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
Results First Received: November 16, 2009  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Pharmacokinetics Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Human Immunodeficiency Virus (HIV) Infection
Interventions: Drug: Maraviroc
Drug: Ritonavir
Drug: Saquinavir

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Two centers took part in this study between 15 July 2008 and 21 November 2008.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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).

Reporting Groups
  Description
Healthy Subjects (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.
Mild Renal Impairment Maraviroc 150 mg once a day (QD) co-administered with saquinavir 1,000 mg/ritonavir 100 mg twice a day (BID) for 7 days.
Moderate Renal Impairment Maraviroc 150 mg every 48 hours co-administered with saquinavir 1,000 mg/ritonavir 100 mg twice a day (BID) for 7 days.
Severe Renal Impairment Maraviroc 300 mg single dose.
ESRD: 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.

Participant Flow for 3 periods

Period 1:   Part 1a: Normal/Mild/Moderate Group
    Healthy Subjects     Mild Renal Impairment     Moderate Renal Impairment     Severe Renal Impairment     ESRD: Single Dose  
STARTED     6     6     6     0     0  
COMPLETED     6     6     5     0     0  
NOT COMPLETED     0     0     1     0     0  
Adverse Event                 0                 0                 1                 0                 0  

Period 2:   Part 1b: Severe Renal Impairment
    Healthy Subjects     Mild Renal Impairment     Moderate Renal Impairment     Severe Renal Impairment     ESRD: Single Dose  
STARTED     0     0     0     6     0  
COMPLETED     0     0     0     6     0  
NOT COMPLETED     0     0     0     0     0  

Period 3:   Part 2: End Stage Renal Disease
    Healthy Subjects     Mild Renal Impairment     Moderate Renal Impairment     Severe Renal Impairment     ESRD: Single Dose  
STARTED     0     0     0     0     6  
COMPLETED     0     0     0     0     6  
NOT COMPLETED     0     0     0     0     0  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Healthy Subjects Subjects with Normal Renal Function (Creatinine Clearance > 80mL/min)
Mild Renal Impairment Subjects with Mild Renal Impairment (Creatinine Clearance >50 and ≤80 mL/min)
Moderate Renal Impairment Subjects with Moderate Renal Impairment (Creatinine Clearance ≥30 and ≤50 mL/min)
Severe Renal Impairment Subjects with Severe Renal Impairment (Creatinine Clearance <30 mL/min)
ESRD on Hemodialysis 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 Total of all reporting groups

Baseline Measures
    Healthy Subjects     Mild Renal Impairment     Moderate Renal Impairment     Severe Renal Impairment     ESRD on Hemodialysis     Total  
Number of Participants  
[units: participants]
  6     6     6     6     6     30  
Age, Customized  
[units: years]
           
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  
Gender  
[units: participants]
           
Female     2     2     2     2     0     8  
Male     4     4     4     4     6     22  



  Outcome Measures
  Hide All Outcome Measures

1.  Primary:   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. ]

Measure Type Primary
Measure Title Area Under the Plasma Concentration Time-curve From Zero to the Last Measured Concentration (AUClast)
Measure 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.  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Pharmacokinetic (PK) parameter analysis population: all subjects treated who have at least 1 of the PK parameters of interest.

Reporting Groups
  Description
Healthy Subjects: Multiple Dose 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.
Mild Renal Impairment: Multiple Dose Maraviroc 150 mg once a day (QD) co-administered with saquinavir 1,000 mg/ritonavir 100 mg twice a day (BID) for 7 days.
Moderate Renal Impairment: Multiple Dose Maraviroc 150 mg every 48 hours co-administered with saquinavir 1,000 mg/ritonavir 100 mg twice a day (BID) for 7 days.
Healthy Subjects: Single Dose Maraviroc 300 mg single dose.
Severe Renal Impairment: Single Dose Maraviroc 300 mg single dose.
ESRD: Single Dose; After Dialysis Maraviroc 300 mg single dose one hour following completion of morning hemodialysis.
ESRD: Single Dose; Before Dialysis Maraviroc 300 mg single dose three hours prior to start of hemodialysis.

