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

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ClinicalTrials.gov Identifier: NCT00717067
Recruitment Status : Completed
First Posted : July 16, 2008
Results First Posted : December 21, 2009
Last Update Posted : November 19, 2010
Sponsor:
Collaborator:
Pfizer
Information provided by:
ViiV Healthcare

Study Description
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Brief Summary:
The purpose of this study is to assess whether a dosing adjustment is needed in patients with renal impairment.

Condition or disease Intervention/treatment Phase
Human Immunodeficiency Virus (HIV) Infection Drug: Maraviroc Drug: Ritonavir Drug: Saquinavir Phase 4

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : July 2008
Actual Primary Completion Date : November 2008
Actual Study Completion Date : November 2008

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Kidney Tests
Drug Information available for: Maraviroc
U.S. FDA Resources

Arms and Interventions
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Arm Intervention/treatment
Experimental: Healthy Subjects
Subjects with Normal Renal Function (Creatinine Clearance > 80mL/min) (I) Maraviroc single dose, followed by (II) Maraviroc + Saquinavir/Ritonavir
 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
Experimental: Mild Renal Impairment
Subjects with Mild Renal Impairment (Creatinine Clearance >50 and ≤80 mL/min)
 Drug: Maraviroc
Maraviroc 150 mg tablet once 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
Experimental: Moderate Renal Impairment
Subjects with Moderate Renal Impairment (Creatinine Clearance ≥30 and ≤50 mL/min)
 Drug: Maraviroc
Maraviroc 150 mg tablet once every 48 hours 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
Experimental: Severe Renal Impairment
Subjects with Severe Renal Impairment (Creatinine Clearance <30 mL/min)
 Drug: Maraviroc
Maraviroc 300 mg (150 mg x 2 tablets) x single dose
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
 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


Outcome Measures
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Primary Outcome Measures :
  1. 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. ]
    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).

  2. AUCtau [ Time Frame: Pre-dose, post-dose hours 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72. ]
    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).

  3. 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. ]
    Maximum observed plasma concentration (Cmax) within the dosing interval; measured in nanograms per milliliter (ng/mL).


Secondary Outcome Measures :
  1. Plasma Protein Binding [ Time Frame: 2 hours post-dose; normal Day -3 and Day 7; mild moderate: Day 7; severe and ESRD: Day 1 ]
    Percent protein binding (protein unbound maraviroc (MVC) fraction [percent free]) was determined by rapid equilibrium dialysis. Percent free = 100 - percent bound.

  2. 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 ]
    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).

  3. 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. ]
    Time (hours) of first occurrence (Tmax); time after dosing when Cmax (maximum plasma concentration) occured.

  4. Half-life (t1/2) [ Time Frame: Pre-dose, post-dose hours 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72. ]
    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.

  5. 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. ]
    Renal clearance (CLR) measured in milliliters per minute (mL/min).

  6. 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. ]
    Ae: amount of drug excreted unchanged in the urine; measured in milligrams (mg).

  7. Hemodialysis Clearance of Maraviroc (MVC) in Subjects With End Stage Renal Disease (ESRD) Undergoing Hemodialysis: CLdD [ Time Frame: Before dialysis ]
    CLdD: dialysate clearance before dialysis; measured in milliliters per minute.

  8. 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 ]
    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.

  9. 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 ]
    Number of subjects with pulse rate < 40 beats per minute (BPM), number of subjects with pulse rate > 120 BPM.

  10. 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 ]
    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.


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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.
Contacts and Locations
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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00717067


Locations
Germany
Pfizer Investigational Site
Berlin, Germany, 10117
Pfizer Investigational Site
Muenchen, Germany, 81241
Sponsors and Collaborators
ViiV Healthcare
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
More Information
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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:
To obtain contact information for a study center near you, click here.  This link exits the ClinicalTrials.gov site

Responsible Party: Director, Clinical Trial Disclosure Group, Pfizer, Inc.
ClinicalTrials.gov Identifier: NCT00717067     History of Changes
Other Study ID Numbers: A4001075
First Posted: July 16, 2008    Key Record Dates
Results First Posted: December 21, 2009
Last Update Posted: November 19, 2010
Last Verified: November 2010

Keywords provided by ViiV Healthcare:
maraviroc, pharmacokinetics, renal impairment

Additional relevant MeSH terms:
Immunologic Deficiency Syndromes
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Ritonavir
Saquinavir
 Maraviroc
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors
CCR5 Receptor Antagonists