PF-04634817 Renal Impairment Study

Study Overview
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Brief Summary
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Patients with renal impairment are the target population for PF-04634817. The clearance mechanism of this drug means that exposure may be increased in subjects with renal impairment. This study will investigate the effect of the drug in subjects with varying degrees of renal impairment. Pharmacokinetics, safety and toleration will be assessed.

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-04634817

Conditions
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Renal Insufficiency

Intervention / Treatment
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* Drug: PF-04634817
* Drug: PF-04634817
* Drug: PF-04634817
* Drug: PF-04634817


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female (non child bearing potential aged 18-75 years Documented renal impairment (mild, moderate or severe using Cockcroft-Gault equation) or matched healthy volunteers (age, weight and gender) Exclusion Criteria: Subjects with acute renal failure Subjects receiving, or likely to receive, CYP450 3A4 inhibitors Abnormal ECG at screening

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 Volunteers<br> | Drug: PF-04634817<br>* Single 50 mg dose administered to subjects with normal renal function (creatinine clearance greater than or equal to 90 ml/min)<br>|
| Experimental: Mild Renal Impairment<br> | Drug: PF-04634817<br>* Single 50 mg dose administered to subjects with mild renal impairment (creatinine clearance 60-89 ml/min)<br>|
| Experimental: Moderate renal impairment<br> | Drug: PF-04634817<br>* Single 50 mg dose administered to subjects with moderate renal impairment (creatinine clearance 30-59 ml/min)<br>|
| Experimental: Severe renal impairment<br> | Drug: PF-04634817<br>* Single 50 mg dose administered to subjects with severe renal impairment (creatinine clearance 15-29 ml/min)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) | pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 16, 24, 32, 40, 48, 56, 64, 72, 84, 96, 108, 120, 132, 144, 156, 216, 312 post dose | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) |  | pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 16, 24, 32, 40, 48, 56, 64, 72, 84, 96, 108, 120, 132, 144, 156, 216, 312 post dose | 
| Maximum Observed Plasma Concentration (Cmax) |  | pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 16, 24, 32, 40, 48, 56, 64, 72, 84, 96, 108, 120, 132, 144, 156, 216, 312 post dose | 
| Apparent Oral Clearance (CL/F) | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. | pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 16, 24, 32, 40, 48, 56, 64, 72, 84, 96, 108, 120, 132, 144, 156, 216, 312 post dose | 
| Apparent Volume of Distribution (Vz/F) | Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed. | pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 16, 24, 32, 40, 48, 56, 64, 72, 84, 96, 108, 120, 132, 144, 156, 216, 312 post dose | 
| Plasma Decay Half-Life (t1/2) | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. | pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 16, 24, 32, 40, 48, 56, 64, 72, 84, 96, 108, 120, 132, 144, 156, 216, 312 post dose | 
| Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - inf)] | AUC (0 - inf)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time. | pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 16, 24, 32, 40, 48, 56, 64, 72, 84, 96, 108, 120, 132, 144, 156, 216, 312 post dose | 
| Area Under the Curve From Time Zero 48 hours[AUC (0 - 48)] | AUC (0 - 48)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to 48h | pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 16, 24, 32, 40, 48, 56, 64, 72, 84, 96, 108, 120, 132, 144, 156, 216, 312 post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urinary Ae48 | Amount of drug excreted unchanged in urine over 48 hours | 0-24, 24-48 post dose | 
| Urinary AE48 (% excreted) | % of drug excreted unchanged in urine over 48 hours | 0-24, 24-48 post dose | 
| Urinary CLR |  | 0-24, 24-48 post dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Subjects with Renal Impairment, healthy