Measured Values
    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  
Number of Participants Analyzed  
[units: participants]
  6     6     5     6     6     6     6  
Area Under the Plasma Concentration Time-curve From Zero to the Last Measured Concentration (AUClast)  
[units: ng*hr/mL]
Geometric Mean ± Standard Deviation
  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  


Statistical Analysis 1 for Area Under the Plasma Concentration Time-curve From Zero to the Last Measured Concentration (AUClast)
Groups [1] Healthy Subjects: Multiple Dose vs. Mild Renal Impairment: Multiple Dose
Method [2] ANOVA
ratio of adjusted geometric means [3] 129.17
90% Confidence Interval ( 92.16 to 181.04 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Ratio (%) test (mild) / reference (normal). AUClast was calculated using the log-linear trapezoidal method.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Area Under the Plasma Concentration Time-curve From Zero to the Last Measured Concentration (AUClast)
Groups [1] Healthy Subjects: Multiple Dose vs. Moderate Renal Impairment: Multiple Dose
Method [2] ANOVA
ratio of adjusted geometric means [3] 88.31
90% Confidence Interval ( 61.97 to 125.83 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Ratio (%) test (moderate) / reference (normal). AUClast was calculated using the log-linear trapezoidal method.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Other relevant estimation information:
  No text entered.

Statistical Analysis 3 for Area Under the Plasma Concentration Time-curve From Zero to the Last Measured Concentration (AUClast)
Groups [1] Healthy Subjects: Single Dose vs. Severe Renal Impairment: Single Dose
Method [2] ANOVA
ratio of adjusted geometric means [3] 322.23
90% Confidence Interval ( 171.97 to 603.78 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Ratio (%) test (severe) / reference (normal). AUClast was calculated using the log-linear trapezoidal method.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Other relevant estimation information:
  No text entered.



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

Measure Type Primary
Measure Title AUCtau
Measure 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.  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
Healthy Subjects: Multiple Dose 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.
Mild Renal Impairment: Multiple Dose Maraviroc 150 mg once a day (QD) co-administered with saquinavir 1,000 mg/ritonavir 100 mg twice a day (BID) for 7 days.
Moderate Renal Impairment: Multiple Dose Maraviroc 150 mg every 48 hours co-administered with saquinavir 1,000 mg/ritonavir 100 mg twice a day (BID) for 7 days.

Measured Values
    Healthy Subjects: Multiple Dose     Mild Renal Impairment: Multiple Dose     Moderate Renal Impairment: Multiple Dose  
Number of Participants Analyzed  
[units: participants]
  6     6     5  
AUCtau  
[units: ng*hr/mL]
Geometric Mean ± Standard Deviation
  5341.4  ± 1498.27     8118.7  ± 2995.27     6193.3  ± 1762.41  


Statistical Analysis 1 for AUCtau
Groups [1] Healthy Subjects: Multiple Dose vs. Mild Renal Impairment: Multiple Dose
Method [2] ANOVA
ratio of adjusted geometric means [3] 151.99
90% Confidence Interval ( 109.53 to 210.92 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Ratio (%) test (mild) / reference (normal).
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for AUCtau
Groups [1] Healthy Subjects: Multiple Dose vs. Moderate Renal Impairment: Multiple Dose
Method [2] ANOVA
ratio of adjusted geometric means [3] 115.95
90% Confidence Interval ( 82.23 to 163.50 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Ratio (%) test (moderate) / reference (normal).
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Other relevant estimation information:
  No text entered.



3.  Primary:   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. ]

Measure Type Primary
Measure Title Maximum Observed Plasma Concentration (Cmax)
Measure 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.  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Pharmacokinetic (PK) parameter analysis population: all subjects treated who have at least 1 of the PK parameters of interest.

Reporting Groups
  Description
Healthy Subjects: Multiple Dose 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.
Mild Renal Impairment: Multiple Dose Maraviroc 150 mg once a day (QD) co-administered with saquinavir 1,000 mg/ritonavir 100 mg twice a day (BID) for 7 days.
Moderate Renal Impairment: Multiple Dose Maraviroc 150 mg every 48 hours co-administered with saquinavir 1,000 mg/ritonavir 100 mg twice a day (BID) for 7 days.
Healthy Subjects: Single Dose Maraviroc 300 mg single dose.
Severe Renal Impairment: Single Dose Maraviroc 300 mg single dose.
ESRD: Single Dose; After Dialysis Maraviroc 300 mg single dose one hour following completion of morning hemodialysis.
ESRD: Single Dose; Before Dialysis Maraviroc 300 mg single dose three hours prior to start of hemodialysis.

