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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 Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Human Immunodeficiency Virus (HIV) Infection
Interventions Drug: Maraviroc
Drug: Ritonavir
Drug: Saquinavir
Enrollment 30
Recruitment Details Two centers took part in this study between 15 July 2008 and 21 November 2008.
Pre-assignment Details Subjects were enrolled into treatment groups (healthy subjects, mild, moderate, severe renal impairment, or end stage renal impairment on hemodialysis) based on creatinine clearance results obtained closest to the dosing date at screening as determined by the Cockcroft-Gault equation (with the exception of subjects undergoing hemodialysis).
Arm/Group Title Healthy Subjects Mild Renal Impairment Moderate Renal Impairment Severe Renal Impairment ESRD: Single Dose
Hide Arm/Group Description (I) Maraviroc single 300 mg dose, followed 4 days later by (II) Maraviroc 150 mg twice a day (BID) co-administered with saquinavir 1,000 mg/ritonavir 100 mg twice a day (BID) for 6 days, and a single dose of both agents on Day 7. Maraviroc 150 mg once a day (QD) co-administered with saquinavir 1,000 mg/ritonavir 100 mg twice a day (BID) for 7 days. Maraviroc 150 mg every 48 hours co-administered with saquinavir 1,000 mg/ritonavir 100 mg twice a day (BID) for 7 days. Maraviroc 300 mg single dose. (I) Maraviroc single dose one hour following completion of morning hemodialysis, followed at least 1 week later by (II) Maraviroc single dose three hours prior to start of hemodialysis.
Period Title: Part 1a: Normal/Mild/Moderate Group
Started 6 6 6 0 0
Completed 6 6 5 0 0
Not Completed 0 0 1 0 0
Reason Not Completed
Adverse Event             0             0             1             0             0
Period Title: Part 1b: Severe Renal Impairment
Started 0 0 0 6 0
Completed 0 0 0 6 0
Not Completed 0 0 0 0 0
Period Title: Part 2: End Stage Renal Disease
Started 0 0 0 0 6
Completed 0 0 0 0 6
Not Completed 0 0 0 0 0
Arm/Group Title Healthy Subjects Mild Renal Impairment Moderate Renal Impairment Severe Renal Impairment ESRD on Hemodialysis Total
Hide Arm/Group Description Subjects with Normal Renal Function (Creatinine Clearance > 80mL/min) 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 Disease Requiring Regular Hemodialysis 3 Times a Week for at Least 6 Weeks Prior to Screening (Creatinine Clearance <30 mL/min) Total of all reporting groups
Overall Number of Baseline Participants 6 6 6 6 6 30
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Number
Unit of measure:  Years
Number Analyzed 6 participants 6 participants 6 participants 6 participants 6 participants 30 participants
18 - 44 years 0 0 1 1 1 3
45 - 64 years 5 4 0 2 4 15
>= 65 years 1 2 5 3 1 12
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 6 participants 6 participants 6 participants 6 participants 30 participants
Female
2
  33.3%
2
  33.3%
2
  33.3%
2
  33.3%
0
   0.0%
8
  26.7%
Male
4
  66.7%
4
  66.7%
4
  66.7%
4
  66.7%
6
 100.0%
22
  73.3%
1.Primary Outcome
Title Area Under the Plasma Concentration Time-curve From Zero to the Last Measured Concentration (AUClast)
Hide 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.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) parameter analysis population: all subjects treated who have at least 1 of the PK parameters of interest.
Arm/Group Title Healthy Subjects: Multiple Dose Mild Renal Impairment: Multiple Dose Moderate Renal Impairment: Multiple Dose Healthy Subjects: Single Dose Severe Renal Impairment: Single Dose ESRD: Single Dose; After Dialysis ESRD: Single Dose; Before Dialysis
Hide Arm/Group Description:
Maraviroc 150 mg twice a day (BID) co-administered with saquinavir 1,000 mg/ritonavir 100 mg twice a day (BID) for 6 days, and a single dose of both agents on Day 7.
Maraviroc 150 mg once a day (QD) co-administered with saquinavir 1,000 mg/ritonavir 100 mg twice a day (BID) for 7 days.
