PF-04634817 Renal Impairment Study

A PHASE 1, SINGLE DOSE, OPEN-LABEL STUDY TO EVALUATE THE EFFECT OF RENAL IMPAIRMENT ON THE PHARMACOKINETICS OF PF-04634817

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 Overview

• Status: Completed
• Conditions: Renal Insufficiency
• Intervention / Treatment: Drug: PF-04634817; Drug: PF-04634817; Drug: PF-04634817; Drug: PF-04634817

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • DeLand, Florida, United States, 32720
      • Avail Clinical Research, LLC
    • Miami, Florida, United States, 33136
      • Unversity of Miami

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Healthy Volunteers	Drug: PF-04634817; Single 50 mg dose administered to subjects with normal renal function (creatinine clearance greater than or equal to 90 ml/min); Drug: PF-04634817; Single 50 mg dose administered to subjects with mild renal impairment (creatinine clearance 60-89 ml/min); Drug: PF-04634817; Single 50 mg dose administered to subjects with moderate renal impairment (creatinine clearance 30-59 ml/min); Drug: PF-04634817; Single 50 mg dose administered to subjects with severe renal impairment (creatinine clearance 15-29 ml/min)
Experimental: Moderate renal impairment	Drug: PF-04634817; Single 50 mg dose administered to subjects with normal renal function (creatinine clearance greater than or equal to 90 ml/min); Drug: PF-04634817; Single 50 mg dose administered to subjects with mild renal impairment (creatinine clearance 60-89 ml/min); Drug: PF-04634817; Single 50 mg dose administered to subjects with moderate renal impairment (creatinine clearance 30-59 ml/min); Drug: PF-04634817; Single 50 mg dose administered to subjects with severe renal impairment (creatinine clearance 15-29 ml/min)
Experimental: Severe renal impairment	Drug: PF-04634817; Single 50 mg dose administered to subjects with normal renal function (creatinine clearance greater than or equal to 90 ml/min); Drug: PF-04634817; Single 50 mg dose administered to subjects with mild renal impairment (creatinine clearance 60-89 ml/min); Drug: PF-04634817; Single 50 mg dose administered to subjects with moderate renal impairment (creatinine clearance 30-59 ml/min); Drug: PF-04634817; Single 50 mg dose administered to subjects with severe renal impairment (creatinine clearance 15-29 ml/min)
Experimental: Mild Renal Impairment	Drug: PF-04634817; Single 50 mg dose administered to subjects with normal renal function (creatinine clearance greater than or equal to 90 ml/min); Drug: PF-04634817; Single 50 mg dose administered to subjects with mild renal impairment (creatinine clearance 60-89 ml/min); Drug: PF-04634817; Single 50 mg dose administered to subjects with moderate renal impairment (creatinine clearance 30-59 ml/min); Drug: PF-04634817; Single 50 mg dose administered to subjects with severe renal impairment (creatinine clearance 15-29 ml/min)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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).	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.	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.	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)		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)	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, 0.5, 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.	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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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).	0-24, 24-48 post dose
Renal Clearance Over a 48-hour Interval(CLr48)	Renal clearance over a 48-hour interval (CLr48) = Ae48/AUC48.	0-24, 24-48 hours post dose

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

General Publications

• Tesch GH, Pullen N, Jesson MI, Schlerman FJ, Nikolic-Paterson DJ. Combined inhibition of CCR2 and ACE provides added protection against progression of diabetic nephropathy in Nos3-deficient mice. Am J Physiol Renal Physiol. 2019 Dec 1;317(6):F1439-F1449. doi: 10.1152/ajprenal.00340.2019. Epub 2019 Sep 30.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): May 10, 2013
• Primary Completion (Actual): September 3, 2013
• Study Completion (Actual): September 3, 2013

Study Registration Dates

• First Submitted: February 12, 2013
• First Submitted That Met QC Criteria: February 12, 2013
• First Posted (Estimated): February 15, 2013

Study Record Updates

• Last Update Posted (Estimated): March 1, 2024
• Last Update Submitted That Met QC Criteria: August 3, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: healthy; Subjects with Renal Impairment
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Renal Insufficiency
• Other Study ID Numbers: B1261008; 2013-000360-29 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.