The purpose of this study is to find out if PF-07081532 ("the active study drug"), is safe and helps treat people with obesity without diabetes to lose weight, and people with diabetes to keep their blood sugar in good control. Individuals diagnosed with diabetes that are on metformin or individuals with obesity without diabetes will be included in the study. Those participating in the diabetes part of the study, will receive either active study drug, placebo, or an approved treatment called Rybelsus. Those in the obesity part of the study, will receive either active study drug or placebo. The study will last for about 36 weeks except for the first 25% of the participants that enter in which case the study will last for approximately 48 weeks. during this time there will be visits every 4 weeks with phone calls in between.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
902
Oral glucagon-like peptide-1 receptor agonist
No drug
Oral Semaglutide
Trinity Clinical Research
Centreville, Alabama, United States
Anaheim Clinical Trials, LLC
Anaheim, California, United States
San Fernando Valley Health Institute
Canoga Park, California, United States
Catalina Research Institute, LLC
Montclair, California, United States
Empire Clinical Research
Pomona, California, United States
Placebo-adjusted, Change From Baseline in Percentage of Glycated Hemoglobin (HbA1c) at Week 32: Cohort 1 (Type 2 Diabetes Mellitus)
Time frame: Baseline (result closest prior to dosing on Day 1), Week 32
Placebo-adjusted, Percent Change From Baseline in Body Weight at Week 32: Cohort 2 (Obesity)
Body weight was measured using a calibrated weighing scale.
Time frame: Baseline (result closest prior to dosing on Day 1), week 32
Percentage of Participants Who Achieved HbA1C <7% at Week 32: Cohort 1 (Type 2 Diabetes Mellitus)
Time frame: Baseline (result closest prior to dosing on Day 1), Week 32
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 32: Cohort 1 (Type 2 Diabetes Mellitus)
Time frame: Baseline (result closest prior to dosing on Day 1), Week 32
Percent Change From Baseline in Body Weight at Week 32: Cohort 1 (Type 2 Diabetes Mellitus)
Body weight was measured using a calibrated weighing scale.
Time frame: Baseline (result closest prior to dosing on Day 1), Week 32
Placebo-adjusted, Change From Baseline in HbA1C in the Rybelsus Arm at Week 32: Cohort 1 (Type 2 Diabetes Mellitus)
This outcome measure was planned to be analyzed only for rybelsus arm and placebo arm as pre-specified in the protocol.
Time frame: Baseline (result closest prior to dosing on Day 1), Week 32
Percentage of Participants Achieving >=5%, >=10%, and >=15% Body Weight Loss at Week 32 Relative to Baseline: Cohort 2 (Obesity)
Time frame: Baseline (result closest prior to dosing on Day 1), Week 32
Absolute Change From Baseline in Waist Circumference at Week 32: Cohort 2 (Obesity)
Waist circumference was measured at midpoint, between lower margin of last palpable rib and top of iliac crest (approximately 1 inch \[2.54 centimeter {cm}\] above the navel). It was measured by using an anthropometric tape (stretch-resistant).
Time frame: Baseline (result closest prior to dosing on Day 1), Week 32
Absolute Change From Baseline in Waist-to-hip Ratio at Week 32: Cohort 2 (Obesity)
The hip circumference was defined as the circumference around the widest portion of the buttocks. Waist circumference was measured at midpoint, between lower margin of last palpable rib and top of iliac crest (approximately 1 inch \[2.54 cm\] above the navel). The measurements were performed using an anthropometric tape (stretch-resistant).
Time frame: Baseline (result closest prior to dosing on Day 1), Week 32
Change From Baseline in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) at Week 32: Cohort 2 (Obesity)
HOMA-IR was calculated as: fasting plasma insulin (\[FPI\]\*(FPG)/405 and measured in terms of mg/dL\* (milliunits per liter).
Time frame: Baseline (result closest prior to dosing on Day 1), Week 32
Change From Baseline in Homeostatic Model Assessment for Insulin Sensitivity (HOMA-S) at Week 32: Cohort 2 (Obesity)
HOMA-S was calculated as (22.5/\[FPI\] \* FPG) \*100 and measured in terms of percentage sensitivity.
