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

This study has been completed.
Sponsor:
Collaborator:
Pfizer
Information provided by:
ViiV Healthcare
ClinicalTrials.gov Identifier:
NCT00717067
First received: July 15, 2008
Last updated: November 10, 2010
Last verified: November 2010

July 15, 2008
November 10, 2010
July 2008
November 2008   (final data collection date for primary outcome measure)
  • Area Under the Plasma Concentration Time-curve From Zero to the Last Measured Concentration (AUClast) [ Time Frame: Pre-dose, post-dose hours 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72. ] [ Designated as safety issue: No ]
    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).
  • AUCtau [ Time Frame: Pre-dose, post-dose hours 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72. ] [ Designated as safety issue: No ]
    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).
  • Maximum Observed Plasma Concentration (Cmax) [ Time Frame: Pre-dose, post-dose hours 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72. ] [ Designated as safety issue: No ]
    Maximum observed plasma concentration (Cmax) within the dosing interval; measured in nanograms per milliliter (ng/mL).
  • Calculate the hemodialysis clearance of MVC in subjects with end stage renal disease (ESRD) undergoing hemodialysis. [ Time Frame: 3 days ] [ Designated as safety issue: No ]
  • Characterize the pharmacokinetics of MVC (300 mg) in healthy subjects, subjects with severe renal impairment and those receiving chronic hemodialysis. [ Time Frame: 3 days ] [ Designated as safety issue: No ]
  • Characterize the pharmacokinetics of MVC (150 mg) in the presence of SQV/r (a potent CYP3A4 inhibitor) in both healthy subjects and subjects with mild and moderate renal impairment. [ Time Frame: 10 days ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00717067 on ClinicalTrials.gov Archive Site
  • Plasma Protein Binding [ Time Frame: 2 hours post-dose; normal Day -3 and Day 7; mild moderate: Day 7; severe and ESRD: Day 1 ] [ Designated as safety issue: No ]
    Percent protein binding (protein unbound maraviroc (MVC) fraction [percent free]) was determined by rapid equilibrium dialysis. Percent free = 100 - percent bound.
  • Area Under the Time Curve From 0 to Infinity (AUCinf) [ Time Frame: Pre-dose, post-dose hours 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 ] [ Designated as safety issue: No ]
    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 of First Occurrence (Tmax) [ Time Frame: Pre-dose, post-dose hours 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72. ] [ Designated as safety issue: No ]
    Time (hours) of first occurrence (Tmax); time after dosing when Cmax (maximum plasma concentration) occured.
  • Half-life (t1/2) [ Time Frame: Pre-dose, post-dose hours 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72. ] [ Designated as safety issue: No ]
    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.
  • Renal Clearance (CLR) in Subjects With Normal, Mild, Moderate and Severe Renal Function [ 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. ] [ Designated as safety issue: No ]
    Renal clearance (CLR) measured in milliliters per minute (mL/min).
  • Derivation of Renal Clearance in Subjects With Normal, Mild, Moderate and Severe Renal Function: Ae [ 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. ] [ Designated as safety issue: No ]
    Ae: amount of drug excreted unchanged in the urine; measured in milligrams (mg).
  • Hemodialysis Clearance of Maraviroc (MVC) in Subjects With End Stage Renal Disease (ESRD) Undergoing Hemodialysis: CLdD [ Time Frame: Before dialysis ] [ Designated as safety issue: No ]
    CLdD: dialysate clearance before dialysis; measured in milliliters per minute.
  • 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 [ 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 ] [ Designated as safety issue: No ]
    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.
  • 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 Pulse Rate < 40 and > 120 Beats Per Minute [ 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 ] [ Designated as safety issue: No ]
    Number of subjects with pulse rate < 40 beats per minute (BPM), number of subjects with pulse rate > 120 BPM.
  • 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 EGC QTC, QTCB and QTCF Intervals [ 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 ] [ Designated as safety issue: No ]
    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.
Assess the safety and tolerability of MVC in the absence and presence of a potent CYP3A4 inhibitor in subjects with various degrees of renal impairment or undergoing hemodialysis. [ Time Frame: 7 days ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Pharmacokinetics, Safety And Toleration Of Maraviroc Administered To Subjects With Various Degrees Of Renal Impaired And Normal Renal Function
An Open-Label, Parallel Group, Single And Multiple Dose Study To Evaluate The Pharmacokinetics, Safety And Toleration Of Maraviroc Administered To Subjects With Various Degrees Of Renal Impaired And Normal Renal Function

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

Not Provided
Interventional
Phase 4
Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Human Immunodeficiency Virus (HIV) Infection
  • Drug: Maraviroc
    Maraviroc 300 mg (150 mg x 2 tablets) x single dose
  • Drug: Maraviroc
    Maraviroc 150 mg tablet twice daily x 7 days
  • Drug: Ritonavir
    Ritonavir 100 mg capsule twice daily x 7 days
  • Drug: Saquinavir
    Saquinavir 1000 mg (500 mg x 2 tablets) twice daily x 7 days
  • Drug: Maraviroc
    Maraviroc 150 mg tablet once daily x 7 days
  • Drug: Maraviroc
    Maraviroc 150 mg tablet once every 48 hours x 7 days
  • Drug: Maraviroc
    Maraviroc 300 mg (150 mg x 2 tablets) x single dose one hour following completion of hemodialysis
  • Drug: Maraviroc
    Maraviroc 300 mg (150 mg x 2 tablets) x single dose three hours prior to start of hemodialysis
  • Experimental: Healthy Subjects
    Subjects with Normal Renal Function (Creatinine Clearance > 80mL/min) (I) Maraviroc single dose, followed by (II) Maraviroc + Saquinavir/Ritonavir
    Interventions:
    • Drug: Maraviroc
    • Drug: Maraviroc
    • Drug: Ritonavir
    • Drug: Saquinavir
  • Experimental: Mild Renal Impairment
    Subjects with Mild Renal Impairment (Creatinine Clearance >50 and ≤80 mL/min)
    Interventions:
    • Drug: Maraviroc
    • Drug: Ritonavir
    • Drug: Saquinavir
  • Experimental: Moderate Renal Impairment
    Subjects with Moderate Renal Impairment (Creatinine Clearance ≥30 and ≤50 mL/min)
    Interventions:
    • Drug: Maraviroc
    • Drug: Ritonavir
    • Drug: Saquinavir
  • Experimental: Severe Renal Impairment
    Subjects with Severe Renal Impairment (Creatinine Clearance <30 mL/min)
    Intervention: Drug: Maraviroc
  • Experimental: ESRD on Hemodialysis
    Subjects with End Stage Renal Impairment receiving Hemodialysis(Creatinine Clearance <30 mL/min) (I) Maraviroc single dose one hour following completion of hemodialysis, followed by (II) Maraviroc single dose three hours prior to start of hemodialysis
    Interventions:
    • Drug: Maraviroc
    • Drug: Maraviroc
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
30
November 2008
November 2008   (final data collection date for primary outcome measure)

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.
Both
18 Years to 85 Years
Yes
Contact information is only displayed when the study is recruiting subjects
Germany
 
NCT00717067
A4001075
No
Director, Clinical Trial Disclosure Group, Pfizer, Inc.
ViiV Healthcare
Pfizer
Study Director: Pfizer CT.gov Call Center Pfizer
ViiV Healthcare
November 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP