Study of Multiple Oral Doses of PF-07081532 in Adult Participants With Type 2 Diabetes Mellitus

A PHASE 1, RANDOMIZED, DOUBLE-BLIND, SPONSOR-OPEN, PLACEBO-CONTROLLED STUDY TO ASSESS THE SAFETY, TOLERABILITY, AND PHARMACOKINETICS OF MULTIPLE ORAL DOSES OF PF-07081532 IN ADULT PARTICIPANTS WITH TYPE 2 DIABETES MELLITUS

This is a Phase 1, randomized, placebo-controlled, double-blind (investigator- and participant-blinded), sponsor-open study of PF-07081532. Study participants will receive the investigational product or placebo every day for 42 days.

The purpose of the study is to evaluate the safety, tolerability and pharmacokinetics (PK) of multiple oral doses of PF-07081532 in participants with inadequately controlled type 2 diabetes mellitus, on metformin and optionally in non-diabetic participants with obesity.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: PF-07081532; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • South Miami, Florida, United States, 33143
      • Qps-Mra, Llc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Females of non childbearing potential;
• Patients with T2DM, inadequately controlled with metformin;
• HbA1c ≥7.0% to ≤10.5% (for T2DM); HbA1c <6.5% (for non-diabetic obese, if enrolled)
• Total body weight >50 kg (110 lbs)
• BMI ≥24.5 to ≤45.5 kg/m2 (T2DM), BMI >30.5 to ≤45.5 kg/m2 (for non-diabetic obese)

Exclusion Criteria

• Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, hepatic, psychiatric, neurological, dermatological, or allergic disease;
• Medical history of T2DM (for non-diabetic obese participants, if enrolled);
• Diagnosis of type 1 diabetes mellitus or secondary forms of diabetes;
• Evidence or history of clinically significant cardiovascular disease;
• Any malignancy not considered cured;
• Acute pancreatitis or history of chronic pancreatitis;
• Acute gallbladder disease;
• Any condition possibly affecting drug absorption;
• Personal or family history of MTC or MEN2;
• Medical or psychiatric condition that may increase the risk of study participation;
• Any vaccination within the 1 week prior to admission to the CRU;
• Previous administration with an investigational drug within 30 days or 5 half-lives preceding first dose;
• Known prior participation in a trial involving PF-07081532;
• A positive urine drug screen at screening or admission;
• Positive testing at screening for HIV, HBsAg, HBcAb, HBsAb or HCVAb;
• Positive COVID-19 test at screening or admission;
• Supine BP ≥160 mm Hg (systolic) or ≥100 mm Hg (diastolic);
• 12-lead ECG clinically relevant abnormalities that may affect participant safety or interpretation of study results;

• Participants with ANY of the following abnormalities in clinical laboratory tests: *AST or ALT level ≥1.5x ULN;

  • Total bilirubin level ≥1.5x ULN;
  • TSH> ULN;
  • Fasting C-peptide <0.8 ng/mL;
  • Serum calcitonin > ULN;
  • Amylase > ULN;
  • Lipase > ULN;
  • eGFR <60 mL/min/1.73m2 (per MDRD equation);
  • FPG >270 mg/dL
• History of alcohol abuse, binge drinking and/or any illicit drug use or dependence within 6 months of Screening;
• Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 60 days prior to dosing;
• History of sensitivity to heparin or heparin induced thrombocytopenia;
• Known intolerance to any GLP-1R agonist.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PF-07081532; multiple dosing, once-daily for 42 days	Drug: PF-07081532; Study Drug, once daily for 42 days
Placebo Comparator: Placebo; multiple dosing, once-daily for 42 days	Drug: Placebo; Placebo, once daily for 42 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-emergent Adverse Events (All Causalities)	An adverse event (AE) was any untoward medical occurrence in clinical study participant, temporally associated with the use of study drug, whether or not considered related to the study drug. A serious AE (SAE) was defined as one of the following: was fatal or life-threatening; resulted in persistent or significant disability/incapacity; constituted a congenital anomaly/birth defect; was medically significant; required inpatient hospitalization or prolongation of existing hospitalization. A severe AE was defined as severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling, limiting self-care activities of daily living. Treatment-emergent AE was defined as an AE with onset date occurring during the on-treatment period (starting after or on the first dose but before the last dose plus at least 28 days). AEs included all SAEs and non-SAEs.	Baseline up to at least 28 days after last dose of study intervention (77 days)
Number of Participants With Treatment-emergent Adverse Events (Treatment Related)	A treatment related adverse event (AE) was any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study drug, considered related to the study drug (assessed by the investigator [Yes/No]). A serious AE (SAE) was defined as one of the following: was fatal or life-threatening; resulted in persistent or significant disability/incapacity; constituted a congenital anomaly/birth defect; was medically significant; required inpatient hospitalization or prolongation of existing hospitalization. A severe AE was defined as severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling, limiting self-care activities of daily living. Treatment-emergent AE was defined as an AE with onset date occurring during the on-treatment period (starting after or on the first dose but before the last dose plus at least 28 days). AEs included all SAEs and non-SAEs.	Baseline up to at least 28 days after last dose of study intervention (77 days)
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)	Following laboratory parameters analyzed for laboratory examination: hemoglobin (HGB); hematocrit; erythrocytes; erythrocytes (Ery.) mean corpuscular volume; Ery. mean corpuscular HGB; Ery. mean corpuscular HGB concentration; platelets; leukocytes; lymphocytes; neutrophils; basophils; eosinophils; monocytes; bilirubin; direct bilirubin; indirect bilirubin; aspartate aminotransferase; alanine aminotransferase; gamma glutamyl transferase; alkaline phosphatase; albumin; urea nitrogen; creatinine; urate; cholesterol; high density lipoprotein (HDL) cholesterol; sodium; potassium; chloride; calcium; bicarbonate; thyroxine; free; thyrotropin; creatine kinase; amylase; triacylglycerol lipase; triglycerides; pH; urine glucose; ketones; urine protein; urine hemoglobin; urobilinogen; urine bilirubin; nitrite; leukocyte esterase; urine erythrocytes; urine leukocytes; epithelial cells; casts; and bacteria.	Baseline up to 7-14 days after last dose of study drug (maximum: 56 days)
Number of Participants With Pre-specified Categorical Post-Baseline Vital Signs Data	Pre-specified categorical criteria included: supine systolic blood pressure (SBP) less than (<) 90 millimeters of mercury (mmHg), supine SBP increase from baseline greater or equal to (>=) 30 mmHg, supine SBP decrease from baseline >=30 mmHg, supine diastolic blood pressure (DBP) <50 mmHg, supine DBP increase from baseline >=20 mmHg, supine DBP decrease from baseline >=20 mmHg, supine pulse rate <40 beats per minutes (bpm), and supine pulse rate greater than (>) 120 bpm. Supine BP was measured with the participant's arm supported at the level of the heart, and recorded to the nearest mmHg after approximately 5 minutes of rest.	Baseline up to 14 days after last dose of study intervention (maximum: 56 days)
Number of Participants With Pre-specified Categorical Post-Baseline Electrocardiogram (ECG) Data	Triplicate 12-lead ECGs were collected using an ECG machine that automatically calculates the heart rate and measures PR, QT, and QTc intervals and QRS complex. Pre-specified categorical criteria included: PR interval greater or equal to 300 msec, PR interval %Chg>=25/50% (%Chg>=25/50% denotes baseline >200 msec and >=25% increase or baseline less than or equal to [<=] 200 msec and >=50% increase), QRS interval >=140 msec, QRS interval increase from baseline >=50%, QT interval corrected using Fridericia's formula (QTcF) >450 msec and <=480 msec, QTcF >480 msec and <=500 msec, QTcF >500 msec, QTcF increase from baseline >30 msec and <=60 msec, and QTcF increase from baseline >60 msec.	Baseline up to 14 days after last dose of study intervention (maximum: 56 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Concentration-Time Profile From 0 to 24 Hours (AUC24) of PF-07081532 on Day 1 and Day 42	AUC24 of PF-07081532 were determined by Linear/Log trapezoidal method on Study Day 1 and Study Day 42. On Study Day 1, participants in Arms of PF-07081532 20-60 mg (T2DM), PF-07081532 40-80 mg (T2DM), and PF-07081532 20-60 mg (obesity) received 20 mg, 40 mg, and 20 mg, respectively. On Study Day 42, participants in Arms of PF-07081532 20-60 mg (T2DM), PF-07081532 40-80 mg (T2DM), and PF-07081532 20-60 mg (obesity) received 60 mg, 80 mg, and 60 mg, respectively.	Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, and 24 hours post dose on Study Day 1 and Study Day 42
Maximum Observed Plasma Concentration (Cmax) of PF-07081532 on Day 1 and Day 42	Cmax of PF-07081532 were observed directly from data from time 0 to 24 hours on Study Day 1 and Study Day 42. On Study Day 1, participants in Arms of PF-07081532 20-60 mg (T2DM), PF-07081532 40-80 mg (T2DM), and PF-07081532 20-60 mg (obesity) received 20 mg, 40 mg, and 20 mg, respectively. On Study Day 42, participants in Arms of PF-07081532 20-60 mg (T2DM), PF-07081532 40-80 mg (T2DM), and PF-07081532 20-60 mg (obesity) received 60 mg, 80 mg, and 60 mg, respectively.	Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, and 24 hours post dose on Study Day 1 and Study Day 42
Time to Reach Cmax (Tmax) of PF-07081532 on Day 1 and Day 42	Tmax of PF-07081532 were observed directly from data as time of first occurrence on Study Day 1 and Study Day 42. On Study Day 1, participants in Arms of PF-07081532 20-60 mg (T2DM), PF-07081532 40-80 mg (T2DM), and PF-07081532 20-60 mg (obesity) received 20 mg, 40 mg, and 20 mg, respectively. On Study Day 42, participants in Arms of PF-07081532 20-60 mg (T2DM), PF-07081532 40-80 mg (T2DM), and PF-07081532 20-60 mg (obesity) received 60 mg, 80 mg, and 60 mg, respectively.	Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, and 24 hours post dose on Study Day 1 and Study Day 42
Terminal Half-life (t1/2) of PF-07081532 on Day 42	t1/2 of PF-07081532 was determined by Loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log linear concentration time curve. Only those data points judged to describe the terminal log linear decline were used in the regression. On Study Day 42, participants in Arms of PF-07081532 20-60 mg (T2DM), PF-07081532 40-80 mg (T2DM), and PF-07081532 20-60 mg (obesity) received 60 mg, 80 mg, and 60 mg, respectively.	Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, and 24 hours post dose on Study Day 42

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): December 22, 2021
• Primary Completion (Actual): June 15, 2022
• Study Completion (Actual): June 15, 2022

Study Registration Dates

• First Submitted: December 2, 2021
• First Submitted That Met QC Criteria: December 2, 2021
• First Posted (Actual): December 15, 2021

Study Record Updates

• Last Update Posted (Actual): August 12, 2024
• Last Update Submitted That Met QC Criteria: March 8, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Obesity; Type 2 Diabetes Mellitus
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: C3991003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• 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