This study will assess tolerability, safety, and pharmacodynamics (PD) of twice daily (BID) administration of PF- 06882961 in adult participants with Type 2 Diabetes Mellitus (T2DM) who are treated with metformin and in non-diabetic adults with obesity
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
151
PF-68882961 will be provided as tablets twice a day (BID)
Placebo comparator will be provided as tablets twice daily for 12 weeks
Number of Participants With Treatment Emergent Adverse Events (AEs) by Severity
An AE was any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. TEAEs were events between first dose of study drug and up to follow-up visit that were absent before treatment or that worsened after treatment. AEs presented below were TEAEs. The investigator was required to use clinical judgment to assess the potential relationship between investigational product and each AE, to define an treatment-related AE. Assessments of AE intensity were defined as mild (easily tolerated, causing minimal discomfort and not interfering with daily activities), moderate (causing sufficient discomfort and interferes with normal daily activities) and severe (preventing normal daily activities).
Time frame: Baseline through follow-up (Day 112)
Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)
Safety laboratory assessments included clinical chemistry, hematology, urinalysis, and other tests. Abnormality was determined at the investigator's discretion.
Time frame: Baseline through Visit 10 (Day 91)
Number of Participants With Vital Signs Meeting the Pre-defined Categorical Summarization Criteria
Vital signs abnormality criteria: 1) supine systolic blood pressure (SBP) \<90 millimeters of mercury (mmHg); 2) supine diastolic blood pressure (DBP) \<50 mmHg; 3) supine pulse rate \<40 or \>120 beats per minute (bpm); 4) change from baseline (increase or decrease) in supine SBP \>=30 mmHg; 5) change from baseline (increase or decrease) in supine DBP \>=20 mmHg.
Time frame: Baseline through Visit 10 (Day 91)
Number of Participants With Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria
ECG assessments included pulse rate (PR), QT, heart rate, QTcF intervals and QRS complex. ECG abnormalities criteria included: PR interval value \>= 300 msec, or baseline (BL) \>200 msec and \>=25% increase from BL, or BL \<=200 msec and \>=50% increase from BL; QRS interval value \>= 140msec, or \>=50% increase from BL; QTcF value \>450 and \<=480 msec, or \>480 and \<=500 msec, or \>500 msec, or increase from BL\>30 and \<=60 msec, or \>60msec.
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Arizona Research Center
Phoenix, Arizona, United States
Unity Health - Searcy Medical Center
Searcy, Arkansas, United States
Catalina Research Institute, LLC
Montclair, California, United States
Desert Oasis Healthcare Medical Group
Palm Springs, California, United States
Rancho Cucamonga Clinical Research
Rancho Cucamonga, California, United States
California Research Foundation
San Diego, California, United States
University Clinical Investigators, Inc.
Tustin, California, United States
Diablo Clinical Research, Inc.
Walnut Creek, California, United States
Emerson Clinical Research Institute
Washington D.C., District of Columbia, United States
Innovative Research of West Florida, Inc.
Clearwater, Florida, United States
...and 28 more locations
Time frame: Baseline through Visit 10 (Day 91)
Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS)
The C-SSRS is an interview-based rating scale to systematically assess suicidal ideation and suicidal behavior. Participants who responded "yes" to the questions will be counted. Data relevant to the assessment of suicidality were mapped to the Columbia-Classification Algorithm of Suicide Assessment (C-CASA) codes.
Time frame: Week 0, 2, 4, 6, 8, 10, 12, 13-14
Number of Participants With Response to Patient Health Questionnaire-9 (PHQ-9)
The PHQ-9 is a 9 item self-report scale for the assessment of depressive symptoms. The PHQ-9 were completed by participants and reviewed by site staff at the pre-defined time points.
Time frame: Week 0, 2, 4, 6, 8, 10, 12, 13-14.
Change From Baseline (CFB) in Fasting Plasma Glucose at Week 2
Baseline was defined as the result closest prior to dosing at Day1. The MMRM model included treatment, time, strata (male versus female) 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. An unstructured covariance matrix was used to estimate the variances and covariance within participant across time points.
Time frame: Baseline, Week 2
CFB in Fasting Plasma Glucose at Week 4
Baseline was defined as the result closest prior to dosing at Day1. The MMRM model included treatment, time, strata (male versus female) 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. An unstructured covariance matrix was used to estimate the variances and covariance within participant across time points.
Time frame: Baseline, Week 4
CFB in Fasting Plasma Glucose at Week 6
Baseline was defined as the result closest prior to dosing at Day1. The MMRM model included treatment, time, strata (male versus female) 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. An unstructured covariance matrix was used to estimate the variances and covariance within participant across time points.
