A Phase I, Randomized, Open-label, 4-period, 4-treatment, Single-dose, Cross-over Study to Assess the Relative Bioavailability of Laroprovstat/Ezetimibe Fixed Combination Drug Products to the Single Therapy Products in Healthy Adults
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- AstraZeneca
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Area under concentration-time curve from time 0 to infinity (AUCinf)
研究概览
简要总结
The purpose of this study is to assess how well laroprovstat and ezetimibe combined in a single tablet to be taken by mouth works and what the body does to the drug (pharmacokinetics) compared with laroprovstat and ezetimibe individual tablets to be taken by mouth (relative bioavailability) as well as to see if there is any effect of eating compared to fasting (food effect) in healthy adults.
详细描述
This is a randomized, open-label, 4-period, single-dose, cross-over study.
The study will comprise of a screening period, 4 treatment periods, and 3 washout periods. The following treatments will be given during the study:
- Treatment A: laroprovstat/ezetimibe fixed combination drug product (FCDP) test formulation in fasted state
- Treatment B: laroprovstat tablet plus ezetimibe reference formulations in fasted state
- Treatment C: laroprovstat/ezetimibe FCDP test formulation in fed state
- Treatment D: laroprovstat/ezetimibe FCDP test formulation-slow variant in fasted state
Participants will be randomly assigned to either of the 3 treatment sequences: ABCD, BCAD, or CABD.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy male and female participants aged 18 to 55 years at the time of signing consent.
- •All females must have a negative pregnancy test at the Screening Visit and on admission to the study site.
- •Females of childbearing potential must not be lactating and if heterosexually active must agree to use an approved method of highly effective contraception.
- •Have a Body mass index (BMI) between 18 and 30 kg/m2 inclusive and weigh at least 50 kg.
排除标准
- •History of any clinically important disease or disorder.
- •History or presence of gastrointestinal, hepatic, or renal disease or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
- •History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity to drugs with a similar chemical structure or class to laroprovstat or ezetimibe.
- •Treatment with any lipid lowering therapy or laroprovstat within the 3 months prior to the Screening Visit.
- •Treatment with drugs for reduction or inhibition of Proprotein convertase subtilisin/kexin type 9 (PCSK9) within the last 12 months prior to the Screening Visit or inclisiran at any time.
研究组 & 干预措施
Treatment C
Each participant will receive single dose treatment of laroprovstat/ezetimibe FCDP test formulation in a fed state.
干预措施: Laroprovstat/ezetimibe FCDP (Drug)
Treatment D
Each participant will receive single dose treatment of laroprovstat/ezetimibe FCDP test formulation (slow variant) in a fasted state.
干预措施: Laroprovstat/ezetimibe FCDP-slow variant (Drug)
Treatment A
Each participant will receive single dose treatment of laroprovstat/ezetimibe FCDP test formulation in a fasted state.
干预措施: Laroprovstat/ezetimibe FCDP (Drug)
Treatment B
Each participant will receive single dose treatment of laroprovstat plus ezetimibe single therapy product (STP) reference formulations in a fasted state.
干预措施: Laroprovstat STP (Drug)
Treatment B
Each participant will receive single dose treatment of laroprovstat plus ezetimibe single therapy product (STP) reference formulations in a fasted state.
干预措施: Ezetimibe STP (Drug)
结局指标
主要结局
Area under concentration-time curve from time 0 to infinity (AUCinf)
时间窗: Day 1 to 11 of Treatment Periods 1, 2, 3, and 4 (each treatment period is 11 days)
To evaluate the relative bioavailability between the FCDPs and the STPs of laroprovstat, ezetimibe (unconjugated), ezetimibe-glucuronide, and total ezetimibe.
Area under concentration-curve from time 0 to the last quantifiable concentration (AUClast)
时间窗: Day 1 to 11 of Treatment Periods 1, 2, 3, and 4 (each treatment period is 11 days)
To evaluate the relative bioavailability between the FCDPs and the STPs of laroprovstat, ezetimibe (unconjugated), ezetimibe-glucuronide, and total ezetimibe.
Maximum observed drug concentration (Cmax)
时间窗: Day 1 to 11 of Treatment Periods 1, 2, 3, and 4 (each treatment period is 11 days)
To evaluate the relative bioavailability between the FCDPs and the STPs of laroprovstat, ezetimibe (unconjugated), ezetimibe-glucuronide, and total ezetimibe.
次要结局
- Plasma Time to reach maximum observed concentration (tmax)(Day 1 to 11 of Treatment Periods 1, 2, 3, and 4 (each treatment period is 11 days))
- Terminal elimination half-life (t½λz)(Day 1 to 11 of Treatment Periods 1, 2, 3, and 4 (each treatment period is 11 days))
- Apparent total body clearance (CL/F)(Day 1 to 11 of Treatment Periods 1, 2, 3, and 4 (each treatment period is 11 days))
- Apparent volume of distribution based on the terminal phase (Vz/F)(Day 1 to 11 of Treatment Periods 1, 2, 3, and 4 (each treatment period is 11 days))
- AUCinf(Day 1 to 11 of Treatment Periods 1, 2, 3, and 4 (each treatment period is 11 days))
- AUClast(Day 1 to 11 of Treatment Periods 1, 2, 3, and 4 (each treatment period is 11 days))
- Cmax(Day 1 to 11 of Treatment Periods 1, 2, 3, and 4 (each treatment period is 11 days))