 1 - Week 26)	Randomized not treated	0	0	1	0	0	0	0	1	0	0	0	0	0
Cohorts 1 and 2(Week 1 - Week 26)	Withdrawal by Subject	11	5	3	7	3	4	6	4	4	0	0	0	0

Baseline characteristics

Characteristic	Cohort 1: PF-06882961 40 mg BID (1-week Titration)	Cohort 1: PF-06882961 80mg BID (1-week Titration)	Cohort 1: PF-06882961 120mg BID (1-week Titration)	Cohorts 1 and 2: PF-06882961 120 mg BID (2-week Titration)	Cohort 1: PF-06882961 160 mg BID (1-week Titration)	Cohorts 1 and 2: PF-06882961 160 mg BID (2-week Titration)	Cohort 1: PF-06882961 200 mg BID (1-week Titration)	Cohorts 1 and 2: Placebo	Cohorts 1 and 2: PF-06882961 200 mg BID (2-week Titration)	Cohort 3: Placebo	Cohort 3: PF-06882961 80mg BID (4-week Titration)	Cohort 3: PF-06882961 140mg BID (4-week Titration)	Cohort 3: PF-06882961 200mg BID (4-week Titration)	Total
Age, Customized 18-44 years	27 Participants	26 Participants	21 Participants	14 Participants	22 Participants	17 Participants	25 Participants	28 Participants	11 Participants	8 Participants	12 Participants	13 Participants	14 Participants	238 Participants
Age, Customized 45-64 years	31 Participants	30 Participants	36 Participants	17 Participants	34 Participants	20 Participants	31 Participants	34 Participants	20 Participants	9 Participants	24 Participants	24 Participants	19 Participants	329 Participants
Age, Customized Greater than or equal to (>=)65 years	4 Participants	7 Participants	7 Participants	7 Participants	7 Participants	0 Participants	7 Participants	9 Participants	5 Participants	2 Participants	1 Participants	0 Participants	3 Participants	59 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	7 Participants	8 Participants	7 Participants	3 Participants	2 Participants	4 Participants	2 Participants	6 Participants	5 Participants	0 Participants	2 Participants	3 Participants	2 Participants	51 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	55 Participants	54 Participants	56 Participants	34 Participants	61 Participants	33 Participants	60 Participants	65 Participants	30 Participants	19 Participants	34 Participants	34 Participants	34 Participants	569 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	1 Participants	1 Participants	1 Participants	0 Participants	0 Participants	1 Participants	0 Participants	1 Participants	0 Participants	1 Participants	0 Participants	0 Participants	6 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	1 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	2 Participants	4 Participants
Race (NIH/OMB) Asian	8 Participants	10 Participants	8 Participants	3 Participants	10 Participants	2 Participants	13 Participants	11 Participants	2 Participants	0 Participants	0 Participants	0 Participants	0 Participants	67 Participants
Race (NIH/OMB) Black or African American	4 Participants	10 Participants	11 Participants	4 Participants	8 Participants	5 Participants	5 Participants	4 Participants	3 Participants	3 Participants	8 Participants	6 Participants	5 Participants	76 Participants
Race (NIH/OMB) More than one race	1 Participants	0 Participants	0 Participants	0 Participants	2 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	3 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	2 Participants
Race (NIH/OMB) White	48 Participants	42 Participants	45 Participants	31 Participants	42 Participants	30 Participants	45 Participants	55 Participants	31 Participants	16 Participants	29 Participants	31 Participants	28 Participants	473 Participants
Sex: Female, Male Female	40 Participants	41 Participants	42 Participants	22 Participants	41 Participants	22 Participants	41 Participants	45 Participants	23 Participants	12 Participants	23 Participants	23 Participants	22 Participants	397 Participants
Sex: Female, Male Male	22 Participants	22 Participants	22 Participants	16 Participants	22 Participants	15 Participants	22 Participants	26 Participants	13 Participants	7 Participants	14 Participants	14 Participants	14 Participants	229 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk	EG006 affected / at risk	EG007 affected / at risk	EG008 affected / at risk	EG009 affected / at risk	EG010 affected / at risk	EG011 affected / at risk	EG012 affected / at risk
deaths Total, all-cause mortality	0 / 71	0 / 62	0 / 63	0 / 64	0 / 38	0 / 63	0 / 37	0 / 63	0 / 36	0 / 19	0 / 37	0 / 37	0 / 36
other Total, other adverse events	29 / 71	46 / 62	53 / 63	51 / 64	31 / 38	56 / 63	29 / 37	56 / 63	26 / 36	13 / 19	28 / 37	33 / 37	34 / 36
serious Total, serious adverse events	1 / 71	2 / 62	1 / 63	0 / 64	1 / 38	1 / 63	0 / 37	5 / 63	1 / 36	0 / 19	2 / 37	2 / 37	3 / 36

Outcome results

Primary

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

Population: Estimand Set 1 included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Cohorts 1 and 2: Placebo	Cohort 3: Percent Change From Baseline in Body Weight at End of Treatment at Week 32	1.40 Percent change	Standard Error 0.018
Cohort 1: PF-06882961 40mg BID (1-week Titration)	Cohort 3: Percent Change From Baseline in Body Weight at End of Treatment at Week 32	-6.92 Percent change	Standard Error 0.014
Cohort 1: PF-06882961 80mg BID (1-week Titration)	Cohort 3: Percent Change From Baseline in Body Weight at End of Treatment at Week 32	-7.15 Percent change	Standard Error 0.014
Cohort 1: PF-06882961 120mg BID (1-week Titration)	Cohort 3: Percent Change From Baseline in Body Weight at End of Treatment at Week 32	-11.65 Percent change	Standard Error 0.014

p-value: <0.000190% CI: [-11.66, -4.63]Mixed Models Analysis

p-value: <0.000190% CI: [-11.83, -4.92]Mixed Models Analysis

p-value: <0.000190% CI: [-16.15, -9.47]Mixed Models Analysis

Primary

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

Population: Estimand Set 1 included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Cohorts 1 and 2: Placebo	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at End of Treatment at Week 26	0.17 Percent change	Standard Error 0.008
Cohort 1: PF-06882961 40mg BID (1-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at End of Treatment at Week 26	-5.43 Percent change	Standard Error 0.009
Cohort 1: PF-06882961 80mg BID (1-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at End of Treatment at Week 26	-4.83 Percent change	Standard Error 0.009
Cohort 1: PF-06882961 120mg BID (1-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at End of Treatment at Week 26	-8.94 Percent change	Standard Error 0.009
Cohorts 1 and 2: PF-06882961 120 mg BID (2-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at End of Treatment at Week 26	-6.43 Percent change	Standard Error 0.012
Cohort 1: PF-06882961 160 mg BID (1-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at End of Treatment at Week 26	-9.36 Percent change	Standard Error 0.01
Cohorts 1 and 2: PF-06882961 160 mg BID (2-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at End of Treatment at Week 26	-6.96 Percent change	Standard Error 0.013
Cohort 1: PF-06882961 200 mg BID (1-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at End of Treatment at Week 26	-8.96 Percent change	Standard Error 0.011
Cohorts 1 and 2: PF-06882961 200 mg BID (2-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at End of Treatment at Week 26	-7.02 Percent change	Standard Error 0.012

p-value: <0.000190% CI: [-7.41, -3.74]Mixed Models Analysis

p-value: <0.000190% CI: [-6.8, -3.16]Mixed Models Analysis

p-value: <0.000190% CI: [-10.89, -7.28]Mixed Models Analysis

p-value: <0.000190% CI: [-8.75, -4.39]Mixed Models Analysis

p-value: <0.000190% CI: [-11.43, -7.56]Mixed Models Analysis

p-value: <0.000190% CI: [-9.41, -4.78]Mixed Models Analysis

p-value: <0.000190% CI: [-11.11, -7.08]Mixed Models Analysis

p-value: <0.000190% CI: [-9.32, -4.99]Mixed Models Analysis

Secondary

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)

Population: Safety analysis set included all participants randomly assigned to study intervention of the study and who took at least 1 dose of study intervention. Here, 'Number Analyzed' signifies participants evaluable for the specified rows.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Cohorts 1 and 2: Placebo	Cohort 1 and 2: Number of Participants With Scores on the Patient Health Questionnaire-9 (PHQ-9) Leading to Study Discontinuation	0 Participants
Cohort 1: PF-06882961 40mg BID (1-week Titration)	Cohort 1 and 2: Number of Participants With Scores on the Patient Health Questionnaire-9 (PHQ-9) Leading to Study Discontinuation	0 Participants
Cohort 1: PF-06882961 80mg BID (1-week Titration)	Cohort 1 and 2: Number of Participants With Scores on the Patient Health Questionnaire-9 (PHQ-9) Leading to Study Discontinuation	0 Participants
Cohort 1: PF-06882961 120mg BID (1-week Titration)	Cohort 1 and 2: Number of Participants With Scores on the Patient Health Questionnaire-9 (PHQ-9) Leading to Study Discontinuation	0 Participants
Cohorts 1 and 2: PF-06882961 120 mg BID (2-week Titration)	Cohort 1 and 2: Number of Participants With Scores on the Patient Health Questionnaire-9 (PHQ-9) Leading to Study Discontinuation	0 Participants
Cohort 1: PF-06882961 160 mg BID (1-week Titration)	Cohort 1 and 2: Number of Participants With Scores on the Patient Health Questionnaire-9 (PHQ-9) Leading to Study Discontinuation	0 Participants
Cohorts 1 and 2: PF-06882961 160 mg BID (2-week Titration)	Cohort 1 and 2: Number of Participants With Scores on the Patient Health Questionnaire-9 (PHQ-9) Leading to Study Discontinuation	0 Participants
Cohort 1: PF-06882961 200 mg BID (1-week Titration)	Cohort 1 and 2: Number of Participants With Scores on the Patient Health Questionnaire-9 (PHQ-9) Leading to Study Discontinuation	0 Participants
Cohorts 1 and 2: PF-06882961 200 mg BID (2-week Titration)	Cohort 1 and 2: Number of Participants With Scores on the Patient Health Questionnaire-9 (PHQ-9) Leading to Study Discontinuation	0 Participants

