Trial to Learn About the Study Medicine (PF-07081532) and Rybelsus in People With Type 2 Diabetes and Separately PF-07081532 in People With Obesity

Study Overview
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Brief Summary
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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.

Official Title
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A PHASE 2, RANDOMIZED, DOUBLE-BLIND, PLACEBO CONTROLLED, DOSE RANGING, DOSE FINDING, PARALLEL GROUP STUDY TO ASSESS EFFICACY AND SAFETY OF PF-07081532, AND OPEN LABEL ORAL SEMAGLUTIDE, IN ADULTS WITH TYPE 2 DIABETES MELLITUS (T2DM) INADEQUATELY CONTROLLED ON METFORMIN, AND SEPARATELY PF-07081532 COMPARED TO MATCHING PLACEBO IN ADULTS WITH OBESITY BUT WITHOUT T2DM

Conditions
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Diabetes Mellitus, Obesity

Intervention / Treatment
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* Drug: PF-07081532
* Other: Placebo
* Drug: Rybelsus


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: T2DM T2DM inadequately controlled with metformin BMI ≥23.0 kg/m2 (≥20.0 kg/m2 in Japan) HbA1C of 7% to 10% (53-86 mmol/mol) FPG ≤270 mg/dL (15 mmol/L) Obesity BMI ≥30.0 kg/m2 HbA1C ≤6.4% (47 mmol/mol) FPG ≤126 mg/dL (7 mmol/L) Exclusion Criteria: Any of the following: Active/current, symptomatic gallbladder disease; History of pancreatitis in the prior 2-months;History of Type 1 Diabetes Mellitus, or secondary forms of diabetes; Any condition affecting drug absorption; Medical history of active liver disease (other than non-alcoholic hepatic steatosis) Use of pharmacological agents with approved indication for weight loss T2DM:Use of any agent (other than metformin)for the explicit purpose of glycemic control;History of diabetic ketoacidosis;Proliferative retinopathy or maculopathy requiring acute treatment; Obesity: Previous or planned weight reduction surgery; Major depressive disorder or other severe psychiatric disorders; Any lifetime history of a suicide attempt; PHQ-9 score ≥15; Response of yes to Question 4 or 5, or on any suicidal behavioral question on the C-SSRS Clinically significant cardiovascular conditions Uncontrolled blood pressure Personal or within first-degree relative family history of MTC or MEN2 Other medical or psychiatric condition that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study Any of the following central lab results: Fasting C-peptide <0.8 ng/mL; ALT or AST ≥2.5x ULN; Direct bilirubin >ULN or T Bili >1.5x ULN except when participants have a history of Gilbert syndrome ; TSH >1.5x ULN or <LLN; Serum calcitonin >ULN; Serum amylase or serum lipase >ULN; eGFR <45 ml/min/1.73 ; Active Hepatitis B, or Hepatitis C; A positive urine drug test for illicit drugs

