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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
32
Single 50 mg dose administered to subjects with normal renal function (creatinine clearance greater than or equal to 90 ml/min)
Single 50 mg dose administered to subjects with mild renal impairment (creatinine clearance 60-89 ml/min)
Single 50 mg dose administered to subjects with moderate renal impairment (creatinine clearance 30-59 ml/min)
Avail Clinical Research, LLC
DeLand, Florida, United States
Unversity of Miami
Miami, Florida, United States
Area Under the Curve From Time Zero to 48 Hours[AUC (0 - 48)]
AUC (0 - 48)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to 48hours.
Time frame: 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 Curve From Time Zero to Last Quantifiable Concentration (AUClast)
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast).
Time frame: 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 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.
Time frame: 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 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 PK modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Time frame: 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
Maximum Observed Plasma Concentration (Cmax)
Time frame: 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)
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Single 50 mg dose administered to subjects with severe renal impairment (creatinine clearance 15-29 ml/min)
Time frame: 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)
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.
Time frame: 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 (t1/2)
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Time frame: 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
Amount of Unchanged Drug Excreted in Urine Over 48 Hours (Ae48)
Amount of unchanged drug excreted in urine over 48 hours (Ae48) = urine concentration x volume of urine.
Time frame: 0-24, 24-48 hours post dose
Percentage of the Dose Excreted Unchanged in the Urine Over 48 Hours (Ae48%)
Percentage (%) of drug excreted unchanged in urine over 48 hours (Ae48%) = Ae48/(dose x 100).
Time frame: 0-24, 24-48 post dose
Renal Clearance Over a 48-hour Interval(CLr48)
Renal clearance over a 48-hour interval (CLr48) = Ae48/AUC48.
Time frame: 0-24, 24-48 hours post dose