A Phase 1, Drug-Drug Interaction Study to Evaluate the Effect of PBI-4050 on the Pharmacokinetics of Midazolam, a Sensitive Cytochrome P450 3A Substrate, in Healthy Adult Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 22
- 试验地点
- 1
- 主要终点
- Change in concentration observed at the end of the dosing interval (Ctrough) for plasma PBI-4050 and its major metabolite
研究概览
简要总结
This study is designed to evaluate the pharmacokinetics (PK) and safety of multiple doses of PBI-4050 combined with midazolam in healthy adult subjects.
详细描述
This is a Phase 1, single-center, open-label, 2-period, fixed sequence study to investigate the effect of multiple doses of PBI-4050 on the PK of midazolam, a cytochrome P450 (CYP) 3A substrate, in healthy adult men and healthy women of non-childbearing potential (WONCBP), and to determine the safety and tolerability of PBI-4050, when co-administered with midazolam.
On Day 1 of Period 1, subjects will receive a single oral dose of midazolam followed by PK sampling of midazolam and its metabolite 1-hydroxymidazolam (1-OH-midazolam). In Period 2, subjects will receive multiple daily doses of PBI-4050 for 5 consecutive days (Day 1 to Day 5) with a single oral dose of midazolam co-administered on Day 5. PK sampling for midazolam and 1-OH-midazolam will be collected for 24 hours following dosing on Day 5. PK sampling for PBI-4050 and its major metabolite will be collected at pre-dose on Days 3, 4, and 5.
There will be a washout period of at least 2 days between midazolam dose in Period 1 and the first PBI-4050 dose in Period 2.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 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
- •Males or females (WONCBP only).
- •Age 18-65 years.
- •Continuous non-smoker who has not used nicotine-containing products for at least 3 months prior to the first dosing.
- •Body mass index (BMI) ≥ 18.0 and ≤ 32.0 kg/m2 at screening.
- •Generally good health.
- •Males willing to use appropriate contraception.
排除标准
- •Significant medical history or physical findings.
- •History or presence of drug allergy or hypersensitivity to treatment ingredients.
- •Gastrointestinal surgery.
- •Pregnant or lactating.
- •Positive urine drug or alcohol screen.
- •Abnormal heart rate or blood pressure.
- •Prescribed systemic or topical medication taken recently, or supplements/remedies interfering with study procedures or safety.
- •Receiving drugs known as significant inducers of CYP2C9, CYP3A4, CYP2C8 and/or CYP1A2 enzymes and/or P-glycoprotein, including St. John's Wort, for 28 days prior to the first dosing and throughout the study.
- •Has been on a diet incompatible with the on-study diet.
- •Recent blood donation or significant blood loss.
- •Recent blood received.
- •Participation in another clinical study within 30 days prior to the first.
研究组 & 干预措施
PBI-4050 and midazolam
Midazolam 2 mg solution once (Period 1), PBI-4050 1200 mg (3 x 400 mg tablets) once per day for 5 days and midazolam 2 mg solution once on last day (Period 2).
干预措施: PBI-4050 and midazolam (Drug)
结局指标
主要结局
Change in concentration observed at the end of the dosing interval (Ctrough) for plasma PBI-4050 and its major metabolite
时间窗: PK sampling for PBI-4050 and its metabolite done at pre-dose on Days 3, 4, and 5 of Peiod 2
Ctrough is the concentration observed at the end of the dosing interval in Period 2.
Change in area under the concentration-time curve (AUC0-inf) for midazolam and 1-OH-midazolam in presence of PBI-4050
时间窗: PK sampling at pre-dose; and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours post-dose on Day 1 in Period 1 and on Day 5 in Period 2
AUC0-inf (AUC from time 0 extrapolated to infinity) of midazolam and 1-OH-midazolam assessed on Day 1 (Period 1) and Day 5 (Period 2)
Change in area under the concentration-time curve (AUC0-t) for midazolam and 1-OH-midazolam in presence of PBI-4050
时间窗: PK sampling at pre-dose; and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours post-dose on Day 1 in Period 1 and on Day 5 in Period 2
AUC0-t (AUC from time 0 to last observed non-zero concentration) of midazolam and 1-OH-midazolam assessed on Day 1 (Period 1) and Day 5 (Period 2)
Change in maximum plasma concentration (Cmax) for midazolam and 1-OH-midazolam in presence of PBI-4050
时间窗: PK sampling at pre-dose; and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours post-dose on Day 1 in Period 1 and on Day 5 in Period 2
Cmax of midazolam and 1-OH-midazolam assessed on Day 1(Period 1) and Day 5 (Period 2)
次要结局
- Adverse Events (AEs) and Serious Adverse Events (SAEs)(10 days)