An Open-label, Single-dose, Parallel Group Study to Assess the Pharmacokinetics of Fevipiprant (QAW039) in Patients With End-stage Renal Disease on Hemodialysis and Optionally in Patients With Severe to Moderate and Mild Renal Impairment Compared to Matched Healthy Volunteers Including a Cross-over Assessment in End-stage Renal Disease Patients on the Effect of Dialysis on Fevipiprant Pharmacokinetics
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 45
- 试验地点
- 1
- 主要终点
- Pharmacokinetics: Plasma concentration of fevipiprant by AUClast
研究概览
简要总结
The aim of the study is to assess whether renal impairment could affect fevipiprant pharmacokinetics (PK) to the extent that dosage adjustment is appropriate for this patient population.
The study also aims to determine the effect of dialysis on the fevipiprant pharmacokinetic profile as the procedure might remove a significant fraction of the drug.
详细描述
The purpose of this study is to determine if the pharmacokinetic profile of fevipiprant is different in patients with renal impariment compared to healthy matched volunteers to an extent that would require an adjustment of the dosage. Data from this study will be used to guide enrollment criteria in future clinical trials and to support regulatory submission and labeling information
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Parallel
- 主要目的
- Treatment
- 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
- •Healthy subjects must satisfy the criteria for normal renal function as evidenced by normal Glomerular Filtration Rate (GFR): eGFR ≥ 90 mL/min/1.73m2; each healthy subject must match in age (+/- 10years), gender, smoking status, and weight (+/- 15%), a patient from the renail impaired patient groups:
- •A body mass index (BMI) within the range of 18 - 36 kg/m2
- •ESRD patients on hemodialysis: an glomerulo filtration rat GFR of < 15 mL/min/1.73 m2
- •patients with severe renal impairment: GFR of< 30 mL/min/1.73m2 (without need of hemodialysis);
- •patients with moderate renal impairment: 30 mL/min/1.73m2 ≤ eGFR < 60 mL/min/1.73m2;
- •patients with mild impairment: 60 mL/min/1.73m2 ≤ eGFR < 90 mL/min/1.73m2
排除标准
- •Pregnant or nursing (lactating) women
- •History or evidence of any inherited bilirubin disease or disorder
- •subjects participating in another study
- •malignancies in the past
- •Hemoglobin levels below 10 g/dL at screening
- •HIV positiv
- •Heavy smokers (≥20 cigarettes per day)
- •Liver disease, as indicated by ALT, γ-GT, AST and alkaline phosphatase which should not exceed twice the upper limit of normal and should be stable (e.g. increased liver values known from previous patient records). Serum bilirubin > 27 μmol/L (1.6 mg/dL)
- •Clinically significant ECG changes and/or arrhythmias
- •Chronic infection with Hepatitis B (HBV) or Hepatitis C (HCV)
研究组 & 干预措施
Group 2
healthy volunteers
干预措施: QAW39A (Drug)
Group 3
severe and moderate renal impaired patients
干预措施: QAW39A2107 (Drug)
Group 4
mild renal impaired patients
干预措施: QAW39A2107 (Drug)
Group 1
ESRD patients
干预措施: QAW039 (Drug)
结局指标
主要结局
Pharmacokinetics: Plasma concentration of fevipiprant by AUClast
时间窗: 68 hours post dose
AUClast is the area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration
Pharmacokinetics: Plasma concentration of fevipiprant by AUCinf
时间窗: 68 hours post dose
AUCinf is the area under the plasma concentration-time curve from time zero to infinity
Pharmacokinetics: Plasma concentration of fevipiprant by Cmax
时间窗: 68 hours post dose
Cmax is the observed maximum plasma concentration following drug administration
Pharmacokinetics: Plasma contentration of fevipiprant by AUC0-68h
时间窗: 68 hours post dose
AUC0-68h is the area under the plasma concentration from time zero to time 68 hours of the last measured concentration above the limit of quantification after dosing
次要结局
- urinary excretion of fevipiprant and metabolite in patients with renal impairment compared to healthy controls(24 hours post dose)
- Relationship between plasma pharmacokinetics of fevipiprant by AUClast and between eGFR as well as creatinine clearance(68 hours post dose)
- Pharmacokinetics of the metabolite CCN362 by AUCinf(68 hours post dose)
- Pharmacokinetics of the metabolite CCN362 by Cmax(68 hours post dose)
- Pharmacokinetics: plasma concentration of fevipiprant in patients with End Stage Renal Disease (ESRD)(68 hours post dose)
- Pharmacokinetics of the metabolite CCN362 by AUClast(68 hours post dose)
- Relationship between plasma pharmacokinetics of fevipiprant by AUCinf and between eGFR as well as creatinine clearance(68 hours post dose)
- Relationship between plasma pharmacokinetics of fevipiprant by Cmax and between eGFR as well as creatinine clearance(68 hours post dose)