Time frame: Baseline (result closest prior to dosing on Day 1), Week 32
Number of Participants With Treatment Emergent Adverse Events (TEAEs): Cohort 1 (Type 2 Diabetes Mellitus)
An adverse event (AE) was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were any AEs that occurred on or after the first dose of treatment but before the last dose plus lag time.
Time frame: From start of treatment up to minimum of 28 days after last dose of treatment administration (maximum up to Week 28)
Number of Participants With Treatment Emergent Adverse Events (TEAEs): Cohort 2 (Obesity)
An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were any AEs that occurred on or after the first dose of treatment but before the last dose plus lag time.
Time frame: From start of treatment up to minimum of 28 days after last dose of treatment administration (maximum up to Week 28)
Number of Participants With Serious Adverse Events (SAEs): Cohort 1 (Type 2 Diabetes Mellitus)
SAE defined as any untoward medical occurrence that, at any dose, met one or more of the following criteria: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); resulted in congenital anomaly/birth defect; was a suspected transmission via a Pfizer product of an infectious agent, pathogenic or non-pathogenic; other important medical events.
Time frame: From start of treatment up to minimum of 28 days after last dose of treatment administration (maximum up to Week 28)
Number of Participants With Serious Adverse Events (SAEs): Cohort 2 (Obesity)
SAE defined as any untoward medical occurrence that, at any dose, met one or more of the following criteria: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); resulted in congenital anomaly/birth defect; was a suspected transmission via a Pfizer product of an infectious agent, pathogenic or non-pathogenic; other important medical events.
Time frame: From start of treatment up to minimum of 28 days after last dose of treatment administration (maximum up to Week 28)
Number of Participants Reporting Adverse Events Leading to Permanent Discontinuation From Study Treatment and Study: Cohort 1 (Type 2 Diabetes Mellitus)
\\ An AE was any untoward medical occurrence in a participants or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. AEs leading to permanent discontinuation from study were those with an AE record indicating the AE caused permanent discontinuation from the study. AEs leading to permanent discontinuation from study treatment were those AEs with an AE record indicating that action taken with study treatment was drug withdrawn but AE did not cause the participant to be discontinued from study.
Time frame: From start of treatment up to minimum of 28 days after last dose of treatment administration (maximum up to Week 28)
Number of Participants Reporting Adverse Events Leading to Permanent Discontinuation From Study Treatment and Study: Cohort 2 (Obesity)
An AE was any untoward medical occurrence in a participants or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. AEs leading to permanent discontinuation from study were those with an AE record indicating the AE caused permanent discontinuation from the study. AEs leading to permanent discontinuation from study treatment were those AEs with an AE record indicating that action taken with study treatment was drug withdrawn but AE did not cause the participant to be discontinued from study.
Time frame: From start of treatment up to minimum of 28 days after last dose of treatment administration (maximum up to Week 28)
Number of Participants With Hypoglycemic Adverse Events (HAE) According to Titration Dose: Cohort 1 (Type 2 Diabetes Mellitus)
Glucose values were monitored using glucometer. Hypoglycemia =plasma/blood glucose value of \<70 mg/dL (3.9 millimoles per liter \[mmol/L\]). Severe HAE: Participant was unable to treat him/herself due to neurological impairment (not age) and required assistance of another person, at least one neurological symptom of memory loss, confusion, uncontrolled behavior etc. Either documented blood glucose\<=54 mg/dL (2.7 mmol/L). Documented symptomatic: An event during which symptoms of HAE were accompanied with plasma/blood glucose \<70 mg/dL and prompt resolution with food intake, SC glucagon, or IV glucose. Probable symptomatic HAE: An event during which symptoms of an HAE were not accompanied by a plasma glucose determination but was presumably caused by a plasma glucose concentration \<70 mg/dL and prompt resolution with food intake, SC glucagon, or IV glucose. Asymptomatic: An event not accompanied by typical symptoms of an HAE, but a plasma/blood glucose value of \<70 mg/dL was reported.
