A Study to Evaluate the Efficacy and Safety of PF-0688296... | NCT04707313 | Trialant
NCT04707313
Sponsor
Pfizer
Status
Completed
Last Update Posted
Nov 5, 2024Actual
Enrollment
628Actual
Phase
Phase 2
Conditions
Obesity
Interventions
Placebo (Cohorts 1 and 2)
PF-06882961 (Cohorts 1 and 2)
Placebo (Cohort 3)
PF-06882961 (Cohort 3)
Countries
United States
Canada
Japan
Taiwan
Protocol Section
Identification Module
NCT ID
NCT04707313
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
C3421019
Secondary IDs
ID
Type
Description
Link
2020-001312-19
EudraCT Number
Brief Title
A Study to Evaluate the Efficacy and Safety of PF-06882961 in Adults With Obesity
Official Title
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
Acronym
Not provided
Organization
PfizerINDUSTRY
Status Module
Record Verification Date
Oct 2024
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Jan 29, 2021Actual
Primary Completion Date
Sep 13, 2023Actual
Completion Date
Oct 11, 2023Actual
First Submitted Date
Jan 11, 2021
First Submission Date that Met QC Criteria
Jan 11, 2021
First Posted Date
Jan 13, 2021Actual
Results Waived
Not provided
Results First Submitted Date
Sep 12, 2024
Results First Submitted that Met QC Criteria
Sep 12, 2024
Results First Posted Date
Oct 9, 2024Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Oct 11, 2024
Last Update Posted Date
Nov 5, 2024Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
PfizerINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
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).
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.
Baseline, Week 26
Cohort 3: Percent Change From Baseline in Body Weight at End of Treatment at Week 32
Percent change from baseline in body weight at end of treatment was reported in this outcome measure. Analysis was performed using MMRM with treatment, time, strata (females versus males) and treatment-by-time interaction as fixed effects, natural log-transformed baseline as a covariate and the (natural log-transformed baseline)-by-time interaction with time fitted as a repeated effect and participant as a random effect. Values were back-transformed from the log scale. Percent change = 100*(back-transformed LS Mean - 1). Baseline was defined as the average of the duplicate measurements collected closest prior to dosing at Day 1.
Baseline, Week 32
Secondary Outcomes
Measure
Description
Time Frame
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).
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
Participants with obesity, defined as a Body Mass Index greater than or equal to 30.0 kg/m2
Stable body weight, defined as <5 kg change (per participant report) for 90 days before visit 1
Exclusion Criteria:
Any condition possibly affecting drug absorption
Current or prior diagnosis of Type 1 or Type 2 diabetes mellitus or secondary forms of diabetes
History of myocardial infarction, unstable angina, arterial revascularization, stroke, heart failure, or transient ischemic attack within 6 months prior to visit 1
Any malignancy not considered cured
Personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 or suspected MTC
History of acute pancreatitis within 180 days (6 months) prior to visit 1 or any history of chronic pancreatitis
Symptomatic gallbladder disease
Medical history or characteristics suggestive of genetic or syndromic obesity or obesity induced by other endocrinological disorders
History of major depressive disorder or other severe psychiatric disorders within the last 2 years
Any lifetime history of a suicide attempt
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
Buckeridge C, Cobain S, Bays HE, Matsuoka O, Fukushima Y, Halstead P, Tsamandouras N, Sherry N, Gorman DN, Saxena AR. Efficacy and safety of danuglipron (PF-06882961) in adults with obesity: A randomized, placebo-controlled, dose-ranging phase 2b study. Diabetes Obes Metab. 2025 Sep;27(9):4915-4926. doi: 10.1111/dom.16534. Epub 2025 Jun 20.
See Also Links
Label
URL
To obtain contact information for a study center near you, click here.
Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.
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.
Recruitment Details
Not provided
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Cohorts 1 and 2: Placebo
Participants received placebo matched to PF-06882961 twice daily (BID), orally for a total of 26 weeks.
The dose will be titrated with 4 weeks of dosing at each step to reach the target dose of 200 mg BID.
Drug: PF-06882961 (Cohort 3)
PF-06882961 (Cohorts 1 and 2)
Drug
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
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.
From first dose of study intervention on Day 1 up to 28-35 days after last dose of study treatment (maximum up to 31 weeks)
Cohort 3: Number of Participants With TEAEs and TESAEs
An AE was any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. An SAE was defined as any untoward medical occurrence that, at any dose met one or more of the criteria such as resulted in death; life threatening; required inpatient hospitalization or prolongation of existing hospitalization; persistent disability or incapacity, congenital anomaly or birth defect; suspected transmission via a Pfizer product of an infectious agent, pathogenic or non-pathogenic. An adverse event is considered treatment-emergent relative to given treatment if the event starts during the effective duration of the treatment (i.e. starting on or after the first dose but before the last dose plus lag time).
From first dose of study intervention on Day 1 up to 28-35 days after last dose of study treatment (maximum up to 37 weeks)
Cohorts 1 and 2: Number of Participants With Laboratory Abnormalities, Without Regard to Baseline Abnormality
From first dose of study intervention on Day 1 up to 28-35 days after last dose of study treatment (up to 37 weeks)
Cohorts 1 and 2: Number of Participants According to Categorization of Vital Signs Data
Vital signs of systolic blood pressure, diastolic blood pressure and pulse rate and were measured using an automated device with the participant in a supine position after five minutes of rest. This reports the number of participants that met the following pre-specified criteria: systolic blood pressure (SBP) <90 millimetres of mercury (mmHg), diastolic blood pressure (DBP) <50 mmHg, pulse rate (PR) <40 beats per minute, >120 beats per minute.
From first dose of study intervention on Day 1 up to 28-35 days after last dose of study treatment (up to 31 weeks)
Cohort 3: Number of Participants According to Categorization of Vital Signs Data
Vital signs of systolic blood pressure, diastolic blood pressure and pulse rate and were measured using an automated device with the participant in a supine position after five minutes of rest. This reports the number of participants that met the following pre-specified criteria: systolic blood pressure (SBP) <90 millimetres of mercury (mmHg), diastolic blood pressure (DBP) <50 mmHg, pulse rate (PR) <40 beats per minute, >120 beats per minute.
From first dose of study intervention on Day 1 up to 28-35 days after last dose of study treatment (up to 37 weeks)
Cohorts 1 and 2: Number of Participants According to Categorization of Electrocardiogram (ECG) Parameters
Standard 12-lead ECGs were measured with the participant in a supine position after at least five minutes of rest. This reports the number of participants that met the following pre-specified criteria for ECG: QRS interval >=140; PR interval >=300; QTCF interval >500.