Maraviroc 150 mg every 48 hours co-administered with saquinavir 1,000 mg/ritonavir 100 mg twice a day (BID) for 7 days.
Maraviroc 300 mg single dose.
Maraviroc 300 mg single dose.
Maraviroc 300 mg single dose one hour following completion of morning hemodialysis.
Maraviroc 300 mg single dose three hours prior to start of hemodialysis.
Overall Number of Participants Analyzed 6 6 5 6 6 6 6
Geometric Mean (Standard Deviation)
Unit of Measure: ng*hr/mL
7356.3  (2313.45) 9502.1  (3599.32) 6496.0  (1795.89) 1320.7  (988.66) 4255.5  (2424.19) 2636.5  (1123.34) 2770.1  (1356.56)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Healthy Subjects: Multiple Dose, Mild Renal Impairment: Multiple Dose
Comments Ratio (%) test (mild) / reference (normal). AUClast was calculated using the log-linear trapezoidal method.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter ratio of adjusted geometric means
Estimated Value 129.17
Confidence Interval 90%
92.16 to 181.04
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Healthy Subjects: Multiple Dose, Moderate Renal Impairment: Multiple Dose
Comments Ratio (%) test (moderate) / reference (normal). AUClast was calculated using the log-linear trapezoidal method.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter ratio of adjusted geometric means
Estimated Value 88.31
Confidence Interval 90%
61.97 to 125.83
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Healthy Subjects: Single Dose, Severe Renal Impairment: Single Dose
Comments Ratio (%) test (severe) / reference (normal). AUClast was calculated using the log-linear trapezoidal method.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter ratio of adjusted geometric means
Estimated Value 322.23
Confidence Interval 90%
171.97 to 603.78
Estimation Comments [Not Specified]
2.Primary Outcome
Title AUCtau
Hide 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.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) parameter analysis population: all subjects treated who have at least 1 of the PK parameters of interest. AUCtau for end stage renal disease subjects was not determined.
Arm/Group Title Healthy Subjects: Multiple Dose Mild Renal Impairment: Multiple Dose Moderate Renal Impairment: Multiple Dose
Hide Arm/Group Description:
Maraviroc 150 mg twice a day (BID) co-administered with saquinavir 1,000 mg/ritonavir 100 mg twice a day (BID) for 6 days, and a single dose of both agents on Day 7.
Maraviroc 150 mg once a day (QD) co-administered with saquinavir 1,000 mg/ritonavir 100 mg twice a day (BID) for 7 days.
Maraviroc 150 mg every 48 hours co-administered with saquinavir 1,000 mg/ritonavir 100 mg twice a day (BID) for 7 days.
Overall Number of Participants Analyzed 6 6 5
Geometric Mean (Standard Deviation)
Unit of Measure: ng*hr/mL
5341.4  (1498.27) 8118.7  (2995.27) 6193.3  (1762.41)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Healthy Subjects: Multiple Dose, Mild Renal Impairment: Multiple Dose
Comments Ratio (%) test (mild) / reference (normal).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter ratio of adjusted geometric means
Estimated Value 151.99
Confidence Interval 90%
109.53 to 210.92
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Healthy Subjects: Multiple Dose, Moderate Renal Impairment: Multiple Dose
Comments Ratio (%) test (moderate) / reference (normal).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter ratio of adjusted geometric means
Estimated Value 115.95
Confidence Interval 90%
82.23 to 163.50
Estimation Comments [Not Specified]
3.Primary Outcome
Title Maximum Observed Plasma Concentration (Cmax)
Hide 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.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) parameter analysis population: all subjects treated who have at least 1 of the PK parameters of interest.
Arm/Group Title Healthy Subjects: Multiple Dose Mild Renal Impairment: Multiple Dose Moderate Renal Impairment: Multiple Dose Healthy Subjects: Single Dose Severe Renal Impairment: Single Dose ESRD: Single Dose; After Dialysis ESRD: Single Dose; Before Dialysis
Hide Arm/Group Description:
Maraviroc 150 mg twice a day (BID) co-administered with saquinavir 1,000 mg/ritonavir 100 mg twice a day (BID) for 6 days, and a single dose of both agents on Day 7.
