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

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

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 Overview

• Status: Terminated
• Conditions: Obesity; Diabetes Mellitus
• Intervention / Treatment: Drug: PF-07081532; Other: Placebo; Drug: Rybelsus

• Study Type: Interventional
• Enrollment (Actual): 902
• Phase: Phase 2

Contacts and Locations

Study Locations

• Bulgaria
  • Stara Zagora, Bulgaria, 6000
    • "Prevencia - 2000 - Medical Center for Prehospital Medical Care" OOD
  • Kyustendil
    • Dupnitsa, Kyustendil, Bulgaria, 2600
      • Medical Centre "Asklepiy"
  • Sofia
    • Botevgrad, Sofia, Bulgaria, 2140
      • MHAT Botevgrad
  • Sofia (stolitsa)
    • Sofia, Sofia (stolitsa), Bulgaria, 1431
      • Diagnostic Consultative Center Aleksandrovska
  • Vratsa
    • Kozloduy, Vratsa, Bulgaria, 3320
      • Medical Center Zdrave 1
• Canada
  • Quebec, Canada, G1W 4R4
    • Centre de Recherche Saint-Louis
  • Quebec, Canada, G1V 4T3
    • Diex Recherche Quebec Inc.
  • British Columbia
    • Victoria, British Columbia, Canada, V8V 4A1
      • Dr. M.B. Jones Inc.
  • New Brunswick
    • Moncton, New Brunswick, Canada, E1G 1A7
      • G A Research Associates
  • Ontario
    • Brampton, Ontario, Canada, L6T 0G1
      • Aggarwal and Associates Limited
    • Guelph, Ontario, Canada, N1H 1B1
      • Dawson Clinical Research
    • London, Ontario, Canada, N5W 6A2
      • Milestone Research Inc.
    • Sarnia, Ontario, Canada, N7T 4X3
      • Bluewater Clinical Research Group Inc.
    • Toronto, Ontario, Canada, M4G 3E8
      • LMC Clinical Research Inc. (Bayview)
  • Quebec
    • Mirabel, Quebec, Canada, J7J 2K8
      • Manna Research Mirabel
    • Victoriaville, Quebec, Canada, G6P 6P6
      • Diex Recherche Victoriavile Inc.
• Czechia
  • Olomouc, Czechia, 779 00
    • Agentura Science Pro
  • Olomouc, Czechia, 779 00
    • Private Practice - Dr. Tomáš Brychta
  • Prague, Czechia, 150 00
    • EUC Klinika Praha
  • Uherske Hradiste, Czechia
    • Clinical Trials Service s.r.o.
  • Jihočeský KRAJ
    • Ceske Budejovice, Jihočeský KRAJ, Czechia, 37011
      • MUDr. Alena Vachova
  • Kralovehradecky KRAY
    • Broumov, Kralovehradecky KRAY, Czechia, 550 01
      • EDUMED s.r.o.
  • Ostrava Město
    • Ostrava, Ostrava Město, Czechia, 700 30
      • Kardiologicka a Angiologicka Ambulance
  • Zlínský KRAJ
    • Uherské Hradiště, Zlínský KRAJ, Czechia, 686 01
      • Clinical Trials Service s.r.o.
• Hungary
  • Budapest, Hungary, 1089
    • ClinDiab Kft.
  • Debrecen, Hungary, 4032
    • Debreceni Egyetem Klinikai Kozpont
  • Debrecen, Hungary, 04032
    • Debreceni Egyetem Klinikai Kozpont
  • Hajdú-bihar
    • Debrecen, Hajdú-bihar, Hungary, 4025
      • Belinus Orvosi és Számitástechnikai Bt
  • Szabolcs-szatmár-bereg
    • Nyíregyháza, Borbánya, Szabolcs-szatmár-bereg, Hungary, 4405
      • Borbánya Praxis
  • Tolna
    • Szekszárd, Tolna, Hungary, 7100
      • CLINFAN Szolgáltató Kft
  • Veszprém
    • Balatonfüred, Veszprém, Hungary, 8230
      • DRC Gyógyszervizsgáló Központ
• Japan
  • Yokohama, Japan, 232-0064
    • Yokohama Minoru Clinic
  • Ibaraki
    • Naka, Ibaraki, Japan, 311-0113
      • Nakakinen clinic
  • Kanagawa
    • Yokohama, Kanagawa, Japan, 232-0064
      • Yokohama Minoru Clinic
  • Osaka
    • Kashiwara, Osaka, Japan, 582-0005
      • Shiraiwa Medical Clinic
    • Suita-shi, Osaka, Japan, 565-0853
      • Medical Corporation Heishinkai OCROM Clinic
  • Tokyo
    • Adachi-ku, Tokyo, Japan, 120-0011
      • Seiwa Clinic
    • Adachi-ku, Tokyo, Japan, 123-0845
      • Seiwa Clinic
    • Chuo-ku, Tokyo, Japan, 103-0027
      • Tokyo-Eki Center-building Clinic
    • Chuo-ku, Tokyo, Japan, 104-0031
      • Fukuwa Clinic
    • Chuo-ku, Tokyo, Japan, 103-0028
      • Medical Corporation Chiseikai Tokyo Center Clinic
    • Shinjuku-ku, Tokyo, Japan, 160-0008
      • Medical Corporation Heishinkai ToCROM Clinic
• Poland
  • Poznan, Poland, 60-589
    • Centrum Zdrowia Metabolicznego Pawel Bogdanski
  • Łódź, Poland, 90-132
    • Gabinet Lekarski Małgorzata Jadwiga Saryusz-Wolska
  • Lubelskie
    • Pulawy, Lubelskie, Poland, 24-100
      • KO-MED Centra Kliniczne Pulawy
  • Małopolskie
    • Oświęcim, Małopolskie, Poland, 32-600
