A Phase 1, Open-Label, Drug-Drug Interaction Study to Evaluate the Potential Effects of Ranitidine on the Pharmacokinetics of Lesinurad in Healthy Adult Male Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 16
- 主要终点
- PK profile of lesinurad from plasma and urine
研究概览
简要总结
This is a drug-drug interaction study in healthy volunteers to evaluate the potential pharmacokinetic (PK) effects of ranitidine on lesinurad.
详细描述
This study will evaluate the potential effect of ranitidine on the pharmacokinetics of lesinurad. An earlier study demonstrated an effect on lesinurad PK in the presence of both calcium-containing and magnesium- and aluminum-containing antacids. The current study will assess whether raising gastric pH, without the presence of these cations, affects lesinurad PK and PD under the fasted state. If an impact is seen, then the optional second cohort will be conducted under the fed state.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •body weight ≥ 50 kg (110 lbs) and body mass index ≥ 18 and ≤ 30 kg/m
- •Screening sUA value ≤ 7.0 mg/dL.
- •free of any clinically significant disease that requires a physician's care and/or would interfere with study evaluations or procedures.
- •Subject has no clinically relevant abnormalties in vital signs, ECG, physical examination or safety laboratory values per the Investigator's judgment.
排除标准
- •history or clinical manifestations of significant metabolic, hematological, pulmonary, cardiovascular, gastrointestinal, neurologic, hepatic renal,urological, or psychiatric disorders.
- •history or suspicion of kidney stones.
- •undergone major surgery within 3 months prior to Day
- •donated blood or experienced significant blood loss (> 450 mL) within 12 weeks prior to Day 1 or gave a plasma donation within 4 weeks prior to the Screening visit.
- •inadequate venous access or unsuitable veins for repeated venipuncture.
研究组 & 干预措施
Sequence 1 fasted
Day 1: Lesinurad 400 mg once daily (qd)
Day 5: Ranitidine 150 mg twice daily (bid)
Day 6: Lesinurad 400 mg (qd) + ranitidine 150 mg (bid). Ranitidine dosed at -2 hours predose and 12 hours postdose of lesinurad.
Day 7: Ranitidine 150 mg (bid)
干预措施: lesinurad 400 mg (Drug)
Sequence 1 fasted
Day 1: Lesinurad 400 mg once daily (qd)
Day 5: Ranitidine 150 mg twice daily (bid)
Day 6: Lesinurad 400 mg (qd) + ranitidine 150 mg (bid). Ranitidine dosed at -2 hours predose and 12 hours postdose of lesinurad.
Day 7: Ranitidine 150 mg (bid)
干预措施: ranitidine 150 mg (Drug)
Sequence 1 fasted
Day 1: Lesinurad 400 mg once daily (qd)
Day 5: Ranitidine 150 mg twice daily (bid)
Day 6: Lesinurad 400 mg (qd) + ranitidine 150 mg (bid). Ranitidine dosed at -2 hours predose and 12 hours postdose of lesinurad.
Day 7: Ranitidine 150 mg (bid)
干预措施: lesinurad 400 mg + ranitidine 150 mg (Drug)
Sequence 2 fasted
Day 1: Ranitidine 150 mg (bid)
Day 2: Lesinurad 400 mg (qd) + ranitidine 150 mg (bid). Ranitidine dosed at -2 hours predose and 12 hours postdose of lesinurad
Day 3: Ranitidine 150 mg (bid)
Day 7: Lesinurad 400 mg (qd)
干预措施: lesinurad 400 mg (Drug)
Sequence 2 fasted
Day 1: Ranitidine 150 mg (bid)
Day 2: Lesinurad 400 mg (qd) + ranitidine 150 mg (bid). Ranitidine dosed at -2 hours predose and 12 hours postdose of lesinurad
Day 3: Ranitidine 150 mg (bid)
Day 7: Lesinurad 400 mg (qd)
干预措施: ranitidine 150 mg (Drug)
Sequence 2 fasted
Day 1: Ranitidine 150 mg (bid)
Day 2: Lesinurad 400 mg (qd) + ranitidine 150 mg (bid). Ranitidine dosed at -2 hours predose and 12 hours postdose of lesinurad
Day 3: Ranitidine 150 mg (bid)
Day 7: Lesinurad 400 mg (qd)
干预措施: lesinurad 400 mg + ranitidine 150 mg (Drug)
结局指标
主要结局
PK profile of lesinurad from plasma and urine
时间窗: Days 1 and 6 (Sequence 1) or Days 2 and 7 (Sequence 2)
Profile in terms of Cmax, Tmax, AUC, CL/F, t1/2 Cmax: maximum concentration; Tmax: time to reach max plasma concentration; AUC: area under the concentration-time curve; CL/F: total body clearance corrected for bioavailability; t1/2: apparent terminal half-life
次要结局
- Incidence of Adverse Events and Changes in Laboratory, Electrocardiogram, and Vital Signs Parameters(6 weeks)
- PD profile of lesinurad from serum(Days 1 and 6 (Sequence 1) or Days 2 and 7 (Sequence 2))