Secondary

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

Population: Estimand Set 1 included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Cohorts 1 and 2: Placebo	Cohort 3: Absolute Change From Baseline in FPG at Weeks 4, 8, 12, 16, 20, 24, 28, 32	Week 8	0.10 Milligram per deciliter	Standard Error 2.523
Cohorts 1 and 2: Placebo	Cohort 3: Absolute Change From Baseline in FPG at Weeks 4, 8, 12, 16, 20, 24, 28, 32	Week 24	-2.80 Milligram per deciliter	Standard Error 2.664
Cohorts 1 and 2: Placebo	Cohort 3: Absolute Change From Baseline in FPG at Weeks 4, 8, 12, 16, 20, 24, 28, 32	Week 20	1.52 Milligram per deciliter	Standard Error 2.175
Cohorts 1 and 2: Placebo	Cohort 3: Absolute Change From Baseline in FPG at Weeks 4, 8, 12, 16, 20, 24, 28, 32	Week 32	-1.81 Milligram per deciliter	Standard Error 3.006
Cohorts 1 and 2: Placebo	Cohort 3: Absolute Change From Baseline in FPG at Weeks 4, 8, 12, 16, 20, 24, 28, 32	Week 28	1.67 Milligram per deciliter	Standard Error 2.518
Cohorts 1 and 2: Placebo	Cohort 3: Absolute Change From Baseline in FPG at Weeks 4, 8, 12, 16, 20, 24, 28, 32	Week 12	-1.28 Milligram per deciliter	Standard Error 2.588
Cohorts 1 and 2: Placebo	Cohort 3: Absolute Change From Baseline in FPG at Weeks 4, 8, 12, 16, 20, 24, 28, 32	Week 4	-1.82 Milligram per deciliter	Standard Error 2.327
Cohorts 1 and 2: Placebo	Cohort 3: Absolute Change From Baseline in FPG at Weeks 4, 8, 12, 16, 20, 24, 28, 32	Week 16	-5.75 Milligram per deciliter	Standard Error 2.348
Cohort 1: PF-06882961 40mg BID (1-week Titration)	Cohort 3: Absolute Change From Baseline in FPG at Weeks 4, 8, 12, 16, 20, 24, 28, 32	Week 16	-5.18 Milligram per deciliter	Standard Error 1.778
Cohort 1: PF-06882961 40mg BID (1-week Titration)	Cohort 3: Absolute Change From Baseline in FPG at Weeks 4, 8, 12, 16, 20, 24, 28, 32	Week 28	-0.15 Milligram per deciliter	Standard Error 2.044
Cohort 1: PF-06882961 40mg BID (1-week Titration)	Cohort 3: Absolute Change From Baseline in FPG at Weeks 4, 8, 12, 16, 20, 24, 28, 32	Week 24	-0.13 Milligram per deciliter	Standard Error 2.088
Cohort 1: PF-06882961 40mg BID (1-week Titration)	Cohort 3: Absolute Change From Baseline in FPG at Weeks 4, 8, 12, 16, 20, 24, 28, 32	Week 20	-1.95 Milligram per deciliter	Standard Error 1.774
Cohort 1: PF-06882961 40mg BID (1-week Titration)	Cohort 3: Absolute Change From Baseline in FPG at Weeks 4, 8, 12, 16, 20, 24, 28, 32	Week 4	-0.83 Milligram per deciliter	Standard Error 1.652
Cohort 1: PF-06882961 40mg BID (1-week Titration)	Cohort 3: Absolute Change From Baseline in FPG at Weeks 4, 8, 12, 16, 20, 24, 28, 32	Week 32	1.28 Milligram per deciliter	Standard Error 2.491
Cohort 1: PF-06882961 40mg BID (1-week Titration)	Cohort 3: Absolute Change From Baseline in FPG at Weeks 4, 8, 12, 16, 20, 24, 28, 32	Week 12	-1.80 Milligram per deciliter	Standard Error 1.883
Cohort 1: PF-06882961 40mg BID (1-week Titration)	Cohort 3: Absolute Change From Baseline in FPG at Weeks 4, 8, 12, 16, 20, 24, 28, 32	Week 8	1.79 Milligram per deciliter	Standard Error 1.748
Cohort 1: PF-06882961 80mg BID (1-week Titration)	Cohort 3: Absolute Change From Baseline in FPG at Weeks 4, 8, 12, 16, 20, 24, 28, 32	Week 16	-2.43 Milligram per deciliter	Standard Error 1.654
Cohort 1: PF-06882961 80mg BID (1-week Titration)	Cohort 3: Absolute Change From Baseline in FPG at Weeks 4, 8, 12, 16, 20, 24, 28, 32	Week 4	0.96 Milligram per deciliter	Standard Error 1.616
Cohort 1: PF-06882961 80mg BID (1-week Titration)	Cohort 3: Absolute Change From Baseline in FPG at Weeks 4, 8, 12, 16, 20, 24, 28, 32	Week 8	-1.16 Milligram per deciliter	Standard Error 1.659
Cohort 1: PF-06882961 80mg BID (1-week Titration)	Cohort 3: Absolute Change From Baseline in FPG at Weeks 4, 8, 12, 16, 20, 24, 28, 32	Week 12	1.56 Milligram per deciliter	Standard Error 1.755
Cohort 1: PF-06882961 80mg BID (1-week Titration)	Cohort 3: Absolute Change From Baseline in FPG at Weeks 4, 8, 12, 16, 20, 24, 28, 32	Week 20	-4.78 Milligram per deciliter	Standard Error 1.687
Cohort 1: PF-06882961 80mg BID (1-week Titration)	Cohort 3: Absolute Change From Baseline in FPG at Weeks 4, 8, 12, 16, 20, 24, 28, 32	Week 24	-2.00 Milligram per deciliter	Standard Error 2.014
Cohort 1: PF-06882961 80mg BID (1-week Titration)	Cohort 3: Absolute Change From Baseline in FPG at Weeks 4, 8, 12, 16, 20, 24, 28, 32	Week 28	-4.53 Milligram per deciliter	Standard Error 1.983
Cohort 1: PF-06882961 80mg BID (1-week Titration)	Cohort 3: Absolute Change From Baseline in FPG at Weeks 4, 8, 12, 16, 20, 24, 28, 32	Week 32	-1.65 Milligram per deciliter	Standard Error 2.446
Cohort 1: PF-06882961 120mg BID (1-week Titration)	Cohort 3: Absolute Change From Baseline in FPG at Weeks 4, 8, 12, 16, 20, 24, 28, 32	Week 24	1.62 Milligram per deciliter	Standard Error 2.158
Cohort 1: PF-06882961 120mg BID (1-week Titration)	Cohort 3: Absolute Change From Baseline in FPG at Weeks 4, 8, 12, 16, 20, 24, 28, 32	Week 8	2.52 Milligram per deciliter	Standard Error 1.72
Cohort 1: PF-06882961 120mg BID (1-week Titration)	Cohort 3: Absolute Change From Baseline in FPG at Weeks 4, 8, 12, 16, 20, 24, 28, 32	Week 32	-1.73 Milligram per deciliter	Standard Error 2.582
Cohort 1: PF-06882961 120mg BID (1-week Titration)	Cohort 3: Absolute Change From Baseline in FPG at Weeks 4, 8, 12, 16, 20, 24, 28, 32	Week 28	0.90 Milligram per deciliter	Standard Error 2.221
Cohort 1: PF-06882961 120mg BID (1-week Titration)	Cohort 3: Absolute Change From Baseline in FPG at Weeks 4, 8, 12, 16, 20, 24, 28, 32	Week 4	3.84 Milligram per deciliter	Standard Error 1.671
Cohort 1: PF-06882961 120mg BID (1-week Titration)	Cohort 3: Absolute Change From Baseline in FPG at Weeks 4, 8, 12, 16, 20, 24, 28, 32	Week 20	-1.39 Milligram per deciliter	Standard Error 1.628
Cohort 1: PF-06882961 120mg BID (1-week Titration)	Cohort 3: Absolute Change From Baseline in FPG at Weeks 4, 8, 12, 16, 20, 24, 28, 32	Week 16	0.88 Milligram per deciliter	Standard Error 1.618
Cohort 1: PF-06882961 120mg BID (1-week Titration)	Cohort 3: Absolute Change From Baseline in FPG at Weeks 4, 8, 12, 16, 20, 24, 28, 32	Week 12	-0.42 Milligram per deciliter	Standard Error 1.761

Secondary

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

Population: Estimand Set 1 included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Cohorts 1 and 2: Placebo	Cohort 3: Absolute Change From Baseline in Percentage HbA1c at Weeks 16, 24 and 32	Week 16	-0.05 Percentage of HbA1c	Standard Error 0.061
Cohorts 1 and 2: Placebo	Cohort 3: Absolute Change From Baseline in Percentage HbA1c at Weeks 16, 24 and 32	Week 32	-0.02 Percentage of HbA1c	Standard Error 0.074
Cohorts 1 and 2: Placebo	Cohort 3: Absolute Change From Baseline in Percentage HbA1c at Weeks 16, 24 and 32	Week 24	0.05 Percentage of HbA1c	Standard Error 0.07
Cohort 1: PF-06882961 40mg BID (1-week Titration)	Cohort 3: Absolute Change From Baseline in Percentage HbA1c at Weeks 16, 24 and 32	Week 16	-0.16 Percentage of HbA1c	Standard Error 0.048
Cohort 1: PF-06882961 40mg BID (1-week Titration)	Cohort 3: Absolute Change From Baseline in Percentage HbA1c at Weeks 16, 24 and 32	Week 32	-0.11 Percentage of HbA1c	Standard Error 0.064
Cohort 1: PF-06882961 40mg BID (1-week Titration)	Cohort 3: Absolute Change From Baseline in Percentage HbA1c at Weeks 16, 24 and 32	Week 24	-0.13 Percentage of HbA1c	Standard Error 0.059
Cohort 1: PF-06882961 80mg BID (1-week Titration)	Cohort 3: Absolute Change From Baseline in Percentage HbA1c at Weeks 16, 24 and 32	Week 24	-0.21 Percentage of HbA1c	Standard Error 0.055
Cohort 1: PF-06882961 80mg BID (1-week Titration)	Cohort 3: Absolute Change From Baseline in Percentage HbA1c at Weeks 16, 24 and 32	Week 16	-0.26 Percentage of HbA1c	Standard Error 0.044
Cohort 1: PF-06882961 80mg BID (1-week Titration)	Cohort 3: Absolute Change From Baseline in Percentage HbA1c at Weeks 16, 24 and 32	Week 32	-0.27 Percentage of HbA1c	Standard Error 0.059
Cohort 1: PF-06882961 120mg BID (1-week Titration)	Cohort 3: Absolute Change From Baseline in Percentage HbA1c at Weeks 16, 24 and 32	Week 16	-0.29 Percentage of HbA1c	Standard Error 0.042
Cohort 1: PF-06882961 120mg BID (1-week Titration)	Cohort 3: Absolute Change From Baseline in Percentage HbA1c at Weeks 16, 24 and 32	Week 32	-0.41 Percentage of HbA1c	Standard Error 0.068
Cohort 1: PF-06882961 120mg BID (1-week Titration)	Cohort 3: Absolute Change From Baseline in Percentage HbA1c at Weeks 16, 24 and 32	Week 24	-0.31 Percentage of HbA1c	Standard Error 0.059

Secondary

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

Population: Estimand Set 1 included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Cohorts 1 and 2: Placebo	Cohort 3: Absolute Change From Baseline in Waist Circumference at End of Treatment at Week 32	0.19 Centimeter	Standard Error 1.967
Cohort 1: PF-06882961 40mg BID (1-week Titration)	Cohort 3: Absolute Change From Baseline in Waist Circumference at End of Treatment at Week 32	-6.27 Centimeter	Standard Error 1.628
Cohort 1: PF-06882961 80mg BID (1-week Titration)	Cohort 3: Absolute Change From Baseline in Waist Circumference at End of Treatment at Week 32	-7.77 Centimeter	Standard Error 1.564
Cohort 1: PF-06882961 120mg BID (1-week Titration)	Cohort 3: Absolute Change From Baseline in Waist Circumference at End of Treatment at Week 32	-11.43 Centimeter	Standard Error 1.698

Secondary

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

Population: Estimand Set 1 included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Cohorts 1 and 2: Placebo	Cohort 3: Absolute Change From Baseline in Waist-to-hip Ratio at End of Treatment at Week 32	0.010 Ratio	Standard Error 0.0128
Cohort 1: PF-06882961 40mg BID (1-week Titration)	Cohort 3: Absolute Change From Baseline in Waist-to-hip Ratio at End of Treatment at Week 32	-0.012 Ratio	Standard Error 0.0113
Cohort 1: PF-06882961 80mg BID (1-week Titration)	Cohort 3: Absolute Change From Baseline in Waist-to-hip Ratio at End of Treatment at Week 32	-0.009 Ratio	Standard Error 0.0108
Cohort 1: PF-06882961 120mg BID (1-week Titration)	Cohort 3: Absolute Change From Baseline in Waist-to-hip Ratio at End of Treatment at Week 32	-0.016 Ratio	Standard Error 0.0121

Secondary

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)

Population: Safety analysis set included all participants randomly assigned to study intervention of the study and who took at least 1 dose of study intervention. Here Overall Number of Participants Analyzed signifies participants who were evaluable for this outcome measure.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Cohorts 1 and 2: Placebo	Cohort 3: Number of Participants According to Categorization of ECG Parameters	QRS interval >=140	0 Participants
Cohorts 1 and 2: Placebo	Cohort 3: Number of Participants According to Categorization of ECG Parameters	PR interval >=300	0 Participants
Cohorts 1 and 2: Placebo	Cohort 3: Number of Participants According to Categorization of ECG Parameters	QTCF interval >500	0 Participants
Cohort 1: PF-06882961 40mg BID (1-week Titration)	Cohort 3: Number of Participants According to Categorization of ECG Parameters	QRS interval >=140	0 Participants
Cohort 1: PF-06882961 40mg BID (1-week Titration)	Cohort 3: Number of Participants According to Categorization of ECG Parameters	PR interval >=300	0 Participants
Cohort 1: PF-06882961 40mg BID (1-week Titration)	Cohort 3: Number of Participants According to Categorization of ECG Parameters	QTCF interval >500	0 Participants
Cohort 1: PF-06882961 80mg BID (1-week Titration)	Cohort 3: Number of Participants According to Categorization of ECG Parameters	QTCF interval >500	0 Participants
Cohort 1: PF-06882961 80mg BID (1-week Titration)	Cohort 3: Number of Participants According to Categorization of ECG Parameters	QRS interval >=140	0 Participants
Cohort 1: PF-06882961 80mg BID (1-week Titration)	Cohort 3: Number of Participants According to Categorization of ECG Parameters	PR interval >=300	0 Participants
Cohort 1: PF-06882961 120mg BID (1-week Titration)	Cohort 3: Number of Participants According to Categorization of ECG Parameters	QRS interval >=140	1 Participants
Cohort 1: PF-06882961 120mg BID (1-week Titration)	Cohort 3: Number of Participants According to Categorization of ECG Parameters	PR interval >=300	0 Participants
Cohort 1: PF-06882961 120mg BID (1-week Titration)	Cohort 3: Number of Participants According to Categorization of ECG Parameters	QTCF interval >500	0 Participants