From first dose of study intervention on Day 1 up to 28-35 days after last dose of study treatment (up to 31 weeks)
Cohort 3: Number of Participants According to Categorization of ECG Parameters
Standard 12-lead ECGs were measured with the participant in a supine position after at least five minutes of rest. This reports the number of participants that met the following pre-specified criteria for ECG: QRS interval >=140; PR interval >=300; QTCF interval >500.
From first dose of study intervention on Day 1 up to 28-35 days after last dose of study treatment (up to 37 weeks)
Cohorts 1 and 2: Number of Participants With Categorical Scores on Columbia-Suicide Severity Rating Scale (C-SSRS) Leading to Study Discontinuation
C-SSRS is an interview-based rating scale to assess suicidal ideation and behavior. Per protocol, any participant with a pre-specified score was required to be evaluated by a mental health professional and, if meeting pre-defined criteria, discontinued from the study.
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.
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.
Cohort 3: Number of Participants With Scores on the PHQ-9 Leading to Study Discontinuation
PHQ-9 is a self-reported, nine-item scale for the assessment of depressive disorder. Per protocol, any participant with a pre-specified score was required to be evaluated by a mental health professional and, if meeting pre-defined criteria, discontinued from the study.
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.
Week 26
Cohort 3: Number of Participants With >=5% Body Weight Loss at End of Treatment
Number of participants with >= 5% body weight loss at end of treatment were reported.
Week 32
Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22
Percent change from baseline in body weight at end of treatment was reported in this outcome measure. Analysis was performed using MMRM with treatment, time, strata (females versus males) and treatment-by-time interaction as fixed effects, natural log-transformed baseline as a covariate and the (natural log-transformed baseline)-by-time interaction with time fitted as a repeated effect and participant as a random effect. Values were back-transformed from the log scale. Percent change = 100*(back-transformed LS Mean - 1). Baseline was defined as the average of the duplicate measurements collected closest prior to dosing at Day 1.
Baseline, Weeks 2, 4, 6, 8, 10, 12,16, 18, 22
Cohort 3: Percent Change From Baseline in Body Weight at Weeks 4, 8, 12, 16, 20, 24 and 28
Percent change from baseline in body weight at end of treatment was reported in this outcome measure. Analysis was performed using MMRM with treatment, time, strata (females versus males) and treatment-by-time interaction as fixed effects, natural log-transformed baseline as a covariate and the (natural log-transformed baseline)-by-time interaction with time fitted as a repeated effect and participant as a random effect. Values were back-transformed from the log scale. Percent change = 100*(back-transformed LS Mean - 1). Baseline was defined as the average of the duplicate measurements collected closest prior to dosing at Day 1.
Baseline, Weeks 4, 8, 12, 16, 20, 24 and 28
Cohorts 1 and 2: Absolute Change From Baseline in Waist Circumference at End of Treatment at Week 26
Absolute change from baseline in waist circumference were reported. Analysis was performed using MMRM model with treatment, time, strata (females versus males) and treatment-by-time interaction as fixed effects, baseline as a covariate and the baseline-by-time interaction with time fitted as a repeated effect and participant as a random effect. Baseline was defined as the average of the duplicate measurements collected closest prior to dosing at Day 1.
Baseline, Week 26
Cohort 3: Absolute Change From Baseline in Waist Circumference at End of Treatment at Week 32
Absolute change from baseline in waist circumference were reported. Analysis was performed using MMRM model with treatment, time, strata (females versus males) and treatment-by-time interaction as fixed effects, baseline as a covariate and the baseline-by-time interaction with time fitted as a repeated effect and participant as a random effect. Baseline was defined as the average of the duplicate measurements collected closest prior to dosing at Day 1.
Baseline, Week 32
Cohorts 1 and 2: Absolute Change From Baseline in Waist-to-hip Ratio at End of Treatment at Week 26
Absolute change from baseline in waist-to-hip ratio at end of treatment were reported. Analysis was performed using MMRM model with treatment, time, strata (females versus males) and treatment-by-time interaction as fixed effects, baseline as a covariate and the baseline-by-time interaction with time fitted as a repeated effect and participant as a random effect. Baseline was defined as the average of the duplicate measurements collected closest prior to dosing at Day 1.
Baseline, Week 26
Cohort 3: Absolute Change From Baseline in Waist-to-hip Ratio at End of Treatment at Week 32
Absolute change from baseline in waist-to-hip ratio at end of treatment were reported. Analysis was performed using MMRM model with treatment, time, strata (females versus males) and treatment-by-time interaction as fixed effects, baseline as a covariate and the baseline-by-time interaction with time fitted as a repeated effect and participant as a random effect. Baseline was defined as the average of the duplicate measurements collected closest prior to dosing at Day 1.
Baseline, Week 32
Cohorts 1 and 2: Absolute Change From Baseline in Percentage Hemoglobin A1c (HbA1c) at Weeks 16 and 26
Absolute change from baseline in HbA1c were reported. Analysis was performed using MMRM model with treatment, time, strata (females versus males) and treatment-by-time interaction as fixed effects, baseline as a covariate and the baseline-by-time interaction with time fitted as a repeated effect and participant as a random effect. Baseline was defined as the average of the duplicate measurements collected closest prior to dosing at Day 1.
Baseline, Weeks 16 and 26
Cohort 3: Absolute Change From Baseline in Percentage HbA1c at Weeks 16, 24 and 32
Absolute change from baseline in HbA1c were reported. Analysis was performed using MMRM model with treatment, time, strata (females versus males) and treatment-by-time interaction as fixed effects, baseline as a covariate and the baseline-by-time interaction with time fitted as a repeated effect and participant as a random effect. Baseline was defined as the average of the duplicate measurements collected closest prior to dosing at Day 1.
Baseline, Weeks 16, 24 and 32
Cohorts 1 and 2: Absolute Change From Baseline in Fasting Plasma Glucose (FPG) at Weeks 2, 4, 6, 8, 10, 12, 16, 18, 22, 26
Absolute change from baseline in FPG were reported. Analysis was performed using MMRM model with treatment, time, strata (females versus males) and treatment-by-time interaction as fixed effects, baseline as a covariate and the baseline-by-time interaction with time fitted as a repeated effect and participant as a random effect. Baseline was defined as the average of the duplicate measurements collected closest prior to dosing at Day 1.
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.
Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32
Anaheim
California
92801
United States
Velocity Clinical Research - Westlake
Los Angeles
California
90057
United States
Alliance for Multispecialty Research, LLC
Coral Gables
Florida
33134
United States
Optimus U Corporation
Miami
Florida
33125
United States
Clinical Neuroscience Solutions, Inc.
