Clinical trial NCT05579977: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Diabetes Mellitus
Obesity
Keywords: Diabetes Mellitus
Obesity
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2022-10-14
Enrollment: 902
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Placebo-adjusted, Change From Baseline in Percentage of Glycated Hemoglobin (HbA1c) at Week 32: Cohort 1 (Type 2 Diabetes Mellitus)
timeFrame: Baseline (result closest prior to dosing on Day 1), Week 32
measure: Placebo-adjusted, Percent Change From Baseline in Body Weight at Week 32: Cohort 2 (Obesity)
timeFrame: Baseline (result closest prior to dosing on Day 1), week 32
Secondary outcomes:
measure: Percentage of Participants Who Achieved HbA1C <7% at Week 32: Cohort 1 (Type 2 Diabetes Mellitus)
timeFrame: Baseline (result closest prior to dosing on Day 1), Week 32
measure: Change From Baseline in Fasting Plasma Glucose (FPG) at Week 32: Cohort 1 (Type 2 Diabetes Mellitus)
timeFrame: Baseline (result closest prior to dosing on Day 1), Week 32
measure: Percent Change From Baseline in Body Weight at Week 32: Cohort 1 (Type 2 Diabetes Mellitus)
timeFrame: Baseline (result closest prior to dosing on Day 1), Week 32
measure: Placebo-adjusted, Change From Baseline in HbA1C in the Rybelsus Arm at Week 32: Cohort 1 (Type 2 Diabetes Mellitus)
timeFrame: Baseline (result closest prior to dosing on Day 1), Week 32
measure: Percentage of Participants Achieving >=5%, >=10%, and >=15% Body Weight Loss at Week 32 Relative to Baseline: Cohort 2 (Obesity)
timeFrame: Baseline (result closest prior to dosing on Day 1), Week 32
measure: Absolute Change From Baseline in Waist Circumference at Week 32: Cohort 2 (Obesity)
timeFrame: Baseline (result closest prior to dosing on Day 1), Week 32
measure: Absolute Change From Baseline in Waist-to-hip Ratio at Week 32: Cohort 2 (Obesity)
timeFrame: Baseline (result closest prior to dosing on Day 1), Week 32
measure: Change From Baseline in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) at Week 32: Cohort 2 (Obesity)
timeFrame: Baseline (result closest prior to dosing on Day 1), Week 32
measure: Change From Baseline in Homeostatic Model Assessment for Insulin Sensitivity (HOMA-S) at Week 32: Cohort 2 (Obesity)
timeFrame: Baseline (result closest prior to dosing on Day 1), Week 32
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs): Cohort 1 (Type 2 Diabetes Mellitus)
timeFrame: From start of treatment up to minimum of 28 days after last dose of treatment administration (maximum up to Week 28)
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs): Cohort 2 (Obesity)
timeFrame: From start of treatment up to minimum of 28 days after last dose of treatment administration (maximum up to Week 28)
measure: Number of Participants With Serious Adverse Events (SAEs): Cohort 1 (Type 2 Diabetes Mellitus)
timeFrame: From start of treatment up to minimum of 28 days after last dose of treatment administration (maximum up to Week 28)
measure: Number of Participants With Serious Adverse Events (SAEs): Cohort 2 (Obesity)
timeFrame: From start of treatment up to minimum of 28 days after last dose of treatment administration (maximum up to Week 28)
measure: Number of Participants Reporting Adverse Events Leading to Permanent Discontinuation From Study Treatment and Study: Cohort 1 (Type 2 Diabetes Mellitus)
timeFrame: From start of treatment up to minimum of 28 days after last dose of treatment administration (maximum up to Week 28)
measure: Number of Participants Reporting Adverse Events Leading to Permanent Discontinuation From Study Treatment and Study: Cohort 2 (Obesity)
timeFrame: From start of treatment up to minimum of 28 days after last dose of treatment administration (maximum up to Week 28)
