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

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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. ]

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2. Primary:

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

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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. ]

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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 ]

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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 ]

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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. ]

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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. ]

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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. ]

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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. ]

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10. Secondary:

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

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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 ]

Show Outcome Measure 11

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 ]

Show Outcome Measure 12

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 ]

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Serious Adverse Events

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Other Adverse Events

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More Information

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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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