Measured Values
    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  
Number of Participants Analyzed  
[units: participants]
  6     6     5     6     6     6     6  
Maximum Observed Plasma Concentration (Cmax)  
[units: ng/mL]
Geometric Mean ± Standard Deviation
  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  


Statistical Analysis 1 for Maximum Observed Plasma Concentration (Cmax)
Groups [1] Healthy Subjects: Multiple Dose vs. Mild Renal Impairment: Multiple Dose
Method [2] ANOVA
ratio of adjusted geometric means [3] 121.01
90% Confidence Interval ( 83.15 to 176.13 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Ratio (%) test (mild) / reference (normal).
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Maximum Observed Plasma Concentration (Cmax)
Groups [1] Healthy Subjects: Multiple Dose vs. Moderate Renal Impairment: Multiple Dose
Method [2] ANOVA
ratio of adjusted geometric means [3] 70.90
90% Confidence Interval ( 47.83 to 105.10 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Ratio (%) test (moderate) / reference (normal).
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Other relevant estimation information:
  No text entered.

Statistical Analysis 3 for Maximum Observed Plasma Concentration (Cmax)
Groups [1] Healthy Subjects: Single Dose vs. Severe Renal Impairment: Single Dose
Method [2] ANOVA
ratio of adjusted geometric means [3] 238.73
90% Confidence Interval ( 106.83 to 533.48 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Ratio (%) test (severe) / reference (normal).
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Other relevant estimation information:
  No text entered.



4.  Secondary:   Plasma Protein Binding   [ Time Frame: 2 hours post-dose; normal Day -3 and Day 7; mild moderate: Day 7; severe and ESRD: Day 1 ]

Measure Type Secondary
Measure Title Plasma Protein Binding
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Pharmacokinetic (PK) parameter analysis population: all subjects treated who have at least 1 of the PK parameters of interest.

Reporting Groups
  Description
Healthy Subjects: Multiple Dose 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.
Mild Renal Impairment: Multiple Dose Maraviroc 150 mg once a day (QD) co-administered with saquinavir 1,000 mg/ritonavir 100 mg twice a day (BID) for 7 days.
Moderate Renal Impairment: Multiple Dose Maraviroc 150 mg every 48 hours co-administered with saquinavir 1,000 mg/ritonavir 100 mg twice a day (BID) for 7 days.
Healthy Subjects: Single Dose Maraviroc 300 mg single dose.
Severe Renal Impairment: Single Dose Maraviroc 300 mg single dose.
ESRD (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.

Measured Values
    Healthy Subjects: Multiple Dose     Mild Renal Impairment: Multiple Dose     Moderate Renal Impairment: Multiple Dose     Healthy Subjects: Single Dose     Severe Renal Impairment: Single Dose     ESRD  
Number of Participants Analyzed  
[units: participants]
  6     6     5     6     6     6  
Plasma Protein Binding  
[units: percentĀ 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  

No statistical analysis provided for Plasma Protein Binding



5.  Secondary:   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 ]

Measure Type Secondary
Measure Title Area Under the Time Curve From 0 to Infinity (AUCinf)
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
Healthy Subjects: Single Dose Maraviroc 300 mg single dose.
Severe Renal Impairment: Single Dose Maraviroc 300 mg single dose.
ESRD: Single Dose; After Dialysis Maraviroc 300 mg single dose one hour following completion of morning hemodialysis.
ESRD: Single Dose; Before Dialysis Maraviroc 300 mg single dose three hours prior to start of hemodialysis.