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PF-07081532 20 mg T2DM<br>PF-07081532 20 mg daily in T2DM | Drug: PF-07081532<br>* Oral glucagon-like peptide-1 receptor agonist<br>|
| Experimental: PF-07081532 40 mg T2DM<br>PF-07081532 40 mg daily in T2DM | Drug: PF-07081532<br>* Oral glucagon-like peptide-1 receptor agonist<br>|
| Experimental: PF-07081532 80 mg T2DM<br>PF-07081532 80 mg daily in T2DM | Drug: PF-07081532<br>* Oral glucagon-like peptide-1 receptor agonist<br>|
| Experimental: PF-07081532 160 mg T2DM<br>PF-07081532 160 mg daily in T2DM | Drug: PF-07081532<br>* Oral glucagon-like peptide-1 receptor agonist<br>|
| Experimental: PF-07081532 260 mg T2DM<br>PF-07081532 260 mg daily in T2DM | Drug: PF-07081532<br>* Oral glucagon-like peptide-1 receptor agonist<br>|
| Placebo Comparator: Placebo T2DM<br>Placebo daily in T2DM | Other: Placebo<br>* No drug<br>|
| Experimental: PF-07081532 80 mg Obesity<br>PF-07081532 80 mg daily in Obesity | Drug: PF-07081532<br>* Oral glucagon-like peptide-1 receptor agonist<br>|
| Experimental: PF-07081532 140 mg Obesity<br>PF-07081532 140 mg daily in Obesity | Drug: PF-07081532<br>* Oral glucagon-like peptide-1 receptor agonist<br>|
| Experimental: PF-07081532 200 mg Obesity (Option 1)<br>PF-07081532 200 mg daily in Obesity | Drug: PF-07081532<br>* Oral glucagon-like peptide-1 receptor agonist<br>|
| Experimental: PF-07081532 200 mg Obesity (Option 2)<br>PF-07081532 200 mg daily in Obesity | Drug: PF-07081532<br>* Oral glucagon-like peptide-1 receptor agonist<br>|
| Experimental: PF-07081532 260 mg Obesity<br>PF-07081532 260 mg daily in Obesity | Drug: PF-07081532<br>* Oral glucagon-like peptide-1 receptor agonist<br>|
| Active Comparator: Rybelsus 14 mg T2DM<br>Semaglutide 14 mg daily in T2DM | Drug: Rybelsus<br>* Oral Semaglutide<br>|
| Placebo Comparator: Placebo Obesity<br>Placebo in Obesity | Other: Placebo<br>* No drug<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Placebo-adjusted, change from baseline in Hemoglobin A1c (HbA1c) at Week 32 in Type 2 Diabetes Mellitus (T2DM) |  | baseline, week 32 | 
| Placebo-adjusted, percent change from baseline in body weight at Week 32 in Obesity |  | baseline, week 32 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants who achieve HbA1C <7% (<53 mmol/mol) at Week 32 in T2DM |  | week 32 | 
| Placebo-adjusted, change from baseline in FPG at Week 32 in T2DM |  | baseline, week 32 | 
| Placebo-adjusted, percent change from baseline in body weight at Week 32 in T2DM |  | baseline, week 32 | 
| Placebo-adjusted, change from baseline in HbA1C at Week 32 with Rybelsus in T2DM |  | baseline, week 32 | 
| Proportion of participants achieving ≥5% body weight loss at Week 32 relative to baseline in Obesity |  | baseline, week 32 | 
| Proportion of participants achieving ≥10% body weight loss at Week 32 relative to baseline in Obesity |  | Week 32 | 
| Proportion of participants achieving≥15% body weight loss at Week 32 relative to baseline in Obesity |  | Week 32 | 
| Placebo-adjusted, absolute change from baseline in waist circumference at Week 32 in Obesity |  | baseline, week 32 | 
| Placebo-adjusted, absolute change from baseline in waist-to hip ratio at Week 32 in Obesity |  | baseline, week 32 | 
| Placebo-adjusted, change from baseline in Homeostatic Model Assessment for Insulin Resistance at Week 32 in Obesity |  | baseline, week 32 | 
| Placebo-adjusted, change from baseline in Homeostatic Model Assessment for Insulin Sensitivity at Week 32 in Obesity |  | baseline, week 32 | 
| To compare PF 07081532 to placebo in the number of participants reporting Adverse Events |  | week 36 and 48 | 
| To compare PF 07081532 to placebo in the number of participants reporting Serious Adverse Events |  | week 36, week 48 | 
| To compare PF 07081532 to placebo in the number of participants reporting Adverse Events leading to discontinuation |  | week 36, week 48 | 
| To compare PF 07081532 to placebo in the number of participants reporting Hypoglycemia |  | Week 36, week 48 | 
| To compare PF 07081532 to placebo in the number of participants with clinical laboratory abnormalities |  | Week 36, week 48 | 
| To compare PF 07081532 to placebo in the number of participants with vital sign abnormalities |  | Week 36, Week 48 | 
| To compare PF 07081532 to placebo in the number of participants with ECG abnormalities |  | Week 34, week 46 | 
| Assessment of mental health as determined by Columbia-Suicide Severity Rating Scale (C-SSRS) in Obesity |  | Week 32 and 44 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes Mellitus, Obesity