Orlando
Florida
32801
United States
ForCare Clinical Research
Tampa
Florida
33613
United States
Clinical Investigation Specialists
Gurnee
Illinois
60031
United States
MediSphere Medical Research Center, LLC
Evansville
Indiana
47714
United States
Velocity Clinical Research, Valparaiso
Valparaiso
Indiana
46383
United States
Cotton O'Neil Clinical Research Center
Topeka
Kansas
66606
United States
L-MARC Research Center
Louisville
Kentucky
40213
United States
ActivMed Practices & Research, LLC
Methuen
Massachusetts
01844
United States
Velocity Clinical Research, Omaha
Omaha
Nebraska
68134
United States
PMG Research of Hickory, LLC
Hickory
North Carolina
28601
United States
PMG Research of Raleigh, LLC
Raleigh
North Carolina
27609
United States
PMG Research of Salisbury, LLC
Salisbury
North Carolina
28144
United States
Accellacare - Wilmington
Wilmington
North Carolina
28401
United States
Lillestol Research LLC
Fargo
North Dakota
58104
United States
Velocity Clinical Research, Inc.
Cleveland
Ohio
44122
United States
Clinical Trials of South Carolina
Moncks Corner
South Carolina
29461
United States
Coastal Carolina Research Center
North Charleston
South Carolina
29405
United States
Palmetto Clinical Research
Summerville
South Carolina
29485
United States
Palmetto Primary Care Physicians (Sub-I physicals only)
Summerville
South Carolina
29485
United States
Internal Medicine and Pediatric Associates of Bristol, PC
Bristol
Tennessee
37620
United States
PMG Research, Inc. d/b/a PMG Research of Knoxville
Knoxville
Tennessee
37938
United States
Clinical Neuroscience Solutions, Inc.
Memphis
Tennessee
38119
United States
Rivergrove Medical Clinic
Winnipeg
Manitoba
R2V 4W3
Canada
Aggarwal and Associates Limited
Brampton
Ontario
L6T 0G1
Canada
Milestone Research , Inc
London
Ontario
N5W 6A2
Canada
Manna Research Toronto
Toronto
Ontario
M9W 4L6
Canada
Ecogene-21
Chicoutimi
Quebec
G7H 7K9
Canada
Alpha Recherche Clinique
Québec
Quebec
G2J 0C4
Canada
Diex Recherche Sherbrooke Inc.
Sherbrooke
Quebec
J1L 0H8
Canada
Centre de Recherche Saint-Louis
Québec
G1W4R4
Canada
Medical Corporation Heishinkai OCROM Clinic
Suita-shi
Osaka
565-0853
Japan
Tokyo Center Clinic
Chuo-ku
Tokyo
103-0028
Japan
Fukuwa Clinic
Chuo-ku
Tokyo
104-0031
Japan
Medical Corporation Heishinkai ToCROM Clinic
Shinjuku-ku
Tokyo
160-0008
Japan
China Medical University Hospital
Taichung
40447
Taiwan
National Cheng Kung University Hospital
Tainan
704
Taiwan
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.
FG002
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.
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.
BG013
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG00071
BG00162
BG00263
BG00364
BG00438
BG00563
BG00637
BG00763
BG00836
BG00919
BG01037
BG01137
BG01236
BG013626
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Customized
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
18-44 years
BG00028
BG00127
BG00226
BG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG00045
BG00140
BG002
Ethnicity (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Hispanic or Latino
BG0006
BG0017
BG002
Race (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
American Indian or Alaska Native
BG0000
BG0010
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
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.
Estimand Set 1 included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.
Posted
Least Squares Mean
Standard Error
Percent change
Baseline, Week 26
ID
Title
Description
OG000
Cohorts 1 and 2: Placebo
Participants received placebo matched to PF-06882961 twice daily (BID), orally for a total of 26 weeks.
OG001
Cohort 1: PF-06882961 40mg 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.
OG002
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.
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.
OG008
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.
Units
Counts
Participants
OG00071
OG00162
OG00263
OG003
Title
Denominators
Categories
Title
Measurements
OG0000.17± 0.008
OG001-5.43± 0.009
OG002-4.83± 0.009
OG003
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Mixed Models Analysis
<.0001
Difference to placebo
-5.60
Standard Error of the Mean
0.012
2-Sided
90
-7.41
-3.74
MMRM:treatment,time,strata(female vs male),treatment-by-time interaction as fixed effect, natural log-transformed baseline as covariate,natural log-transformed baseline-by-time interaction with time fitted:repeated effect, participant:random effect.
Superiority
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.
Estimand Set 1 included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.
Posted
Least Squares Mean
Standard Error
Percent change
Baseline, Week 32
ID
Title
Description
OG000
Cohort 3: Placebo
Participants received placebo matched to PF-06882961 BID, orally for 32 weeks.
OG001
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.
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).
Safety analysis set included all participants randomly assigned to study intervention of the study and who took at least 1 dose of study intervention.
Posted
Count of Participants
Participants
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)
ID
Title
Description
OG000
Cohorts 1 and 2: Placebo
Participants received placebo matched to PF-06882961 twice daily (BID), orally for a total of 26 weeks.
OG001
Cohort 1: PF-06882961 40mg BID (1-week Titration)
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).
Safety analysis set included all participants randomly assigned to study intervention of the study and who took at least 1 dose of study intervention.
Posted
Count of Participants
Participants
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)
ID
Title
Description
OG000
Cohort 3: Placebo
Participants received placebo matched to PF-06882961 BID, orally for 32 weeks.
OG001
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.
Secondary
Cohorts 1 and 2: Number of Participants With Laboratory Abnormalities, Without Regard to Baseline Abnormality
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.
Posted
Count of Participants
Participants
From first dose of study intervention on Day 1 up to 28-35 days after last dose of study treatment (up to 31 weeks)
ID
Title
Description
OG000
Cohorts 1 and 2: Placebo
Participants received placebo matched to PF-06882961 twice daily (BID), orally for a total of 26 weeks.
Secondary
Cohort 3: Number of Participants With Laboratory Abnormalities, Without Regard to Baseline Abnormality
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.
Posted
Count of Participants
Participants
From first dose of study intervention on Day 1 up to 28-35 days after last dose of study treatment (up to 37 weeks)
ID
Title
Description
OG000
Cohort 3: Placebo
Participants received placebo matched to PF-06882961 BID, orally for 32 weeks.
Secondary
Cohorts 1 and 2: Number of Participants According to Categorization of Vital Signs Data
Vital signs of systolic blood pressure, diastolic blood pressure and pulse rate and were measured using an automated device with the participant in a supine position after five minutes of rest. This reports the number of participants that met the following pre-specified criteria: systolic blood pressure (SBP) <90 millimetres of mercury (mmHg), diastolic blood pressure (DBP) <50 mmHg, pulse rate (PR) <40 beats per minute, >120 beats per minute.