Time frame: Baseline, Week 6
CFB in Fasting Plasma Glucose at Week 8
Baseline was defined as the result closest prior to dosing at Day1. The MMRM model included treatment, time, strata (male versus female) 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. An unstructured covariance matrix was used to estimate the variances and covariance within participant across time points.
Time frame: Baseline, Week 8
CFB in Fasting Plasma Glucose at Week 10
Baseline was defined as the result closest prior to dosing at Day1. The MMRM model included treatment, time, strata (male versus female) 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. An unstructured covariance matrix was used to estimate the variances and covariance within participant across time points.
Time frame: Baseline, Week 10
CFB in Fasting Plasma Glucose at Week 12
Baseline was defined as the result closest prior to dosing at Day1. The MMRM model included treatment, time, strata (male versus female) 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. An unstructured covariance matrix was used to estimate the variances and covariance within participant across time points.
Time frame: Baseline, Week 12
CFB in Glycolated Hemoglobin A1c (HbA1c) at Week 2
Baseline was defined as the result closest prior to dosing at Day1. The MMRM model included treatment, time, strata (male versus female) 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. An unstructured covariance matrix was used to estimate the variances and covariance within participant across time points.
Time frame: Baseline, Week 2
CFB in Glycolated HbA1c at Week 4
Baseline was defined as the result closest prior to dosing at Day1. The MMRM model included treatment, time, strata (male versus female) 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. An unstructured covariance matrix was used to estimate the variances and covariance within participant across time points.
Time frame: Baseline, Week 4
CFB in Glycolated HbA1c at Week 6
Baseline was defined as the result closest prior to dosing at Day1. The MMRM model included treatment, time, strata (male versus female) 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. An unstructured covariance matrix was used to estimate the variances and covariance within participant across time points.
Time frame: Baseline, Week 6
CFB in Glycolated HbA1c at Week 8
Baseline was defined as the result closest prior to dosing at Day1. The MMRM model included treatment, time, strata (male versus female) 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. An unstructured covariance matrix was used to estimate the variances and covariance within participant across time points.
Time frame: Baseline, Week 8
CFB in Glycolated HbA1c at Week 10
Baseline was defined as the result closest prior to dosing at Day1. The MMRM model included treatment, time, strata (male versus female) 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. An unstructured covariance matrix was used to estimate the variances and covariance within participant across time points.
Time frame: Baseline, Week 10
CFB in Glycolated HbA1c at Week 12
Baseline was defined as the result closest prior to dosing at Day1. The MMRM model included treatment, time, strata (male versus female) 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. An unstructured covariance matrix was used to estimate the variances and covariance within participant across time points.
Time frame: Baseline, Week 12
CFB in Body Weight at Week 2 (Participants With T2DM)
Baseline was defined as the average of a duplicate measurement closest prior to dosing at Day 1. The MMRM model included treatment, time, strata (male versus female) 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. An unstructured covariance matrix was used to estimate the variances and covariance within participant across time points. Average of the duplicate measurements (where applicable) was used in analyses.
Time frame: Baseline, Week 2
CFB in Body Weight at Week 4 (Participants With T2DM)
Baseline was defined as the average of a duplicate measurement closest prior to dosing at Day 1. The MMRM model included treatment, time, strata (male versus female) 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. An unstructured covariance matrix was used to estimate the variances and covariance within participant across time points. Average of the duplicate measurements (where applicable) was used in analyses.
Time frame: Baseline, Week 4
CFB in Body Weight at Week 6 (Participants With T2DM)
Baseline was defined as the average of a duplicate measurement closest prior to dosing at Day 1. The MMRM model included treatment, time, strata (male versus female) 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. An unstructured covariance matrix was used to estimate the variances and covariance within participant across time points. Average of the duplicate measurements (where applicable) was used in analyses.
Time frame: Baseline, Week 6
CFB in Body Weight at Week 8 (Participants With T2DM)
Baseline was defined as the average of a duplicate measurement closest prior to dosing at Day 1. The MMRM model included treatment, time, strata (male versus female) 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. An unstructured covariance matrix was used to estimate the variances and covariance within participant across time points. Average of the duplicate measurements (where applicable) was used in analyses.
Time frame: Baseline, Week 8
CFB in Body Weight at Week 10 (Participants With T2DM)
Baseline was defined as the average of a duplicate measurement closest prior to dosing at Day 1. The MMRM model included treatment, time, strata (male versus female) 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. An unstructured covariance matrix was used to estimate the variances and covariance within participant across time points. Average of the duplicate measurements (where applicable) was used in analyses.