measure: Number of Participants With Hypoglycemic Adverse Events (HAE) According to Titration Dose: Cohort 1 (Type 2 Diabetes Mellitus)
timeFrame: Up to week 28
measure: Number of Participants With Hypoglycemic Adverse Events According to Titration Dose: Cohort 2 (Obesity)
timeFrame: Up to week 28
measure: Number of Participants With Vital Sign Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)
timeFrame: Up to week 28
measure: Number of Participants With Vital Sign Abnormalities: Cohort 2 (Obesity)
timeFrame: Up to week 28
measure: Number of Participants With Clinical Laboratory Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)
timeFrame: Up to week 28
measure: Number of Participants With Clinical Laboratory Abnormalities: Cohort 2 (Obesity)
timeFrame: Up to week 28
measure: Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)
timeFrame: Up to week 28
measure: Number of Participants With ECG Abnormalities: Cohort 2 (Obesity)
timeFrame: Up to week 28
measure: Number of Participants According to Columbia-Suicide Severity Rating Scale (C-SSRS) Category: Cohort 2 (Obesity) Only
timeFrame: Baseline (result closest prior to dosing on Day 1), anytime post-baseline (Up to Week 28)
Other outcomes:
measure: Placebo-adjusted, Change From Baseline in Percentage of Glycated Hemoglobin (HbA1c) at Week 16: Cohort 1 (Type 2 Diabetes Mellitus)
timeFrame: Baseline [(Baseline is defined as the result closest prior to dosing at Visit 3 (Day 1)], at Week 16
measure: Placebo-adjusted, Percent Change From Baseline in Body Weight at Week 20: Cohort 2 (Obesity)
timeFrame: Baseline [(Baseline is defined as the result closest prior to dosing at Visit 3 (Day 1)], at Week 20
measure: Change From Baseline in Fasting Plasma Glucose (FPG) at Week 16: Cohort 1 (Type 2 Diabetes Mellitus)
timeFrame: Baseline [(Baseline is defined as the result closest prior to dosing at Visit 3 (Day 1)], at Week 16
measure: Percent Change From Baseline in Body Weight at Week 16: Cohort 1 (Type 2 Diabetes Mellitus)
timeFrame: Baseline [(Baseline is defined as the result closest prior to dosing at Visit 3 (Day 1)], at Week 16
measure: 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)
timeFrame: Baseline [(Baseline is defined as the result closest prior to dosing at Visit 3 (Day 1)], at Week 16
measure: Absolute Change From Baseline in Waist Circumference at Week 12 and 24: Cohort 2 (Obesity)
timeFrame: Baseline [(Baseline is defined as the result closest prior to dosing at Visit 3 (Day 1)], Week 12, 24
measure: Absolute Change From Baseline in Waist-to-hip Ratio at Week 12 and Week 24: Cohort 2 (Obesity)
timeFrame: Baseline [(Baseline is defined as the result closest prior to dosing at Visit 3 (Day 1)], week 12, 24
measure: Change From Baseline in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) at Week 16: Cohort 2 (Obesity)
timeFrame: Baseline [(Baseline is defined as the result closest prior to dosing at Visit 3 (Day 1)], at Week 16
measure: Change From Baseline in Homeostatic Model Assessment for Insulin Sensitivity (HOMA-S) at Week 16: Cohort 2 (Obesity)
timeFrame: Baseline [(Baseline is defined as the result closest prior to dosing at Visit 3 (Day 1)], at Week 16
Locations:
city: Centreville
country: United States
facility: Trinity Clinical Research
state: Alabama
city: Anaheim
country: United States
facility: Anaheim Clinical Trials, LLC
state: California
city: Canoga Park
country: United States
facility: San Fernando Valley Health Institute
state: California
city: Montclair
country: United States
facility: Catalina Research Institute, LLC
state: California
city: Pomona
country: United States
facility: Empire Clinical Research
state: California
city: Tustin
country: United States
facility: University Clinical Investigators, Inc.
state: California
city: Walnut Creek
country: United States
facility: Diablo Clinical Research, Inc.
