Open-label, Single Center, Non-randomized, Fixed Sequence Phase 1 Drug-drug Interaction Study With LEO 32731 and Midazolam
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- LEO Pharma
- 入组人数
- 32
- 试验地点
- 1
- 主要终点
- Pharmacokinetic (PK) parameters of midazolam AUC0-t
研究概览
简要总结
This is a single center, non-randomized, open-label, fixed sequence study to investigate the effect of multiple oral dosing of LEO 32731 (up-titrated), on CYP3A activity in healthy male subjects using midazolam as a probe CYP3A substrate.
The study will be conducted in two seamless parts:
Part I - Maximal Tolerated Dose (MTD) Part II - Drug-Drug Interaction with midazolam
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Subjects will, prior to any study related activities, have given their written informed consent to participate in the study and to abide by the study restrictions.
- •Subjects will be males between 18 and 55 years of age, inclusive.
- •Subjects will have a body mass index (BMI) between 18.0 and 30.0 kg/m2 inclusive.
- •Subjects must be in good health, as determined by medical history, physical examination, vital signs assessment, 12-lead ECG, and clinical laboratory evaluations.
- •Subjects (including those who have had a vasectomy) must agree to use condoms with spermicide during each sexual intercourse or must agree to be abstinent starting at first drug administration until 3 month after the final dosing.
- •Also subjects must agree not to donate sperm in the same time period.
- •Subjects' female partner of childbearing potential must use an additional acceptable method of contraception. Eligible methods are: hormonal contraceptives (oral, injected, implanted, transdermal), intrauterine devices or systems (e.g. hormonal and non-hormonal IUD), barrier methods (condom and diaphragm, condom and cervical cap, etc.) in combination with a spermicide.
排除标准
- •Subjects who have received any prescribed systemic or topical medication within 14 days of the first dose administration unless in the opinion of the Investigator the medication will not interfere with the study procedures or compromise safety.
- •Subjects who have used any non-prescribed systemic or topical medication (including herbal remedies) within 7 days of the first dose administration (excluding occasional use of paracetamol or ibuprofen, e.g. in case of pain).
- •Subjects who have received any medications, including St John's Wort known to alter drug absorption or elimination processes (change the enzyme levels) within 30 days of the first dose administration of study drug.
- •Subjects who are still participating in a clinical study (e.g. attending follow-up visits) or who have participated in a clinical study involving administration of an investigational drug with new chemical entity within the past 60 days, or a marketed drug compound within the past 30 days prior to the first dosing.
- •Subjects who have donated any blood, plasma or platelets in 3 months prior to first dosing or who have made donations on more than 3 occasions within the 12 months preceding the first dose administration.
研究组 & 干预措施
All subjects
Part I - Maximum Tolerated Dose: All subjects will receive oral doses of LEO 32731 up-titrated from 10 mg bid on Days 1-3, 20 mg bid on Days 4-6 and 40 mg bid on Days 7-12.
Part II - Drug-Drug Interaction: All subjects will receive oral doses of LEO 32731 in dose schedule decided upon data from Part I. Subjects will receive a single oral dose of 2.5 mg midazolam on Day -1 prior to the first dose of LEO 32731 and on Days 4, 7 and 17 of multiple dosing with LEO 32731.
干预措施: LEO 32731 (Drug)
All subjects
Part I - Maximum Tolerated Dose: All subjects will receive oral doses of LEO 32731 up-titrated from 10 mg bid on Days 1-3, 20 mg bid on Days 4-6 and 40 mg bid on Days 7-12.
Part II - Drug-Drug Interaction: All subjects will receive oral doses of LEO 32731 in dose schedule decided upon data from Part I. Subjects will receive a single oral dose of 2.5 mg midazolam on Day -1 prior to the first dose of LEO 32731 and on Days 4, 7 and 17 of multiple dosing with LEO 32731.
干预措施: Midazolam (Drug)
结局指标
主要结局
Pharmacokinetic (PK) parameters of midazolam AUC0-t
时间窗: Day -1 and Day 17
PK parameters AUC0-t will be analyzed on Day -1 and Day 17.
Pharmacokinetic (PK) parameters of midazolam Cmax
时间窗: Day -1 and Day 17
PK parameter Cmax will be analyzed on Day -1 and Day 17.
次要结局
- AUC0-t midazolam(Day 4 and Day 7)
- AUC0-inf of midazolam(Day -1 and Day 17)
- Cmax of midazolam(Day 4 and Day 7)
- Tmax of midazolam(Day -1 and Day 17)
- t1/2 of midazolam(Day -1 and Day 17)
- Vz/F of midazolam(Day -1 and Day 17)
- CL/F of midazolam(Day -1 and Day 17)