Maraviroc 150 mg once a day (QD) co-administered with saquinavir 1,000 mg/ritonavir 100 mg twice a day (BID) for 7 days.
Maraviroc 150 mg every 48 hours co-administered with saquinavir 1,000 mg/ritonavir 100 mg twice a day (BID) for 7 days.
Maraviroc 300 mg single dose.
Maraviroc 300 mg single dose.
Maraviroc 300 mg single dose one hour following completion of morning hemodialysis.
Maraviroc 300 mg single dose three hours prior to start of hemodialysis.
Overall Number of Participants Analyzed 6 6 5 6 6 6 6
Geometric Mean (Standard Deviation)
Unit of Measure: ng/mL
950.91  (220.368) 1150.74  (392.167) 674.20  (275.722) 335.60  (393.024) 801.16  (525.656) 576.7  (339.27) 478.5  (198.81)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Healthy Subjects: Multiple Dose, Mild Renal Impairment: Multiple Dose
Comments Ratio (%) test (mild) / reference (normal).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter ratio of adjusted geometric means
Estimated Value 121.01
Confidence Interval 90%
83.15 to 176.13
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Healthy Subjects: Multiple Dose, Moderate Renal Impairment: Multiple Dose
Comments Ratio (%) test (moderate) / reference (normal).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter ratio of adjusted geometric means
Estimated Value 70.90
Confidence Interval 90%
47.83 to 105.10
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Healthy Subjects: Single Dose, Severe Renal Impairment: Single Dose
Comments Ratio (%) test (severe) / reference (normal).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter ratio of adjusted geometric means
Estimated Value 238.73
Confidence Interval 90%
106.83 to 533.48
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Plasma Protein Binding
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) parameter analysis population: all subjects treated who have at least 1 of the PK parameters of interest.
Arm/Group Title Healthy Subjects: Multiple Dose Mild Renal Impairment: Multiple Dose Moderate Renal Impairment: Multiple Dose Healthy Subjects: Single Dose Severe Renal Impairment: Single Dose ESRD
Hide Arm/Group Description:
Maraviroc 150 mg twice a day (BID) co-administered with saquinavir 1,000 mg/ritonavir 100 mg twice a day (BID) for 6 days, and a single dose of both agents on Day 7.
Maraviroc 150 mg once a day (QD) co-administered with saquinavir 1,000 mg/ritonavir 100 mg twice a day (BID) for 7 days.
Maraviroc 150 mg every 48 hours co-administered with saquinavir 1,000 mg/ritonavir 100 mg twice a day (BID) for 7 days.
Maraviroc 300 mg single dose.
Maraviroc 300 mg single dose.
(I) Maraviroc 300 mg single dose one hour following completion of morning hemodialysis, followed at least 1 week later by (II) Maraviroc 300 mg single dose three hours prior to start of hemodialysis.
Overall Number of Participants Analyzed 6 6 5 6 6 6
Measure Type: Number
Unit of Measure: percent free
minimum protein unbound MVC fraction 19.7 15.3 18.1 14.6 19.2 18.2
maximum protein unbound MVC fraction 26.6 29.1 31.6 28.2 28.1 27.8
5.Secondary Outcome
Title Area Under the Time Curve From 0 to Infinity (AUCinf)
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) parameter analysis population: all subjects treated who have at least 1 of the PK parameters of interest. AUC infinity was not determined for subjects in the multiple dose treatment groups.
Arm/Group Title Healthy Subjects: Single Dose Severe Renal Impairment: Single Dose ESRD: Single Dose; After Dialysis ESRD: Single Dose; Before Dialysis
Hide Arm/Group Description:
Maraviroc 300 mg single dose.
Maraviroc 300 mg single dose.
Maraviroc 300 mg single dose one hour following completion of morning hemodialysis.
Maraviroc 300 mg single dose three hours prior to start of hemodialysis.
Overall Number of Participants Analyzed 6 6 6 6
Geometric Mean (Standard Deviation)
Unit of Measure: ng*hr/mL
1348.4  (986.65) 4367.7  (2518.78) 2677.4  (1149.85) 2805.5  (1374.71)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Healthy Subjects: Single Dose, Severe Renal Impairment: Single Dose
Comments Ratio (%) test (severe) / reference (normal).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter ratio of adjusted geometric means
Estimated Value 323.91
Confidence Interval 90%
174.32 to 601.88
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Time of First Occurrence (Tmax)
Hide 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.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) parameter analysis population: all subjects treated who have at least 1 of the PK parameters of interest.
