Pharmacokinetics, Safety And Toleration Of Maraviroc Administered To Subjects With Various Degrees Of Renal Impaired And Normal Renal Function
- Conditions
- Human Immunodeficiency Virus (HIV) Infection
- Interventions
- Registration Number
- NCT00717067
- Lead Sponsor
- ViiV Healthcare
- Brief Summary
The purpose of this study is to assess whether a dosing adjustment is needed in patients with renal impairment.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 30
- 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.
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Healthy Subjects Maraviroc Subjects with Normal Renal Function (Creatinine Clearance \> 80mL/min) (I) Maraviroc single dose, followed by (II) Maraviroc + Saquinavir/Ritonavir Healthy Subjects Saquinavir Subjects with Normal Renal Function (Creatinine Clearance \> 80mL/min) (I) Maraviroc single dose, followed by (II) Maraviroc + Saquinavir/Ritonavir Healthy Subjects Ritonavir Subjects with Normal Renal Function (Creatinine Clearance \> 80mL/min) (I) Maraviroc single dose, followed by (II) Maraviroc + Saquinavir/Ritonavir Mild Renal Impairment Maraviroc Subjects with Mild Renal Impairment (Creatinine Clearance \>50 and ≤80 mL/min) Mild Renal Impairment Ritonavir Subjects with Mild Renal Impairment (Creatinine Clearance \>50 and ≤80 mL/min) Mild Renal Impairment Saquinavir Subjects with Mild Renal Impairment (Creatinine Clearance \>50 and ≤80 mL/min) Moderate Renal Impairment Maraviroc Subjects with Moderate Renal Impairment (Creatinine Clearance ≥30 and ≤50 mL/min) Severe Renal Impairment Maraviroc Subjects with Severe Renal Impairment (Creatinine Clearance \<30 mL/min) Moderate Renal Impairment Ritonavir Subjects with Moderate Renal Impairment (Creatinine Clearance ≥30 and ≤50 mL/min) Moderate Renal Impairment Saquinavir Subjects with Moderate Renal Impairment (Creatinine Clearance ≥30 and ≤50 mL/min) ESRD on Hemodialysis Maraviroc Subjects with End Stage Renal Impairment receiving Hemodialysis(Creatinine Clearance \<30 mL/min) (I) Maraviroc single dose one hour following completion of hemodialysis, followed by (II) Maraviroc single dose three hours prior to start of hemodialysis
- Primary Outcome Measures
Name Time Method Area Under the Plasma Concentration Time-curve From Zero to the Last Measured Concentration (AUClast) Pre-dose, post-dose hours 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72. 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).
AUCtau Pre-dose, post-dose hours 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72. 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).
Maximum Observed Plasma Concentration (Cmax) Pre-dose, post-dose hours 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72. Maximum observed plasma concentration (Cmax) within the dosing interval; measured in nanograms per milliliter (ng/mL).
- Secondary Outcome Measures
Name Time Method Plasma Protein Binding 2 hours post-dose; normal Day -3 and Day 7; mild moderate: Day 7; severe and ESRD: Day 1 Percent protein binding (protein unbound maraviroc (MVC) fraction \[percent free\]) was determined by rapid equilibrium dialysis. Percent free = 100 - percent bound.
Area Under the Time Curve From 0 to Infinity (AUCinf) Pre-dose, post-dose hours 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 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 of First Occurrence (Tmax) Pre-dose, post-dose hours 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72. Time (hours) of first occurrence (Tmax); time after dosing when Cmax (maximum plasma concentration) occured.
Half-life (t1/2) Pre-dose, post-dose hours 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72. 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.
Renal Clearance (CLR) in Subjects With Normal, Mild, Moderate and Severe Renal Function 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. Renal clearance (CLR) measured in milliliters per minute (mL/min).
Derivation of Renal Clearance in Subjects With Normal, Mild, Moderate and Severe Renal Function: Ae 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. Ae: amount of drug excreted unchanged in the urine; measured in milligrams (mg).
Hemodialysis Clearance of Maraviroc (MVC) in Subjects With End Stage Renal Disease (ESRD) Undergoing Hemodialysis: CLdD Before dialysis CLdD: dialysate clearance before dialysis; measured in milliliters per minute.
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 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 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.
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 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 Number of subjects with pulse rate \< 40 beats per minute (BPM), number of subjects with pulse rate \> 120 BPM.
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 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 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.
Trial Locations
- Locations (1)
Pfizer Investigational Site
🇩🇪Muenchen, Germany