A Clinical Trial of the Study Medicine (PF-07081532) in People With Diabetes and Kidney Dysfunction

Study Overview
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Brief Summary
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The purpose of this study is to understand the effects of kidney functional impairment may have on the study medicine (PF-07081532). People with certain level of kidney functional impairment may process PF-07081532 differently from healthy people. PF-07081532 is developed as a potential treatment for type II diabetes. Participants will take the study medicine as a tablet by mouth once at the study clinic and then will stay at the study clinic for about 7 days. During that time, the study team will monitor their treatment experience and take some blood samples to test the level of PF-07081532. This will help us understand if certain degree of kidney functional impairment will have an effect on the study medicine PF-07081532.

Official Title
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A PHASE 1, OPEN-LABEL, SINGLE-DOSE, PARALLEL-GROUP STUDY TO EVALUATE THE PHARMACOKINETICS OF PF-07081532 IN ADULT PARTICIPANTS WITH TYPE 2 DIABETES MELLITUS WITH VARYING DEGREES OF RENAL IMPAIRMENT RELATIVE TO PARTICIPANTS WITHOUT RENAL IMPAIRMENT

Conditions
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Type 2 Diabetes, Renal Impairment

Intervention / Treatment
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* Drug: PF-07081532


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Stable renal function (for participants not on dialysis) defined as ≤25% difference between 2 measurements of BSA-unnormalized eGFR A prior diagnosis of T2DM with an HbA1c ≥6% and ≤10.5% Women may be of child-bearing potential BMI of 17.5 to 45.4 kg/m2 NORMAL FUNCTION (GROUP 1): Normal renal function (mean eGFR ≥90 mL/min) based on an average of measures from Screening visits S1 and S2 (eGFR should be calculated using the 2021 CKD EPI Scr-Scys combined equation: Demographically comparable to participants with impaired renal function at Screening A body weight within ±15 kg of the mean body weight of the pooled renal impairment groups (Groups 2, 3 and 4) An age within ±10 years of the mean age of the pooled renal impairment groups (Groups 2, 3 and 4) Attempts will be made to ensure that the male to female distribution in Group 1 is comparable to that in the pooled renal impairment groups (Groups 2, 3 and 4). Exclusion Criteria: Diagnosis of type 1 diabetes mellitus or secondary forms of diabetes, or history of diabetic ketoacidosis. History of myocardial infarction, unstable angina, arterial revascularization, stroke, New York Heart Association Functional Class II-IV heart failure, or transient ischemic attack within 3 months of Screening Personal or family history of MTC or MEN2, or participants with suspected MTC per the investigator's judgement. History of acute pancreatitis within 6 months before Screening or any history of chronic pancreatitis. Urinary incontinence. Participants with acute renal disease. Renal allograft recipients. Participants who have previously received a kidney, liver, or heart transplant.

Ages Eligible for Study
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Minimum Age: 18 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>Participants without renal impairment will receive a single 20 mg dose of PF 07081532, administered orally | Drug: PF-07081532<br>* One PF-07081532 20 mg tablet, administered orally<br>|
| Experimental: Group 2<br>Participants with mild renal impairment will receive a single 20 mg dose of PF 07081532, administered orally | Drug: PF-07081532<br>* One PF-07081532 20 mg tablet, administered orally<br>|
| Experimental: Group 3<br>Participants with moderate renal impairment will receive a single 20 mg dose of PF 07081532, administered orally | Drug: PF-07081532<br>* One PF-07081532 20 mg tablet, administered orally<br>|
| Experimental: Group 4<br>Participants with severe renal impairment will receive a single 20 mg dose of PF 07081532, administered orally | Drug: PF-07081532<br>* One PF-07081532 20 mg tablet, administered orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration (Cmax) |  | up to day 7 | 
| AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). |  | up to day 7 | 
| AUCinfu= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf) for unbound drug |  | up to day 7 | 
| Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) |  | up to day 7 | 
| Area under the plasma concentration time-curve from zero to the last measured concentration (AUClastu) for unbound drug. |  | up to day 7 | 
| Cmax, u is the highest measured unbound plasma concentration during the dosing interval. |  | up to day 7 | 
| Fraction of unbound drug in plasma; Cu/C where Cu represents unbound concentration and C represents total concentration |  | day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs) |  | Baseline to Day 29 | 
| Number of Participants With Treatment Emergent Clinically Significant Clinical Laboratory Abnormalities |  | Baseline to Day 7 | 
| Number of Participants With Treatment Emergent Clinically Significant Change from Baseline in Vital Signs Abnormalities |  | Baseline to Day 7 | 
| Number of Participants With Treatment emergent Clinically Significant Abnormal ECG |  | Baseline to Day 7 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 2 Diabetes, Renal impairment