A Phase 1, Randomized, Open-Label, Crossover Study to Assess the Relative Bioavailability of Lesinurad/Allopurinol Fixed Dose Combination Tablets and Coadministered Lesinurad and Allopurinol Tablets and the Effect of Food on the Pharmacokinetics of Lesinurad/Allopurinol Fixed Dose Combination Tablets in Healthy Adult Male Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 116
- 主要终点
- Pharmacokinetics (PK) endpoints in terms of maximum observed concentration (Cmax) for lesinurad/allopurinol 200/300 and 200/200 FDC tablets relative to lesinurad and allopurinol monocomponent tablets
研究概览
简要总结
This study will assess relative bioavailability of lesinurad/allopurinol fixed dose combination (FDC), its individual components and the effect of food.
详细描述
The study comprises 2 parts. Part 1 will assess the relative BA of lesinurad/allopurinol FDC and monocomponents in fasted subjects. Part 2 will assess the effect of food on the PK of FDC tablets.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Body mass index ranging between 18 kg/m2 and 40 kg/m
- •Screening serum urate level is ≤ 7.0 mg/dL.
排除标准
- •Asian subject who has a positive test for the HLA-B*5801 allele.
- •History or suspicion of kidney stones.
- •Estimated creatinine clearance, as determined at Screening, of < 90 mL/min calculated by the Cockcroft-Gault formula using ideal body weight.
- •Undergone major surgery within 3 months prior to Screening.
- •Donated blood or experienced significant blood loss (> 450 mL) within 12 weeks prior to Day 1or has given a plasma donation within 4 weeks prior to Day
- •Inadequate venous access or unsuitable veins for repeated venipuncture.
- •Received any strong or moderate enzyme-inducing drug or product within 2 months prior to Screening.
研究组 & 干预措施
Sequence AB
Day 1: lesinurad/allopurinol FDC tablets (Treatment A); Day 8: lesinurad + allopurinol (Treatment B)
干预措施: lesinurad/allopurinol 200/300 FDC tablets (Drug)
Sequence AB
Day 1: lesinurad/allopurinol FDC tablets (Treatment A); Day 8: lesinurad + allopurinol (Treatment B)
干预措施: lesinurad 200 mg (Drug)
Sequence AB
Day 1: lesinurad/allopurinol FDC tablets (Treatment A); Day 8: lesinurad + allopurinol (Treatment B)
干预措施: allopurinol 300 mg (Drug)
Sequence BA
Day 1: lesinurad + allopurinol (Treatment B); Day 8: lesinurad/allopurinol FDC tablets (Treatment A).
干预措施: lesinurad/allopurinol 200/300 FDC tablets (Drug)
Sequence BA
Day 1: lesinurad + allopurinol (Treatment B); Day 8: lesinurad/allopurinol FDC tablets (Treatment A).
干预措施: lesinurad 200 mg (Drug)
Sequence BA
Day 1: lesinurad + allopurinol (Treatment B); Day 8: lesinurad/allopurinol FDC tablets (Treatment A).
干预措施: allopurinol 300 mg (Drug)
Sequence CD
Day 1: lesinurad/allopurinol FDC tablets (Treatment C [fasted]); Day 8: lesinurad/allopurinol FDC tablets (Treatment D [fed]).
干预措施: lesinurad/allopurinol 200/300 FDC tablets (Drug)
Sequence DC
Day 1: lesinurad/allopurinol FDC tablets (Treatment D [fed]); Day 8: lesinurad/allopurinol FDC tablets (Treatment C [fasted]).
干预措施: lesinurad/allopurinol 200/300 FDC tablets (Drug)
Sequence EF
Day 1: lesinurad/allopurinol 200/200 FDC tablets (Treatment E); Day 8: coadministered lesinurad 200 mg + allopurinol 200 mg (100 mg × 2)
干预措施: lesinurad 200 mg (Drug)
Sequence FE
Day 1: coadministered lesinurad 200 mg + allopurinol 200 mg (100 mg × 2) (Treatment F); Day 8: lesinurad/allopurinol 200/200 FDC tablets (Treatment E).
干预措施: lesinurad 200 mg (Drug)
Sequence EF
Day 1: lesinurad/allopurinol 200/200 FDC tablets (Treatment E); Day 8: coadministered lesinurad 200 mg + allopurinol 200 mg (100 mg × 2)
干预措施: lesinurad/allopurinol 200/200 FDC tablets (Drug)
Sequence EF
Day 1: lesinurad/allopurinol 200/200 FDC tablets (Treatment E); Day 8: coadministered lesinurad 200 mg + allopurinol 200 mg (100 mg × 2)
干预措施: allopurinol 200 mg (Drug)
Sequence FE
Day 1: coadministered lesinurad 200 mg + allopurinol 200 mg (100 mg × 2) (Treatment F); Day 8: lesinurad/allopurinol 200/200 FDC tablets (Treatment E).
干预措施: lesinurad/allopurinol 200/200 FDC tablets (Drug)
Sequence FE
Day 1: coadministered lesinurad 200 mg + allopurinol 200 mg (100 mg × 2) (Treatment F); Day 8: lesinurad/allopurinol 200/200 FDC tablets (Treatment E).
干预措施: allopurinol 200 mg (Drug)
结局指标
主要结局
Pharmacokinetics (PK) endpoints in terms of maximum observed concentration (Cmax) for lesinurad/allopurinol 200/300 and 200/200 FDC tablets relative to lesinurad and allopurinol monocomponent tablets
时间窗: Days 1 and Day 8
Cmax is the maximum observed concentration of a drug after administration
PK endpoints in terms of time of occurrence of maximum observed concentration (tmax) for lesinurad/allopurinol 200/300 and 200/200 FDC tablets relative to lesinurad and allopurinol monocomponent tablets
时间窗: Day 1 and Day 8
Tmax is the time of occurrence of cmax
PK endpoints in terms of area under the plasma concentration time curve from zero to the last quantifiable sampling timepoint (AUC last) for lesinurad/allopurinol 200/300 and 200/200 FDC tablets relative to lesinurad and allopurinol monocomponent tablets
时间窗: Day 1 and Day 8
AUC last is the area under the plasma concentration time curve from zero to the last quantifiable sampling timepoint
PK endpoints in terms of area under the plasma concentration time curve from and from zero to infinity (AUC 0-∞) for lesinurad/allopurinol 200/300 and 200/200 FDC tablets relative to lesinurad and allopurinol monocomponent tablets
时间窗: Day 1 and Day 8
AUC 0-∞ is a meausre of total concentration from time zero to infinity
PK endpoints in terms of apparent terminal half-life (t1/2) for lesinurad/allopurinol 200/300 and 200/200 FDC tablets relative to lesinurad and allopurinol monocomponent tablets
时间窗: Day 1 and Day 8
t1/2 is a measure of apparent terminal half-life
次要结局
- Incidence of Adverse Events in terms of changes in laboratory parameters(6 weeks)
- Incidence of Adverse Events in terms of electrocardiogram parameters(6 weeks)
- Incidence of Adverse Events in terms of vital signs(6 weeks)
- Incidence of Adverse Events in terms of physical examination findings(6 weeks)