Study to Evaluate the Pharmacokinetics, Safety, Tolerability of 100 mg Multiple Doses of GLPG0634 in Subjects With Renal Impairment Compared to Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Galapagos NV
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Area under the plasma drug concentration-time curve over 24 hours (AUC0-24h)
研究概览
简要总结
This will be an open label study to assess the influence of renal impairment on the pharmacokinetics (PK) of GLPG0634 and its metabolite after once daily oral administrations of 100 mg GLPG0634 for 10 days in subjects with renal impairment and matched healthy controls.
Also, safety and tolerability of once daily oral doses of GLPG0634 for 10 days in subjects with renal impairment and matched healthy controls will be evaluated.
详细描述
The study will be divided in two parts.
In Part 1, 3 subjects with severe renal impairment or end-stage renal disease (ESRD) not yet requiring dialysis (Group 1) will be recruited first. Thereafter, 3 subjects with normal renal function (Group 2) will be recruited. If a substantial effect on the PK in renal impaired subjects is observed on Day 10, the sponsor may elect to stop Part 1 of the study without enrolling the complete set of subjects and Part 2 will be initiated. In case no substantial effect on the PK is observed, 3 further subjects in both Group 1 and 2 will be recruited and analysed. If a substantial effect on the PK is observed, the study will proceed to Part 2. Part 2 of the study will not be conducted, if in Part 1 no substantial difference in PK is seen.
In Part 2, Group 3 (mild renal impairment) and Group 4 (moderate renal impairment) will be recruited first. After completion of the mild and moderate impairment groups, Group 5 (normal renal function) will be recruited.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 79 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Male and female white subjects between 18-79 years of age (inclusive)
- •Subjects must have a BMI between 18-34 kg/m², inclusive
- •Part 1, Group 1: subject with severe renal impairment or ESRD, not on dialysis : eGFR between 15-29 mL/min/1.73 m2 or <15 mL/min/1.73m²
- •Part 1, Group 2: subject with normal renal function: eGFR ≥90 mL/min/1.73m²
- •Part 2, Group 3: subject with mild renal impairment: eGFR between 60-89 mL/min/1.73 m²
- •Part 2, Group 4:subject with moderate renal impairment: eGFR between 30-59 mL/min/1.73 m²
- •Part 2, Group 5: subject with normal renal function: eGFR ≥90 mL/min/1.73 m²
- •Subjects must be judged to be in good health (subjects with normal renal function)/in a stable condition and acceptable for study participation (subjects with renal impairment) based upon the results of a medical history, physical examination, vital signs, 12-lead ECG, and laboratory profile
排除标准
- •A subject with a known hypersensitivity to ingredients of the study medication or a significant allergic reaction to any drug
- •Subject has previously participated in a GLPG0634 study or has previously received GLPG0634
- •Concurrent participation or participation within 8 weeks prior to the initial study drug administration in a drug/device or biologic investigational research study
- •A subject with active drug or alcohol abuse within 2 years prior to the initial study drug administration
- •A subject who has a current child wish
- •Female subject less than 6 months post-partum, post-abortion or post-lactation prior to study drug administration or is pregnant or breastfeeding
研究组 & 干预措施
Part 1 - Severe renal impairment
Part 1 - Group 1: subjects with severe renal impairment or end-stage renal disease (ESRD), not on dialysis: Estimated glomerular filtration rate (eGFR) between 15-29 mL/min/1.73 m2 or <15 mL/min/1.73m² will be administered GLPG0634 100 mg once daily for 10 days
干预措施: GLPG0634 (Drug)
Part 1: Normal renal function
Part 1 - Group 2: subjects with normal renal function: eGFR ≥90 mL/min/1.73m² will be administered GLPG0634 100 mg once daily for 10 days
干预措施: GLPG0634 (Drug)
Part 2 - Mild renal impairment
Part 2 - Group 3: subjects with mild renal impairment: eGFR between 60-89 mL/min/1.73 m² will be administered GLPG0634 100 mg once daily for 10 days
干预措施: GLPG0634 (Drug)
Part 2 - Moderate renal impairment
Part 2 - Group 4:subjects with moderate renal impairment: eGFR between 30-59 mL/min/1.73 m² will be administered GLPG0634 100 mg once daily for 10 days
干预措施: GLPG0634 (Drug)
Part 2 - Normal renal function
Part 2 - Group 5: subjects with normal renal function: eGFR ≥90 mL/min/1.73 m² will be administered GLPG0634 100 mg once daily for 10 days
干预措施: GLPG0634 (Drug)
结局指标
主要结局
Area under the plasma drug concentration-time curve over 24 hours (AUC0-24h)
时间窗: Between Day 1 at pre-dose up to 168 h after the last dose on Day 10 (Day 17)
AUC0-24h of GLPG0634 and its metabolite after single and multiple dosing in subjects with renal impairment versus subjects with normal renal function
Maximum observed plasma concentration (Cmax)
时间窗: Between Day 1 at pre-dose up to 168 h after the last dose on Day 10 (Day 17)
Cmax of GLPG0634 and its metabolite after single and multiple dosing in subjects with renal impairment versus subjects with normal renal function
次要结局
- Apparent terminal half-life (t1/2,λz)(Between Day 1 at pre-dose up to 168 h after the last dose on Day 10 (Day 17))
- Accumulation ratio (Rac)(Between Day 1 at pre-dose up to 168 h after the last dose on Day 10 (Day 17))
- The number of subjects with adverse events(From screening up to 10 days after last dose (Day 20))
- Cumulative amount excreted in urine expressed in μg and % of the dose administered (Ae)(Between dosing on Day 1 up to 48 h after dosing on Day 10 (Day 12))
- Area under the plasma drug concentration-time curve from zero to the last sampling time at which concentrations were at or above the limit of quantification (AUC0-z)(Between Day 1 at pre-dose up to 168 h after the last dose on Day 10 (Day 17))
- Plasma concentration observed at 24 h post-dose (C24h)(Between Day 1 at pre-dose up to 168 h after the last dose on Day 10 (Day 17))
- Area under the plasma drug concentration-time curve, extrapolated to infinity (AUC0-∞)(Between Day 1 at pre-dose up to 168 h after the last dose on Day 10 (Day 17))
- Average plasma concentration (Cavg)(Between Day 1 at pre-dose up to 168 h after the last dose on Day 10 (Day 17))
- Time of occurrence of Cmax (tmax)(Between Day 1 at pre-dose up to 168 h after the last dose on Day 10 (Day 17))
- The number of subjects with abnormal vital signs(From screening up to 10 days after last dose (Day 20))
- Renal clearance (CLR)(Between dosing on Day 1 up to 48 h after dosing on Day 10 (Day 12))
- Metabolite over parent ratio of AUC0-24h (R)(Between Day 1 at pre-dose up to 168 h after the last dose on Day 10 (Day 17))
- The number of subjects with abnormal laboratory parameters(From screening up to 10 days after last dose (Day 20))
- The number of subjects with abnormal electrocardiogram (ECG)(From screening up to 10 days after last dose (Day 20))
- The number of subjects with abnormal physical examination(From screening up to 10 days after last dose (Day 20))