Measured Values
    Healthy Subjects: Single Dose     Severe Renal Impairment: Single Dose     ESRD: Single Dose; After Dialysis     ESRD: Single Dose; Before Dialysis  
Number of Participants Analyzed  
[units: participants]
  6     6     6     6  
Area Under the Time Curve From 0 to Infinity (AUCinf)  
[units: ng*hr/mL]
Geometric Mean ± Standard Deviation
  1348.4  ± 986.65     4367.7  ± 2518.78     2677.4  ± 1149.85     2805.5  ± 1374.71  


Statistical Analysis 1 for Area Under the Time Curve From 0 to Infinity (AUCinf)
Groups [1] Healthy Subjects: Single Dose vs. Severe Renal Impairment: Single Dose
Method [2] ANOVA
ratio of adjusted geometric means [3] 323.91
90% Confidence Interval ( 174.32 to 601.88 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Ratio (%) test (severe) / reference (normal).
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Other relevant estimation information:
  No text entered.



6.  Secondary:   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. ]

Measure Type Secondary
Measure Title Time of First Occurrence (Tmax)
Measure 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.  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Pharmacokinetic (PK) parameter analysis population: all subjects treated who have at least 1 of the PK parameters of interest.

Reporting Groups
  Description
Healthy Subjects: Multiple Dose 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.
Mild Renal Impairment: Multiple Dose Maraviroc 150 mg once a day (QD) co-administered with saquinavir 1,000 mg/ritonavir 100 mg twice a day (BID) for 7 days.
Moderate Renal Impairment: Multiple Dose Maraviroc 150 mg every 48 hours co-administered with saquinavir 1,000 mg/ritonavir 100 mg twice a day (BID) for 7 days.
Healthy Subjects: Single Dose Maraviroc 300 mg single dose.
Severe Renal Impairment: Single Dose Maraviroc 300 mg single dose.
ESRD: Single Dose; After Dialysis Maraviroc 300 mg single dose one hour following completion of morning hemodialysis.
ESRD: Single Dose; Before Dialysis Maraviroc 300 mg single dose three hours prior to start of hemodialysis.

Measured Values
    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  
Number of Participants Analyzed  
[units: participants]
  6     6     5     6     6     6     6  
Time of First Occurrence (Tmax)  
[units: hours]
Median ( Full Range )
  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 )  

No statistical analysis provided for Time of First Occurrence (Tmax)



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

Measure Type Secondary
Measure Title Half-life (t1/2)
Measure 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.  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Pharmacokinetic (PK) parameter analysis population: all subjects treated who have at least 1 of the PK parameters of interest.

Reporting Groups
  Description
Healthy Subjects: Multiple Dose 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.
Mild Renal Impairment: Multiple Dose Maraviroc 150 mg once a day (QD) co-administered with saquinavir 1,000 mg/ritonavir 100 mg twice a day (BID) for 7 days.
Moderate Renal Impairment: Multiple Dose Maraviroc 150 mg every 48 hours co-administered with saquinavir 1,000 mg/ritonavir 100 mg twice a day (BID) for 7 days.
Healthy Subjects: Single Dose Maraviroc 300 mg single dose.
Severe Renal Impairment: Single Dose Maraviroc 300 mg single dose.
ESRD: Single Dose; After Dialysis Maraviroc 300 mg single dose one hour following completion of morning hemodialysis.
ESRD: Single Dose; Before Dialysis Maraviroc 300 mg single dose three hours prior to start of hemodialysis.

Measured Values
    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  
Number of Participants Analyzed  
[units: participants]
  6     6     5     6     6     6     6  
Half-life (t1/2)  
[units: hour]
Mean ± Standard Deviation
  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  

No statistical analysis provided for Half-life (t1/2)



8.  Secondary:   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. ]

Measure Type Secondary
Measure Title Renal Clearance (CLR) in Subjects With Normal, Mild, Moderate and Severe Renal Function
Measure 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.  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Pharmacokinetic (PK) parameter analysis population: all subjects treated who have at least 1 of the PK parameters of interest.

Reporting Groups
  Description
Healthy Subjects: Multiple Dose 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.
Mild Renal Impairment: Multiple Dose Maraviroc 150 mg once a day (QD) co-administered with saquinavir 1,000 mg/ritonavir 100 mg twice a day (BID) for 7 days.
Moderate Renal Impairment: Multiple Dose Maraviroc 150 mg every 48 hours co-administered with saquinavir 1,000 mg/ritonavir 100 mg twice a day (BID) for 7 days.
Healthy Subjects: Single Dose Maraviroc 300 mg single dose.
Severe Renal Impairment: Single Dose Maraviroc 300 mg single dose.