Secondary

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)

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Cohorts 1 and 2: Placebo	Cohort 3: Number of Participants According to Categorization of Vital Signs Data	DBP Value < 50	0 Participants
Cohorts 1 and 2: Placebo	Cohort 3: Number of Participants According to Categorization of Vital Signs Data	SBP Value < 90	0 Participants
Cohorts 1 and 2: Placebo	Cohort 3: Number of Participants According to Categorization of Vital Signs Data	PR <40 beats per minute	0 Participants
Cohorts 1 and 2: Placebo	Cohort 3: Number of Participants According to Categorization of Vital Signs Data	PR >120 beats per minute	0 Participants
Cohort 1: PF-06882961 40mg BID (1-week Titration)	Cohort 3: Number of Participants According to Categorization of Vital Signs Data	SBP Value < 90	0 Participants
Cohort 1: PF-06882961 40mg BID (1-week Titration)	Cohort 3: Number of Participants According to Categorization of Vital Signs Data	PR <40 beats per minute	0 Participants
Cohort 1: PF-06882961 40mg BID (1-week Titration)	Cohort 3: Number of Participants According to Categorization of Vital Signs Data	PR >120 beats per minute	0 Participants
Cohort 1: PF-06882961 40mg BID (1-week Titration)	Cohort 3: Number of Participants According to Categorization of Vital Signs Data	DBP Value < 50	0 Participants
Cohort 1: PF-06882961 80mg BID (1-week Titration)	Cohort 3: Number of Participants According to Categorization of Vital Signs Data	PR <40 beats per minute	0 Participants
Cohort 1: PF-06882961 80mg BID (1-week Titration)	Cohort 3: Number of Participants According to Categorization of Vital Signs Data	SBP Value < 90	0 Participants
Cohort 1: PF-06882961 80mg BID (1-week Titration)	Cohort 3: Number of Participants According to Categorization of Vital Signs Data	PR >120 beats per minute	0 Participants
Cohort 1: PF-06882961 80mg BID (1-week Titration)	Cohort 3: Number of Participants According to Categorization of Vital Signs Data	DBP Value < 50	1 Participants
Cohort 1: PF-06882961 120mg BID (1-week Titration)	Cohort 3: Number of Participants According to Categorization of Vital Signs Data	PR >120 beats per minute	0 Participants
Cohort 1: PF-06882961 120mg BID (1-week Titration)	Cohort 3: Number of Participants According to Categorization of Vital Signs Data	SBP Value < 90	0 Participants
Cohort 1: PF-06882961 120mg BID (1-week Titration)	Cohort 3: Number of Participants According to Categorization of Vital Signs Data	DBP Value < 50	0 Participants
Cohort 1: PF-06882961 120mg BID (1-week Titration)	Cohort 3: Number of Participants According to Categorization of Vital Signs Data	PR <40 beats per minute	0 Participants

Secondary

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

Population: Estimand Set 1 included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Here, Number of Participants analyzed signifies number of participants evaluable for this outcome measure.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Cohorts 1 and 2: Placebo	Cohort 3: Number of Participants With >=5% Body Weight Loss at End of Treatment	0 Participants
Cohort 1: PF-06882961 40mg BID (1-week Titration)	Cohort 3: Number of Participants With >=5% Body Weight Loss at End of Treatment	9 Participants
Cohort 1: PF-06882961 80mg BID (1-week Titration)	Cohort 3: Number of Participants With >=5% Body Weight Loss at End of Treatment	11 Participants
Cohort 1: PF-06882961 120mg BID (1-week Titration)	Cohort 3: Number of Participants With >=5% Body Weight Loss at End of Treatment	10 Participants

90% CI: [3.1, 373.85]

90% CI: [10.55, 1533.46]

90% CI: [3.05, 366.64]

Secondary

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)

Population: Safety analysis set included all participants randomly assigned to study intervention of the study and who took at least 1 dose of study intervention. Here, Number of Participants analyzed signifies number of participants evaluable for this outcome measure.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Cohorts 1 and 2: Placebo	Cohort 3: Number of Participants With Categorical Scores on C-SSRS Leading to Study Discontinuation	0 Participants
Cohort 1: PF-06882961 40mg BID (1-week Titration)	Cohort 3: Number of Participants With Categorical Scores on C-SSRS Leading to Study Discontinuation	0 Participants
Cohort 1: PF-06882961 80mg BID (1-week Titration)	Cohort 3: Number of Participants With Categorical Scores on C-SSRS Leading to Study Discontinuation	0 Participants
Cohort 1: PF-06882961 120mg BID (1-week Titration)	Cohort 3: Number of Participants With Categorical Scores on C-SSRS Leading to Study Discontinuation	0 Participants

Secondary

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)

Population: Safety analysis set included all participants randomly assigned to study intervention of the study and who took at least 1 dose of study intervention. Here Number of Participants Analyzed signifies participants who were evaluable for this outcome measure.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Cohorts 1 and 2: Placebo	Cohort 3: Number of Participants With Laboratory Abnormalities, Without Regard to Baseline Abnormality	15 Participants
Cohort 1: PF-06882961 40mg BID (1-week Titration)	Cohort 3: Number of Participants With Laboratory Abnormalities, Without Regard to Baseline Abnormality	31 Participants
Cohort 1: PF-06882961 80mg BID (1-week Titration)	Cohort 3: Number of Participants With Laboratory Abnormalities, Without Regard to Baseline Abnormality	34 Participants
Cohort 1: PF-06882961 120mg BID (1-week Titration)	Cohort 3: Number of Participants With Laboratory Abnormalities, Without Regard to Baseline Abnormality	32 Participants

Secondary

Cohort 3: Number of Participants With Scores on the PHQ-9 Leading to Study Discontinuation

Time frame: Week 0 (Baseline), 4, 8, 12, 16, 20, 24, 28, 32, Follow-up (Week 37)

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Cohorts 1 and 2: Placebo	Cohort 3: Number of Participants With Scores on the PHQ-9 Leading to Study Discontinuation	0 Participants
Cohort 1: PF-06882961 40mg BID (1-week Titration)	Cohort 3: Number of Participants With Scores on the PHQ-9 Leading to Study Discontinuation	0 Participants
Cohort 1: PF-06882961 80mg BID (1-week Titration)	Cohort 3: Number of Participants With Scores on the PHQ-9 Leading to Study Discontinuation	0 Participants
Cohort 1: PF-06882961 120mg BID (1-week Titration)	Cohort 3: Number of Participants With Scores on the PHQ-9 Leading to Study Discontinuation	0 Participants

Secondary

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)

Population: Safety analysis set included all participants randomly assigned to study intervention of the study and who took at least 1 dose of study intervention.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Cohorts 1 and 2: Placebo	Cohort 3: Number of Participants With TEAEs and TESAEs	TEAEs	13 Participants
Cohorts 1 and 2: Placebo	Cohort 3: Number of Participants With TEAEs and TESAEs	TESAEs	0 Participants
Cohort 1: PF-06882961 40mg BID (1-week Titration)	Cohort 3: Number of Participants With TEAEs and TESAEs	TEAEs	30 Participants
Cohort 1: PF-06882961 40mg BID (1-week Titration)	Cohort 3: Number of Participants With TEAEs and TESAEs	TESAEs	2 Participants
Cohort 1: PF-06882961 80mg BID (1-week Titration)	Cohort 3: Number of Participants With TEAEs and TESAEs	TESAEs	2 Participants
Cohort 1: PF-06882961 80mg BID (1-week Titration)	Cohort 3: Number of Participants With TEAEs and TESAEs	TEAEs	34 Participants
Cohort 1: PF-06882961 120mg BID (1-week Titration)	Cohort 3: Number of Participants With TEAEs and TESAEs	TEAEs	34 Participants
Cohort 1: PF-06882961 120mg BID (1-week Titration)	Cohort 3: Number of Participants With TEAEs and TESAEs	TESAEs	3 Participants

Secondary

Cohort 3: Percent Change From Baseline in Body Weight at Weeks 4, 8, 12, 16, 20, 24 and 28

Time frame: Baseline, Weeks 4, 8, 12, 16, 20, 24 and 28

Population: Estimand Set 1 included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Cohorts 1 and 2: Placebo	Cohort 3: Percent Change From Baseline in Body Weight at Weeks 4, 8, 12, 16, 20, 24 and 28	Week 24	0.36 Percent Change	Standard Error 0.015
Cohorts 1 and 2: Placebo	Cohort 3: Percent Change From Baseline in Body Weight at Weeks 4, 8, 12, 16, 20, 24 and 28	Week 16	0.03 Percent Change	Standard Error 0.011
Cohorts 1 and 2: Placebo	Cohort 3: Percent Change From Baseline in Body Weight at Weeks 4, 8, 12, 16, 20, 24 and 28	Week 28	1.06 Percent Change	Standard Error 0.017
Cohorts 1 and 2: Placebo	Cohort 3: Percent Change From Baseline in Body Weight at Weeks 4, 8, 12, 16, 20, 24 and 28	Week 20	0.38 Percent Change	Standard Error 0.014
Cohorts 1 and 2: Placebo	Cohort 3: Percent Change From Baseline in Body Weight at Weeks 4, 8, 12, 16, 20, 24 and 28	Week 8	-0.06 Percent Change	Standard Error 0.006
Cohorts 1 and 2: Placebo	Cohort 3: Percent Change From Baseline in Body Weight at Weeks 4, 8, 12, 16, 20, 24 and 28	Week 4	-0.37 Percent Change	Standard Error 0.004
Cohorts 1 and 2: Placebo	Cohort 3: Percent Change From Baseline in Body Weight at Weeks 4, 8, 12, 16, 20, 24 and 28	Week 12	-0.08 Percent Change	Standard Error 0.008
Cohort 1: PF-06882961 40mg BID (1-week Titration)	Cohort 3: Percent Change From Baseline in Body Weight at Weeks 4, 8, 12, 16, 20, 24 and 28	Week 4	-1.38 Percent Change	Standard Error 0.003
Cohort 1: PF-06882961 40mg BID (1-week Titration)	Cohort 3: Percent Change From Baseline in Body Weight at Weeks 4, 8, 12, 16, 20, 24 and 28	Week 8	-2.07 Percent Change	Standard Error 0.004
Cohort 1: PF-06882961 40mg BID (1-week Titration)	Cohort 3: Percent Change From Baseline in Body Weight at Weeks 4, 8, 12, 16, 20, 24 and 28	Week 16	-4.13 Percent Change	Standard Error 0.008
Cohort 1: PF-06882961 40mg BID (1-week Titration)	Cohort 3: Percent Change From Baseline in Body Weight at Weeks 4, 8, 12, 16, 20, 24 and 28	Week 24	-5.65 Percent Change	Standard Error 0.011
Cohort 1: PF-06882961 40mg BID (1-week Titration)	Cohort 3: Percent Change From Baseline in Body Weight at Weeks 4, 8, 12, 16, 20, 24 and 28	Week 28	-6.37 Percent Change	Standard Error 0.013
Cohort 1: PF-06882961 40mg BID (1-week Titration)	Cohort 3: Percent Change From Baseline in Body Weight at Weeks 4, 8, 12, 16, 20, 24 and 28	Week 12	-2.80 Percent Change	Standard Error 0.006
Cohort 1: PF-06882961 40mg BID (1-week Titration)	Cohort 3: Percent Change From Baseline in Body Weight at Weeks 4, 8, 12, 16, 20, 24 and 28	Week 20	-5.17 Percent Change	Standard Error 0.01
Cohort 1: PF-06882961 80mg BID (1-week Titration)	Cohort 3: Percent Change From Baseline in Body Weight at Weeks 4, 8, 12, 16, 20, 24 and 28	Week 20	-5.25 Percent Change	Standard Error 0.009
Cohort 1: PF-06882961 80mg BID (1-week Titration)	Cohort 3: Percent Change From Baseline in Body Weight at Weeks 4, 8, 12, 16, 20, 24 and 28	Week 24	-6.39 Percent Change	Standard Error 0.011
Cohort 1: PF-06882961 80mg BID (1-week Titration)	Cohort 3: Percent Change From Baseline in Body Weight at Weeks 4, 8, 12, 16, 20, 24 and 28	Week 8	-1.93 Percent Change	Standard Error 0.004
Cohort 1: PF-06882961 80mg BID (1-week Titration)	Cohort 3: Percent Change From Baseline in Body Weight at Weeks 4, 8, 12, 16, 20, 24 and 28	Week 12	-2.88 Percent Change	Standard Error 0.005
Cohort 1: PF-06882961 80mg BID (1-week Titration)	Cohort 3: Percent Change From Baseline in Body Weight at Weeks 4, 8, 12, 16, 20, 24 and 28	Week 16	-3.99 Percent Change	Standard Error 0.007
Cohort 1: PF-06882961 80mg BID (1-week Titration)	Cohort 3: Percent Change From Baseline in Body Weight at Weeks 4, 8, 12, 16, 20, 24 and 28	Week 4	-0.95 Percent Change	Standard Error 0.003
Cohort 1: PF-06882961 80mg BID (1-week Titration)	Cohort 3: Percent Change From Baseline in Body Weight at Weeks 4, 8, 12, 16, 20, 24 and 28	Week 28	-6.74 Percent Change	Standard Error 0.012
Cohort 1: PF-06882961 120mg BID (1-week Titration)	Cohort 3: Percent Change From Baseline in Body Weight at Weeks 4, 8, 12, 16, 20, 24 and 28	Week 28	-10.44 Percent Change	Standard Error 0.013
Cohort 1: PF-06882961 120mg BID (1-week Titration)	Cohort 3: Percent Change From Baseline in Body Weight at Weeks 4, 8, 12, 16, 20, 24 and 28	Week 24	-9.20 Percent Change	Standard Error 0.011
Cohort 1: PF-06882961 120mg BID (1-week Titration)	Cohort 3: Percent Change From Baseline in Body Weight at Weeks 4, 8, 12, 16, 20, 24 and 28	Week 4	-1.02 Percent Change	Standard Error 0.003
Cohort 1: PF-06882961 120mg BID (1-week Titration)	Cohort 3: Percent Change From Baseline in Body Weight at Weeks 4, 8, 12, 16, 20, 24 and 28	Week 8	-1.89 Percent Change	Standard Error 0.004
Cohort 1: PF-06882961 120mg BID (1-week Titration)	Cohort 3: Percent Change From Baseline in Body Weight at Weeks 4, 8, 12, 16, 20, 24 and 28	Week 12	-2.96 Percent Change	Standard Error 0.006
Cohort 1: PF-06882961 120mg BID (1-week Titration)	Cohort 3: Percent Change From Baseline in Body Weight at Weeks 4, 8, 12, 16, 20, 24 and 28	Week 16	-4.73 Percent Change	Standard Error 0.008
Cohort 1: PF-06882961 120mg BID (1-week Titration)	Cohort 3: Percent Change From Baseline in Body Weight at Weeks 4, 8, 12, 16, 20, 24 and 28	Week 20	-7.10 Percent Change	Standard Error 0.01