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.
Posted
Count of Participants
Participants
From first dose of study intervention on Day 1 up to 28-35 days after last dose of study treatment (up to 31 weeks)
ID
Title
Description
OG000
Cohorts 1 and 2: Placebo
Participants received placebo matched to PF-06882961 twice daily (BID), orally for a total of 26 weeks.
OG001
Cohort 1: PF-06882961 40mg 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.
OG002
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.
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.
Posted
Count of Participants
Participants
From first dose of study intervention on Day 1 up to 28-35 days after last dose of study treatment (up to 37 weeks)
ID
Title
Description
OG000
Cohort 3: Placebo
Participants received placebo matched to PF-06882961 BID, orally for 32 weeks.
OG001
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.
Cohorts 1 and 2: Number of Participants According to Categorization of Electrocardiogram (ECG) Parameters
Standard 12-lead ECGs were measured with the participant in a supine position after at least five minutes of rest. This reports the number of participants that met the following pre-specified criteria for ECG: QRS interval >=140; PR interval >=300; QTCF interval >500.
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.
Posted
Count of Participants
Participants
From first dose of study intervention on Day 1 up to 28-35 days after last dose of study treatment (up to 31 weeks)
ID
Title
Description
OG000
Cohorts 1 and 2: Placebo
Participants received placebo matched to PF-06882961 twice daily (BID), orally for a total of 26 weeks.
OG001
Cohort 1: PF-06882961 40mg 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.
OG002
Cohort 1: PF-06882961 80mg BID (1-week Titration)
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.
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.
Posted
Count of Participants
Participants
From first dose of study intervention on Day 1 up to 28-35 days after last dose of study treatment (up to 37 weeks)
ID
Title
Description
OG000
Cohort 3: Placebo
Participants received placebo matched to PF-06882961 BID, orally for 32 weeks.
OG001
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.
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.
Secondary
Cohorts 1 and 2: Number of Participants With Categorical Scores on Columbia-Suicide Severity Rating Scale (C-SSRS) Leading to Study Discontinuation
C-SSRS is an interview-based rating scale to assess suicidal ideation and behavior. Per protocol, any participant with a pre-specified score was required to be evaluated by a mental health professional and, if meeting pre-defined criteria, discontinued from the study.
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.
Participants received placebo matched to PF-06882961 twice daily (BID), orally for a total of 26 weeks.
OG001
Cohort 1: PF-06882961 40mg 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.
OG002
Cohort 1: PF-06882961 80mg BID (1-week Titration)
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.
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.
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.
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.
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."
Participants received placebo matched to PF-06882961 twice daily (BID), orally for a total of 26 weeks.
OG001
Cohort 1: PF-06882961 40mg 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.
OG002
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.
Secondary
Cohort 3: Number of Participants With Scores on the PHQ-9 Leading to Study Discontinuation
PHQ-9 is a self-reported, nine-item scale for the assessment of depressive disorder. Per protocol, any participant with a pre-specified score was required to be evaluated by a mental health professional and, if meeting pre-defined criteria, discontinued from the study.
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."
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.
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.
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.
Posted
Count of Participants
Participants
Week 26
ID
Title
Description
OG000
Cohorts 1 and 2: Placebo
Participants received placebo matched to PF-06882961 twice daily (BID), orally for a total of 26 weeks.
OG001
Cohort 1: PF-06882961 40mg 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.
OG002
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.
OG003
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.
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.
Posted
Count of Participants
Participants
Week 32
ID
Title
Description
OG000
Cohort 3: Placebo
Participants received placebo matched to PF-06882961 BID, orally for 32 weeks.
OG001
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.
Cohorts 1 and 2: Percent Change From Baseline in Body Weight at Weeks 2, 4, 6, 8, 10, 12,16, 18, 22
Percent change from baseline in body weight at end of treatment was reported in this outcome measure. Analysis was performed using MMRM with treatment, time, strata (females versus males) and treatment-by-time interaction as fixed effects, natural log-transformed baseline as a covariate and the (natural log-transformed baseline)-by-time interaction with time fitted as a repeated effect and participant as a random effect. Values were back-transformed from the log scale. Percent change = 100*(back-transformed LS Mean - 1). Baseline was defined as the average of the duplicate measurements collected closest prior to dosing at Day 1.
Estimand Set 1 included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.
Posted
Least Squares Mean
Standard Error
Percent Change
Baseline, Weeks 2, 4, 6, 8, 10, 12,16, 18, 22
ID
Title
Description
OG000
Cohorts 1 and 2: Placebo
Participants received placebo matched to PF-06882961 twice daily (BID), orally for a total of 26 weeks.
OG001
Cohort 1: PF-06882961 40mg 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.
OG002
Secondary
Cohort 3: Percent Change From Baseline in Body Weight at Weeks 4, 8, 12, 16, 20, 24 and 28
Percent change from baseline in body weight at end of treatment was reported in this outcome measure. Analysis was performed using MMRM with treatment, time, strata (females versus males) and treatment-by-time interaction as fixed effects, natural log-transformed baseline as a covariate and the (natural log-transformed baseline)-by-time interaction with time fitted as a repeated effect and participant as a random effect. Values were back-transformed from the log scale. Percent change = 100*(back-transformed LS Mean - 1). Baseline was defined as the average of the duplicate measurements collected closest prior to dosing at Day 1.
Estimand Set 1 included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.
Posted
Least Squares Mean
Standard Error
Percent Change
Baseline, Weeks 4, 8, 12, 16, 20, 24 and 28
ID
Title
Description
OG000
Cohort 3: Placebo
Participants received placebo matched to PF-06882961 BID, orally for 32 weeks.
OG001
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.
Cohorts 1 and 2: Absolute Change From Baseline in Waist Circumference at End of Treatment at Week 26
Absolute change from baseline in waist circumference were reported. Analysis was performed using MMRM model with treatment, time, strata (females versus males) and treatment-by-time interaction as fixed effects, baseline as a covariate and the baseline-by-time interaction with time fitted as a repeated effect and participant as a random effect. Baseline was defined as the average of the duplicate measurements collected closest prior to dosing at Day 1.
Estimand Set 1 included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.
Posted
Least Squares Mean
Standard Error
Centimeter
Baseline, Week 26
ID
Title
Description
OG000
Cohorts 1 and 2: Placebo
Participants received placebo matched to PF-06882961 twice daily (BID), orally for a total of 26 weeks.
OG001
Cohort 1: PF-06882961 40mg 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.
OG002
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.
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.
Estimand Set 1 included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.