state: California
city: Clearwater
country: United States
facility: Innovative Research of West Florida
state: Florida
city: Jacksonville
country: United States
facility: Jacksonville Center for Clinical Research
state: Florida
city: Mount Dora
country: United States
facility: Adult Medicine of Lake County
state: Florida
city: Roswell
country: United States
facility: Endocrine Research Solutions, Inc.
state: Georgia
city: Chicago
country: United States
facility: Cedar Crosse Research Center
state: Illinois
city: Skokie
country: United States
facility: Evanston Premier Healthcare Research LLC
state: Illinois
city: West Des Moines
country: United States
facility: Iowa Diabetes and Endocrinology Research Center
state: Iowa
city: Fort Washington
country: United States
facility: Anderson Medical Research
state: Maryland
city: Saint Peters
country: United States
facility: StudyMetrix Research
state: Missouri
city: Butte
country: United States
facility: Mercury Street Medical Group, PLLC
state: Montana
city: Berlin
country: United States
facility: Hassman Research Institute
state: New Jersey
city: Trenton
country: United States
facility: Premier Research
state: New Jersey
city: Greensboro
country: United States
facility: Medication Management
state: North Carolina
city: Cincinnati
country: United States
facility: Meridian Clinical Research, LLC
state: Ohio
city: Norman
country: United States
facility: Alliance for Multispecialty Research, LLC
state: Oklahoma
city: Beaver
country: United States
facility: Heritage Valley Multispecialty Group, Inc
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Preferred Primary Care Physicians, Preferred Clinical Research (Ofc 18)
state: Pennsylvania
city: Uniontown
country: United States
facility: Preferred Primary Care Physicians
state: Pennsylvania
city: East Greenwich
country: United States
facility: Velocity Clinical Research, Providence
state: Rhode Island
city: Morristown
country: United States
facility: HealthStar Physicians, P.C.
state: Tennessee
city: Morristown
country: United States
facility: Healthstar Physicians
state: Tennessee
city: Austin
country: United States
facility: Elligo Clinical Research Center
state: Texas
city: Dallas
country: United States
facility: Velocity Clinical Research, Dallas
state: Texas
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Katy
country: United States
facility: Medical Colleagues of Texas, LLP
state: Texas
city: Paris
country: United States
facility: Tapia Internal Medicine Clinic
state: Texas
city: San Antonio
country: United States
facility: Northeast Clinical Research of San Antonio
state: Texas
city: Shavano Park
country: United States
facility: Consano Clinical Research, LLC
state: Texas
city: Sugar Land
country: United States
facility: Sugar Lakes Family Practice
state: Texas
city: Saint George
country: United States
facility: Chrysalis Clinical Research
state: Utah
city: Saint George
country: United States
facility: Southwest Internal Medicine
state: Utah
city: Manassas
country: United States
facility: Manassas Clinical Research Center
state: Virginia
city: Dupnitsa
country: Bulgaria
facility: Medical Centre "Asklepiy"
state: Kyustendil
city: Sofia
country: Bulgaria
facility: Diagnostic Consultative Center Aleksandrovska
state: Sofia (stolitsa)
city: Botevgrad
country: Bulgaria
facility: MHAT Botevgrad
state: Sofia
city: Kozloduy
country: Bulgaria
facility: Medical Center Zdrave 1
state: Vratsa
city: Stara Zagora
country: Bulgaria
facility: "Prevencia - 2000 - Medical Center for Prehospital Medical Care" OOD
city: Victoria
country: Canada
facility: Dr. M.B. Jones Inc.
state: British Columbia
city: Moncton
country: Canada
facility: G A Research Associates
state: New Brunswick
city: Brampton
country: Canada
facility: Aggarwal and Associates Limited
state: Ontario
city: Guelph
country: Canada
facility: Dawson Clinical Research
state: Ontario
city: London
country: Canada
facility: Milestone Research Inc.
state: Ontario
city: Sarnia
country: Canada
facility: Bluewater Clinical Research Group Inc.