Secondary

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

Time frame: Baseline, Weeks 2, 4, 6, 8, 10, 12, 16, 18, 22, 26

Population: Estimand Set 1 included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Cohorts 1 and 2: Placebo	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	Week 16	0.50 Milligram per deciliter	Standard Error 1.352
Cohorts 1 and 2: Placebo	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	Week 26	3.34 Milligram per deciliter	Standard Error 1.22
Cohorts 1 and 2: Placebo	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	Week 22	4.83 Milligram per deciliter	Standard Error 1.494
Cohorts 1 and 2: Placebo	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	Week 4	3.38 Milligram per deciliter	Standard Error 1.082
Cohorts 1 and 2: Placebo	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	Week 8	1.61 Milligram per deciliter	Standard Error 0.956
Cohorts 1 and 2: Placebo	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	Week 18	4.34 Milligram per deciliter	Standard Error 1.407
Cohorts 1 and 2: Placebo	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	Week 10	2.47 Milligram per deciliter	Standard Error 1.146
Cohorts 1 and 2: Placebo	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	Week 12	2.57 Milligram per deciliter	Standard Error 1.229
Cohorts 1 and 2: Placebo	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	Week 2	3.22 Milligram per deciliter	Standard Error 0.903
Cohorts 1 and 2: Placebo	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	Week 6	1.45 Milligram per deciliter	Standard Error 0.936
Cohort 1: PF-06882961 40mg BID (1-week Titration)	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	Week 22	0.38 Milligram per deciliter	Standard Error 1.872
Cohort 1: PF-06882961 40mg BID (1-week Titration)	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	Week 10	-2.52 Milligram per deciliter	Standard Error 1.264
Cohort 1: PF-06882961 40mg BID (1-week Titration)	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	Week 12	-2.70 Milligram per deciliter	Standard Error 1.408
Cohort 1: PF-06882961 40mg BID (1-week Titration)	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	Week 26	-3.37 Milligram per deciliter	Standard Error 1.499
Cohort 1: PF-06882961 40mg BID (1-week Titration)	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	Week 4	-2.75 Milligram per deciliter	Standard Error 1.196
Cohort 1: PF-06882961 40mg BID (1-week Titration)	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	Week 6	-4.28 Milligram per deciliter	Standard Error 1.021
Cohort 1: PF-06882961 40mg BID (1-week Titration)	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	Week 18	-0.44 Milligram per deciliter	Standard Error 1.634
Cohort 1: PF-06882961 40mg BID (1-week Titration)	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	Week 8	-3.72 Milligram per deciliter	Standard Error 1.068
Cohort 1: PF-06882961 40mg BID (1-week Titration)	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	Week 2	-2.93 Milligram per deciliter	Standard Error 0.963
Cohort 1: PF-06882961 40mg BID (1-week Titration)	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	Week 16	-2.67 Milligram per deciliter	Standard Error 1.523
Cohort 1: PF-06882961 80mg BID (1-week Titration)	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	Week 22	-3.22 Milligram per deciliter	Standard Error 1.712
Cohort 1: PF-06882961 80mg BID (1-week Titration)	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	Week 26	-3.43 Milligram per deciliter	Standard Error 1.469
Cohort 1: PF-06882961 80mg BID (1-week Titration)	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	Week 6	-2.29 Milligram per deciliter	Standard Error 1.035
Cohort 1: PF-06882961 80mg BID (1-week Titration)	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	Week 18	-3.73 Milligram per deciliter	Standard Error 1.593
Cohort 1: PF-06882961 80mg BID (1-week Titration)	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	Week 10	-1.79 Milligram per deciliter	Standard Error 1.251
Cohort 1: PF-06882961 80mg BID (1-week Titration)	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	Week 2	-2.56 Milligram per deciliter	Standard Error 0.939
Cohort 1: PF-06882961 80mg BID (1-week Titration)	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	Week 16	-2.04 Milligram per deciliter	Standard Error 1.537
Cohort 1: PF-06882961 80mg BID (1-week Titration)	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	Week 8	-3.15 Milligram per deciliter	Standard Error 1.103
Cohort 1: PF-06882961 80mg BID (1-week Titration)	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	Week 4	-2.97 Milligram per deciliter	Standard Error 1.166
Cohort 1: PF-06882961 80mg BID (1-week Titration)	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	Week 12	-0.77 Milligram per deciliter	Standard Error 1.377
Cohort 1: PF-06882961 120mg BID (1-week Titration)	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	Week 4	-3.59 Milligram per deciliter	Standard Error 1.155
Cohort 1: PF-06882961 120mg BID (1-week Titration)	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	Week 12	-2.24 Milligram per deciliter	Standard Error 1.492
Cohort 1: PF-06882961 120mg BID (1-week Titration)	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	Week 18	0.19 Milligram per deciliter	Standard Error 1.77
Cohort 1: PF-06882961 120mg BID (1-week Titration)	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	Week 16	-2.56 Milligram per deciliter	Standard Error 1.619
Cohort 1: PF-06882961 120mg BID (1-week Titration)	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	Week 8	-2.56 Milligram per deciliter	Standard Error 1.13
Cohort 1: PF-06882961 120mg BID (1-week Titration)	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	Week 10	-4.74 Milligram per deciliter	Standard Error 1.353
Cohort 1: PF-06882961 120mg BID (1-week Titration)	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	Week 6	-6.38 Milligram per deciliter	Standard Error 1.044
Cohort 1: PF-06882961 120mg BID (1-week Titration)	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	Week 2	-4.02 Milligram per deciliter	Standard Error 0.94
Cohort 1: PF-06882961 120mg BID (1-week Titration)	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	Week 26	-4.02 Milligram per deciliter	Standard Error 1.555
Cohort 1: PF-06882961 120mg BID (1-week Titration)	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	Week 22	-4.27 Milligram per deciliter	Standard Error 1.842
Cohorts 1 and 2: PF-06882961 120 mg BID (2-week Titration)	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	Week 22	-1.78 Milligram per deciliter	Standard Error 2.502
Cohorts 1 and 2: PF-06882961 120 mg BID (2-week Titration)	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	Week 12	-1.22 Milligram per deciliter	Standard Error 1.889
Cohorts 1 and 2: PF-06882961 120 mg BID (2-week Titration)	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	Week 26	-3.75 Milligram per deciliter	Standard Error 2.059
Cohorts 1 and 2: PF-06882961 120 mg BID (2-week Titration)	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	Week 2	-2.02 Milligram per deciliter	Standard Error 1.245
Cohorts 1 and 2: PF-06882961 120 mg BID (2-week Titration)	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	Week 4	-0.83 Milligram per deciliter	Standard Error 1.443
Cohorts 1 and 2: PF-06882961 120 mg BID (2-week Titration)	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	Week 6	-4.17 Milligram per deciliter	Standard Error 1.29
Cohorts 1 and 2: PF-06882961 120 mg BID (2-week Titration)	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	Week 8	-2.77 Milligram per deciliter	Standard Error 1.385
Cohorts 1 and 2: PF-06882961 120 mg BID (2-week Titration)	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	Week 10	-2.60 Milligram per deciliter	Standard Error 1.662
Cohorts 1 and 2: PF-06882961 120 mg BID (2-week Titration)	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	Week 16	-6.99 Milligram per deciliter	Standard Error 2.143
Cohorts 1 and 2: PF-06882961 120 mg BID (2-week Titration)	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	Week 18	-0.96 Milligram per deciliter	Standard Error 2.294
Cohort 1: PF-06882961 160 mg BID (1-week Titration)	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	Week 6	-3.46 Milligram per deciliter	Standard Error 1.102
Cohort 1: PF-06882961 160 mg BID (1-week Titration)	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	Week 16	-6.62 Milligram per deciliter	Standard Error 1.926
Cohort 1: PF-06882961 160 mg BID (1-week Titration)	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	Week 26	-6.00 Milligram per deciliter	Standard Error 1.804
Cohort 1: PF-06882961 160 mg BID (1-week Titration)	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	Week 12	-4.86 Milligram per deciliter	Standard Error 1.686
Cohort 1: PF-06882961 160 mg BID (1-week Titration)	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	Week 2	-4.51 Milligram per deciliter	Standard Error 0.957
Cohort 1: PF-06882961 160 mg BID (1-week Titration)	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	Week 22	-2.03 Milligram per deciliter	Standard Error 2.205
Cohort 1: PF-06882961 160 mg BID (1-week Titration)	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	Week 4	-4.81 Milligram per deciliter	Standard Error 1.199
Cohort 1: PF-06882961 160 mg BID (1-week Titration)	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	Week 10	-4.17 Milligram per deciliter	Standard Error 1.498
Cohort 1: PF-06882961 160 mg BID (1-week Titration)	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	Week 8	-4.48 Milligram per deciliter	Standard Error 1.177
Cohort 1: PF-06882961 160 mg BID (1-week Titration)	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	Week 18	-4.76 Milligram per deciliter	Standard Error 2.03
Cohorts 1 and 2: PF-06882961 160 mg BID (2-week Titration)	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	Week 10	-5.26 Milligram per deciliter	Standard Error 1.702
Cohorts 1 and 2: PF-06882961 160 mg BID (2-week Titration)	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	Week 8	-4.07 Milligram per deciliter	Standard Error 1.438
Cohorts 1 and 2: PF-06882961 160 mg BID (2-week Titration)	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	Week 16	-5.73 Milligram per deciliter	Standard Error 2.338
Cohorts 1 and 2: PF-06882961 160 mg BID (2-week Titration)	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	Week 6	-3.06 Milligram per deciliter	Standard Error 1.371
Cohorts 1 and 2: PF-06882961 160 mg BID (2-week Titration)	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	Week 18	-5.23 Milligram per deciliter	Standard Error 2.684
Cohorts 1 and 2: PF-06882961 160 mg BID (2-week Titration)	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	Week 4	-2.56 Milligram per deciliter	Standard Error 1.504
Cohorts 1 and 2: PF-06882961 160 mg BID (2-week Titration)	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	Week 22	-1.65 Milligram per deciliter	Standard Error 2.888
Cohorts 1 and 2: PF-06882961 160 mg BID (2-week Titration)	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	Week 2	-1.16 Milligram per deciliter	Standard Error 1.265
Cohorts 1 and 2: PF-06882961 160 mg BID (2-week Titration)	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	Week 12	-4.65 Milligram per deciliter	Standard Error 1.908
Cohorts 1 and 2: PF-06882961 160 mg BID (2-week Titration)	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	Week 26	-3.50 Milligram per deciliter	Standard Error 2.29
Cohort 1: PF-06882961 200 mg BID (1-week Titration)	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	Week 10	-5.35 Milligram per deciliter	Standard Error 1.525
Cohort 1: PF-06882961 200 mg BID (1-week Titration)	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	Week 22	-4.64 Milligram per deciliter	Standard Error 2.46
Cohort 1: PF-06882961 200 mg BID (1-week Titration)	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	Week 8	-4.90 Milligram per deciliter	Standard Error 1.248
Cohort 1: PF-06882961 200 mg BID (1-week Titration)	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	Week 16	-4.67 Milligram per deciliter	Standard Error 2.011
Cohort 1: PF-06882961 200 mg BID (1-week Titration)	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	Week 18	0.11 Milligram per deciliter	Standard Error 2.175
Cohort 1: PF-06882961 200 mg BID (1-week Titration)	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	Week 6	-4.32 Milligram per deciliter	Standard Error 1.095
Cohort 1: PF-06882961 200 mg BID (1-week Titration)	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	Week 12	-3.01 Milligram per deciliter	Standard Error 1.716
Cohort 1: PF-06882961 200 mg BID (1-week Titration)	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	Week 26	-6.60 Milligram per deciliter	Standard Error 2.01
Cohort 1: PF-06882961 200 mg BID (1-week Titration)	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	Week 2	-2.82 Milligram per deciliter	Standard Error 0.939
Cohort 1: PF-06882961 200 mg BID (1-week Titration)	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	Week 4	-6.24 Milligram per deciliter	Standard Error 1.164
Cohorts 1 and 2: PF-06882961 200 mg BID (2-week Titration)	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	Week 26	-5.01 Milligram per deciliter	Standard Error 2.172
Cohorts 1 and 2: PF-06882961 200 mg BID (2-week Titration)	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	Week 22	-5.08 Milligram per deciliter	Standard Error 2.58
Cohorts 1 and 2: PF-06882961 200 mg BID (2-week Titration)	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	Week 18	0.53 Milligram per deciliter	Standard Error 2.189
Cohorts 1 and 2: PF-06882961 200 mg BID (2-week Titration)	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	Week 2	-2.93 Milligram per deciliter	Standard Error 1.25
Cohorts 1 and 2: PF-06882961 200 mg BID (2-week Titration)	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	Week 12	-3.19 Milligram per deciliter	Standard Error 1.764
Cohorts 1 and 2: PF-06882961 200 mg BID (2-week Titration)	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	Week 8	-2.82 Milligram per deciliter	Standard Error 1.367
Cohorts 1 and 2: PF-06882961 200 mg BID (2-week Titration)	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	Week 10	-2.85 Milligram per deciliter	Standard Error 1.558
Cohorts 1 and 2: PF-06882961 200 mg BID (2-week Titration)	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	Week 16	-5.24 Milligram per deciliter	Standard Error 2.097
Cohorts 1 and 2: PF-06882961 200 mg BID (2-week Titration)	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	Week 4	-3.86 Milligram per deciliter	Standard Error 1.485
Cohorts 1 and 2: PF-06882961 200 mg BID (2-week Titration)	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	Week 6	-4.64 Milligram per deciliter	Standard Error 1.311

