Multiple Escalating Oral Doses Study 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 randomized, placebo-controlled, double-blind (investigator- and participant-blinded), sponsor-open, dose-escalating study of PF-07081532 in patients with Type 2 diabetes on metformin (Parts A and C). The study may also enroll non-diabetic participants with obesity (Part B). Study participants will receive an investigational product or placebo every day for up to 28 days (Part A) or up to 42 days (Part B, optional; Part C, optional). The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics (PK) of multiple oral doses of PF-07081532 in participants with inadequately controlled T2DM on metformin and optionally in non-diabetic obese participants.

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

Conditions
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Diabetes Mellitus Type 2

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


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria for participants enrolling with T2DM: Type 2 Diabetes treated with a stable dose of metformin at least 500 mg per day for at least 2 months prior to screening visit and use of no other medications for glycemic control. HbA1c value between 7.0% and 10.5%, inclusive. Key Exclusion Criterion for participants enrolling with T2DM: -Type 1 Diabetes or secondary forms of diabetes. Key Inclusion Criterion for participants enrolling with obesity: -Obese (as indicated by screening BMI) non-diabetic adults. Key Exclusion Criterion for participants enrolling with obesity: --Type 1 or Type 2 Diabetes or secondary forms of diabetes.

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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Accepts Healthy Volunteers

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: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active Obesity<br>Part B | Other: Placebo<br>* Placebo once daily for up to 42 days.<br>Drug: Clopidogrel<br>* Part B may include a drug-drug interaction study using open-label clopidogrel. Clopidrogrel may be given as two single doses of 75 mg administered on day -2 and day 41.<br>* Other names: Plavix;|
| Placebo Comparator: Placebo Obesity<br>Part B | Other: Placebo<br>* Placebo once daily for up to 42 days.<br>Drug: Clopidogrel<br>* Part B may include a drug-drug interaction study using open-label clopidogrel. Clopidrogrel may be given as two single doses of 75 mg administered on day -2 and day 41.<br>* Other names: Plavix;|
| Experimental: Active T2DM<br>Parts A and C | Drug: PF-07081532<br>* Investigational Drug once daily for up to 42 days; multiple ascending dose design.<br>|
| Placebo Comparator: Placebo T2DM<br>Parts A and C | Drug: PF-07081532<br>* Investigational Drug once daily for up to 42 days; multiple ascending dose design.<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 up to a minimum of 28 days after last administration of investigational product. | 
| Number of Participants with Laboratory Abnormalities |  | From Baseline to 7-14 days following last dose administration. | 
| Number of Participants with Clinically Significant Change from Baseline in Vital Signs |  | From Baseline to 7-14 days following last dose administration. | 
| Number of Participants with Abnormal Electrocardiogram |  | From Baseline to 7-14 days following last dose administration. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC24: Area under the Curve from time zero to 24 hours post dose. |  | Part A: 0-24 hours post-dose on selected study days from day 1 to day 28. Parts B/C (if conducted): 0-24 hours post-dose on selected study days from day 1 to day 42. | 
| Cmax: Maximum Observed Plasma Concentration |  | Part A: selected study days from day 1 to day 28. Parts B/C (if conducted): selected study days from day 1 to day 42. | 
| Tmax: Time to Reach Maximum Observed Plasma Concentration |  | Part A: selected study days from day 1 to day 28. Parts B/C (if conducted): selected study days from day 1 to day 42. | 
| t 1/2: Time measured for the plasma concentration to decrease by one-half. |  | Part A: Day 28 0-72 hours post-dose. Parts B/C (if conducted): also day 42 0-72 hours post-dose. | 
| Ae24: Cumulative Amount of Drug Recovered Unchanged in Urine | Ae24 is the cumulative amount of drug recovered unchanged in urine over 24 hours. Cumulative amount is calculated as sum of urine drug concentration in sample volume for each collection interval. Sample volume = (urine weight in gram [g]/1.020) where 1.020 g/mL is the approximate specific gravity of urine. | Part A: Day 28 (0-24 hrs). Part C (if conducted): Day 42 (0-24 hrs). | 
| Ae24%: Percentage of dose recovered in urine as unchanged drug | Calculated as 100 x Ae24 divided by the dose administered | Part A: Day 28 (0-24 hrs). Part C (if conducted): Day 42 (0-24 hrs). | 
| CLr: Renal Clearance | Renal clearance is calculated as cumulative amount of drug recovered unchanged in urine during the dosing interval (Ae24) divided by area under the plasma concentration time curve from time zero to end of dosing interval (AUC24), where dosing interval is 24 hours. | Part A: Day 28 (0-24 hrs). Part C (if conducted): Day 42 (0-24 hrs). |