Arm/Group Title Healthy Subjects: Multiple Dose Mild Renal Impairment: Multiple Dose Moderate Renal Impairment: Multiple Dose Healthy Subjects: Single Dose Severe Renal Impairment: Single Dose ESRD: Single Dose; After Dialysis ESRD: Single Dose; Before Dialysis
Hide Arm/Group Description:
Maraviroc 150 mg twice a day (BID) co-administered with saquinavir 1,000 mg/ritonavir 100 mg twice a day (BID) for 6 days, and a single dose of both agents on Day 7.
Maraviroc 150 mg once a day (QD) co-administered with saquinavir 1,000 mg/ritonavir 100 mg twice a day (BID) for 7 days.
Maraviroc 150 mg every 48 hours co-administered with saquinavir 1,000 mg/ritonavir 100 mg twice a day (BID) for 7 days.
Maraviroc 300 mg single dose.
Maraviroc 300 mg single dose.
Maraviroc 300 mg single dose one hour following completion of morning hemodialysis.
Maraviroc 300 mg single dose three hours prior to start of hemodialysis.
Overall Number of Participants Analyzed 6 6 5 6 6 6 6
Median (Full Range)
Unit of Measure: hours
1.000
(0.50 to 2.00)
1.500
(0.50 to 4.00)
2.000
(0.50 to 4.02)
2.500
(0.50 to 4.02)
2.500
(0.50 to 4.00)
3.000
(1.00 to 4.00)
2.000
(0.50 to 4.17)
7.Secondary Outcome
Title Half-life (t1/2)
Hide 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.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) parameter analysis population: all subjects treated who have at least 1 of the PK parameters of interest.
Arm/Group Title Healthy Subjects: Multiple Dose Mild Renal Impairment: Multiple Dose Moderate Renal Impairment: Multiple Dose Healthy Subjects: Single Dose Severe Renal Impairment: Single Dose ESRD: Single Dose; After Dialysis ESRD: Single Dose; Before Dialysis
Hide Arm/Group Description:
Maraviroc 150 mg twice a day (BID) co-administered with saquinavir 1,000 mg/ritonavir 100 mg twice a day (BID) for 6 days, and a single dose of both agents on Day 7.
Maraviroc 150 mg once a day (QD) co-administered with saquinavir 1,000 mg/ritonavir 100 mg twice a day (BID) for 7 days.
Maraviroc 150 mg every 48 hours co-administered with saquinavir 1,000 mg/ritonavir 100 mg twice a day (BID) for 7 days.
Maraviroc 300 mg single dose.
Maraviroc 300 mg single dose.
Maraviroc 300 mg single dose one hour following completion of morning hemodialysis.
Maraviroc 300 mg single dose three hours prior to start of hemodialysis.
Overall Number of Participants Analyzed 6 6 5 6 6 6 6
Mean (Standard Deviation)
Unit of Measure: hour
14.22  (1.166) 16.84  (5.568) 16.99  (3.141) 14.36  (4.030) 17.29  (4.171) 15.03  (3.329) 13.86  (1.051)
8.Secondary Outcome
Title Renal Clearance (CLR) in Subjects With Normal, Mild, Moderate and Severe Renal Function
Hide 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.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) parameter analysis population: all subjects treated who have at least 1 of the PK parameters of interest.
Arm/Group Title Healthy Subjects: Multiple Dose Mild Renal Impairment: Multiple Dose Moderate Renal Impairment: Multiple Dose Healthy Subjects: Single Dose Severe Renal Impairment: Single Dose
Hide Arm/Group Description:
Maraviroc 150 mg twice a day (BID) co-administered with saquinavir 1,000 mg/ritonavir 100 mg twice a day (BID) for 6 days, and a single dose of both agents on Day 7.
Maraviroc 150 mg once a day (QD) co-administered with saquinavir 1,000 mg/ritonavir 100 mg twice a day (BID) for 7 days.