Secondary

Cohorts 1 and 2: Absolute Change From Baseline in Percentage Hemoglobin A1c (HbA1c) at Weeks 16 and 26

Time frame: Baseline, Weeks 16 and 26

Population: Estimand Set 1 included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Cohorts 1 and 2: Placebo	Cohorts 1 and 2: Absolute Change From Baseline in Percentage Hemoglobin A1c (HbA1c) at Weeks 16 and 26	Week 16	0.00 Percentage of HbA1c	Standard Error 0.034
Cohorts 1 and 2: Placebo	Cohorts 1 and 2: Absolute Change From Baseline in Percentage Hemoglobin A1c (HbA1c) at Weeks 16 and 26	Week 26	0.01 Percentage of HbA1c	Standard Error 0.036
Cohort 1: PF-06882961 40mg BID (1-week Titration)	Cohorts 1 and 2: Absolute Change From Baseline in Percentage Hemoglobin A1c (HbA1c) at Weeks 16 and 26	Week 26	-0.17 Percentage of HbA1c	Standard Error 0.045
Cohort 1: PF-06882961 40mg BID (1-week Titration)	Cohorts 1 and 2: Absolute Change From Baseline in Percentage Hemoglobin A1c (HbA1c) at Weeks 16 and 26	Week 16	-0.24 Percentage of HbA1c	Standard Error 0.039
Cohort 1: PF-06882961 80mg BID (1-week Titration)	Cohorts 1 and 2: Absolute Change From Baseline in Percentage Hemoglobin A1c (HbA1c) at Weeks 16 and 26	Week 26	-0.13 Percentage of HbA1c	Standard Error 0.044
Cohort 1: PF-06882961 80mg BID (1-week Titration)	Cohorts 1 and 2: Absolute Change From Baseline in Percentage Hemoglobin A1c (HbA1c) at Weeks 16 and 26	Week 16	-0.24 Percentage of HbA1c	Standard Error 0.039
Cohort 1: PF-06882961 120mg BID (1-week Titration)	Cohorts 1 and 2: Absolute Change From Baseline in Percentage Hemoglobin A1c (HbA1c) at Weeks 16 and 26	Week 16	-0.26 Percentage of HbA1c	Standard Error 0.042
Cohort 1: PF-06882961 120mg BID (1-week Titration)	Cohorts 1 and 2: Absolute Change From Baseline in Percentage Hemoglobin A1c (HbA1c) at Weeks 16 and 26	Week 26	-0.22 Percentage of HbA1c	Standard Error 0.046
Cohorts 1 and 2: PF-06882961 120 mg BID (2-week Titration)	Cohorts 1 and 2: Absolute Change From Baseline in Percentage Hemoglobin A1c (HbA1c) at Weeks 16 and 26	Week 26	-0.16 Percentage of HbA1c	Standard Error 0.064
Cohorts 1 and 2: PF-06882961 120 mg BID (2-week Titration)	Cohorts 1 and 2: Absolute Change From Baseline in Percentage Hemoglobin A1c (HbA1c) at Weeks 16 and 26	Week 16	-0.25 Percentage of HbA1c	Standard Error 0.056
Cohort 1: PF-06882961 160 mg BID (1-week Titration)	Cohorts 1 and 2: Absolute Change From Baseline in Percentage Hemoglobin A1c (HbA1c) at Weeks 16 and 26	Week 16	-0.29 Percentage of HbA1c	Standard Error 0.05
Cohort 1: PF-06882961 160 mg BID (1-week Titration)	Cohorts 1 and 2: Absolute Change From Baseline in Percentage Hemoglobin A1c (HbA1c) at Weeks 16 and 26	Week 26	-0.31 Percentage of HbA1c	Standard Error 0.055
Cohorts 1 and 2: PF-06882961 160 mg BID (2-week Titration)	Cohorts 1 and 2: Absolute Change From Baseline in Percentage Hemoglobin A1c (HbA1c) at Weeks 16 and 26	Week 26	-0.13 Percentage of HbA1c	Standard Error 0.07
Cohorts 1 and 2: PF-06882961 160 mg BID (2-week Titration)	Cohorts 1 and 2: Absolute Change From Baseline in Percentage Hemoglobin A1c (HbA1c) at Weeks 16 and 26	Week 16	-0.18 Percentage of HbA1c	Standard Error 0.061
Cohort 1: PF-06882961 200 mg BID (1-week Titration)	Cohorts 1 and 2: Absolute Change From Baseline in Percentage Hemoglobin A1c (HbA1c) at Weeks 16 and 26	Week 16	-0.23 Percentage of HbA1c	Standard Error 0.053
Cohort 1: PF-06882961 200 mg BID (1-week Titration)	Cohorts 1 and 2: Absolute Change From Baseline in Percentage Hemoglobin A1c (HbA1c) at Weeks 16 and 26	Week 26	-0.17 Percentage of HbA1c	Standard Error 0.062
Cohorts 1 and 2: PF-06882961 200 mg BID (2-week Titration)	Cohorts 1 and 2: Absolute Change From Baseline in Percentage Hemoglobin A1c (HbA1c) at Weeks 16 and 26	Week 26	-0.26 Percentage of HbA1c	Standard Error 0.064
Cohorts 1 and 2: PF-06882961 200 mg BID (2-week Titration)	Cohorts 1 and 2: Absolute Change From Baseline in Percentage Hemoglobin A1c (HbA1c) at Weeks 16 and 26	Week 16	-0.24 Percentage of HbA1c	Standard Error 0.054

Secondary

Cohorts 1 and 2: Absolute Change From Baseline in Waist Circumference at End of Treatment at Week 26

Time frame: Baseline, Week 26

Population: Estimand Set 1 included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Cohorts 1 and 2: Placebo	Cohorts 1 and 2: Absolute Change From Baseline in Waist Circumference at End of Treatment at Week 26	-1.25 Centimeter	Standard Error 0.826
Cohort 1: PF-06882961 40mg BID (1-week Titration)	Cohorts 1 and 2: Absolute Change From Baseline in Waist Circumference at End of Treatment at Week 26	-6.49 Centimeter	Standard Error 0.995
Cohort 1: PF-06882961 80mg BID (1-week Titration)	Cohorts 1 and 2: Absolute Change From Baseline in Waist Circumference at End of Treatment at Week 26	-5.75 Centimeter	Standard Error 0.943
Cohort 1: PF-06882961 120mg BID (1-week Titration)	Cohorts 1 and 2: Absolute Change From Baseline in Waist Circumference at End of Treatment at Week 26	-6.19 Centimeter	Standard Error 1.023
Cohorts 1 and 2: PF-06882961 120 mg BID (2-week Titration)	Cohorts 1 and 2: Absolute Change From Baseline in Waist Circumference at End of Treatment at Week 26	-5.98 Centimeter	Standard Error 1.338
Cohort 1: PF-06882961 160 mg BID (1-week Titration)	Cohorts 1 and 2: Absolute Change From Baseline in Waist Circumference at End of Treatment at Week 26	-9.05 Centimeter	Standard Error 1.174
Cohorts 1 and 2: PF-06882961 160 mg BID (2-week Titration)	Cohorts 1 and 2: Absolute Change From Baseline in Waist Circumference at End of Treatment at Week 26	-7.41 Centimeter	Standard Error 1.49
Cohort 1: PF-06882961 200 mg BID (1-week Titration)	Cohorts 1 and 2: Absolute Change From Baseline in Waist Circumference at End of Treatment at Week 26	-7.56 Centimeter	Standard Error 1.281
Cohorts 1 and 2: PF-06882961 200 mg BID (2-week Titration)	Cohorts 1 and 2: Absolute Change From Baseline in Waist Circumference at End of Treatment at Week 26	-6.36 Centimeter	Standard Error 1.35

Secondary

Cohorts 1 and 2: Absolute Change From Baseline in Waist-to-hip Ratio at End of Treatment at Week 26

