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
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Area Under the Plasma Concentration Time-curve From Zero to the Last Measured Concentration (AUClast)
研究概览
简要总结
The purpose of this study is to assess whether a dosing adjustment is needed in patients with renal impairment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Healthy Subjects
Subjects with Normal Renal Function (Creatinine Clearance > 80mL/min) (I) Maraviroc single dose, followed by (II) Maraviroc + Saquinavir/Ritonavir
干预措施: Maraviroc (Drug)
Healthy Subjects
Subjects with Normal Renal Function (Creatinine Clearance > 80mL/min) (I) Maraviroc single dose, followed by (II) Maraviroc + Saquinavir/Ritonavir
干预措施: Ritonavir (Drug)
Healthy Subjects
Subjects with Normal Renal Function (Creatinine Clearance > 80mL/min) (I) Maraviroc single dose, followed by (II) Maraviroc + Saquinavir/Ritonavir
干预措施: Saquinavir (Drug)
Mild Renal Impairment
Subjects with Mild Renal Impairment (Creatinine Clearance >50 and ≤80 mL/min)
干预措施: Maraviroc (Drug)
Mild Renal Impairment
Subjects with Mild Renal Impairment (Creatinine Clearance >50 and ≤80 mL/min)
干预措施: Ritonavir (Drug)
Mild Renal Impairment
Subjects with Mild Renal Impairment (Creatinine Clearance >50 and ≤80 mL/min)
干预措施: Saquinavir (Drug)
Moderate Renal Impairment
Subjects with Moderate Renal Impairment (Creatinine Clearance ≥30 and ≤50 mL/min)
干预措施: Maraviroc (Drug)
Moderate Renal Impairment
Subjects with Moderate Renal Impairment (Creatinine Clearance ≥30 and ≤50 mL/min)
干预措施: Ritonavir (Drug)
Moderate Renal Impairment
Subjects with Moderate Renal Impairment (Creatinine Clearance ≥30 and ≤50 mL/min)
干预措施: Saquinavir (Drug)
Severe Renal Impairment
Subjects with Severe Renal Impairment (Creatinine Clearance <30 mL/min)
干预措施: Maraviroc (Drug)
ESRD on Hemodialysis
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
干预措施: Maraviroc (Drug)
结局指标
主要结局
Area Under the Plasma Concentration Time-curve From Zero to the Last Measured Concentration (AUClast)
时间窗: 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
时间窗: 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)
时间窗: 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).
次要结局
- Plasma Protein Binding(2 hours post-dose; normal Day -3 and Day 7; mild moderate: Day 7; severe and ESRD: Day 1)
- 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)
- Time of First Occurrence (Tmax)(Pre-dose, post-dose hours 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72.)
- Half-life (t1/2)(Pre-dose, post-dose hours 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72.)
- 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.)
- 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.)
- Hemodialysis Clearance of Maraviroc (MVC) in Subjects With End Stage Renal Disease (ESRD) Undergoing Hemodialysis: CLdD(Before dialysis)
- 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)
- 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)
- 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)