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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Type 2 Diabetes Mellitus

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


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PF-07081532<br>multiple dosing, once-daily for 42 days | Drug: PF-07081532<br>* Study Drug, once daily for 42 days<br>|
| Placebo Comparator: Placebo<br>multiple dosing, once-daily for 42 days | Drug: Placebo<br>* Placebo, once daily for 42 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-emergent treatment-related adverse events |  | Baseline to minimum 28 days after last administration of investigational product | 
| Number of participants with clinically significant, abnormal safety laboratory tests |  | Baseline to 7-14 days after last administration of investigational product | 
| Number of participants with clinically significant, abnormal vital sign parameters |  | Baseline to 7-14 days after last administration of investigational product | 
| Number of participants with clinically significant, abnormal 12-lead ECG parameters |  | Baseline to 7-14 days after last administration of investigational product | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the curve from 0 to 24 hours post-dose (AUC24) of PF-07081532 plasma concentration |  | Day 1 | 
| Area under the curve from 0 to 24 hours post-dose (AUC24) of PF-07081532 plasma concentration |  | Day 42 | 
| Maximum Observed Plasma Concentration (Cmax) of PF-07081532 |  | Day 1 | 
| Maximum Observed Plasma Concentration (Cmax) of PF-07081532 |  | Day 42 | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07081532 |  | Day 1 | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07081532 |  | Day 42 | 
| Plasma Decay Half-Life (t1/2) of PF-07081532 |  | Day 42 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 2 Diabetes Mellitus, Obesity