Time frame: Baseline, Week 26

Population: Estimand Set 1 included all participants randomly assigned to study intervention in Part A and who took at least 1 dose of study intervention.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Cohorts 1 and 2: Placebo	Cohorts 1 and 2: Absolute Change From Baseline in Waist-to-hip Ratio at End of Treatment at Week 26	-0.002 Ratio	Standard Error 0.0064
Cohort 1: PF-06882961 40mg BID (1-week Titration)	Cohorts 1 and 2: Absolute Change From Baseline in Waist-to-hip Ratio at End of Treatment at Week 26	-0.002 Ratio	Standard Error 0.0076
Cohort 1: PF-06882961 80mg BID (1-week Titration)	Cohorts 1 and 2: Absolute Change From Baseline in Waist-to-hip Ratio at End of Treatment at Week 26	-0.015 Ratio	Standard Error 0.0073
Cohort 1: PF-06882961 120mg BID (1-week Titration)	Cohorts 1 and 2: Absolute Change From Baseline in Waist-to-hip Ratio at End of Treatment at Week 26	0.001 Ratio	Standard Error 0.0078
Cohorts 1 and 2: PF-06882961 120 mg BID (2-week Titration)	Cohorts 1 and 2: Absolute Change From Baseline in Waist-to-hip Ratio at End of Treatment at Week 26	-0.014 Ratio	Standard Error 0.0104
Cohort 1: PF-06882961 160 mg BID (1-week Titration)	Cohorts 1 and 2: Absolute Change From Baseline in Waist-to-hip Ratio at End of Treatment at Week 26	-0.015 Ratio	Standard Error 0.009
Cohorts 1 and 2: PF-06882961 160 mg BID (2-week Titration)	Cohorts 1 and 2: Absolute Change From Baseline in Waist-to-hip Ratio at End of Treatment at Week 26	-0.014 Ratio	Standard Error 0.0114
Cohort 1: PF-06882961 200 mg BID (1-week Titration)	Cohorts 1 and 2: Absolute Change From Baseline in Waist-to-hip Ratio at End of Treatment at Week 26	-0.007 Ratio	Standard Error 0.0098
Cohorts 1 and 2: PF-06882961 200 mg BID (2-week Titration)	Cohorts 1 and 2: Absolute Change From Baseline in Waist-to-hip Ratio at End of Treatment at Week 26	0.004 Ratio	Standard Error 0.0104

Secondary

Cohorts 1 and 2: Number of Participants According to Categorization of Electrocardiogram (ECG) Parameters

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)

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Cohorts 1 and 2: Placebo	Cohorts 1 and 2: Number of Participants According to Categorization of Electrocardiogram (ECG) Parameters	PR interval >=300	0 Participants
Cohorts 1 and 2: Placebo	Cohorts 1 and 2: Number of Participants According to Categorization of Electrocardiogram (ECG) Parameters	QTCF interval >500	0 Participants
Cohorts 1 and 2: Placebo	Cohorts 1 and 2: Number of Participants According to Categorization of Electrocardiogram (ECG) Parameters	QRS interval >=140	0 Participants
Cohort 1: PF-06882961 40mg BID (1-week Titration)	Cohorts 1 and 2: Number of Participants According to Categorization of Electrocardiogram (ECG) Parameters	PR interval >=300	0 Participants
Cohort 1: PF-06882961 40mg BID (1-week Titration)	Cohorts 1 and 2: Number of Participants According to Categorization of Electrocardiogram (ECG) Parameters	QTCF interval >500	0 Participants
Cohort 1: PF-06882961 40mg BID (1-week Titration)	Cohorts 1 and 2: Number of Participants According to Categorization of Electrocardiogram (ECG) Parameters	QRS interval >=140	0 Participants
Cohort 1: PF-06882961 80mg BID (1-week Titration)	Cohorts 1 and 2: Number of Participants According to Categorization of Electrocardiogram (ECG) Parameters	QTCF interval >500	0 Participants
Cohort 1: PF-06882961 80mg BID (1-week Titration)	Cohorts 1 and 2: Number of Participants According to Categorization of Electrocardiogram (ECG) Parameters	QRS interval >=140	1 Participants
Cohort 1: PF-06882961 80mg BID (1-week Titration)	Cohorts 1 and 2: Number of Participants According to Categorization of Electrocardiogram (ECG) Parameters	PR interval >=300	0 Participants
Cohort 1: PF-06882961 120mg BID (1-week Titration)	Cohorts 1 and 2: Number of Participants According to Categorization of Electrocardiogram (ECG) Parameters	PR interval >=300	0 Participants
Cohort 1: PF-06882961 120mg BID (1-week Titration)	Cohorts 1 and 2: Number of Participants According to Categorization of Electrocardiogram (ECG) Parameters	QRS interval >=140	0 Participants
Cohort 1: PF-06882961 120mg BID (1-week Titration)	Cohorts 1 and 2: Number of Participants According to Categorization of Electrocardiogram (ECG) Parameters	QTCF interval >500	0 Participants
Cohorts 1 and 2: PF-06882961 120 mg BID (2-week Titration)	Cohorts 1 and 2: Number of Participants According to Categorization of Electrocardiogram (ECG) Parameters	QRS interval >=140	0 Participants
Cohorts 1 and 2: PF-06882961 120 mg BID (2-week Titration)	Cohorts 1 and 2: Number of Participants According to Categorization of Electrocardiogram (ECG) Parameters	PR interval >=300	0 Participants
Cohorts 1 and 2: PF-06882961 120 mg BID (2-week Titration)	Cohorts 1 and 2: Number of Participants According to Categorization of Electrocardiogram (ECG) Parameters	QTCF interval >500	0 Participants
Cohort 1: PF-06882961 160 mg BID (1-week Titration)	Cohorts 1 and 2: Number of Participants According to Categorization of Electrocardiogram (ECG) Parameters	QRS interval >=140	1 Participants
Cohort 1: PF-06882961 160 mg BID (1-week Titration)	Cohorts 1 and 2: Number of Participants According to Categorization of Electrocardiogram (ECG) Parameters	QTCF interval >500	0 Participants
Cohort 1: PF-06882961 160 mg BID (1-week Titration)	Cohorts 1 and 2: Number of Participants According to Categorization of Electrocardiogram (ECG) Parameters	PR interval >=300	0 Participants
Cohorts 1 and 2: PF-06882961 160 mg BID (2-week Titration)	Cohorts 1 and 2: Number of Participants According to Categorization of Electrocardiogram (ECG) Parameters	PR interval >=300	0 Participants
Cohorts 1 and 2: PF-06882961 160 mg BID (2-week Titration)	Cohorts 1 and 2: Number of Participants According to Categorization of Electrocardiogram (ECG) Parameters	QTCF interval >500	0 Participants
Cohorts 1 and 2: PF-06882961 160 mg BID (2-week Titration)	Cohorts 1 and 2: Number of Participants According to Categorization of Electrocardiogram (ECG) Parameters	QRS interval >=140	0 Participants
Cohort 1: PF-06882961 200 mg BID (1-week Titration)	Cohorts 1 and 2: Number of Participants According to Categorization of Electrocardiogram (ECG) Parameters	QTCF interval >500	0 Participants
Cohort 1: PF-06882961 200 mg BID (1-week Titration)	Cohorts 1 and 2: Number of Participants According to Categorization of Electrocardiogram (ECG) Parameters	QRS interval >=140	0 Participants
Cohort 1: PF-06882961 200 mg BID (1-week Titration)	Cohorts 1 and 2: Number of Participants According to Categorization of Electrocardiogram (ECG) Parameters	PR interval >=300	0 Participants
Cohorts 1 and 2: PF-06882961 200 mg BID (2-week Titration)	Cohorts 1 and 2: Number of Participants According to Categorization of Electrocardiogram (ECG) Parameters	QRS interval >=140	0 Participants
Cohorts 1 and 2: PF-06882961 200 mg BID (2-week Titration)	Cohorts 1 and 2: Number of Participants According to Categorization of Electrocardiogram (ECG) Parameters	PR interval >=300	0 Participants
Cohorts 1 and 2: PF-06882961 200 mg BID (2-week Titration)	Cohorts 1 and 2: Number of Participants According to Categorization of Electrocardiogram (ECG) Parameters	QTCF interval >500	0 Participants

Secondary

Cohorts 1 and 2: Number of Participants According to Categorization of Vital Signs Data

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)

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Cohorts 1 and 2: Placebo	Cohorts 1 and 2: Number of Participants According to Categorization of Vital Signs Data	DBP Value < 50	0 Participants
Cohorts 1 and 2: Placebo	Cohorts 1 and 2: Number of Participants According to Categorization of Vital Signs Data	PR <40 beats per minute	0 Participants
Cohorts 1 and 2: Placebo	Cohorts 1 and 2: Number of Participants According to Categorization of Vital Signs Data	PR >120 beats per minute	0 Participants
Cohorts 1 and 2: Placebo	Cohorts 1 and 2: Number of Participants According to Categorization of Vital Signs Data	SBP Value < 90	0 Participants
Cohort 1: PF-06882961 40mg BID (1-week Titration)	Cohorts 1 and 2: Number of Participants According to Categorization of Vital Signs Data	PR <40 beats per minute	0 Participants
Cohort 1: PF-06882961 40mg BID (1-week Titration)	Cohorts 1 and 2: Number of Participants According to Categorization of Vital Signs Data	SBP Value < 90	0 Participants
Cohort 1: PF-06882961 40mg BID (1-week Titration)	Cohorts 1 and 2: Number of Participants According to Categorization of Vital Signs Data	PR >120 beats per minute	0 Participants
Cohort 1: PF-06882961 40mg BID (1-week Titration)	Cohorts 1 and 2: Number of Participants According to Categorization of Vital Signs Data	DBP Value < 50	0 Participants
Cohort 1: PF-06882961 80mg BID (1-week Titration)	Cohorts 1 and 2: Number of Participants According to Categorization of Vital Signs Data	PR <40 beats per minute	0 Participants
Cohort 1: PF-06882961 80mg BID (1-week Titration)	Cohorts 1 and 2: Number of Participants According to Categorization of Vital Signs Data	DBP Value < 50	1 Participants
Cohort 1: PF-06882961 80mg BID (1-week Titration)	Cohorts 1 and 2: Number of Participants According to Categorization of Vital Signs Data	PR >120 beats per minute	0 Participants
Cohort 1: PF-06882961 80mg BID (1-week Titration)	Cohorts 1 and 2: Number of Participants According to Categorization of Vital Signs Data	SBP Value < 90	1 Participants
Cohort 1: PF-06882961 120mg BID (1-week Titration)	Cohorts 1 and 2: Number of Participants According to Categorization of Vital Signs Data	DBP Value < 50	0 Participants
Cohort 1: PF-06882961 120mg BID (1-week Titration)	Cohorts 1 and 2: Number of Participants According to Categorization of Vital Signs Data	PR <40 beats per minute	0 Participants
Cohort 1: PF-06882961 120mg BID (1-week Titration)	Cohorts 1 and 2: Number of Participants According to Categorization of Vital Signs Data	SBP Value < 90	0 Participants
Cohort 1: PF-06882961 120mg BID (1-week Titration)	Cohorts 1 and 2: Number of Participants According to Categorization of Vital Signs Data	PR >120 beats per minute	0 Participants
Cohorts 1 and 2: PF-06882961 120 mg BID (2-week Titration)	Cohorts 1 and 2: Number of Participants According to Categorization of Vital Signs Data	PR >120 beats per minute	0 Participants
Cohorts 1 and 2: PF-06882961 120 mg BID (2-week Titration)	Cohorts 1 and 2: Number of Participants According to Categorization of Vital Signs Data	PR <40 beats per minute	0 Participants
Cohorts 1 and 2: PF-06882961 120 mg BID (2-week Titration)	Cohorts 1 and 2: Number of Participants According to Categorization of Vital Signs Data	SBP Value < 90	1 Participants
Cohorts 1 and 2: PF-06882961 120 mg BID (2-week Titration)	Cohorts 1 and 2: Number of Participants According to Categorization of Vital Signs Data	DBP Value < 50	0 Participants
Cohort 1: PF-06882961 160 mg BID (1-week Titration)	Cohorts 1 and 2: Number of Participants According to Categorization of Vital Signs Data	DBP Value < 50	0 Participants
Cohort 1: PF-06882961 160 mg BID (1-week Titration)	Cohorts 1 and 2: Number of Participants According to Categorization of Vital Signs Data	SBP Value < 90	2 Participants
Cohort 1: PF-06882961 160 mg BID (1-week Titration)	Cohorts 1 and 2: Number of Participants According to Categorization of Vital Signs Data	PR >120 beats per minute	0 Participants
Cohort 1: PF-06882961 160 mg BID (1-week Titration)	Cohorts 1 and 2: Number of Participants According to Categorization of Vital Signs Data	PR <40 beats per minute	0 Participants
Cohorts 1 and 2: PF-06882961 160 mg BID (2-week Titration)	Cohorts 1 and 2: Number of Participants According to Categorization of Vital Signs Data	PR <40 beats per minute	0 Participants
Cohorts 1 and 2: PF-06882961 160 mg BID (2-week Titration)	Cohorts 1 and 2: Number of Participants According to Categorization of Vital Signs Data	DBP Value < 50	0 Participants
Cohorts 1 and 2: PF-06882961 160 mg BID (2-week Titration)	Cohorts 1 and 2: Number of Participants According to Categorization of Vital Signs Data	SBP Value < 90	1 Participants
Cohorts 1 and 2: PF-06882961 160 mg BID (2-week Titration)	Cohorts 1 and 2: Number of Participants According to Categorization of Vital Signs Data	PR >120 beats per minute	0 Participants
Cohort 1: PF-06882961 200 mg BID (1-week Titration)	Cohorts 1 and 2: Number of Participants According to Categorization of Vital Signs Data	SBP Value < 90	0 Participants
Cohort 1: PF-06882961 200 mg BID (1-week Titration)	Cohorts 1 and 2: Number of Participants According to Categorization of Vital Signs Data	PR <40 beats per minute	0 Participants
Cohort 1: PF-06882961 200 mg BID (1-week Titration)	Cohorts 1 and 2: Number of Participants According to Categorization of Vital Signs Data	DBP Value < 50	0 Participants
Cohort 1: PF-06882961 200 mg BID (1-week Titration)	Cohorts 1 and 2: Number of Participants According to Categorization of Vital Signs Data	PR >120 beats per minute	0 Participants
Cohorts 1 and 2: PF-06882961 200 mg BID (2-week Titration)	Cohorts 1 and 2: Number of Participants According to Categorization of Vital Signs Data	PR >120 beats per minute	0 Participants
Cohorts 1 and 2: PF-06882961 200 mg BID (2-week Titration)	Cohorts 1 and 2: Number of Participants According to Categorization of Vital Signs Data	SBP Value < 90	0 Participants
Cohorts 1 and 2: PF-06882961 200 mg BID (2-week Titration)	Cohorts 1 and 2: Number of Participants According to Categorization of Vital Signs Data	PR <40 beats per minute	0 Participants
Cohorts 1 and 2: PF-06882961 200 mg BID (2-week Titration)	Cohorts 1 and 2: Number of Participants According to Categorization of Vital Signs Data	DBP Value < 50	0 Participants

Secondary

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

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Cohorts 1 and 2: Placebo	Cohorts 1 and 2: Number of Participants With >= 5% Body Weight Loss at End of Treatment	6 Participants
Cohort 1: PF-06882961 40mg BID (1-week Titration)	Cohorts 1 and 2: Number of Participants With >= 5% Body Weight Loss at End of Treatment	16 Participants
Cohort 1: PF-06882961 80mg BID (1-week Titration)	Cohorts 1 and 2: Number of Participants With >= 5% Body Weight Loss at End of Treatment	15 Participants
Cohort 1: PF-06882961 120mg BID (1-week Titration)	Cohorts 1 and 2: Number of Participants With >= 5% Body Weight Loss at End of Treatment	17 Participants
Cohorts 1 and 2: PF-06882961 120 mg BID (2-week Titration)	Cohorts 1 and 2: Number of Participants With >= 5% Body Weight Loss at End of Treatment	12 Participants
Cohort 1: PF-06882961 160 mg BID (1-week Titration)	Cohorts 1 and 2: Number of Participants With >= 5% Body Weight Loss at End of Treatment	15 Participants
Cohorts 1 and 2: PF-06882961 160 mg BID (2-week Titration)	Cohorts 1 and 2: Number of Participants With >= 5% Body Weight Loss at End of Treatment	6 Participants
Cohort 1: PF-06882961 200 mg BID (1-week Titration)	Cohorts 1 and 2: Number of Participants With >= 5% Body Weight Loss at End of Treatment	12 Participants
Cohorts 1 and 2: PF-06882961 200 mg BID (2-week Titration)	Cohorts 1 and 2: Number of Participants With >= 5% Body Weight Loss at End of Treatment	8 Participants

90% CI: [8.28, 71.95]

90% CI: [4.56, 35.08]

90% CI: [2.81, 19.3]

Comparison: Logistic regression models (included terms for treatment, strata \[females versus males\] and baseline body weight as a covariate) were applied to the imputed datasets from the multiple imputation method above and parameter estimates were combined using standard multiple imputation techniques.90% CI: [2.62, 16.53]

90% CI: [5.39, 37.66]

90% CI: [11.35, 80.2]

90% CI: [2.91, 33.53]

Secondary

Cohorts 1 and 2: Number of Participants With Categorical Scores on Columbia-Suicide Severity Rating Scale (C-SSRS) Leading to Study Discontinuation

Time frame: Week 0 (Baseline), 2, 4, 6, 8, 10, 12, 16, 18, 22, 26, Follow-up (Week 31)

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Cohorts 1 and 2: Placebo	Cohorts 1 and 2: Number of Participants With Categorical Scores on Columbia-Suicide Severity Rating Scale (C-SSRS) Leading to Study Discontinuation	0 Participants
Cohort 1: PF-06882961 40mg BID (1-week Titration)	Cohorts 1 and 2: Number of Participants With Categorical Scores on Columbia-Suicide Severity Rating Scale (C-SSRS) Leading to Study Discontinuation	0 Participants
Cohort 1: PF-06882961 80mg BID (1-week Titration)	Cohorts 1 and 2: Number of Participants With Categorical Scores on Columbia-Suicide Severity Rating Scale (C-SSRS) Leading to Study Discontinuation	0 Participants
Cohort 1: PF-06882961 120mg BID (1-week Titration)	Cohorts 1 and 2: Number of Participants With Categorical Scores on Columbia-Suicide Severity Rating Scale (C-SSRS) Leading to Study Discontinuation	0 Participants
Cohorts 1 and 2: PF-06882961 120 mg BID (2-week Titration)	Cohorts 1 and 2: Number of Participants With Categorical Scores on Columbia-Suicide Severity Rating Scale (C-SSRS) Leading to Study Discontinuation	0 Participants
Cohort 1: PF-06882961 160 mg BID (1-week Titration)	Cohorts 1 and 2: Number of Participants With Categorical Scores on Columbia-Suicide Severity Rating Scale (C-SSRS) Leading to Study Discontinuation	0 Participants
Cohorts 1 and 2: PF-06882961 160 mg BID (2-week Titration)	Cohorts 1 and 2: Number of Participants With Categorical Scores on Columbia-Suicide Severity Rating Scale (C-SSRS) Leading to Study Discontinuation	0 Participants
Cohort 1: PF-06882961 200 mg BID (1-week Titration)	Cohorts 1 and 2: Number of Participants With Categorical Scores on Columbia-Suicide Severity Rating Scale (C-SSRS) Leading to Study Discontinuation	0 Participants
Cohorts 1 and 2: PF-06882961 200 mg BID (2-week Titration)	Cohorts 1 and 2: Number of Participants With Categorical Scores on Columbia-Suicide Severity Rating Scale (C-SSRS) Leading to Study Discontinuation	0 Participants

Secondary

Cohorts 1 and 2: Number of Participants With Laboratory Abnormalities, Without Regard to Baseline Abnormality

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)

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Cohorts 1 and 2: Placebo	Cohorts 1 and 2: Number of Participants With Laboratory Abnormalities, Without Regard to Baseline Abnormality	66 Participants
Cohort 1: PF-06882961 40mg BID (1-week Titration)	Cohorts 1 and 2: Number of Participants With Laboratory Abnormalities, Without Regard to Baseline Abnormality	56 Participants
Cohort 1: PF-06882961 80mg BID (1-week Titration)	Cohorts 1 and 2: Number of Participants With Laboratory Abnormalities, Without Regard to Baseline Abnormality	60 Participants
Cohort 1: PF-06882961 120mg BID (1-week Titration)	Cohorts 1 and 2: Number of Participants With Laboratory Abnormalities, Without Regard to Baseline Abnormality	57 Participants
Cohorts 1 and 2: PF-06882961 120 mg BID (2-week Titration)	Cohorts 1 and 2: Number of Participants With Laboratory Abnormalities, Without Regard to Baseline Abnormality	37 Participants
Cohort 1: PF-06882961 160 mg BID (1-week Titration)	Cohorts 1 and 2: Number of Participants With Laboratory Abnormalities, Without Regard to Baseline Abnormality	54 Participants
Cohorts 1 and 2: PF-06882961 160 mg BID (2-week Titration)	Cohorts 1 and 2: Number of Participants With Laboratory Abnormalities, Without Regard to Baseline Abnormality	33 Participants
Cohort 1: PF-06882961 200 mg BID (1-week Titration)	Cohorts 1 and 2: Number of Participants With Laboratory Abnormalities, Without Regard to Baseline Abnormality	59 Participants
Cohorts 1 and 2: PF-06882961 200 mg BID (2-week Titration)	Cohorts 1 and 2: Number of Participants With Laboratory Abnormalities, Without Regard to Baseline Abnormality	33 Participants

Secondary

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)

Population: Safety analysis set included all participants randomly assigned to study intervention of the study and who took at least 1 dose of study intervention.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Cohorts 1 and 2: Placebo	Cohorts 1 and 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious AEs (TESAEs)	TEAEs	50 Participants
Cohorts 1 and 2: Placebo	Cohorts 1 and 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious AEs (TESAEs)	TESAEs	1 Participants
Cohort 1: PF-06882961 40mg BID (1-week Titration)	Cohorts 1 and 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious AEs (TESAEs)	TESAEs	2 Participants
Cohort 1: PF-06882961 40mg BID (1-week Titration)	Cohorts 1 and 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious AEs (TESAEs)	TEAEs	52 Participants
Cohort 1: PF-06882961 80mg BID (1-week Titration)	Cohorts 1 and 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious AEs (TESAEs)	TEAEs	59 Participants
Cohort 1: PF-06882961 80mg BID (1-week Titration)	Cohorts 1 and 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious AEs (TESAEs)	TESAEs	1 Participants
Cohort 1: PF-06882961 120mg BID (1-week Titration)	Cohorts 1 and 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious AEs (TESAEs)	TESAEs	0 Participants
Cohort 1: PF-06882961 120mg BID (1-week Titration)	Cohorts 1 and 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious AEs (TESAEs)	TEAEs	54 Participants
Cohorts 1 and 2: PF-06882961 120 mg BID (2-week Titration)	Cohorts 1 and 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious AEs (TESAEs)	TESAEs	1 Participants
Cohorts 1 and 2: PF-06882961 120 mg BID (2-week Titration)	Cohorts 1 and 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious AEs (TESAEs)	TEAEs	32 Participants
Cohort 1: PF-06882961 160 mg BID (1-week Titration)	Cohorts 1 and 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious AEs (TESAEs)	TESAEs	1 Participants
Cohort 1: PF-06882961 160 mg BID (1-week Titration)	Cohorts 1 and 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious AEs (TESAEs)	TEAEs	59 Participants
Cohorts 1 and 2: PF-06882961 160 mg BID (2-week Titration)	Cohorts 1 and 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious AEs (TESAEs)	TEAEs	30 Participants
Cohorts 1 and 2: PF-06882961 160 mg BID (2-week Titration)	Cohorts 1 and 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious AEs (TESAEs)	TESAEs	0 Participants
Cohort 1: PF-06882961 200 mg BID (1-week Titration)	Cohorts 1 and 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious AEs (TESAEs)	TESAEs	5 Participants
Cohort 1: PF-06882961 200 mg BID (1-week Titration)	Cohorts 1 and 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious AEs (TESAEs)	TEAEs	59 Participants
Cohorts 1 and 2: PF-06882961 200 mg BID (2-week Titration)	Cohorts 1 and 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious AEs (TESAEs)	TESAEs	1 Participants
Cohorts 1 and 2: PF-06882961 200 mg BID (2-week Titration)	Cohorts 1 and 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious AEs (TESAEs)	TEAEs	30 Participants