Posted
Least Squares Mean
Standard Error
Centimeter
Baseline, Week 32
ID
Title
Description
OG000
Cohort 3: Placebo
Participants received placebo matched to PF-06882961 BID, orally for 32 weeks.
OG001
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.
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.
Secondary
Cohorts 1 and 2: Absolute Change From Baseline in Waist-to-hip Ratio at End of Treatment at Week 26
Absolute change from baseline in waist-to-hip ratio at end of treatment were reported. Analysis was performed using MMRM model with treatment, time, strata (females versus males) and treatment-by-time interaction as fixed effects, baseline as a covariate and the baseline-by-time interaction with time fitted as a repeated effect and participant as a random effect. Baseline was defined as the average of the duplicate measurements collected closest prior to dosing at Day 1.
Estimand Set 1 included all participants randomly assigned to study intervention in Part A and who took at least 1 dose of study intervention.
Posted
Least Squares Mean
Standard Error
Ratio
Baseline, Week 26
ID
Title
Description
OG000
Cohorts 1 and 2: Placebo
Participants received placebo matched to PF-06882961 twice daily (BID), orally for a total of 26 weeks.
OG001
Cohort 1: PF-06882961 40mg 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.
OG002
Cohort 1: PF-06882961 80mg BID (1-week Titration)
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.
Estimand Set 1 included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.
Posted
Least Squares Mean
Standard Error
Ratio
Baseline, Week 32
ID
Title
Description
OG000
Cohort 3: Placebo
Participants received placebo matched to PF-06882961 BID, orally for 32 weeks.
OG001
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.
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.
Secondary
Cohorts 1 and 2: Absolute Change From Baseline in Percentage Hemoglobin A1c (HbA1c) at Weeks 16 and 26
Absolute change from baseline in HbA1c were reported. Analysis was performed using MMRM model with treatment, time, strata (females versus males) and treatment-by-time interaction as fixed effects, baseline as a covariate and the baseline-by-time interaction with time fitted as a repeated effect and participant as a random effect. Baseline was defined as the average of the duplicate measurements collected closest prior to dosing at Day 1.
Estimand Set 1 included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.
Posted
Least Squares Mean
Standard Error
Percentage of HbA1c
Baseline, Weeks 16 and 26
ID
Title
Description
OG000
Cohorts 1 and 2: Placebo
Participants received placebo matched to PF-06882961 twice daily (BID), orally for a total of 26 weeks.
OG001
Cohort 1: PF-06882961 40mg 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.
OG002
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.
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.
Estimand Set 1 included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.
Posted
Least Squares Mean
Standard Error
Percentage of HbA1c
Baseline, Weeks 16, 24 and 32
ID
Title
Description
OG000
Cohort 3: Placebo
Participants received placebo matched to PF-06882961 BID, orally for 32 weeks.
OG001
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.
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.
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
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.
Estimand Set 1 included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.
Participants received placebo matched to PF-06882961 twice daily (BID), orally for a total of 26 weeks.
OG001
Cohort 1: PF-06882961 40mg 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.
OG002
Cohort 1: PF-06882961 80mg BID (1-week Titration)
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.
Estimand Set 1 included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.
Posted
Least Squares Mean
Standard Error
Milligram per deciliter
Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32
ID
Title
Description
OG000
Cohort 3: Placebo
Participants received placebo matched to PF-06882961 BID, orally for 32 weeks.
OG001
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.
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.
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 Week 31 for Cohort 1 and 2; maximum up to Week 37 for Cohort 3)
Description
An AE was any untoward medical occurrence in a participant temporally associated with use of study intervention, whether or not considered related to study intervention. Same event may appear as both non-SAE and SAE; however, what is presented are distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. All-causality non-SAEs occurring in >=5% of participants in any treatment group are included below.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Cohorts 1 and 2: Placebo
Participants received placebo matched to PF-06882961 twice daily (BID), orally for a total of 26 weeks.
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.
0
36
3
36
34
36
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Acute myocardial infarction
Cardiac disorders
MedDRA v26.0
Non-systematic Assessment
EG0000 affected71 at risk
EG0010 affected62 at risk
EG0020 affected63 at risk
EG0030 affected64 at risk
EG0041 affected38 at risk
EG0050 affected63 at risk
EG0060 affected37 at risk
EG0070 affected63 at risk
EG0080 affected36 at risk
EG0090 affected19 at risk
EG0100 affected37 at risk
EG0110 affected37 at risk
EG0120 affected36 at risk
Small intestinal obstruction
Gastrointestinal disorders
MedDRA v26.0
Non-systematic Assessment
EG0000 affected71 at risk
EG0010 affected62 at risk
EG0020 affected63 at risk
EG003
Cholecystitis acute
Hepatobiliary disorders
MedDRA v26.0
Non-systematic Assessment
EG0000 affected71 at risk
EG0010 affected62 at risk
EG0020 affected63 at risk
EG003
Appendicitis
Infections and infestations
MedDRA v26.0
Non-systematic Assessment
EG0000 affected71 at risk
EG0011 affected62 at risk
EG0020 affected63 at risk
EG003
COVID-19
Infections and infestations
MedDRA v26.0
Non-systematic Assessment
EG0000 affected71 at risk
EG0010 affected62 at risk
EG0020 affected63 at risk
EG003
COVID-19 pneumonia
Infections and infestations
MedDRA v26.0
Non-systematic Assessment
EG0000 affected71 at risk
EG0010 affected62 at risk
EG0020 affected63 at risk
EG003
Cystitis
Infections and infestations
MedDRA v26.0
Non-systematic Assessment
EG0001 affected71 at risk
EG0010 affected62 at risk
EG0020 affected63 at risk
EG003
Pneumonia
Infections and infestations
MedDRA v26.0
Non-systematic Assessment
EG0000 affected71 at risk
EG0010 affected62 at risk
EG0020 affected63 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA v26.0
Non-systematic Assessment
EG0000 affected71 at risk
EG0010 affected62 at risk
EG0021 affected63 at risk
EG003
Clavicle fracture
Injury, poisoning and procedural complications
MedDRA v26.0
Non-systematic Assessment
EG0000 affected71 at risk
EG0010 affected62 at risk
EG0020 affected63 at risk
EG003
Skin laceration
Injury, poisoning and procedural complications
MedDRA v26.0
Non-systematic Assessment
EG0000 affected71 at risk
EG0010 affected62 at risk
EG0020 affected63 at risk
EG003
Squamous cell carcinoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA v26.0
Non-systematic Assessment
EG0000 affected71 at risk
EG0010 affected62 at risk
EG0020 affected63 at risk
EG003
Presyncope
Nervous system disorders
MedDRA v26.0
Non-systematic Assessment
EG0000 affected71 at risk
EG0011 affected62 at risk
EG0020 affected63 at risk
EG003
Aortic valve stenosis
Cardiac disorders
MedDRA v26.0
Non-systematic Assessment
EG0000 affected71 at risk
EG0010 affected62 at risk
EG0020 affected63 at risk
EG003
Atrial fibrillation
Cardiac disorders
MedDRA v26.0
Non-systematic Assessment
EG0000 affected71 at risk
EG0010 affected62 at risk
EG0020 affected63 at risk
EG003
Bundle branch block left
Cardiac disorders
MedDRA v26.0
Non-systematic Assessment
EG0000 affected71 at risk
EG0010 affected62 at risk
EG0020 affected63 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA v26.0
Non-systematic Assessment
EG0000 affected71 at risk
EG0010 affected62 at risk
EG0020 affected63 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA v26.0
Non-systematic Assessment
EG0000 affected71 at risk
EG0010 affected62 at risk
EG0020 affected63 at risk
EG003
Pharyngitis streptococcal
Infections and infestations
MedDRA v26.0
Non-systematic Assessment
EG0000 affected71 at risk
EG0010 affected62 at risk
EG0020 affected63 at risk
EG003
Lymphoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA v26.0
Non-systematic Assessment
EG0000 affected71 at risk
EG0010 affected62 at risk
EG0020 affected63 at risk
EG003
Ovarian germ cell teratoma benign
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA v26.0
Non-systematic Assessment
EG0000 affected71 at risk
EG0010 affected62 at risk
EG0020 affected63 at risk
EG003
Pulmonary embolism
Respiratory, thoracic and mediastinal disorders
MedDRA v26.0
Non-systematic Assessment
EG0000 affected71 at risk
EG0010 affected62 at risk
EG0020 affected63 at risk
EG003
Superficial vein thrombosis
Vascular disorders
MedDRA v26.0
Non-systematic Assessment
EG0000 affected71 at risk
EG0010 affected62 at risk
EG0020 affected63 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Abdominal discomfort
Gastrointestinal disorders
MedDRA v26.0
Non-systematic Assessment
EG0000 affected71 at risk
EG0014 affected62 at risk
EG0022 affected63 at risk
EG0030 affected64 at risk
EG0041 affected38 at risk
EG0053 affected63 at risk
EG0060 affected37 at risk
EG0075 affected63 at risk
EG0081 affected36 at risk
EG0090 affected19 at risk
EG0102 affected37 at risk
EG0111 affected37 at risk
EG0122 affected36 at risk
Abdominal distension
Gastrointestinal disorders
MedDRA v26.0
Non-systematic Assessment
EG0001 affected71 at risk
EG0013 affected62 at risk
EG0023 affected63 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA v26.0
Non-systematic Assessment
EG0004 affected71 at risk
EG0013 affected62 at risk
EG0025 affected63 at risk
EG003
Abdominal pain upper
Gastrointestinal disorders
MedDRA v26.0
Non-systematic Assessment
EG0002 affected71 at risk
EG0013 affected62 at risk
EG0022 affected63 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA v26.0
Non-systematic Assessment
EG0003 affected71 at risk
EG0018 affected62 at risk
EG00210 affected63 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA v26.0
Non-systematic Assessment
EG0007 affected71 at risk
EG0015 affected62 at risk
EG00217 affected63 at risk
EG003
Dyspepsia
Gastrointestinal disorders
MedDRA v26.0
Non-systematic Assessment
EG0001 affected71 at risk
EG0016 affected62 at risk
EG00211 affected63 at risk
EG003
Eructation
Gastrointestinal disorders
MedDRA v26.0
Non-systematic Assessment
EG0000 affected71 at risk
EG0011 affected62 at risk
EG0021 affected63 at risk
EG003
Flatulence
Gastrointestinal disorders
MedDRA v26.0
Non-systematic Assessment
EG0001 affected71 at risk
EG0014 affected62 at risk
EG0021 affected63 at risk
EG003
Gastrooesophageal reflux disease
Gastrointestinal disorders
MedDRA v26.0
Non-systematic Assessment
EG0000 affected71 at risk
EG0017 affected62 at risk
EG0028 affected63 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA v26.0
Non-systematic Assessment
EG00011 affected71 at risk
EG00128 affected62 at risk
EG00239 affected63 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA v26.0
Non-systematic Assessment
EG0002 affected71 at risk
EG00110 affected62 at risk
EG00224 affected63 at risk
EG003
Chills
General disorders
MedDRA v26.0
Non-systematic Assessment
EG0000 affected71 at risk
EG0011 affected62 at risk
EG0022 affected63 at risk
EG003
Fatigue
General disorders
MedDRA v26.0
Non-systematic Assessment
EG0005 affected71 at risk
EG0013 affected62 at risk
EG0024 affected63 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA v26.0
Non-systematic Assessment
EG0003 affected71 at risk
EG0014 affected62 at risk
EG0028 affected63 at risk
EG003
Fall
Injury, poisoning and procedural complications
MedDRA v26.0
Non-systematic Assessment
EG0001 affected71 at risk
EG0013 affected62 at risk
EG0021 affected63 at risk
EG003
SARS-CoV-2 test positive
Investigations
MedDRA v26.0
Non-systematic Assessment
EG0003 affected71 at risk
EG0013 affected62 at risk
EG0020 affected63 at risk
EG003
Decreased appetite
Metabolism and nutrition disorders
MedDRA v26.0
Non-systematic Assessment
EG0001 affected71 at risk
EG0013 affected62 at risk
EG0026 affected63 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA v26.0
Non-systematic Assessment
EG0003 affected71 at risk
EG0012 affected62 at risk
EG0025 affected63 at risk
EG003
Dizziness
Nervous system disorders
MedDRA v26.0
Non-systematic Assessment
EG0002 affected71 at risk
EG0014 affected62 at risk
EG0021 affected63 at risk
EG003
Headache
Nervous system disorders
MedDRA v26.0
Non-systematic Assessment
EG0008 affected71 at risk
EG0016 affected62 at risk
EG00211 affected63 at risk
EG003
Tremor
Nervous system disorders
MedDRA v26.0
Non-systematic Assessment
EG0000 affected71 at risk
EG0011 affected62 at risk
EG0021 affected63 at risk
EG003
Nephrolithiasis
Renal and urinary disorders
MedDRA v26.0
Non-systematic Assessment
EG0000 affected71 at risk
EG0010 affected62 at risk
EG0020 affected63 at risk
EG003
Pruritus
Skin and subcutaneous tissue disorders
MedDRA v26.0
Non-systematic Assessment
EG0004 affected71 at risk
EG0010 affected62 at risk
EG0020 affected63 at risk
EG003
Hot flush
Vascular disorders
MedDRA v26.0
Non-systematic Assessment
EG0000 affected71 at risk
EG0010 affected62 at risk
EG0020 affected63 at risk
EG003
Palpitations
Cardiac disorders
MedDRA v26.0
Non-systematic Assessment
EG0000 affected71 at risk
EG0010 affected62 at risk
EG0020 affected63 at risk
EG003
Ocular discomfort
Eye disorders
MedDRA v26.0
Non-systematic Assessment
EG0000 affected71 at risk
EG0010 affected62 at risk
EG0020 affected63 at risk
EG003
Abdominal wall haematoma
Gastrointestinal disorders
MedDRA v26.0
Non-systematic Assessment
EG0000 affected71 at risk
EG0010 affected62 at risk
EG0020 affected63 at risk
EG003
Dry mouth
Gastrointestinal disorders
MedDRA v26.0
Non-systematic Assessment
EG0000 affected71 at risk
EG0010 affected62 at risk
EG0020 affected63 at risk
EG003
Chest discomfort
General disorders
MedDRA v26.0
Non-systematic Assessment
EG0000 affected71 at risk
EG0010 affected62 at risk
EG0020 affected63 at risk
EG003
Seasonal allergy
Immune system disorders
MedDRA v26.0
Non-systematic Assessment
EG0000 affected71 at risk
EG0010 affected62 at risk
EG0020 affected63 at risk
EG003
Acute sinusitis
Infections and infestations
MedDRA v26.0
Non-systematic Assessment
EG0000 affected71 at risk
EG0010 affected62 at risk
EG0020 affected63 at risk
EG003
COVID-19
Infections and infestations
MedDRA v26.0
Non-systematic Assessment
EG0000 affected71 at risk
EG0010 affected62 at risk
EG0020 affected63 at risk
EG003
Gastroenteritis
Infections and infestations
MedDRA v26.0
Non-systematic Assessment
EG0000 affected71 at risk
EG0010 affected62 at risk
EG0020 affected63 at risk
EG003
Gastroenteritis viral
Infections and infestations
MedDRA v26.0
Non-systematic Assessment
EG0000 affected71 at risk
EG0010 affected62 at risk
EG0020 affected63 at risk
EG003
Nasopharyngitis
Infections and infestations
MedDRA v26.0
Non-systematic Assessment
EG0000 affected71 at risk
EG0010 affected62 at risk
EG0020 affected63 at risk
EG003
Pharyngitis streptococcal
Infections and infestations
MedDRA v26.0
Non-systematic Assessment
EG0000 affected71 at risk
EG0010 affected62 at risk
EG0020 affected63 at risk
EG003
Sinusitis
Infections and infestations
MedDRA v26.0
Non-systematic Assessment
EG0000 affected71 at risk
EG0010 affected62 at risk
EG0020 affected63 at risk
EG003
Tooth abscess
Infections and infestations
MedDRA v26.0
Non-systematic Assessment
EG0000 affected71 at risk
EG0010 affected62 at risk
EG0020 affected63 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedDRA v26.0
Non-systematic Assessment
EG0000 affected71 at risk
EG0010 affected62 at risk
EG0020 affected63 at risk
EG003
Contusion
Injury, poisoning and procedural complications
MedDRA v26.0
Non-systematic Assessment
EG0000 affected71 at risk
EG0010 affected62 at risk
EG0020 affected63 at risk
EG003
Road traffic accident
Injury, poisoning and procedural complications
MedDRA v26.0
Non-systematic Assessment
EG0000 affected71 at risk
EG0010 affected62 at risk
EG0020 affected63 at risk
EG003
Alanine aminotransferase increased
Investigations
MedDRA v26.0
Non-systematic Assessment
EG0000 affected71 at risk
EG0010 affected62 at risk
EG0020 affected63 at risk
EG003
Lipase increased
Investigations
MedDRA v26.0
Non-systematic Assessment
EG0000 affected71 at risk
EG0010 affected62 at risk
EG0020 affected63 at risk
EG003
Weight increased
Investigations
MedDRA v26.0
Non-systematic Assessment
EG0000 affected71 at risk
EG0010 affected62 at risk
EG0020 affected63 at risk
EG003
Hypoglycaemia
Metabolism and nutrition disorders
MedDRA v26.0
Non-systematic Assessment
EG0000 affected71 at risk
EG0010 affected62 at risk
EG0020 affected63 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA v26.0
Non-systematic Assessment
EG0000 affected71 at risk
EG0010 affected62 at risk
EG0020 affected63 at risk
EG003
Bursitis
Musculoskeletal and connective tissue disorders
MedDRA v26.0
Non-systematic Assessment
EG0000 affected71 at risk
EG0010 affected62 at risk
EG0020 affected63 at risk
EG003
Intervertebral disc protrusion
Musculoskeletal and connective tissue disorders
MedDRA v26.0
Non-systematic Assessment
EG0000 affected71 at risk
EG0010 affected62 at risk
EG0020 affected63 at risk
EG003
Neck pain
Musculoskeletal and connective tissue disorders
MedDRA v26.0
Non-systematic Assessment
EG0000 affected71 at risk
EG0010 affected62 at risk
EG0020 affected63 at risk
EG003
Osteoarthritis
Musculoskeletal and connective tissue disorders
MedDRA v26.0
Non-systematic Assessment
EG0000 affected71 at risk
EG0010 affected62 at risk
EG0020 affected63 at risk
EG003
Pain in extremity
Musculoskeletal and connective tissue disorders
MedDRA v26.0
Non-systematic Assessment
EG0000 affected71 at risk
EG0010 affected62 at risk
EG0020 affected63 at risk
EG003
Radiculopathy
Nervous system disorders
MedDRA v26.0
Non-systematic Assessment
EG0000 affected71 at risk
EG0010 affected62 at risk
EG0020 affected63 at risk
EG003
Somnolence
Nervous system disorders
MedDRA v26.0
Non-systematic Assessment
EG0000 affected71 at risk
EG0010 affected62 at risk
EG0020 affected63 at risk
EG003
Anxiety
Psychiatric disorders
MedDRA v26.0
Non-systematic Assessment
EG0000 affected71 at risk
EG0010 affected62 at risk
EG0020 affected63 at risk
EG003
Cough
Respiratory, thoracic and mediastinal disorders
MedDRA v26.0
Non-systematic Assessment
EG0000 affected71 at risk
EG0010 affected62 at risk
EG0020 affected63 at risk
EG003
Nasal congestion
Respiratory, thoracic and mediastinal disorders
MedDRA v26.0
Non-systematic Assessment
EG0000 affected71 at risk
EG0010 affected62 at risk
EG0020 affected63 at risk
EG003
Respiratory symptom
Respiratory, thoracic and mediastinal disorders
MedDRA v26.0
Non-systematic Assessment
EG0000 affected71 at risk
EG0010 affected62 at risk
EG0020 affected63 at risk
EG003
Hypertension
Vascular disorders
MedDRA v26.0
Non-systematic Assessment
EG0000 affected71 at risk
EG0010 affected62 at risk
EG0020 affected63 at risk
EG003
Prehypertension
Vascular disorders
MedDRA v26.0
Non-systematic Assessment
EG0000 affected71 at risk
EG0010 affected62 at risk
EG0020 affected63 at risk
EG003
Varicose vein
Vascular disorders
MedDRA v26.0
Non-systematic Assessment
EG0000 affected71 at risk
EG0010 affected62 at risk
EG0020 affected63 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from the study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
MMRM:treatment,time,strata(female vs male),treatment-by-time interaction as fixed effect, natural log-transformed baseline as covariate,natural log-transformed baseline-by-time interaction with time fitted:repeated effect, participant:random effect.
