Study To Evaluate The Effect Of Renal Impairment On The Pharmacokinetics Of PF-04991532

Study Overview
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Brief Summary
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The primary purpose of this study is to evaluate the pharmacokinetics, safety and tolerability of a single oral dose of PF-04991532 in subjects with renal impairment.

Official Title
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A Phase 1, Single-Dose, Open-Label Study To Evaluate The Effect Of Renal Impairment On The Pharmacokinetics Of PF-04991532

Conditions
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Healthy, Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: PF-04991532
* Drug: PF-04991532
* Drug: PF-04991532
* Drug: PF-04991532


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Stable renal function defined as <20% difference between two measurements of serum creatinine obtained on two occasions separated by at least 72 hours to 14 days; the second determination must be obtained within the 28-day period prior to the start of study medication administration. CrCl value at Screening (average of two values obtained within two weeks apart before dosing) will be used for study enrollment. Body Mass Index (BMI) of 17.5 to 40 kg/m2; and a total body weight >50 kg (110 lbs). Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. Exclusion Criteria: Pregnant or nursing females; females of childbearing potential who are unwilling or unable to use an acceptable method of nonhormonal contraception as outlined in this protocol from at least 14 days prior to the first dose of study medication. Subjects with recent (within the last 6 months) history of myocardial infarction, unstable angina, coronary revascularization, stroke or transient ischemic attack (TIA). Subjects with severe heart failure (New York Heart Association Functional Class IV) at Screening. Subjects with acute renal disease.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: healthy controls<br>healthy subjects (creatinine clearance > 90 mL/min) | Drug: PF-04991532<br>* single dose 300-mg<br>|
| Experimental: ESRD / severe renal insufficiency<br>Severe (creatinine clearance 15 to 29 mL/min) OR ESRD (creatinine clearnace <15 mL/min OR requiring dialysis) | Drug: PF-04991532<br>* single dose 300-mg<br>|
| Experimental: Moderate renal impairment<br>Moderate (creatinine clearance = 30 to 59 mL/min) | Drug: PF-04991532<br>* single dose 300-mg<br>|
| Experimental: Mild renal impairment<br>Mild (creatinine clearance = 60 to 89 mL/min) | Drug: PF-04991532<br>* single dose 300-mg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration versus time curve (AUClast) |  | 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 hrs | 
| Maximum observed plasma concentration (Cmax) |  | 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 hrs | 
| Time of maximum observed plasma concentration (Tmax) |  | 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 hrs | 
| Renal Clearance (Clr) |  | 0 to 24 hours | 
| Amount of drug excreted (Ae) |  | 0 to 24 hours |