Maraviroc 150 mg every 48 hours co-administered with saquinavir 1,000 mg/ritonavir 100 mg twice a day (BID) for 7 days.
Maraviroc 300 mg single dose.
Maraviroc 300 mg single dose.
Overall Number of Participants Analyzed 6 6 6 6 6
Geometric Mean (Standard Deviation)
Unit of Measure: mL/min
105.7  (56.00) 77.2  (36.71) 62.5  (12.57) 110.0  (38.67) 26.6  (18.84)
9.Secondary Outcome
Title Derivation of Renal Clearance in Subjects With Normal, Mild, Moderate and Severe Renal Function: Ae
Hide 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.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) parameter analysis population: all subjects treated who have at least 1 of the PK parameters of interest.
Arm/Group Title Healthy Subjects: Multiple Dose Mild Renal Impairment: Multiple Dose Moderate Renal Impairment: Multiple Dose Healthy Subjects: Single Dose Severe Renal Impairment: Single Dose
Hide Arm/Group Description:
Maraviroc 150 mg twice a day (BID) co-administered with saquinavir 1,000 mg/ritonavir 100 mg twice a day (BID) for 6 days, and a single dose of both agents on Day 7.
Maraviroc 150 mg once a day (QD) co-administered with saquinavir 1,000 mg/ritonavir 100 mg twice a day (BID) for 7 days.
Maraviroc 150 mg every 48 hours co-administered with saquinavir 1,000 mg/ritonavir 100 mg twice a day (BID) for 7 days.
Maraviroc 300 mg single dose.
Maraviroc 300 mg single dose.
Overall Number of Participants Analyzed 6 6 5 6 6
Mean (Standard Deviation)
Unit of Measure: mg
41.6  (22.45) 39.1  (11.23) 24.9  (8.88) 10.8  (7.41) 8.4  (6.35)
10.Secondary Outcome
Title Hemodialysis Clearance of Maraviroc (MVC) in Subjects With End Stage Renal Disease (ESRD) Undergoing Hemodialysis: CLdD
Hide Description CLdD: dialysate clearance before dialysis; measured in milliliters per minute.
Time Frame Before dialysis
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) parameter analysis population: all subjects treated who have at least 1 of the PK parameters of interest.
Arm/Group Title ESRD: Single Dose; Before Dialysis
Hide Arm/Group Description:
Maraviroc 300 mg single dose three hours prior to start of hemodialysis
Overall Number of Participants Analyzed 6
Geometric Mean (Standard Deviation)
Unit of Measure: mL/min
36.42  (12.710)
11.Secondary Outcome
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
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set: all subjects who received study medication. BL: Baseline.
Arm/Group Title Healthy Subjects: Multiple Dose Mild Renal Impairment: Multiple Dose Moderate Renal Impairment: Multiple Dose Healthy Subjects: Single Dose Severe Renal Impairment: Single Dose ESRD: Single Dose; After Dialysis ESRD: Single Dose; Before Dialysis
Hide Arm/Group Description:
Maraviroc 150 mg twice a day (BID) co-administered with saquinavir 1,000 mg/ritonavir 100 mg twice a day (BID) for 6 days, and a single dose of both agents on Day 7.
Maraviroc 150 mg once a day (QD) co-administered with saquinavir 1,000 mg/ritonavir 100 mg twice a day (BID) for 7 days.
Maraviroc 150 mg every 48 hours co-administered with saquinavir 1,000 mg/ritonavir 100 mg twice a day (BID) for 7 days.
Maraviroc 300 mg single dose.
Maraviroc 300 mg single dose.
Maraviroc 300 mg single dose one hour following completion of morning hemodialysis.
Maraviroc 300 mg single dose three hours prior to start of hemodialysis.
Overall Number of Participants Analyzed 6 6 5 6 6 6 6
Measure Type: Number
Unit of Measure: subjects
BL Supine Systolic Blood Pressure (BP) <90 mmHg 0 0 0 0 0 0 0
Maximum Increase from BL: Supine Systolic BP≥ 30 0 0 0 0 0 0 0
Maximum Decrease from BL: Supine Systolic BP ≥ 30 0 0 0 0 0 1 0
BL Supine Diastolic Blood Pressure (BP) <50 mmHg 0 0 0 0 0 0 0
Maximum Increase from BL: Supine Diastolic BP≥ 20 0 0 1 0 0 0 0
Maximun Decrease from BL: Supine Diastolic BP ≥20 0 0 0 0 0 0 0
12.Secondary Outcome
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
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set: all subjects who received study medication.