Time frame: Baseline, Week 10
CFB in Body Weight at Week 12 (Participants With T2DM)
Baseline was defined as the average of a duplicate measurement closest prior to dosing at Day 1. The MMRM model included treatment, time, strata (male versus female) 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. An unstructured covariance matrix was used to estimate the variances and covariance within participant across time points. Average of the duplicate measurements (where applicable) was used in analyses.
Time frame: Baseline, Week 12
CFB in Body Weight at Week 2 (Non-diabetic Participants With Obesity)
Body weight were measured in duplicate as indicated. The second weight measurement were obtained at least 1-2 minutes apart from the first weight measurement. Weight were recorded using a calibrated scale (with the same scale used if possible for the duration of the study) reporting weight in kilograms (kg), and accuracy to the nearest 0.1 kg; ie, the device distinguished a difference between 68.4 kg vs 68.3 kg. The scale was placed on a stable, flat surface. Weight measurement was taken under the following conditions: participant is in a fasted state; after void of urine; after removal of shoes, bulky layers of clothing and jackets so that only light clothing remained; while remaining was during the measurement.
Time frame: Baseline, Week 2
CFB in Body Weight at Week 4 (Non-diabetic Participants With Obesity)
Body weight were measured in duplicate as indicated. The second weight measurement were obtained at least 1-2 minutes apart from the first weight measurement. Weight were recorded using a calibrated scale (with the same scale used if possible for the duration of the study) reporting weight in kilograms (kg), and accuracy to the nearest 0.1 kg; ie, the device distinguished a difference between 68.4 kg vs 68.3 kg. The scale was placed on a stable, flat surface. Weight measurement was taken under the following conditions: participant is in a fasted state; after void of urine; after removal of shoes, bulky layers of clothing and jackets so that only light clothing remained; while remaining was during the measurement.
Time frame: Baseline, Week 4
CFB in Body Weight at Week 6 (Non-diabetic Participants With Obesity)
Body weight were measured in duplicate as indicated. The second weight measurement were obtained at least 1-2 minutes apart from the first weight measurement. Weight were recorded using a calibrated scale (with the same scale used if possible for the duration of the study) reporting weight in kilograms (kg), and accuracy to the nearest 0.1 kg; ie, the device distinguished a difference between 68.4 kg vs 68.3 kg. The scale was placed on a stable, flat surface. Weight measurement was taken under the following conditions: participant is in a fasted state; after void of urine; after removal of shoes, bulky layers of clothing and jackets so that only light clothing remained; while remaining was during the measurement.
Time frame: Baseline, Week 6
CFB in Body Weight at Week 8 (Non-diabetic Participants With Obesity)
Body weight were measured in duplicate as indicated. The second weight measurement were obtained at least 1-2 minutes apart from the first weight measurement. Weight were recorded using a calibrated scale (with the same scale used if possible for the duration of the study) reporting weight in kilograms (kg), and accuracy to the nearest 0.1 kg; ie, the device distinguished a difference between 68.4 kg vs 68.3 kg. The scale was placed on a stable, flat surface. Weight measurement was taken under the following conditions: participant is in a fasted state; after void of urine; after removal of shoes, bulky layers of clothing and jackets so that only light clothing remained; while remaining was during the measurement.
Time frame: Baseline, Week 8
CFB in Body Weight at Week 10 (Non-diabetic Participants With Obesity)
Body weight were measured in duplicate as indicated. The second weight measurement were obtained at least 1-2 minutes apart from the first weight measurement. Weight were recorded using a calibrated scale (with the same scale used if possible for the duration of the study) reporting weight in kilograms (kg), and accuracy to the nearest 0.1 kg; ie, the device distinguished a difference between 68.4 kg vs 68.3 kg. The scale was placed on a stable, flat surface. Weight measurement was taken under the following conditions: participant is in a fasted state; after void of urine; after removal of shoes, bulky layers of clothing and jackets so that only light clothing remained; while remaining was during the measurement.
Time frame: Baseline, Week 10
CFB in Body Weight at Week 12 (Non-diabetic Participants With Obesity)
Body weight were measured in duplicate as indicated. The second weight measurement were obtained at least 1-2 minutes apart from the first weight measurement. Weight were recorded using a calibrated scale (with the same scale used if possible for the duration of the study) reporting weight in kilograms (kg), and accuracy to the nearest 0.1 kg; ie, the device distinguished a difference between 68.4 kg vs 68.3 kg. The scale was placed on a stable, flat surface. Weight measurement was taken under the following conditions: participant is in a fasted state; after void of urine; after removal of shoes, bulky layers of clothing and jackets so that only light clothing remained; while remaining was during the measurement.
Time frame: Baseline, Week 12