Pharmacokinetics, Safety And Toleration Of Maraviroc Administered To Subjects With Various Degrees Of Renal Impaired And Normal Renal Function

Phase 4CompletedNCT00717067

ViiV Healthcare30 enrolled

Overview

The purpose of this study is to assess whether a dosing adjustment is needed in patients with renal impairment.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Human Immunodeficiency Virus (HIV) Infection

Interventions

MaravirocDRUG

Maraviroc 300 mg (150 mg x 2 tablets) x single dose

MaravirocDRUG

Maraviroc 150 mg tablet twice daily x 7 days

RitonavirDRUG

Ritonavir 100 mg capsule twice daily x 7 days

Saquinavir

Eligibility

Sex: ALLMin age: 18 YearsMax age: 85 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Stable Renal Function defined as ≤20% (25% for normal renal function) difference between 2 measurements of serum creatinine obtained on 2 occasions separated by at least 2 weeks. * Body Mass Index (BMI) of approximately 18 to 40 kg/m2 inclusive. * Total body weight \>50 kg (110 lbs). * Male or female subjects between the ages of 18 and 85 years. Exclusion Criteria: * Subjects with acute renal disease and/or history of renal transplant. * Supine BP at Screening ≥160 mm Hg systolic or ≥95 mm Hg diastolic. * Supine BP at Screening ≤80 mm Hg systolic or ≤40 mm Hg diastolic.

Locations (2)

Pfizer Investigational Site

Berlin, Germany

Pfizer Investigational Site

München, Germany

Outcomes

Primary Outcomes

Area Under the Plasma Concentration Time-curve From Zero to the Last Measured Concentration (AUClast)

Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) measured in nanograms \* hour divided by milliliters (ng\*hr/mL).

Time frame: Pre-dose, post-dose hours 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72.

AUCtau

AUCtau: area under the plasma concentration-time profile from time zero to the end of the dosing interval (tau); measured in nanograms \* hours divided by milliliters (ng.hr/mL).

Time frame: Pre-dose, post-dose hours 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72.

Maximum Observed Plasma Concentration (Cmax)

Maximum observed plasma concentration (Cmax) within the dosing interval; measured in nanograms per milliliter (ng/mL).

Time frame: Pre-dose, post-dose hours 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72.

Secondary Outcomes

Plasma Protein Binding

Percent protein binding (protein unbound maraviroc (MVC) fraction \[percent free\]) was determined by rapid equilibrium dialysis. Percent free = 100 - percent bound.

Time frame: 2 hours post-dose; normal Day -3 and Day 7; mild moderate: Day 7; severe and ESRD: Day 1

Area Under the Time Curve From 0 to Infinity (AUCinf)

Area under the plasma concentration-time profile from time zero to the time infinate in subjects who received single dose treatment; measured in nanograms \* hour divided by millilters (ng\*hr/mL).

Time frame: Pre-dose, post-dose hours 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72

Time of First Occurrence (Tmax)

Time (hours) of first occurrence (Tmax); time after dosing when Cmax (maximum plasma concentration) occured.

Data from ClinicalTrials.gov

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Saquinavir 1000 mg (500 mg x 2 tablets) twice daily x 7 days

MaravirocDRUG

Maraviroc 150 mg tablet once daily x 7 days

RitonavirDRUG

Ritonavir 100 mg capsule twice daily x 7 days

SaquinavirDRUG

Saquinavir 1000 mg (500 mg x 2 tablets) twice daily x 7 days

MaravirocDRUG

Maraviroc 150 mg tablet once every 48 hours x 7 days

RitonavirDRUG

Ritonavir 100 mg capsule twice daily x 7 days

SaquinavirDRUG

Saquinavir 1000 mg (500 mg x 2 tablets) twice daily x 7 days

MaravirocDRUG

Maraviroc 300 mg (150 mg x 2 tablets) x single dose

MaravirocDRUG

Maraviroc 300 mg (150 mg x 2 tablets) x single dose one hour following completion of hemodialysis

MaravirocDRUG

Maraviroc 300 mg (150 mg x 2 tablets) x single dose three hours prior to start of hemodialysis

Time frame: Pre-dose, post-dose hours 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72.

Half-life (t1/2)

Elimination half-life (t1/2) measured in hours: time required for half the quantity of maraviroc to be metabolized or eliminated by normal biological processes.

Time frame: Pre-dose, post-dose hours 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72.

Renal Clearance (CLR) in Subjects With Normal, Mild, Moderate and Severe Renal Function

Renal clearance (CLR) measured in milliliters per minute (mL/min).

Time frame: Hour 0 (prior to MVC dosing [single dose] or prior to last MVC dose [multiple dose]) to 72 hours post-dose ; hours 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72.

Derivation of Renal Clearance in Subjects With Normal, Mild, Moderate and Severe Renal Function: Ae

Ae: amount of drug excreted unchanged in the urine; measured in milligrams (mg).

Time frame: Hour 0 (prior to MVC dosing [single dose] or prior to last MVC dose [multiple dose]) to 72 hours post-dose ; hours 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72.

Hemodialysis Clearance of Maraviroc (MVC) in Subjects With End Stage Renal Disease (ESRD) Undergoing Hemodialysis: CLdD

CLdD: dialysate clearance before dialysis; measured in milliliters per minute.

Time frame: Before dialysis

Safety and Tolerability of Maraviroc in the Absence and Presence of a Potent CYP3A4 Inhibitor in Subjects With Various Degrees of Renal Impairment or Undergoing Hemodialysis: Number of Subjects With Maximum Increase and Decrease in Supine Blood Pressure

Number of subjects with absolute values of supine systolic blood pressure (BP) measured in millimeters of mercury (mm/Hg), range: \<90 mmHg; and supine diastolic blood pressure, range: \<50 mmHg. Number of subjects with a maximum increase and decrease from Baseline in supine systolic BP ≥ 30 mmHg. Number of subjects with a maximum increase and decrease from Baseline in supine diastolic BP ≥ 20 mmHg.

Time frame: Normal renal function: screening, Day -3 to Day -1; normal, mild and moderate RI: Day 7 to Day 10 and follow-up; severe RI: Day 1 to Day 4 and follow-up; ESRD: Day 1, Day 4, and follow-up

Number of subjects with pulse rate \< 40 beats per minute (BPM), number of subjects with pulse rate \> 120 BPM.

Time frame: Normal renal function: screening, Day -3 to Day -1; normal, mild and moderate RI: Day 7 to Day 10 and follow-up; severe RI: Day 1 to Day 4 and follow-up; ESRD: Day 1, Day 4, and follow-up

Single 12-lead ECG: number of subjects with maximum QTC interval, maximum QTCB interval (Bazett's correction), and maximum QTCF interval (Friderica's correction) measured in milliseconds (msec); range: 450 to \<480 msec, 480 to \<500 msec, and \>500 msec. Maximum QTC interval increase from Baseline; citeria: change = ≥ 30 msec to \< 60 msec, and change = ≥ 60 msec.

Time frame: Normal renal function: screening, Day -3 and Day -1; normal renal function, mild and moderate RI: Day 7 to Day 9 and follow-up; severe RI: screening, Day 1, Day 3, Day 4, and follow-up; ESRD: screening, Day 1, Day 3, Day 4, and follow-up