Arm/Group Title Healthy Subjects: Multiple Dose Mild Renal Impairment: Multiple Dose Moderate Renal Impairment: Multiple Dose Healthy Subjects: Single Dose Severe Renal Impairment: Single Dose ESRD: Single Dose; After Dialysis ESRD: Single Dose; Before Dialysis
Hide Arm/Group Description:
Maraviroc 150 mg twice a day (BID) co-administered with saquinavir 1,000 mg/ritonavir 100 mg twice a day (BID) for 6 days, and a single dose of both agents on Day 7.
Maraviroc 150 mg once a day (QD) co-administered with saquinavir 1,000 mg/ritonavir 100 mg twice a day (BID) for 7 days.
Maraviroc 150 mg every 48 hours co-administered with saquinavir 1,000 mg/ritonavir 100 mg twice a day (BID) for 7 days.
Maraviroc 300 mg single dose.
Maraviroc 300 mg single dose.
Maraviroc 300 mg single dose one hour following completion of morning hemodialysis.
Maraviroc 300 mg single dose three hours prior to start of hemodialysis.
Overall Number of Participants Analyzed 6 6 5 6 6 6 6
Measure Type: Number
Unit of Measure: bpm
Supine Pulse Rate <40 BPM 0 0 0 0 0 0 0
Supine Pulse Rate >120 BPM 0 0 0 0 0 0 0
13.Secondary Outcome
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
Hide 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
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Hide Analysis Population Description
Safety analysis set: all subjects who received study medication.
Arm/Group Title Healthy Subjects: Multiple Dose Mild Renal Impairment: Multiple Dose Moderate Renal Impairment: Multiple Dose Healthy Subjects: Single Dose Severe Renal Impairment: Single Dose ESRD: Single Dose; After Dialysis ESRD: Single Dose; Before Dialysis
Hide Arm/Group Description:
Maraviroc 150 mg twice a day (BID) co-administered with saquinavir 1,000 mg/ritonavir 100 mg twice a day (BID) for 6 days, and a single dose of both agents on Day 7.
Maraviroc 150 mg once a day (QD) co-administered with saquinavir 1,000 mg/ritonavir 100 mg twice a day (BID) for 7 days.
Maraviroc 150 mg every 48 hours co-administered with saquinavir 1,000 mg/ritonavir 100 mg twice a day (BID) for 7 days.
Maraviroc 300 mg single dose.
Maraviroc 300 mg single dose.
Maraviroc 300 mg single dose one hour following completion of morning hemodialysis.
Maraviroc 300 mg single dose three hours prior to start of hemodialysis.
Overall Number of Participants Analyzed 6 6 5 6 6 6 6
Measure Type: Number
Unit of Measure: subjects
Maximum QTC Interval: 450 to < 480 msec 1 0 0 1 2 1 0
Maximum QTC Interval: 480 to < 500 msec 0 0 0 0 0 0 0
Maximum QTC Interval: > 500 msec 0 0 0 0 0 0 0
Maximum QTCB Interval: 450 to < 480 msec 1 0 0 1 1 0 0
Maximum QTCB Interval: 480 to < 500 msec 0 0 0 0 0 0 0
Maximum QTCB Interval: > 500 msec 0 0 0 0 0 0 0
Maximum QTCF Interval: 450 to 480 msec 1 0 0 0 1 0 0
Maximum QTCF Interval: 480 to < 500 msec 0 0 0 0 0 0 0
Maximum QTCF Interval: > 500 msec 0 0 0 0 0 0 0
Max. QTC Interval Increase from BL: change ≥30 <60 0 0 0 0 0 0 1
QTC Interval Increase from BL: change ≥ 60 0 0 0 0 0 0 0
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Healthy Subjects Mild Renal Impairment Moderate Renal Impairment Healthy Subjects: Single Dose Severe Renal Impairment: ESRD: Dosing After Dialysis ESRD: Dosing Before Dialysis
Hide Arm/Group Description Maraviroc 150 mg twice a day (BID) co-administered with saquinavir 1,000 mg/ritonavir 100 mg twice a day (BID) for 7 days. Maraviroc 150 mg once a day (QD) co-administered with saquinavir 1,000 mg/ritonavir 100 mg twice a day (BID) for 7 days. Maraviroc 150 milligrams (mg) every 48 hours co-administered with saquinavir 1,000 mg/ritonavir 100 mg twice a day (BID) for 7 days. Maraviroc 300 mg single dose. Maraviroc 300 mg single dose. Maraviroc 300 mg single dose one hour following completion of morning hemodialysis. Maraviroc 300 mg single dose three hours prior to start of hemodialysis.