state: Ontario
city: Toronto
country: Canada
facility: LMC Clinical Research Inc. (Bayview)
state: Ontario
city: Mirabel
country: Canada
facility: Manna Research Mirabel
state: Quebec
city: Victoriaville
country: Canada
facility: Diex Recherche Victoriavile Inc.
state: Quebec
city: Quebec
country: Canada
facility: Diex Recherche Quebec Inc.
city: Quebec
country: Canada
facility: Centre de Recherche Saint-Louis
city: Ceske Budejovice
country: Czechia
facility: MUDr. Alena Vachova
state: Jihočeský KRAJ
city: Broumov
country: Czechia
facility: EDUMED s.r.o.
state: Kralovehradecky KRAY
city: Ostrava
country: Czechia
facility: Kardiologicka a Angiologicka Ambulance
state: Ostrava Město
city: Uherské Hradiště
country: Czechia
facility: Clinical Trials Service s.r.o.
state: Zlínský KRAJ
city: Olomouc
country: Czechia
facility: Agentura Science Pro
city: Olomouc
country: Czechia
facility: Private Practice - Dr. Tomáš Brychta
city: Prague
country: Czechia
facility: EUC Klinika Praha
city: Uherske Hradiste
country: Czechia
facility: Clinical Trials Service s.r.o.
city: Debrecen
country: Hungary
facility: Belinus Orvosi és Számitástechnikai Bt
state: Hajdú-bihar
city: Nyíregyháza, Borbánya
country: Hungary
facility: Borbánya Praxis
state: Szabolcs-szatmár-bereg
city: Szekszárd
country: Hungary
facility: CLINFAN Szolgáltató Kft
state: Tolna
city: Balatonfüred
country: Hungary
facility: DRC Gyógyszervizsgáló Központ
state: Veszprém
city: Budapest
country: Hungary
facility: ClinDiab Kft.
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Kozpont
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Kozpont
city: Naka
country: Japan
facility: Nakakinen clinic
state: Ibaraki
city: Yokohama
country: Japan
facility: Yokohama Minoru Clinic
state: Kanagawa
city: Kashiwara
country: Japan
facility: Shiraiwa Medical Clinic
state: Osaka
city: Suita-shi
country: Japan
facility: Medical Corporation Heishinkai OCROM Clinic
state: Osaka
city: Adachi-ku
country: Japan
facility: Seiwa Clinic
state: Tokyo
city: Adachi-ku
country: Japan
facility: Seiwa Clinic
state: Tokyo
city: Chuo-ku
country: Japan
facility: Tokyo-Eki Center-building Clinic
state: Tokyo
city: Chuo-ku
country: Japan
facility: Medical Corporation Chiseikai Tokyo Center Clinic
state: Tokyo
city: Chuo-ku
country: Japan
facility: Fukuwa Clinic
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Medical Corporation Heishinkai ToCROM Clinic
state: Tokyo
city: Yokohama
country: Japan
facility: Yokohama Minoru Clinic
city: Pulawy
country: Poland
facility: KO-MED Centra Kliniczne Pulawy
state: Lubelskie
city: Oświęcim
country: Poland
facility: Oświęcimskie Centrum Badań Klinicznych
state: Małopolskie
city: Bialystok
country: Poland
facility: Zdrowie Osteo-Medic
state: Podlaskie
city: Gdansk
country: Poland
facility: Centrum Badan Klinicznych PI-House sp. z o.o.
state: Pomorskie
city: Poznan
country: Poland
facility: Centrum Zdrowia Metabolicznego Pawel Bogdanski
city: Łódź
country: Poland
facility: Gabinet Lekarski Małgorzata Jadwiga Saryusz-Wolska
city: Ruda Slaska
country: Poland
facility: NZOZ Przychodnia Specjalistyczna Andrzej Wittek, Henryk Rudzki
state: Śląskie
city: San Juan
country: Puerto Rico
facility: Latin Clinical Trial Center
city: San Juan
country: Puerto Rico
facility: GCM Medical Group, PSC - Hato Rey Site
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: