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

• ClinicalTrials.gov Identifier: NCT05579977
• Recruitment Status: Terminated
• First Posted: October 14, 2022
• Last Update Posted: February 20, 2024
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: October 11, 2022
• First Posted Date: October 14, 2022
• Last Update Posted Date: February 20, 2024
• Actual Study Start Date: October 27, 2022
• Actual Primary Completion Date: July 14, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 11, 2022)

• Placebo-adjusted, change from baseline in Hemoglobin A1c (HbA1c) at Week 32 in Type 2 Diabetes Mellitus (T2DM) [ Time Frame: baseline, week 32 ]
• Placebo-adjusted, percent change from baseline in body weight at Week 32 in Obesity [ Time Frame: baseline, week 32 ]

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 11, 2022)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• Official Title: 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

Brief Summary

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• Diabetes Mellitus
• Obesity

Intervention

• Drug: PF-07081532
  Oral glucagon-like peptide-1 receptor agonist
• Other: Placebo
  No drug
• Drug: Rybelsus
  Oral Semaglutide

Study Arms

• Experimental: PF-07081532 20 mg T2DM
  PF-07081532 20 mg daily in T2DM
  Intervention: Drug: PF-07081532
• Experimental: PF-07081532 40 mg T2DM
  PF-07081532 40 mg daily in T2DM
  Intervention: Drug: PF-07081532
• Experimental: PF-07081532 80 mg T2DM
  PF-07081532 80 mg daily in T2DM
  Intervention: Drug: PF-07081532
• Experimental: PF-07081532 160 mg T2DM
  PF-07081532 160 mg daily in T2DM
  Intervention: Drug: PF-07081532
• Experimental: PF-07081532 260 mg T2DM
  PF-07081532 260 mg daily in T2DM
  Intervention: Drug: PF-07081532
• Placebo Comparator: Placebo T2DM
  Placebo daily in T2DM
  Intervention: Other: Placebo
• Experimental: PF-07081532 80 mg Obesity
  PF-07081532 80 mg daily in Obesity
  Intervention: Drug: PF-07081532
• Experimental: PF-07081532 140 mg Obesity
  PF-07081532 140 mg daily in Obesity
  Intervention: Drug: PF-07081532
• Experimental: PF-07081532 200 mg Obesity (Option 1)
  PF-07081532 200 mg daily in Obesity
  Intervention: Drug: PF-07081532
• Experimental: PF-07081532 200 mg Obesity (Option 2)
  PF-07081532 200 mg daily in Obesity
  Intervention: Drug: PF-07081532
• Experimental: PF-07081532 260 mg Obesity
  PF-07081532 260 mg daily in Obesity
  Intervention: Drug: PF-07081532
• Active Comparator: Rybelsus 14 mg T2DM
  Semaglutide 14 mg daily in T2DM
  Intervention: Drug: Rybelsus
• Placebo Comparator: Placebo Obesity
  Placebo in Obesity
  Intervention: Other: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: June 26, 2023): 902
• Original Estimated Enrollment (submitted: October 11, 2022): 780
• Actual Study Completion Date: September 22, 2023
• Actual Primary Completion Date: July 14, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Bulgaria, Canada, Czechia, Hungary, Japan, Poland, Puerto Rico, United States

Administrative Information

• NCT Number: NCT05579977
• Other Study ID Numbers: C3991004; 2022-002834-15 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: 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.
• URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

• Current Responsible Party: Pfizer
• Original Responsible Party: Same as current
• Current Study Sponsor: Pfizer
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: February 2024