A Randomized, Open-label, Replicate, Crossover, 4-period Study to Assess the Bioequivalence of Lesinurad/Allopurinol Fixed-dose Combination 200/300 mg Tablets From Ardea Biosciences, Inc. (Test Drug) Versus Lesinurad, 200 mg Tablet From AstraZeneca (Comparator 1) Coadministered With Zyloric®, Allopurinol 300 mg Tablet From Aspen Pharma Industria Farmaceutica Ltda. (Comparator 2) in Healthy Female and Male Adult Subjects, Under Fasting Conditions.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 32
- 试验地点
- 1
- 主要终点
- Pharmacokinetics (PK) endpoints in terms of maximum observed concentration (Cmax) for lesinurad/allopurinol 200/300 FDC tablets relative to lesinurad and allopurinol monocomponent tablets
研究概览
简要总结
To assess the bioequivalence between lesinurad/allopurinol 200/300 FDC tablets and coadministered lesinurad and allopurinol tablets in the fasted state based on the pharmacokinetic (PK) evaluation of lesinurad and allopurinol in healthy adult subjects.
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
- All
- 接受健康志愿者
- 是
入选标准
- •Body mass index ranging between 18.5 kg/m2 and 30 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 current diagnosis of kidney stones.
- •Estimated creatinine clearance, as determined at Screening, of ≤ 80 mL/min calculated by the Cockcroft-Gault formula using ideal body weight.
- •Undergone major surgery within 3 months prior to Screening.
- •Donated blood within 4 weeks prior to Day 1 or experienced an event (other than blood donation) of significant blood loss (> 450 mL) within 12 weeks prior to Day 1 or 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 ABBA
Treatment A: Lesinurad/Allopurinol FDC Tablets - 200/300 mg (test product); Treatment B: lesinurad, tablets, 200 mg + Zyloric®, allopurinol, tablet, 300 mg (comparator 1 + comparator 2).
干预措施: lesinurad/allopurinol 200/300 FDC tablets (Drug)
Sequence ABBA
Treatment A: Lesinurad/Allopurinol FDC Tablets - 200/300 mg (test product); Treatment B: lesinurad, tablets, 200 mg + Zyloric®, allopurinol, tablet, 300 mg (comparator 1 + comparator 2).
干预措施: lesinurad 200 mg (Drug)
Sequence ABBA
Treatment A: Lesinurad/Allopurinol FDC Tablets - 200/300 mg (test product); Treatment B: lesinurad, tablets, 200 mg + Zyloric®, allopurinol, tablet, 300 mg (comparator 1 + comparator 2).
干预措施: allopurinol 300 mg (Drug)
Sequence BABA
Treatment A: Lesinurad/Allopurinol FDC Tablets - 200/300 mg (test product); Treatment B: lesinurad, tablets, 200 mg + Zyloric®, allopurinol, tablet, 300 mg (comparator 1 + comparator 2).
干预措施: lesinurad/allopurinol 200/300 FDC tablets (Drug)
Sequence BABA
Treatment A: Lesinurad/Allopurinol FDC Tablets - 200/300 mg (test product); Treatment B: lesinurad, tablets, 200 mg + Zyloric®, allopurinol, tablet, 300 mg (comparator 1 + comparator 2).
干预措施: lesinurad 200 mg (Drug)
Sequence BABA
Treatment A: Lesinurad/Allopurinol FDC Tablets - 200/300 mg (test product); Treatment B: lesinurad, tablets, 200 mg + Zyloric®, allopurinol, tablet, 300 mg (comparator 1 + comparator 2).
干预措施: allopurinol 300 mg (Drug)
Sequence ABAB
Treatment A: Lesinurad/Allopurinol FDC Tablets - 200/300 mg (test product); Treatment B: lesinurad, tablets, 200 mg + Zyloric®, allopurinol, tablet, 300 mg (comparator 1 + comparator 2).
干预措施: lesinurad/allopurinol 200/300 FDC tablets (Drug)
Sequence ABAB
Treatment A: Lesinurad/Allopurinol FDC Tablets - 200/300 mg (test product); Treatment B: lesinurad, tablets, 200 mg + Zyloric®, allopurinol, tablet, 300 mg (comparator 1 + comparator 2).
干预措施: lesinurad 200 mg (Drug)
Sequence ABAB
Treatment A: Lesinurad/Allopurinol FDC Tablets - 200/300 mg (test product); Treatment B: lesinurad, tablets, 200 mg + Zyloric®, allopurinol, tablet, 300 mg (comparator 1 + comparator 2).
干预措施: allopurinol 300 mg (Drug)
Sequence BAAB
Treatment A: Lesinurad/Allopurinol FDC Tablets - 200/300 mg (test product); Treatment B: lesinurad, tablets, 200 mg + Zyloric®, allopurinol, tablet, 300 mg (comparator 1 + comparator 2).
干预措施: lesinurad/allopurinol 200/300 FDC tablets (Drug)
Sequence BAAB
Treatment A: Lesinurad/Allopurinol FDC Tablets - 200/300 mg (test product); Treatment B: lesinurad, tablets, 200 mg + Zyloric®, allopurinol, tablet, 300 mg (comparator 1 + comparator 2).
干预措施: lesinurad 200 mg (Drug)
Sequence BAAB
Treatment A: Lesinurad/Allopurinol FDC Tablets - 200/300 mg (test product); Treatment B: lesinurad, tablets, 200 mg + Zyloric®, allopurinol, tablet, 300 mg (comparator 1 + comparator 2).
干预措施: allopurinol 300 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 FDC tablets relative to lesinurad and allopurinol monocomponent tablets
时间窗: Days 1, 8, 15 and 22
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 FDC tablets relative to lesinurad and allopurinol monocomponent tablets
时间窗: Days 1, 8, 15 and 22
Tmax is the time of occurrence of cmax
PK endpoints in terms of apparent terminal half-life (t1/2) for lesinurad/allopurinol 200/300 FDC tablets relative to lesinurad and allopurinol monocomponent tablets
时间窗: Days 1, 8, 15 and 22
t1/2 is a measure of apparent terminal half-life
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 FDC tablets relative to lesinurad and allopurinol monocomponent tablets
时间窗: Days 1, 8, 15 and 22
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 FDC tablets relative to lesinurad and allopurinol monocomponent tablets
时间窗: Days 1, 8, 15 and 22
AUC 0-∞ is a meausre of total concentration from time zero to infinity
次要结局
- Incidence of Adverse Events in terms of changes in laboratory parameters(26 days)
- Incidence of Adverse Events in terms of vital signs(26 days)
- Incidence of Adverse Events in terms of physical examination findings(26 days)
- Incidence of Adverse Events in terms of electrocardiogram parameters(26 days)