Time frame: Up to week 28
Number of Participants With Hypoglycemic Adverse Events According to Titration Dose: Cohort 2 (Obesity)
Glucose values were monitored using glucometer. Hypoglycemia =plasma/blood glucose value of \<70 mg/dL (3.9 mmol/L). Severe HAE: Participant was unable to treat him/herself due to neurological impairment (not age) and required assistance of another person, at least one neurological symptom of memory loss, confusion, uncontrolled behavior etc. Either documented blood glucose\<=54 mg/dL (2.7 mmol/L). Documented symptomatic: An event during which symptoms of HAE were accompanied with plasma/blood glucose \<70 mg/dL u and prompt resolution with food intake, SC glucagon, or IV glucose. Probable symptomatic HAE: An event during which symptoms of an HAE were not accompanied by a plasma glucose determination but was presumably caused by a plasma glucose concentration \<70 mg/dL and prompt resolution with food intake, SC glucagon, or IV glucose. Asymptomatic: An event not accompanied by typical symptoms of an HAE, but a plasma/blood glucose value of \<70 mg/dL was reported.
Time frame: Up to week 28
Number of Participants With Vital Sign Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)
Vital signs included blood pressure and pulse rate and were measured with the participants in a seated position after at least 5 minutes of rest for the participant. Criteria for abnormalities included: Systolic Blood Pressure (millimeter of mercury \[mmHg\]): value more than (\>) 200 and value less than (\<) 90; Diastolic blood pressure: value \> 100 and \< 40; Pulse rate: (beats per minute \[BPM\]): value \< 40 and \> 110.
Time frame: Up to week 28
Number of Participants With Vital Sign Abnormalities: Cohort 2 (Obesity)
Vital signs included blood pressure and pulse rate and were measured with the participants in a seated position after at least 5 minutes of rest for the participant. Criteria for abnormalities included: Systolic blood pressure (mmHg): value \> 200 and value \< 90; Diastolic blood pressure: value \> 100 and \< 40; Pulse rate: (BPM): value \< 40 and \> 110.
Time frame: Up to week 28
Number of Participants With Clinical Laboratory Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)
Hematology: platelets (10\^9/L)\< 0.5\*lower limit of normal (LLN); leukocytes\< 0.6\*LLN and \>1.5\*upper limit of normal (ULN); lymphocytes and neutrophils \<0.8\*LLN and \>1.2\*ULN; basophils, eosinophils, monocytes:\>1.2\*ULN; prothrombin time (sec) \>1.1\*ULN; prothrombin international normalized ratio \>1.1\*ULN; clinical chemistry: bilirubin (mg/dL), indirect bilirubin:\>1.5\*ULN; aspartate and alanine aminotransferase, gamma glutamyl transferase (U/L):\>3.0\*ULN; urea nitrogen and creatinine (mg/dL)\>1.3\* ULN;HDL cholesterol (mg/dL)\<0.8\*LLN; LDL (mg/dL)\>1.2\*ULN, Triglycerides (mg/dL):\>1.3\*ULN; Potassium (milliequivalents per liter) \< 0.9\*LLN and \> 1.1\* ULN; calcium (mg/dL)\< 0.9\*LLN, Thyroxine (nanograms/dL\<0.8\*LLN and \>1.2\*ULN, HbA1C (%)\>1.3\*ULN; Amylase, Lipase (U/L) and Glucose -Fasting (mg/dL)\>1.5\*ULN; urinalysis: pH\> 8; urine glucose, ketones, protein, hemoglobin, nitrite and leukocyte esterase\>=1. Number of participants with abnormalities in any of the laboratory parameters is reported.