All-Cause Mortality
Healthy Subjects Mild Renal Impairment Moderate Renal Impairment Healthy Subjects: Single Dose Severe Renal Impairment: ESRD: Dosing After Dialysis ESRD: Dosing Before Dialysis
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Healthy Subjects Mild Renal Impairment Moderate Renal Impairment Healthy Subjects: Single Dose Severe Renal Impairment: ESRD: Dosing After Dialysis ESRD: Dosing Before Dialysis
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/6 (0.00%)      0/6 (0.00%)      0/6 (0.00%)      0/6 (0.00%)      0/6 (0.00%)      0/6 (0.00%)      0/6 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Healthy Subjects Mild Renal Impairment Moderate Renal Impairment Healthy Subjects: Single Dose Severe Renal Impairment: ESRD: Dosing After Dialysis ESRD: Dosing Before Dialysis
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/6 (33.33%)      6/6 (100.00%)      6/6 (100.00%)      1/6 (16.67%)      3/6 (50.00%)      2/6 (33.33%)      1/6 (16.67%)    
Eye disorders               
conjunctival hyperaemia  1  0/6 (0.00%)  0 1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
visual impairment  1  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
Gastrointestinal disorders               
abdominal distension  1  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
abdominal pain upper  1  1/6 (16.67%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
constipation  1  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
diarrhea  1  1/6 (16.67%)  1/6 (16.67%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
dry mouth  1  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%) 
dyspepsia  1  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
flatulence  1  2/6 (33.33%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
nausea  1  1/6 (16.67%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  1/6 (16.67%) 
vomiting  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%) 
General disorders               
fatigue  1  0/6 (0.00%)  2/6 (33.33%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
pain  1  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
sensation of foreign body  1  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
Infections and infestations               
rhinitis  1  1/6 (16.67%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
Injury, poisoning and procedural complications               
wound  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%) 
Investigations               
blood bilirubin increased  1  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
blood creatinine increased  1  0/6 (0.00%)  4/6 (66.67%)  4/6 (66.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
blood urea increased  1  0/6 (0.00%)  3/6 (50.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
renal function test abnormal  1  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
Metabolism and nutrition disorders               
dehydration  1  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
hyperuricaemia  1  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
hypokalaemia  1  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
Musculoskeletal and connective tissue disorders               
muscle spasms  1  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
Nervous system disorders               
dizziness  1  1/6 (16.67%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
headache  1  2/6 (33.33%)  3/6 (50.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
paraesthesia  1  0/6 (0.00%)  1/6 (16.67%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
Renal and urinary disorders               
nocturia  1  0/6 (0.00%)  3/6 (50.00%)  3/6 (50.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
renal pain  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%) 
Respiratory, thoracic and mediastinal disorders               
cough  1  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
throat irritation  1  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
Skin and subcutaneous tissue disorders               
hyperhidrosis  1  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
pruritus  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%) 
Vascular disorders               
orthostatic hypotension  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 11.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Pfizer has the right to review disclosures, requesting a delay of < 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), < 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc
Phone: 1-800-718-1021
Responsible Party: Director, Clinical Trial Disclosure Group, Pfizer, Inc.
ClinicalTrials.gov Identifier: NCT00717067     History of Changes
Other Study ID Numbers: A4001075
First Submitted: July 15, 2008
First Posted: July 16, 2008
Results First Submitted: November 16, 2009
Results First Posted: December 21, 2009
Last Update Posted: November 19, 2010