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

Human Immunodeficiency Virus (HIV) Infection Clinical Trial

Official title:

An Open-Label, Parallel Group, Single And Multiple Dose Study To Evaluate The Pharmacokinetics, Safety And Toleration Of Maraviroc Administered To Subjects With Various Degrees Of Renal Impaired And Normal Renal Function

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00717067
• Other study ID #: A4001075
• Status: Completed
• Phase: Phase 4
• First received: July 15, 2008
• Last updated: November 10, 2010
• Start date: July 2008
• Est. completion date: November 2008

Study information

• Verified date: November 2010
• Source: ViiV Healthcare
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: November 2008
• Est. primary completion date: November 2008
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

• Stable Renal Function defined as =20% (25% for normal renal function) difference between 2 measurements of serum creatinine obtained on 2 occasions separated by at least 2 weeks.

• Body Mass Index (BMI) of approximately 18 to 40 kg/m2 inclusive.

• Total body weight >50 kg (110 lbs).

• Male or female subjects between the ages of 18 and 85 years.

Exclusion Criteria:

• Subjects with acute renal disease and/or history of renal transplant.

• Supine BP at Screening =160 mm Hg systolic or =95 mm Hg diastolic.

• Supine BP at Screening =80 mm Hg systolic or =40 mm Hg diastolic.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• HIV Infections
• Human Immunodeficiency Virus (HIV) Infection
• Immunologic Deficiency Syndromes

Intervention

Drug:
• Maraviroc
Maraviroc 300 mg (150 mg x 2 tablets) x single dose
• Maraviroc
Maraviroc 150 mg tablet twice daily x 7 days
• Ritonavir
Ritonavir 100 mg capsule twice daily x 7 days
• Saquinavir
Saquinavir 1000 mg (500 mg x 2 tablets) twice daily x 7 days
• Maraviroc
Maraviroc 150 mg tablet once daily x 7 days
• Ritonavir
Ritonavir 100 mg capsule twice daily x 7 days
• Saquinavir
Saquinavir 1000 mg (500 mg x 2 tablets) twice daily x 7 days
• Maraviroc
Maraviroc 150 mg tablet once every 48 hours x 7 days
• Ritonavir
Ritonavir 100 mg capsule twice daily x 7 days
• Saquinavir
Saquinavir 1000 mg (500 mg x 2 tablets) twice daily x 7 days
• Maraviroc
Maraviroc 300 mg (150 mg x 2 tablets) x single dose
• Maraviroc
Maraviroc 300 mg (150 mg x 2 tablets) x single dose one hour following completion of hemodialysis
• Maraviroc
Maraviroc 300 mg (150 mg x 2 tablets) x single dose three hours prior to start of hemodialysis

Locations

Country	Name	City	State
Germany	Pfizer Investigational Site	Berlin
Germany	Pfizer Investigational Site	Muenchen

Sponsors (2)

Lead Sponsor	Collaborator
ViiV Healthcare	Pfizer

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area Under the Plasma Concentration Time-curve From Zero to the Last Measured Concentration (AUClast)	Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) measured in nanograms * hour divided by milliliters (ng*hr/mL).	Pre-dose, post-dose hours 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72.	No
Primary	AUCtau	AUCtau: area under the plasma concentration-time profile from time zero to the end of the dosing interval (tau); measured in nanograms * hours divided by milliliters (ng.hr/mL).	Pre-dose, post-dose hours 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72.	No
Primary	Maximum Observed Plasma Concentration (Cmax)	Maximum observed plasma concentration (Cmax) within the dosing interval; measured in nanograms per milliliter (ng/mL).	Pre-dose, post-dose hours 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72.	No
Secondary	Plasma Protein Binding	Percent protein binding (protein unbound maraviroc (MVC) fraction [percent free]) was determined by rapid equilibrium dialysis. Percent free = 100 - percent bound.	2 hours post-dose; normal Day -3 and Day 7; mild moderate: Day 7; severe and ESRD: Day 1	No
Secondary	Area Under the Time Curve From 0 to Infinity (AUCinf)	Area under the plasma concentration-time profile from time zero to the time infinate in subjects who received single dose treatment; measured in nanograms * hour divided by millilters (ng*hr/mL).	Pre-dose, post-dose hours 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72	No
Secondary	Time of First Occurrence (Tmax)	Time (hours) of first occurrence (Tmax); time after dosing when Cmax (maximum plasma concentration) occured.	Pre-dose, post-dose hours 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72.	No
Secondary	Half-life (t1/2)	Elimination half-life (t1/2) measured in hours: time required for half the quantity of maraviroc to be metabolized or eliminated by normal biological processes.	Pre-dose, post-dose hours 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72.	No
Secondary	Renal Clearance (CLR) in Subjects With Normal, Mild, Moderate and Severe Renal Function	Renal clearance (CLR) measured in milliliters per minute (mL/min).	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.	No
Secondary	Derivation of Renal Clearance in Subjects With Normal, Mild, Moderate and Severe Renal Function: Ae	Ae: amount of drug excreted unchanged in the urine; measured in milligrams (mg).	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.	No
Secondary	Hemodialysis Clearance of Maraviroc (MVC) in Subjects With End Stage Renal Disease (ESRD) Undergoing Hemodialysis: CLdD	CLdD: dialysate clearance before dialysis; measured in milliliters per minute.	Before dialysis	No
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	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.	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	No
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	Number of subjects with pulse rate < 40 beats per minute (BPM), number of subjects with pulse rate > 120 BPM.	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	No
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	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.	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	No

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