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

History of Changes

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

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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
STARTED	6	6	6
COMPLETED	6	6	5
NOT COMPLETED	0	0	1
Adverse Event	0	0	1

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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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
ratio of adjusted geometric means ^[2]	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 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
ratio of adjusted geometric means ^[2]	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 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
ratio of adjusted geometric means ^[2]	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 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
ratio of adjusted geometric means ^[2]	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 estimation information:
	No text entered.

Statistical Analysis 2 for AUCtau

Groups ^[1]	Healthy Subjects: Multiple Dose vs. Moderate Renal Impairment: Multiple Dose
ratio of adjusted geometric means ^[2]	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 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
ratio of adjusted geometric means ^[2]	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 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
ratio of adjusted geometric means ^[2]	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 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
ratio of adjusted geometric means ^[2]	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 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: 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

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
ratio of adjusted geometric means ^[2]	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 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

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

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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:

	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.
	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.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: 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.

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

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