A Randomised Double-blind, Placebo-controlled, Ascending Multiple Dose Phase 1 Study of CDP923 in Healthy Volunteers to Assess Safety, Tolerability, Pharmacokinetics and Food Effect
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 37
- 试验地点
- 1
- 主要终点
- Change from baseline in clinical chemistry after multiple doses of lucerastat
研究概览
简要总结
The objectives of this study were to evaluate the safety and tolerability of lucerastat and to determine its pharmacokinetic profile after multiple dosing. Also, the potential effect of food on the pharmacokinetics of lucerastat was explored following a single dose of 500 mg.
详细描述
The subjects were to be enrolled sequentially to three dose groups, starting with the lowest dose level. Subjects could participate in only one Group. Progression to an increased dose of lucerastat was permitted only after review of all data from the previous cohort suggested that it was safe to do so.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Signed informed consent form.
- •Male subjects aged from 18 to 45 years at screening.
- •Body weight between 50 and 100 kg and body mass index (BMI) between 18.0 and 29.0 kg/m2 at screening.
- •Healthy on the basis of physical examination, cardiovascular assessments and laboratory tests.
排除标准
- •History or clinical evidence of any disease or medical / surgical condition or treatment, which may put the subject at risk of participation in the study or may interfere with the absorption, distribution, metabolism or excretion of the study treatments.
- •Serious adverse reaction or hypersensitivity to any drug.
- •Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol.
研究组 & 干预措施
Cohort 1 (200 mg)
Six subjects received 200 mg of lucerastat twice daily for 7 consecutive days in fasting conditions
干预措施: Lucerastat (Drug)
Cohort 2 (500 mg)
Six subjects received 500 mg of lucerastat as a single dose in the morning of Day 1 in fed conditions. After a 5-day washout, they received the same dose twice daily for 7 consecutive days in fasting conditions
干预措施: Lucerastat (Drug)
Cohort 3 (500 mg)
Six subjects received 500 mg of lucerastat twice daily for 7 consecutive days in fasting conditions
干预措施: Lucerastat (Drug)
Cohort 4 (1000 mg)
Six subjects received 1 g of lucerastat for 7 consecutive days in fasting conditions
干预措施: Lucerastat (Drug)
Placebo cohorts 1 to 4
Twelve subjects received matched placebo (3 subjects per cohort, except for Cohort 3 where 4 subjects received placebo)
干预措施: Placebo (Drug)
结局指标
主要结局
Change from baseline in clinical chemistry after multiple doses of lucerastat
时间窗: Up to Day 9
Change from baseline in heart rate after multiple doses of lucerastat
时间窗: Up to Day 9
Dose proportionality in lucerastat pharmacokinetics assessed by maximum plasma concentration (Cmax)
时间窗: PK blood samples were collected on Day 7, at pre-dose and at scheduled time points up to 48 hours after the morning dose
Cmax was used to assess dose proportionality across all dose groups
Dose proportionality in lucerastat pharmacokinetics assessed by area under the concentration-time curve (AUC)
时间窗: PK blood samples were collected on Day 7, at pre-dose and at scheduled time points up to 48 hours after the morning dose on Day 7
AUC from time zero to infinity \[AUC(0-inf)\] was used to assess dose proportionality across all dose groups
Terminal elimination half-life (t1/2)
时间窗: PK blood samples were collected on Day 7, at pre-dose and at scheduled time points up to 48 hours after the morning dose on Day 7
t1/2 was calculated from the plasma concentrations-time curves of lucerastat after multiple doses
Food effect on lucerastat pharmacokinetics assessed by Cmax
时间窗: PK blood samples were collected on Day 1, at pre-dose and at scheduled time points up to 12 hours after the morning dose
Potential food effect on pharmacokinetic parameters of lucerastat was tested by comparing Cmax in fed vs fasted state in the 500 mg cohort (cohort 2)
Food effect on lucerastat pharmacokinetics assessed by AUC
时间窗: PK blood samples were collected on Day 1, at pre-dose and at scheduled time points up to 12 hours after the morning dose
Potential food effect on pharmacokinetic parameters of lucerastat was tested by comparing AUC in fed versus fasted state in the 500 mg cohort (cohort 2)
Number of participants with adverse events (AEs)
时间窗: From baseline up to Day 14 (end of study)
An AE was defined as any untoward medical occurrence in a clinical investigation subject, which did not necessarily have a causal relationship with the treatment
Change from baseline in haematology after multiple doses of lucerastat
时间窗: Up to Day 9
次要结局
- Change from baseline in body weight after multiple doses of lucerastat(At Day 9)
- Change from baseline in haematology after a single dose of lucerastat(At 24 hours post dose)
- Change from baseline in clinical chemistry after a single dose of lucerastat(At 24 hours post dose)
- Change from baseline in heart rate after a single dose of lucerastat(At 24 hours post dose)
- Change from baseline in blood pressure after a single dose of lucerastat(Up to 24 hours post dose)
- Change from baseline in electrocardiogram (ECG) variables after a single dose of lucerastat(Up to 24 hours post dose)
- Stool frequency after multiple doses of lucerastat(Every day up to Day 9)