Superiority
OG000
OG003
Mixed Models Analysis
<.0001
Difference to Placebo
-9.10
Standard Error of the Mean
0.012
2-Sided
90
-10.89
-7.28
MMRM:treatment,time,strata(female vs male),treatment-by-time interaction as fixed effect, natural log-transformed baseline as covariate,natural log-transformed baseline-by-time interaction with time fitted:repeated effect, participant:random effect.
Superiority
OG004
Mixed Models Analysis
<.0001
Difference to Placebo
-6.60
Standard Error of the Mean
0.014
2-Sided
90
-8.75
-4.39
MMRM:treatment,time,strata(female vs male),treatment-by-time interaction as fixed effect, natural log-transformed baseline as covariate,natural log-transformed baseline-by-time interaction with time fitted:repeated effect, participant:random effect.
Superiority
OG005
Mixed Models Analysis
<.0001
Difference to Placebo
-9.52
Standard Error of the Mean
0.013
2-Sided
90
-11.43
-7.56
MMRM:treatment,time,strata(female vs male),treatment-by-time interaction as fixed effect, natural log-transformed baseline as covariate,natural log-transformed baseline-by-time interaction with time fitted:repeated effect, participant:random effect.
Superiority
OG006
Mixed Models Analysis
<.0001
Difference to Placebo
-7.12
Standard Error of the Mean
0.015
2-Sided
90
-9.41
-4.78
MMRM:treatment,time,strata(female vs male),treatment-by-time interaction as fixed effect, natural log-transformed baseline as covariate,natural log-transformed baseline-by-time interaction with time fitted:repeated effect, participant:random effect.
Superiority
OG007
Mixed Models Analysis
<.0001
Difference to Placebo
-9.12
Standard Error of the Mean
0.013
2-Sided
90
-11.11
-7.08
MMRM:treatment,time,strata(female vs male),treatment-by-time interaction as fixed effect, natural log-transformed baseline as covariate,natural log-transformed baseline-by-time interaction with time fitted:repeated effect, participant:random effect.
Superiority
OG008
Mixed Models Analysis
<.0001
Difference to Placebo
-7.18
Standard Error of the Mean
0.014
2-Sided
90
-9.32
-4.99
MMRM:treatment,time,strata(female vs male),treatment-by-time interaction as fixed effect, natural log-transformed baseline as covariate,natural log-transformed baseline-by-time interaction with time fitted:repeated effect, participant:random effect.
Superiority
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.
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.
Units
Counts
Participants
OG00019
OG00137
OG00237
OG00336
Title
Denominators
Categories
Title
Measurements
OG0001.40± 0.018
OG001-6.92± 0.014
OG002-7.15± 0.014
OG003-11.65± 0.014
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Mixed Models Analysis
<.0001
Difference to Placebo
-8.21
Standard Error of the Mean
0.023
2-Sided
90
-11.66
-4.63
MMRM:treatment,time,strata(female vs male),treatment-by-time interaction as fixed effect, natural log-transformed baseline as covariate,natural log-transformed baseline-by-time interaction with time fitted:repeated effect, participant:random effect.
Superiority
OG000
OG002
Mixed Models Analysis
<.0001
Difference to placebo
-8.44
Standard Error of the Mean
0.023
2-Sided
90
-11.83
-4.92
MMRM:treatment,time,strata(female vs male),treatment-by-time interaction as fixed effect, natural log-transformed baseline as covariate,natural log-transformed baseline-by-time interaction with time fitted:repeated effect, participant:random effect.
Superiority
OG000
OG003
Mixed Models Analysis
<.0001
Difference to Placebo
-12.87
Standard Error of the Mean
0.023
2-Sided
90
-16.15
-9.47
MMRM:treatment,time,strata(female vs male),treatment-by-time interaction as fixed effect, natural log-transformed baseline as covariate,natural log-transformed baseline-by-time interaction with time fitted:repeated effect, participant:random effect.
Superiority
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.
OG002
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.
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.
OG008
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.
Units
Counts
Participants
OG00044
OG00127
OG00230
OG00326
OG00414
OG00518
OG00611
OG00714
OG00813
Title
Denominators
Categories
Title
Measurements
OG0006
OG00116
OG00215
OG00317
OG00412
OG00515
OG0066
OG00712
OG0088
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Odds Ratio (OR)
7.37
2-Sided
90
2.81
19.30
Superiority
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.
OG000
OG002
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.
Odds Ratio (OR)
6.58
2-Sided
90
2.62
16.53
Superiority
OG000
OG003
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.
Odds Ratio (OR)
16.33
2-Sided
90
6.47
41.24
Superiority
OG000
OG004
Odds Ratio (OR)
14.24
2-Sided
90
5.39
37.66
Superiority
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.
OG000
OG005
Odds Ratio (OR)
30.17
2-Sided
90
11.35
80.20
Superiority
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.
OG000
OG006
Odds Ratio (OR)
9.88
2-Sided
90
2.91
33.53
Superiority
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.
OG000
OG007
Odds Ratio (OR)
24.41
2-Sided
90
8.28
71.95
Superiority
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.
OG000
OG008
Odds Ratio (OR)
12.65
2-Sided
90
4.56
35.08
Superiority
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.
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.
Units
Counts
Participants
OG00011
OG00113
OG00215
OG00311
Title
Denominators
Categories
Title
Measurements
OG0000
OG0019
OG00211
OG00310
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Odds Ratio (OR)
33.43
2-Sided
90
3.05
366.64
Superiority
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.
OG000
OG002
Odds Ratio (OR)
34.04
2-Sided
90
3.10
373.85
Superiority
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.
OG000
OG003
Odds Ratio (OR)
127.21
2-Sided
90
10.55
1533.46
Superiority
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.
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.