An Open-label, Parallel-group, Single Dose Study to Assess the Pharmacokinetics of LCQ908 in Patients With Mild, Moderate and Severe Renal Impairment Compared to Age, Gender and Weight-matched Healthy Volunteers.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 58
- 试验地点
- 1
- 主要终点
- Area under the plasma concentration-time profile from time zero to the time of the last quantifiable concentration (AUClast) of LCQ908
研究概览
简要总结
This study will compare the pharmacokinetics of LCQ908 in subjects with varying degrees of renal impairment to healthy subjects
研究设计
- 研究类型
- Interventional
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Individuals with renal impairment only
- •Estimated Creatinine Clearance (CLcr) by the Cockroft-Gault equation ≤80mL/min;
- •Mild renal impairment defined as CLcr 50-80 mL/min
- •Moderate renal impairment defined as CLcr 30-50 mL/min
- •Severe renal impairment defined as CLcr <30 mL/min
- •Healthy subjects only • Estimated CLcr by the Cockroft-Gault equation >80mL/min
排除标准
- •All Individuals
- •A past medical history of clinically significant ECG abnormalities or a family history of a prolonged QT-interval syndrome.
- •Female subjects must be of non child bearing potential or use an effective method of contraception.
- •Individuals with renal impairment
- •Renal transplant at any time.
- •Subjects undergoing any method of dialysis (hemodialysis, peritoneal dialysis) within the last 3 months.
- •History of clinically significant chronic or recurrent urinary tract infection active and requiring antibiotic treatment within the past 30 days.
- •Any medication that is contraindicated in moderate or severe renally impaired population
- •Healthy subjects
- •History or presence of impaired renal function as indicated by clinically significantly abnormal creatinine or BUN and/or urea values, or abnormal urinary constituents (e.g., albuminuria)
- •Evidence of urinary obstruction or difficulty in voiding at screening
- •History or presence of hepatitis B or C and/or positive Hepatitis B surface antigen (HBsAg) or Hepatitis C test result at screening.
- •Other protocol-defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
LCQ908 (mild renal impairment plus healthy volunteers)
Healthy subjects will be matched pair-wise by, sex, race, age (±15 years) and weight (±20%) to subjects with mild renal impairment and will receive a single 40 mg dose of LCQ908.
干预措施: LCQ908 (Drug)
LCQ908 (moderate renal impairment plus healthy volunteers)
Healthy subjects will be matched pair-wise by, sex, race, age (±15 years) and weight (±20%) to subjects with moderate renal impairment and will receive a single 40 mg dose of LCQ908.
干预措施: LCQ908 (Drug)
LCQ908 (severe renal impairment plus healthy volunteers)
Healthy subjects will be matched pair-wise by, sex, race, age (±15 years) and weight (±20%) to subjects with severe renal impairment and will receive a single 40 mg dose of LCQ908.
干预措施: LCQ908 (Drug)
结局指标
主要结局
Area under the plasma concentration-time profile from time zero to the time of the last quantifiable concentration (AUClast) of LCQ908
时间窗: Serial blood draws conducted on Day 1 (treatment day) followed by additional blood draws on Days 2-10,12, 14, 17, 21 and 29 post dosing
Maximum plasma concentration (Cmax) of LCQ908
时间窗: Serial blood draws conducted on Day 1 (treatment day) followed by additional blood draws on Days 2-10,12, 14, 17, 21 and 29 post dosing
Area under the plasma concentration-time profile from time zero extrapolated to infinite time [AUC(0-inf)] of LCQ908
时间窗: Serial blood draws conducted on Day 1 (treatment day) followed by additional blood draws on Days 2-10,12, 14, 17, 21 and 29 post dosing
次要结局
- LCQ908 protein binding: unbound observed maximum plasma (Cmax) of LCQ908(10 and 24 hours)
- Number of participants with adverse events (AEs), serious adverse events (SAEs) and death(Day 29)
- The apparent systemic clearance (CL/F) of LCQ908 following extra vascular administration(Serial blood draws conducted on Day 1 (treatment day) followed by additional blood draws on Days 2-10,12, 14, 17, 21 and 29 post dosing)
- The time required for the concentration of the drug to reach half of its original value(Serial blood draws conducted on Day 1 (treatment day) followed by additional blood draws on Days 2-10,12, 14, 17, 21 and 29 post dosing)
- LCQ908 protein binding: unbound apparent systemic clearance from plasma (CL/Fu) following extra vascular administration(10 and 24 hours)
- Time to maximum plasma concentration of LCQ908(Serial blood draws conducted on Day 1 (treatment day) followed by additional blood draws on Days 2-10,12, 14, 17, 21 and 29 post dosing)
- Apparent volume of distribution of LCQ908 during the terminal elimination phase following extra vascular administration(Serial blood draws conducted on Day 1 (treatment day) followed by additional blood draws on Days 2-10,12, 14, 17, 21 and 29 post dosing)
- LCQ908 protein binding: unbound area under curve (AUCc) of LCQ908(10 and 24 hours)