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

Primary Purpose

Human Immunodeficiency Virus (HIV) Infection

Status
Completed
Phase
Phase 4
Locations
Germany
Study Type
Interventional
Intervention
Maraviroc
Maraviroc
Ritonavir
Saquinavir
Maraviroc
Ritonavir
Saquinavir
Maraviroc
Ritonavir
Saquinavir
Maraviroc
Maraviroc
Maraviroc
Sponsored by
ViiV Healthcare
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Human Immunodeficiency Virus (HIV) Infection focused on measuring maraviroc, pharmacokinetics, renal impairment

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • Pfizer Investigational Site
  • Pfizer Investigational Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Healthy Subjects

Mild Renal Impairment

Moderate Renal Impairment

Severe Renal Impairment

ESRD on Hemodialysis

Arm Description

Subjects with Normal Renal Function (Creatinine Clearance > 80mL/min) (I) Maraviroc single dose, followed by (II) Maraviroc + Saquinavir/Ritonavir

Subjects with Mild Renal Impairment (Creatinine Clearance >50 and ≤80 mL/min)

Subjects with Moderate Renal Impairment (Creatinine Clearance ≥30 and ≤50 mL/min)

Subjects with Severe Renal Impairment (Creatinine Clearance <30 mL/min)

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Plasma Protein Binding
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)
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 (hours) of first occurrence (Tmax); time after dosing when Cmax (maximum plasma concentration) occured.
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.
Renal Clearance (CLR) in Subjects With Normal, Mild, Moderate and Severe Renal Function
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
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
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
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
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
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.

Full Information

First Posted
July 15, 2008
Last Updated
November 10, 2010
Sponsor
ViiV Healthcare
Collaborators
Pfizer
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1. Study Identification

Unique Protocol Identification Number
NCT00717067
Brief Title
Pharmacokinetics, Safety And Toleration Of Maraviroc Administered To Subjects With Various Degrees Of Renal Impaired And Normal Renal Function
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 Type
Interventional

2. Study Status

Record Verification Date
November 2010
Overall Recruitment Status
Completed
Study Start Date
July 2008 (undefined)
Primary Completion Date
November 2008 (Actual)
Study Completion Date
November 2008 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
ViiV Healthcare
Collaborators
Pfizer

4. Oversight

Data Monitoring Committee
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Human Immunodeficiency Virus (HIV) Infection
Keywords
maraviroc, pharmacokinetics, renal impairment

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
30 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Healthy Subjects
Arm Type
Experimental
Arm Description
Subjects with Normal Renal Function (Creatinine Clearance > 80mL/min) (I) Maraviroc single dose, followed by (II) Maraviroc + Saquinavir/Ritonavir
Arm Title
Mild Renal Impairment
Arm Type
Experimental
Arm Description
Subjects with Mild Renal Impairment (Creatinine Clearance >50 and ≤80 mL/min)
Arm Title
Moderate Renal Impairment
Arm Type
Experimental
Arm Description
Subjects with Moderate Renal Impairment (Creatinine Clearance ≥30 and ≤50 mL/min)
Arm Title
Severe Renal Impairment
Arm Type
Experimental
Arm Description
Subjects with Severe Renal Impairment (Creatinine Clearance <30 mL/min)
Arm Title
ESRD on Hemodialysis
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Maraviroc
Intervention Description
Maraviroc 300 mg (150 mg x 2 tablets) x single dose
Intervention Type
Drug
Intervention Name(s)
Maraviroc
Intervention Description
Maraviroc 150 mg tablet twice daily x 7 days
Intervention Type
Drug
Intervention Name(s)
Ritonavir
Intervention Description
Ritonavir 100 mg capsule twice daily x 7 days
Intervention Type
Drug
Intervention Name(s)
Saquinavir
Intervention Description
Saquinavir 1000 mg (500 mg x 2 tablets) twice daily x 7 days
Intervention Type
Drug
Intervention Name(s)
Maraviroc
Intervention Description
Maraviroc 150 mg tablet once daily x 7 days
Intervention Type
Drug
Intervention Name(s)
Ritonavir
Intervention Description
Ritonavir 100 mg capsule twice daily x 7 days
Intervention Type
Drug
Intervention Name(s)
Saquinavir
Intervention Description
Saquinavir 1000 mg (500 mg x 2 tablets) twice daily x 7 days
Intervention Type
Drug
Intervention Name(s)
Maraviroc
Intervention Description
Maraviroc 150 mg tablet once every 48 hours x 7 days
Intervention Type
Drug
Intervention Name(s)
Ritonavir
Intervention Description
Ritonavir 100 mg capsule twice daily x 7 days
Intervention Type
Drug
Intervention Name(s)
Saquinavir
Intervention Description
Saquinavir 1000 mg (500 mg x 2 tablets) twice daily x 7 days
Intervention Type
Drug
Intervention Name(s)
Maraviroc
Intervention Description
Maraviroc 300 mg (150 mg x 2 tablets) x single dose
Intervention Type
Drug
Intervention Name(s)
Maraviroc
Intervention Description
Maraviroc 300 mg (150 mg x 2 tablets) x single dose one hour following completion of hemodialysis
Intervention Type
Drug
Intervention Name(s)
Maraviroc
Intervention Description
Maraviroc 300 mg (150 mg x 2 tablets) x single dose three hours prior to start of hemodialysis
Primary Outcome Measure Information:
Title
Area Under the Plasma Concentration Time-curve From Zero to the Last Measured Concentration (AUClast)
Description
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.
Title
AUCtau
Description
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.
Title
Maximum Observed Plasma Concentration (Cmax)
Description
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 Outcome Measure Information:
Title
Plasma Protein Binding
Description
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
Title
Area Under the Time Curve From 0 to Infinity (AUCinf)
Description
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
Title
Time of First Occurrence (Tmax)
Description
Time (hours) of first occurrence (Tmax); time after dosing when Cmax (maximum plasma concentration) occured.
Time Frame
Pre-dose, post-dose hours 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72.
Title
Half-life (t1/2)
Description
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.
Title
Renal Clearance (CLR) in Subjects With Normal, Mild, Moderate and Severe Renal Function
Description
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.
Title
Derivation of Renal Clearance in Subjects With Normal, Mild, Moderate and Severe Renal Function: Ae
Description
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.
Title
Hemodialysis Clearance of Maraviroc (MVC) in Subjects With End Stage Renal Disease (ESRD) Undergoing Hemodialysis: CLdD
Description
CLdD: dialysate clearance before dialysis; measured in milliliters per minute.
Time Frame
Before dialysis
Title
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
Description
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
Title
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
Description
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
Title
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
Description
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
Pfizer Investigational Site
City
Berlin
ZIP/Postal Code
10117
Country
Germany
Facility Name
Pfizer Investigational Site
City
Muenchen
ZIP/Postal Code
81241
Country
Germany

12. IPD Sharing Statement

Links:
URL
https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=A4001075&StudyName=Pharmacokinetics%2C%20Safety%20And%20Toleration%20Of%0AMaraviroc%20Administered%20To%20Subjects%20With%20Various%20Degrees%20Of%20Renal%20Impaired%20And%20Normal%20Renal%20Fu
Description
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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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