      • Oswiecimskie Centrum Badan Klinicznych
  • Podlaskie
    • Bialystok, Podlaskie, Poland, 15-351
      • Zdrowie Osteo-Medic
  • Pomorskie
    • Gdansk, Pomorskie, Poland, 80-546
      • Centrum Badan Klinicznych PI-House sp. z o.o.
  • Śląskie
    • Ruda Slaska, Śląskie, Poland, 41-709
      • NZOZ Przychodnia Specjalistyczna Andrzej Wittek, Henryk Rudzki
• Puerto Rico
  • San Juan, Puerto Rico, 00909
    • Latin Clinical Trial Center
  • San Juan, Puerto Rico, 00917
    • GCM Medical Group, PSC - Hato Rey Site
• United States
  • Alabama
    • Centreville, Alabama, United States, 35042
      • Trinity Clinical Research
  • California
    • Anaheim, California, United States, 92801
      • Anaheim Clinical Trials, LLC
    • Canoga Park, California, United States, 91304
      • San Fernando Valley Health Institute
    • Montclair, California, United States, 91763
      • Catalina Research Institute, LLC
    • Pomona, California, United States, 91767
      • Empire Clinical Research
    • Tustin, California, United States, 92780
      • University Clinical Investigators, Inc.
    • Walnut Creek, California, United States, 94598
      • Diablo Clinical Research, Inc.
  • Florida
    • Clearwater, Florida, United States, 33756
      • Innovative Research of West Florida
    • Jacksonville, Florida, United States, 32216
      • Jacksonville Center for Clinical Research
    • Mount Dora, Florida, United States, 32757
      • Adult Medicine of Lake County
  • Georgia
    • Roswell, Georgia, United States, 30076
      • Endocrine Research Solutions, Inc.
  • Illinois
    • Chicago, Illinois, United States, 60607
      • Cedar Crosse Research Center
    • Skokie, Illinois, United States, 60077
      • Evanston Premier Healthcare Research LLC
  • Iowa
    • West Des Moines, Iowa, United States, 50265
      • Iowa Diabetes and Endocrinology Research Center
  • Maryland
    • Fort Washington, Maryland, United States, 20744
      • Anderson Medical Research
  • Missouri
    • Saint Peters, Missouri, United States, 63303
      • StudyMetrix Research
  • Montana
    • Butte, Montana, United States, 59701
      • Mercury Street Medical Group, PLLC
  • New Jersey
    • Berlin, New Jersey, United States, 08009
      • Hassman Research Institute
    • Trenton, New Jersey, United States, 08611
      • Premier Research
  • North Carolina
    • Greensboro, North Carolina, United States, 27405
      • Medication Management
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Meridian Clinical Research, LLC
  • Oklahoma
    • Norman, Oklahoma, United States, 73069
      • Alliance for Multispecialty Research, LLC
  • Pennsylvania
    • Beaver, Pennsylvania, United States, 15009
      • Heritage Valley Multispecialty Group, Inc
    • Pittsburgh, Pennsylvania, United States, 15236
      • Preferred Primary Care Physicians, Preferred Clinical Research (Ofc 18)
    • Uniontown, Pennsylvania, United States, 15401
      • Preferred Primary Care Physicians
  • Rhode Island
    • East Greenwich, Rhode Island, United States, 02818
      • Velocity Clinical Research, Providence
  • Tennessee
    • Morristown, Tennessee, United States, 37813
      • HealthStar Physicians
    • Morristown, Tennessee, United States, 37813
      • HealthStar Physicians, P.C.
  • Texas
    • Austin, Texas, United States, 78738
      • Elligo Clinical Research Center
    • Dallas, Texas, United States, 75390
      • UT Southwestern Medical Center
    • Dallas, Texas, United States, 75230
      • Velocity Clinical Research, Dallas
    • Katy, Texas, United States, 77450
      • Medical Colleagues of Texas, LLP
    • Paris, Texas, United States, 75462
      • Tapia Internal Medicine Clinic
    • San Antonio, Texas, United States, 78233
      • Northeast Clinical Research of San Antonio
    • Shavano Park, Texas, United States, 78231
      • Consano Clinical Research, LLC
    • Sugar Land, Texas, United States, 77479
      • Sugar Lakes Family Practice
  • Utah
    • Saint George, Utah, United States, 84790
      • Chrysalis Clinical Research
    • Saint George, Utah, United States, 84790
      • Southwest Internal Medicine
  • Virginia
    • Manassas, Virginia, United States, 20110
      • Manassas Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

13

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Placebo-adjusted, Change From Baseline in Percentage of Glycated Hemoglobin (HbA1c) at Week 32: Cohort 1 (Type 2 Diabetes Mellitus)		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.	Baseline (result closest prior to dosing on Day 1), week 32

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Achieved HbA1C <7% at Week 32: Cohort 1 (Type 2 Diabetes Mellitus)		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)		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.	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.	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)		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).	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).	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).	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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	Baseline (result closest prior to dosing on Day 1), anytime post-baseline (Up to Week 28)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Placebo-adjusted, Change From Baseline in Percentage of Glycated Hemoglobin (HbA1c) at Week 16: Cohort 1 (Type 2 Diabetes Mellitus)	Analysis was performed using mixed model repeated measures (MMRM) model including treatment, gender strata and time as fixed effects, baseline*time interaction, time*treatment interaction, and baseline as a covariate with time fitted as a repeated effect and participant as a random effect.	Baseline [(Baseline is defined as the result closest prior to dosing at Visit 3 (Day 1)], at Week 16
Placebo-adjusted, Percent Change From Baseline in Body Weight at Week 20: Cohort 2 (Obesity)	Body weight was measured using a calibrated weighing scale. Analysis was performed using MMRM model including treatment, gender strata and time as fixed effects, baseline*time interaction, time*treatment interaction, and baseline as a covariate with time fitted as a repeated effect and participant as a random effect.	Baseline [(Baseline is defined as the result closest prior to dosing at Visit 3 (Day 1)], at Week 20
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 16: Cohort 1 (Type 2 Diabetes Mellitus)		Baseline [(Baseline is defined as the result closest prior to dosing at Visit 3 (Day 1)], at Week 16
Percent Change From Baseline in Body Weight at Week 16: Cohort 1 (Type 2 Diabetes Mellitus)	Body weight was measured using a calibrated weighing scale.	Baseline [(Baseline is defined as the result closest prior to dosing at Visit 3 (Day 1)], at Week 16
Placebo-adjusted, Change From Baseline in Percentage of HbA1C in the Rybelsus Arm Versus Placebo Arm at Week 16: Cohort 1 (Type 2 Diabetes Mellitus)	Analysis was performed using MMRM model including treatment, gender strata and time as fixed effects, baseline*time interaction, time*treatment interaction, and baseline as a covariate with time fitted as a repeated effect and participant as a random effect. This outcome measure was planned to be analyzed only for rybelsus arm and placebo arm as pre-specified in the protocol.	Baseline [(Baseline is defined as the result closest prior to dosing at Visit 3 (Day 1)], at Week 16
Absolute Change From Baseline in Waist Circumference at Week 12 and 24: 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 cm] above the navel). It was measured by using an anthropometric tape (stretch-resistant).	Baseline [(Baseline is defined as the result closest prior to dosing at Visit 3 (Day 1)], Week 12, 24
Absolute Change From Baseline in Waist-to-hip Ratio at Week 12 and Week 24: 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).	Baseline [(Baseline is defined as the result closest prior to dosing at Visit 3 (Day 1)], week 12, 24
Change From Baseline in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) at Week 16: Cohort 2 (Obesity)	HOMA-IR was calculated as: ([FPI]*(FPG)/405 in terms of Mg/dL* (milliunits per liter).	Baseline [(Baseline is defined as the result closest prior to dosing at Visit 3 (Day 1)], at Week 16
Change From Baseline in Homeostatic Model Assessment for Insulin Sensitivity (HOMA-S) at Week 16: Cohort 2 (Obesity)	HOMA-S was calculated as (22.5/[FPI]*FPG)) *100 and measured in terms of. percentage sensitivity.	Baseline [(Baseline is defined as the result closest prior to dosing at Visit 3 (Day 1)], at Week 16

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): October 27, 2022
• Primary Completion (Actual): July 14, 2023
• Study Completion (Actual): September 22, 2023

Study Registration Dates

• First Submitted: October 11, 2022
• First Submitted That Met QC Criteria: October 11, 2022
• First Posted (Actual): October 14, 2022

Study Record Updates

• Last Update Posted (Actual): August 1, 2024
• Last Update Submitted That Met QC Criteria: July 9, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Obesity; Diabetes Mellitus
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Overnutrition; Nutrition Disorders; Overweight; Body Weight; Diabetes Mellitus; Obesity; Hypoglycemic Agents; Physiological Effects of Drugs; Glucagon-Like Peptide-1 Receptor Agonists; Semaglutide
• Other Study ID Numbers: C3991004; 2022-002834-15 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No