Time frame: Up to week 28
Number of Participants With Clinical Laboratory Abnormalities: Cohort 2 (Obesity)
Hematology: platelets (10\^9/L)\< 0.5\* LLN; leukocytes\< 0.6\*LLN and \>1.5\*ULN; lymphocytes and neutrophils \<0.8\*LLN and \>1.2\*ULN; basophils, eosinophils, monocytes:\>1.2\*ULN; prothrombin time (sec) \>1.1\*ULN; prothrombin international normalized ratio \>1.1\*ULN; clinical chemistry: bilirubin (mg/dL), indirect bilirubin:\>1.5\*ULN; aspartate and alanine aminotransferase, gamma glutamyl transferase (U/L):\>3.0\*ULN; urea nitrogen and creatinine (mg/dL)\>1.3\* ULN;HDL cholesterol (mg/dL)\<0.8\*LLN; LDL (mg/dL)\>1.2\*ULN, Triglycerides (mg/dL):\>1.3\*ULN; Potassium (milliequivalents per liter) \< 0.9\*LLN and \> 1.1\* ULN; calcium (mg/dL)\< 0.9\*LLN, Thyroxine (nanograms/dL\<0.8\*LLN and \>1.2\*ULN, HbA1C (%)\>1.3\*ULN; Amylase, Lipase (U/L) and Glucose -Fasting (mg/dL)\>1.5\*ULN; urinalysis: pH\> 8; urine glucose, ketones, protein, hemoglobin, nitrite and leukocyte esterase\>=1. Number of participants with abnormalities in any of the laboratory parameters is reported.
Time frame: Up to week 28
Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)
Standard 12-lead ECGs were performed after the participant had rested quietly for more than 10 minutes in a supine position utilizing an ECG machine that automatically calculated the heart rate and measured PR interval, QT interval, QT interval corrected using Fridericia's formula (QTcF), and QRS complex. ECG abnormalities were categorized as: PR interval (milliseconds \[msec\]), Value \>= 300; percent change (%Chg) greater than equal (\>=) 25/50%. QRS duration (msec): Value \>= 140 and %Chg \>= 50%. QT interval (msec): Value \> 500; QTCF interval (msec): 450 \< Value \<= 480, 480 \< Value \<= 500, Value \> 500; 30 \<= Change (Chg) \<= 60; Chg \> 60.
Time frame: Up to week 28
Number of Participants With ECG Abnormalities: Cohort 2 (Obesity)
Standard 12-lead ECGs were performed after the participant had rested quietly for more than 10 minutes in a supine position utilizing an ECG machine that automatically calculated the heart rate and measured PR interval, QT interval, QTcF, and QRS complex. ECG abnormalities were categorized as: PR interval msec, Value \>= 300; percentage change (%Chg) \>= 25/50%. QRS duration (msec): Value \>= 140 and %Chg \>= 50%. QT interval (msec): Value \> 500; QTCF interval (msec): 450 \< Value \<= 480, 480 \< Value \<= 500, Value \> 500; 30 \<= Change (Chg) \<= 60; Chg \> 60.
Time frame: Up to week 28
Number of Participants According to Columbia-Suicide Severity Rating Scale (C-SSRS) Category: Cohort 2 (Obesity) Only
C-SSRS is an interview-based rating scale to assess suicidal ideation and suicidal behavior and had a binary response (yes/no). C-SSRS data was mapped to C-CASA per Guidance for Industry: Suicidal Ideation and Behavior: Prospective Assessment of Occurrence in Clinical Trials. A participant was said to have suicidal behavior in case of any of following events: 1) completed suicide; 2) suicide attempt; or 3) preparatory acts toward imminent suicidal behavior. A participant showed suicidal ideation if they responded 'yes' to any of the 5 questions, 'Wish to be dead; Non-Specific Active Suicidal Thoughts Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act; active Suicidal Ideation with Some Intent to Act, without Specific Plan; Active Suicidal Ideation with Specific Plan and Intent. The participant was said to exhibit Self-injurious behavior, no suicidal intent if they responded as Yes to 'Has participant engaged in Non-suicidal Self-Injurious Behavior
Time frame: Baseline (result closest prior to dosing on Day 1), anytime post-baseline (Up to Week 28)
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