A Randomized, Double-blind, Placebo-controlled, Single Ascending and Multiple Ascending Dose Study of the Safety, Tolerability, Pharmacokinetics(PK) and Pharmacodynamics(PD) of Lomitapide in Japanese and Caucasian Volunteers With Elevated Low-density-lipoprotein(LDL-C)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 72
- 试验地点
- 1
- 主要终点
- Cmax for Lomitapide
研究概览
简要总结
This is a randomized, double-blind, placebo-controlled, single ascending dose (SAD) and multiple ascending dose (MAD) study of orally administered lomitapide in healthy male Japanese and Caucasian subjects with elevated LDL-C. The purpose for this study is to evaluate the PK and PD of lomitapide in Japanese subjects as compared to Caucasian subjects.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 20 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Subject is a healthy male or female, Caucasian or Japanese, aged 20 - 45 years, inclusive, at screening.
- •Subject has a BMI of 18.5 - 30 kg/m2 inclusive at screening.
- •Subjects must have a screening LDL-C measurement and the mean of Day 5 and Day 6 measurements greater than or equal to 110mg/dL.
- •Subjects must agree to use acceptable methods of contraception (details provided in the protocol)
- •Subjects must be capable of understanding and complying with the requirements of the protocol and must have signed the informed consent form prior to undergoing any study-related procedures.
排除标准
- •Subject has a clinically significant disease or any condition or disease that might affect drug absorption, distribution or excretion.
- •Any clinically significant abnormal laboratory, vital signs or other safety findings as determined by medical history, physical examination or other evaluations conducted at screening or on admission.
- •Electrocardiogram (ECG) abnormalities in the standard 12-lead ECG (at screening) which in the opinion of the Investigator is clinically relevant or will interfere with the ECG analysis.
- •History or current evidence of any clinically relevant cardiovascular, pulmonary, hepatic, renal, gastrointestinal, haematological, endocrinological, metabolic, neurological, psychiatric or other disease.
- •Positive results in any of the serology tests for Hepatitis B Surface Antigen (HbsAg), anti-Hepatitis core antibody (anti-HBc Ig G [and anti-HBc IgM if IgG is positive], Hepatitis C antibodies (anti-HCV), and HIV 1 and 2 antibodies, (anti-HIV 1/2) at screening.
- •Confirmed positive results from urine drug screen or from the alcohol breath test at screening and on admission (Day -1).
- •History or clinical evidence of alcohol or drug abuse.
- •Mentally handicapped.
- •Participation in a drug trial within 90 days prior to first drug administration.
- •Use of any medication (including over-the-counter (OTC) medication) within 2 weeks prior to admission (Day -1) or within less than 10 times the elimination half-life of the respective drug, or anticipated concomitant medication during the treatment periods.
- •Use of any substance inhibiting CYP3A4 enzymes within 2 weeks prior to admission (Day -1).
- •Donation of more than 500 mL of blood within 90 days prior to drug administration.
- •Subjects who smoke more than 10 cigarettes or equivalent amount of tobacco per day and/or who cannot stop smoking for the duration of the study whilst in the CPU.
- •Treatment with herbal supplements during the 7 days prior to dosing, or use of vitamins during 48 hours prior to admission (Day -1).
- •Any circumstances or conditions, which, in the opinion of the PI, may affect full participation in the trial or compliance with the protocol.
- •Legal incapacity or limited legal capacity at screening.
- •Subjects who are vegetarians, vegans or have any dietary restrictions conflicting with the study standardised menus.
- •If female, subject was pregnant or lactating (females of child bearing potential must have negative pregnancy tests at screening and admission).
研究组 & 干预措施
Cohort 1
12 Japanese and 12 Caucasian subjects. 10 out of 12 will receive 10 mg lomitapide and 2 will receive placebo.
干预措施: lomitapide (Drug)
Cohort 2
8 Japanese and 8 Caucasian subjects. 6 out of 8 subjects will receive 20 mg lomitapide and 2 will receive placebo.
干预措施: lomitapide (Drug)
Cohort 3
8 Japanese and 8 Caucasian subjects. 6 out of 8 subjects will receive 40 mg lomitapide and 2 will receive placebo.
干预措施: lomitapide (Drug)
Cohort 4
8 Japanese and 8 Caucasian subjects. 6 out of 8 subjects will receive 60 mg lomitapide and 2 will receive placebo.
干预措施: lomitapide (Drug)
结局指标
主要结局
Cmax for Lomitapide
时间窗: 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 27
Maximum observed plasma concentration for lomitapide
Tmax for Lomitapide
时间窗: 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 27
Time to maximum observed concentration for lomitapide
AUC0-∞ for Lomitapide
时间窗: 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 7
Area under the plasma concentration versus time curve from zero to infinity for lomitapide
AUC0-t for Lomitapide
时间窗: 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 27
Area under the plasma concentration versus time curve from hour 0 to the last measurable concentration for lomitapide
t1/2 for Lomitapide
时间窗: 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 27
Apparent terminal elimination half-life for lomitapide
次要结局
- Tmax for M1(1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 27)
- t1/2 for M1(1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 27)
- AUC0-∞ for M3(1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 7)
- AUC0-∞ for M1(1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 7)
- Cmax for M1(1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 27)
- Cmax for M3(1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 27)
- Tmax for M3(1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 27)
- t1/2 for M3(1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 27)
- AUC0-t for M3(1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 27)
- AUC0-t for M1(1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose on Day 27)