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PF-04634817 Renal Impairment Study

Phase 1
Completed
Conditions
Renal Insufficiency
Interventions
Registration Number
NCT01791855
Lead Sponsor
Pfizer
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
32
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Moderate renal impairmentPF-04634817-
Severe renal impairmentPF-04634817-
Healthy VolunteersPF-04634817-
Mild Renal ImpairmentPF-04634817-
Primary Outcome Measures
NameTimeMethod
Plasma Decay Half-Life (t1/2)Pre-dose, 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 hours post dose

Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

Area Under the Curve From Time Zero to 48 Hours[AUC (0 - 48)]Pre-dose, 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 hours post dose

AUC (0 - 48)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to 48hours.

Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)Pre-dose, 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 hours post dose

Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast).

Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - Inf)]Pre-dose, 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 hours post dose

AUC (0 - inf)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time.

Apparent Oral Clearance (CL/F)Pre-dose, 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 hours post dose

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 PK modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.

Maximum Observed Plasma Concentration (Cmax)Pre-dose, 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 hours post dose
Time to Reach Maximum Observed Plasma Concentration (Tmax)Pre-dose, 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 hours post dose
Apparent Volume of Distribution (Vz/F)Pre-dose, 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 hours post dose

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.

Secondary Outcome Measures
NameTimeMethod
Renal Clearance Over a 48-hour Interval(CLr48)0-24, 24-48 hours post dose

Renal clearance over a 48-hour interval (CLr48) = Ae48/AUC48.

Amount of Unchanged Drug Excreted in Urine Over 48 Hours (Ae48)0-24, 24-48 hours post dose

Amount of unchanged drug excreted in urine over 48 hours (Ae48) = urine concentration x volume of urine.

Percentage of the Dose Excreted Unchanged in the Urine Over 48 Hours (Ae48%)0-24, 24-48 post dose

Percentage (%) of drug excreted unchanged in urine over 48 hours (Ae48%) = Ae48/(dose x 100).

Trial Locations

Locations (2)

Unversity of Miami

🇺🇸

Miami, Florida, United States

Avail Clinical Research, LLC

🇺🇸

DeLand, Florida, United States

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