Measured Values
    Healthy Subjects: Multiple Dose     Mild Renal Impairment: Multiple Dose     Moderate Renal Impairment: Multiple Dose     Healthy Subjects: Single Dose     Severe Renal Impairment: Single Dose  
Number of Participants Analyzed  
[units: participants]
  6     6     6     6     6  
Renal Clearance (CLR) in Subjects With Normal, Mild, Moderate and Severe Renal Function  
[units: mL/min]
Geometric Mean ± Standard Deviation
  105.7  ± 56.00     77.2  ± 36.71     62.5  ± 12.57     110.0  ± 38.67     26.6  ± 18.84  

No statistical analysis provided for Renal Clearance (CLR) in Subjects With Normal, Mild, Moderate and Severe Renal Function



9.  Secondary:   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. ]

Measure Type Secondary
Measure Title Derivation of Renal Clearance in Subjects With Normal, Mild, Moderate and Severe Renal Function: Ae
Measure 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.  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Pharmacokinetic (PK) parameter analysis population: all subjects treated who have at least 1 of the PK parameters of interest.

Reporting Groups
  Description
Healthy Subjects: Multiple Dose 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.
Mild Renal Impairment: Multiple Dose Maraviroc 150 mg once a day (QD) co-administered with saquinavir 1,000 mg/ritonavir 100 mg twice a day (BID) for 7 days.
Moderate Renal Impairment: Multiple Dose Maraviroc 150 mg every 48 hours co-administered with saquinavir 1,000 mg/ritonavir 100 mg twice a day (BID) for 7 days.
Healthy Subjects: Single Dose Maraviroc 300 mg single dose.
Severe Renal Impairment: Single Dose Maraviroc 300 mg single dose.

Measured Values
    Healthy Subjects: Multiple Dose     Mild Renal Impairment: Multiple Dose     Moderate Renal Impairment: Multiple Dose     Healthy Subjects: Single Dose     Severe Renal Impairment: Single Dose  
Number of Participants Analyzed  
[units: participants]
  6     6     5     6     6  
Derivation of Renal Clearance in Subjects With Normal, Mild, Moderate and Severe Renal Function: Ae  
[units: mg]
Mean ± Standard Deviation
  41.6  ± 22.45     39.1  ± 11.23     24.9  ± 8.88     10.8  ± 7.41     8.4  ± 6.35  

No statistical analysis provided for Derivation of Renal Clearance in Subjects With Normal, Mild, Moderate and Severe Renal Function: Ae



10.  Secondary:   Hemodialysis Clearance of Maraviroc (MVC) in Subjects With End Stage Renal Disease (ESRD) Undergoing Hemodialysis: CLdD   [ Time Frame: Before dialysis ]

Measure Type Secondary
Measure Title Hemodialysis Clearance of Maraviroc (MVC) in Subjects With End Stage Renal Disease (ESRD) Undergoing Hemodialysis: CLdD
Measure Description CLdD: dialysate clearance before dialysis; measured in milliliters per minute.
Time Frame Before dialysis  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Pharmacokinetic (PK) parameter analysis population: all subjects treated who have at least 1 of the PK parameters of interest.

Reporting Groups
  Description
ESRD: Single Dose; Before Dialysis Maraviroc 300 mg single dose three hours prior to start of hemodialysis

Measured Values
    ESRD: Single Dose; Before Dialysis  
Number of Participants Analyzed  
[units: participants]
  6  
Hemodialysis Clearance of Maraviroc (MVC) in Subjects With End Stage Renal Disease (ESRD) Undergoing Hemodialysis: CLdD  
[units: mL/min]
Geometric Mean ± Standard Deviation
  36.42  ± 12.710  

No statistical analysis provided for Hemodialysis Clearance of Maraviroc (MVC) in Subjects With End Stage Renal Disease (ESRD) Undergoing Hemodialysis: CLdD



11.  Secondary:   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 ]

Measure Type Secondary
Measure 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
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety analysis set: all subjects who received study medication. BL: Baseline.