Secondary

Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22

Time frame: Baseline, Weeks 2, 4, 6, 8, 10, 12,16, 18, 22

Population: Estimand Set 1 included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Cohorts 1 and 2: Placebo	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 22	-0.18 Percent Change	Standard Error 0.007
Cohorts 1 and 2: Placebo	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 12	-0.44 Percent Change	Standard Error 0.004
Cohorts 1 and 2: Placebo	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 4	-0.15 Percent Change	Standard Error 0.002
Cohorts 1 and 2: Placebo	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 18	-0.50 Percent Change	Standard Error 0.006
Cohorts 1 and 2: Placebo	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 2	-0.13 Percent Change	Standard Error 0.001
Cohorts 1 and 2: Placebo	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 6	-0.24 Percent Change	Standard Error 0.003
Cohorts 1 and 2: Placebo	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 16	-0.40 Percent Change	Standard Error 0.005
Cohorts 1 and 2: Placebo	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 10	-0.50 Percent Change	Standard Error 0.004
Cohorts 1 and 2: Placebo	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 8	-0.41 Percent Change	Standard Error 0.003
Cohort 1: PF-06882961 40mg BID (1-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 8	-2.93 Percent Change	Standard Error 0.003
Cohort 1: PF-06882961 40mg BID (1-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 6	-2.26 Percent Change	Standard Error 0.003
Cohort 1: PF-06882961 40mg BID (1-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 2	-0.85 Percent Change	Standard Error 0.001
Cohort 1: PF-06882961 40mg BID (1-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 22	-5.06 Percent Change	Standard Error 0.008
Cohort 1: PF-06882961 40mg BID (1-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 16	-4.73 Percent Change	Standard Error 0.006
Cohort 1: PF-06882961 40mg BID (1-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 12	-3.89 Percent Change	Standard Error 0.005
Cohort 1: PF-06882961 40mg BID (1-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 4	-1.65 Percent Change	Standard Error 0.002
Cohort 1: PF-06882961 40mg BID (1-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 18	-4.94 Percent Change	Standard Error 0.006
Cohort 1: PF-06882961 40mg BID (1-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 10	-3.47 Percent Change	Standard Error 0.004
Cohort 1: PF-06882961 80mg BID (1-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 10	-3.33 Percent Change	Standard Error 0.004
Cohort 1: PF-06882961 80mg BID (1-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 2	-0.54 Percent Change	Standard Error 0.001
Cohort 1: PF-06882961 80mg BID (1-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 4	-1.69 Percent Change	Standard Error 0.002
Cohort 1: PF-06882961 80mg BID (1-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 6	-2.37 Percent Change	Standard Error 0.003
Cohort 1: PF-06882961 80mg BID (1-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 8	-2.86 Percent Change	Standard Error 0.003
Cohort 1: PF-06882961 80mg BID (1-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 12	-3.88 Percent Change	Standard Error 0.004
Cohort 1: PF-06882961 80mg BID (1-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 16	-4.01 Percent Change	Standard Error 0.006
Cohort 1: PF-06882961 80mg BID (1-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 18	-4.68 Percent Change	Standard Error 0.006
Cohort 1: PF-06882961 80mg BID (1-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 22	-5.00 Percent Change	Standard Error 0.007
Cohort 1: PF-06882961 120mg BID (1-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 22	-8.10 Percent Change	Standard Error 0.008
Cohort 1: PF-06882961 120mg BID (1-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 8	-3.89 Percent Change	Standard Error 0.003
Cohort 1: PF-06882961 120mg BID (1-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 16	-6.98 Percent Change	Standard Error 0.006
Cohort 1: PF-06882961 120mg BID (1-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 6	-2.96 Percent Change	Standard Error 0.003
Cohort 1: PF-06882961 120mg BID (1-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 2	-0.98 Percent Change	Standard Error 0.001
Cohort 1: PF-06882961 120mg BID (1-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 4	-1.99 Percent Change	Standard Error 0.002
Cohort 1: PF-06882961 120mg BID (1-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 10	-4.82 Percent Change	Standard Error 0.004
Cohort 1: PF-06882961 120mg BID (1-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 18	-7.33 Percent Change	Standard Error 0.007
Cohort 1: PF-06882961 120mg BID (1-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 12	-5.31 Percent Change	Standard Error 0.005
Cohorts 1 and 2: PF-06882961 120 mg BID (2-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 2	-0.58 Percent Change	Standard Error 0.002
Cohorts 1 and 2: PF-06882961 120 mg BID (2-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 22	-6.43 Percent Change	Standard Error 0.01
Cohorts 1 and 2: PF-06882961 120 mg BID (2-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 4	-1.26 Percent Change	Standard Error 0.003
Cohorts 1 and 2: PF-06882961 120 mg BID (2-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 12	-4.49 Percent Change	Standard Error 0.006
Cohorts 1 and 2: PF-06882961 120 mg BID (2-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 10	-3.92 Percent Change	Standard Error 0.005
Cohorts 1 and 2: PF-06882961 120 mg BID (2-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 16	-5.49 Percent Change	Standard Error 0.008
Cohorts 1 and 2: PF-06882961 120 mg BID (2-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 18	-6.33 Percent Change	Standard Error 0.008
Cohorts 1 and 2: PF-06882961 120 mg BID (2-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 8	-3.33 Percent Change	Standard Error 0.004
Cohorts 1 and 2: PF-06882961 120 mg BID (2-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 6	-1.99 Percent Change	Standard Error 0.003
Cohort 1: PF-06882961 160 mg BID (1-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 18	-7.50 Percent Change	Standard Error 0.007
Cohort 1: PF-06882961 160 mg BID (1-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 12	-5.66 Percent Change	Standard Error 0.005
Cohort 1: PF-06882961 160 mg BID (1-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 4	-1.71 Percent Change	Standard Error 0.002
Cohort 1: PF-06882961 160 mg BID (1-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 8	-3.87 Percent Change	Standard Error 0.004
Cohort 1: PF-06882961 160 mg BID (1-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 16	-7.04 Percent Change	Standard Error 0.007
Cohort 1: PF-06882961 160 mg BID (1-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 2	-0.87 Percent Change	Standard Error 0.001
Cohort 1: PF-06882961 160 mg BID (1-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 22	-8.63 Percent Change	Standard Error 0.009
Cohort 1: PF-06882961 160 mg BID (1-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 10	-4.67 Percent Change	Standard Error 0.004
Cohort 1: PF-06882961 160 mg BID (1-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 6	-2.84 Percent Change	Standard Error 0.003
Cohorts 1 and 2: PF-06882961 160 mg BID (2-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 6	-1.93 Percent Change	Standard Error 0.004
Cohorts 1 and 2: PF-06882961 160 mg BID (2-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 4	-0.93 Percent Change	Standard Error 0.003
Cohorts 1 and 2: PF-06882961 160 mg BID (2-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 8	-2.34 Percent Change	Standard Error 0.004
Cohorts 1 and 2: PF-06882961 160 mg BID (2-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 10	-3.20 Percent Change	Standard Error 0.005
Cohorts 1 and 2: PF-06882961 160 mg BID (2-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 12	-3.98 Percent Change	Standard Error 0.006
Cohorts 1 and 2: PF-06882961 160 mg BID (2-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 2	-0.22 Percent Change	Standard Error 0.002
Cohorts 1 and 2: PF-06882961 160 mg BID (2-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 16	-5.15 Percent Change	Standard Error 0.008
Cohorts 1 and 2: PF-06882961 160 mg BID (2-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 22	-6.57 Percent Change	Standard Error 0.011
Cohorts 1 and 2: PF-06882961 160 mg BID (2-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 18	-5.57 Percent Change	Standard Error 0.009
Cohort 1: PF-06882961 200 mg BID (1-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 16	-6.56 Percent Change	Standard Error 0.007
Cohort 1: PF-06882961 200 mg BID (1-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 2	-0.96 Percent Change	Standard Error 0.001
Cohort 1: PF-06882961 200 mg BID (1-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 10	-4.54 Percent Change	Standard Error 0.004
Cohort 1: PF-06882961 200 mg BID (1-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 6	-2.97 Percent Change	Standard Error 0.003
Cohort 1: PF-06882961 200 mg BID (1-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 18	-7.27 Percent Change	Standard Error 0.007
Cohort 1: PF-06882961 200 mg BID (1-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 22	-8.23 Percent Change	Standard Error 0.009
Cohort 1: PF-06882961 200 mg BID (1-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 8	-3.83 Percent Change	Standard Error 0.004
Cohort 1: PF-06882961 200 mg BID (1-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 12	-5.33 Percent Change	Standard Error 0.005
Cohort 1: PF-06882961 200 mg BID (1-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 4	-1.98 Percent Change	Standard Error 0.002
Cohorts 1 and 2: PF-06882961 200 mg BID (2-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 18	-5.80 Percent Change	Standard Error 0.008
Cohorts 1 and 2: PF-06882961 200 mg BID (2-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 16	-5.18 Percent Change	Standard Error 0.008
Cohorts 1 and 2: PF-06882961 200 mg BID (2-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 8	-2.94 Percent Change	Standard Error 0.004
Cohorts 1 and 2: PF-06882961 200 mg BID (2-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 6	-1.99 Percent Change	Standard Error 0.004
Cohorts 1 and 2: PF-06882961 200 mg BID (2-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 2	-0.53 Percent Change	Standard Error 0.002
Cohorts 1 and 2: PF-06882961 200 mg BID (2-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 10	-3.83 Percent Change	Standard Error 0.005
Cohorts 1 and 2: PF-06882961 200 mg BID (2-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 22	-6.60 Percent Change	Standard Error 0.01
Cohorts 1 and 2: PF-06882961 200 mg BID (2-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 4	-1.28 Percent Change	Standard Error 0.003
Cohorts 1 and 2: PF-06882961 200 mg BID (2-week Titration)	Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22	Week 12	-4.34 Percent Change	Standard Error 0.006

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026

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

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Keywords

Brief summary

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Pre-assignment details

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Cohort 3: Percent Change From Baseline in Body Weight at End of Treatment at Week 32

Cohorts 1 and 2: Percent Change From Baseline in Body Weight at End of Treatment at Week 26

Cohort 1 and 2: Number of Participants With Scores on the Patient Health Questionnaire-9 (PHQ-9) Leading to Study Discontinuation

Cohort 3: Absolute Change From Baseline in FPG at Weeks 4, 8, 12, 16, 20, 24, 28, 32

Cohort 3: Absolute Change From Baseline in Percentage HbA1c at Weeks 16, 24 and 32

Cohort 3: Absolute Change From Baseline in Waist Circumference at End of Treatment at Week 32

Cohort 3: Absolute Change From Baseline in Waist-to-hip Ratio at End of Treatment at Week 32

Cohort 3: Number of Participants According to Categorization of ECG Parameters

Cohort 3: Number of Participants According to Categorization of Vital Signs Data

Cohort 3: Number of Participants With >=5% Body Weight Loss at End of Treatment

Cohort 3: Number of Participants With Categorical Scores on C-SSRS Leading to Study Discontinuation

Cohort 3: Number of Participants With Laboratory Abnormalities, Without Regard to Baseline Abnormality

Cohort 3: Number of Participants With Scores on the PHQ-9 Leading to Study Discontinuation

Cohort 3: Number of Participants With TEAEs and TESAEs

Cohort 3: Percent Change From Baseline in Body Weight at Weeks 4, 8, 12, 16, 20, 24 and 28

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

Cohorts 1 and 2: Absolute Change From Baseline in Percentage Hemoglobin A1c (HbA1c) at Weeks 16 and 26

Cohorts 1 and 2: Absolute Change From Baseline in Waist Circumference at End of Treatment at Week 26

Cohorts 1 and 2: Absolute Change From Baseline in Waist-to-hip Ratio at End of Treatment at Week 26

Cohorts 1 and 2: Number of Participants According to Categorization of Electrocardiogram (ECG) Parameters

Cohorts 1 and 2: Number of Participants According to Categorization of Vital Signs Data

Cohorts 1 and 2: Number of Participants With >= 5% Body Weight Loss at End of Treatment

Cohorts 1 and 2: Number of Participants With Categorical Scores on Columbia-Suicide Severity Rating Scale (C-SSRS) Leading to Study Discontinuation

Cohorts 1 and 2: Number of Participants With Laboratory Abnormalities, Without Regard to Baseline Abnormality

Cohorts 1 and 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious AEs (TESAEs)

Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22