Reporting Groups
  Description
Healthy Subjects: Multiple Dose 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.
Mild Renal Impairment: Multiple Dose Maraviroc 150 mg once a day (QD) co-administered with saquinavir 1,000 mg/ritonavir 100 mg twice a day (BID) for 7 days.
Moderate Renal Impairment: Multiple Dose Maraviroc 150 mg every 48 hours co-administered with saquinavir 1,000 mg/ritonavir 100 mg twice a day (BID) for 7 days.
Healthy Subjects: Single Dose Maraviroc 300 mg single dose.
Severe Renal Impairment: Single Dose Maraviroc 300 mg single dose.
ESRD: Single Dose; After Dialysis Maraviroc 300 mg single dose one hour following completion of morning hemodialysis.
ESRD: Single Dose; Before Dialysis Maraviroc 300 mg single dose three hours prior to start of hemodialysis.

Measured Values
    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  
Number of Participants Analyzed  
[units: participants]
  6     6     5     6     6     6     6  
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  
[units: 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  

No statistical analysis provided for 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



12.  Secondary:   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 ]

Measure Type Secondary
Measure 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
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety analysis set: all subjects who received study medication.

Reporting Groups
  Description
Healthy Subjects: Multiple Dose 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.
Mild Renal Impairment: Multiple Dose Maraviroc 150 mg once a day (QD) co-administered with saquinavir 1,000 mg/ritonavir 100 mg twice a day (BID) for 7 days.
Moderate Renal Impairment: Multiple Dose Maraviroc 150 mg every 48 hours co-administered with saquinavir 1,000 mg/ritonavir 100 mg twice a day (BID) for 7 days.
Healthy Subjects: Single Dose Maraviroc 300 mg single dose.
Severe Renal Impairment: Single Dose Maraviroc 300 mg single dose.
ESRD: Single Dose; After Dialysis Maraviroc 300 mg single dose one hour following completion of morning hemodialysis.
ESRD: Single Dose; Before Dialysis Maraviroc 300 mg single dose three hours prior to start of hemodialysis.

Measured Values
    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  
Number of Participants Analyzed  
[units: participants]
  6     6     5     6     6     6     6  
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  
[units: 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  

No statistical analysis provided for 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



13.  Secondary:   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 ]

Measure Type Secondary
Measure 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
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety analysis set: all subjects who received study medication.

Reporting Groups
  Description
Healthy Subjects: Multiple Dose 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.
Mild Renal Impairment: Multiple Dose Maraviroc 150 mg once a day (QD) co-administered with saquinavir 1,000 mg/ritonavir 100 mg twice a day (BID) for 7 days.
Moderate Renal Impairment: Multiple Dose Maraviroc 150 mg every 48 hours co-administered with saquinavir 1,000 mg/ritonavir 100 mg twice a day (BID) for 7 days.
Healthy Subjects: Single Dose Maraviroc 300 mg single dose.
Severe Renal Impairment: Single Dose Maraviroc 300 mg single dose.
ESRD: Single Dose; After Dialysis Maraviroc 300 mg single dose one hour following completion of morning hemodialysis.
ESRD: Single Dose; Before Dialysis Maraviroc 300 mg single dose three hours prior to start of hemodialysis.

Measured Values
    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  
Number of Participants Analyzed  
[units: participants]
  6     6     5     6     6     6     6  
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  
[units: 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  

No statistical analysis provided for 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




  Serious Adverse Events


  Other Adverse Events


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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.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.  


Results Point of Contact:  
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc
phone: 1-800-718-1021
e-mail: ClinicalTrials.govCallCenter@pfizer.com


No publications provided


Responsible Party: Director, Clinical Trial Disclosure Group, Pfizer, Inc.
ClinicalTrials.gov Identifier: NCT00717067     History of Changes
Other Study ID Numbers: A4001075
Study First Received: July 15, 2008
Results First Received: November 16, 2009
Last Updated: November 10, 2010
Health Authority: United States: Food and Drug Administration