A Phase 1, Open-label Study With Two Independent Parts: Collecting Samples for Metabolites in Safety Testing Analysis of Zibotentan After Repeated Administration (Part 1); and a Randomised, Cross-over, Three Period, Three-treatment, Single Dose Study to Assess the Relative Bioavailability of Different Formulations of Zibotentan and Dapagliflozin (Part 2) in Healthy Adult Participants
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 27
- 试验地点
- 1
- 主要终点
- Part 1: Metabolites in Safety Testing sampling
研究概览
简要总结
The study will have 2 independent parts:
Part 1 of the study is intended to collect samples for Metabolites in Safety Testing (MIST) analysis after administration of multiple doses of zibotentan.
Part 2 of the study is designed to evaluate the relative bioavailability of zibotentan and dapagliflozin after dosing with two different fixed-dose combination (FDC) formulations and dosing with separate formulations of zibotentan and dapagliflozin.
详细描述
Part 1 will be an open-label, non-randomised, single treatment period. A single treatment period during which participants will be resident at the study centre from 2 days before dosing (Day -2) until the morning of Day 6.
Part 2 will be an open-label, randomised, 3-period, 3-treatment, cross-over single dose study. Participants will be randomised to one of 3 treatment sequences and will receive 3 single-dose study interventions. Participants will be resident at the study centre from 2 days before dosing (Day -2) until Day 3 of the last treatment sequence.
Participants who were enrolled in Part 1 may not be enrolled in Part 2.
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 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •For inclusion in the study participants should fulfil the following criteria:
- •Participants with suitable veins for cannulation or repeated venipuncture.
- •Females must have a negative pregnancy test at the Screening Visit and within 24 hours prior to dosing, must not be lactating and must be of non- childbearing potential
- •Male participant must adhere to the contraception methods.
- •Have a BMI between 18 and 29.9 kg/m^2 inclusive and weigh at least 50 kg and no more than 100 kg inclusive.
- •Provision of signed and dated, written informed consent prior to any study specific procedures.
排除标准
- •Participants will not enter the study if any of the following exclusion criteria are fulfilled:
- •History or presence of gastrointestinal, hepatic or renal disease or any important disease or disorder.
- •Any clinically important illness, medical/surgical procedure or trauma within 4 weeks of the first administration of study intervention.
- •Any clinically significant abnormalities in clinical chemistry, haematology, or urinalysis.
- •Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody, and Human immunodeficiency virus antibody.
- •Abnormal vital signs. 6 History of drug abuse or alcohol abuse.
- •History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity.
- •Participants who are vegans or have medical dietary restrictions.
- •Participants tested positive for COVID-19 at the time of randomisation or have been previously hospitalised with COVID-19 infection.
研究组 & 干预措施
Part 2: Treatment Sequence ABC
Each participant will receive 3 single-dose treatments of zibotentan and dapagliflozin (Treatment A; Treatment B; Treatment C) in 3 treatment periods, separated by a washout period of at least 7 days between treatment periods.
干预措施: Zibotentan/Dapagliflozin - Formulation 1 (Treatment B) (Drug)
Part 1
Participants will be administered with zibotentan once daily for 5 days.
干预措施: Zibotentan (Treatment A) (Drug)
Part 2: Treatment Sequence ABC
Each participant will receive 3 single-dose treatments of zibotentan and dapagliflozin (Treatment A; Treatment B; Treatment C) in 3 treatment periods, separated by a washout period of at least 7 days between treatment periods.
干预措施: Zibotentan (Treatment A) (Drug)
Part 2: Treatment Sequence ABC
Each participant will receive 3 single-dose treatments of zibotentan and dapagliflozin (Treatment A; Treatment B; Treatment C) in 3 treatment periods, separated by a washout period of at least 7 days between treatment periods.
干预措施: Dapagliflozin (Treatment A) (Drug)
Part 2: Treatment Sequence ABC
Each participant will receive 3 single-dose treatments of zibotentan and dapagliflozin (Treatment A; Treatment B; Treatment C) in 3 treatment periods, separated by a washout period of at least 7 days between treatment periods.
干预措施: Zibotentan/Dapagliflozin - Formulation 2 (Treatment C) (Drug)
Part 2: Treatment Sequence BCA
Each participant will receive 3 single-dose treatments of zibotentan and dapagliflozin (Treatment B; Treatment C; Treatment A) in 3 treatment periods, separated by a washout period of at least 7 days between treatment periods.
干预措施: Zibotentan (Treatment A) (Drug)
Part 2: Treatment Sequence BCA
Each participant will receive 3 single-dose treatments of zibotentan and dapagliflozin (Treatment B; Treatment C; Treatment A) in 3 treatment periods, separated by a washout period of at least 7 days between treatment periods.
干预措施: Dapagliflozin (Treatment A) (Drug)
Part 2: Treatment Sequence BCA
Each participant will receive 3 single-dose treatments of zibotentan and dapagliflozin (Treatment B; Treatment C; Treatment A) in 3 treatment periods, separated by a washout period of at least 7 days between treatment periods.
干预措施: Zibotentan/Dapagliflozin - Formulation 1 (Treatment B) (Drug)
Part 2: Treatment Sequence BCA
Each participant will receive 3 single-dose treatments of zibotentan and dapagliflozin (Treatment B; Treatment C; Treatment A) in 3 treatment periods, separated by a washout period of at least 7 days between treatment periods.
干预措施: Zibotentan/Dapagliflozin - Formulation 2 (Treatment C) (Drug)
Part 2: Treatment Sequence CAB
Each participant will receive 3 single-dose treatments of zibotentan and dapagliflozin (Treatment C; Treatment A; Treatment B) in 3 treatment periods, separated by a washout period of at least 7 days between treatment periods.
干预措施: Zibotentan (Treatment A) (Drug)
Part 2: Treatment Sequence CAB
Each participant will receive 3 single-dose treatments of zibotentan and dapagliflozin (Treatment C; Treatment A; Treatment B) in 3 treatment periods, separated by a washout period of at least 7 days between treatment periods.
干预措施: Dapagliflozin (Treatment A) (Drug)
Part 2: Treatment Sequence CAB
Each participant will receive 3 single-dose treatments of zibotentan and dapagliflozin (Treatment C; Treatment A; Treatment B) in 3 treatment periods, separated by a washout period of at least 7 days between treatment periods.
干预措施: Zibotentan/Dapagliflozin - Formulation 1 (Treatment B) (Drug)
Part 2: Treatment Sequence CAB
Each participant will receive 3 single-dose treatments of zibotentan and dapagliflozin (Treatment C; Treatment A; Treatment B) in 3 treatment periods, separated by a washout period of at least 7 days between treatment periods.
干预措施: Zibotentan/Dapagliflozin - Formulation 2 (Treatment C) (Drug)
结局指标
主要结局
Part 1: Metabolites in Safety Testing sampling
时间窗: Day 1 through Day 6 (pre-dose, 30 min; 1, 2, 4, 6, 8, 12 and 24 hours post dose)
Plasma sample will be collected to understand the PK profiling of zibotentan metabolites and to meet the regulatory requirements.
Part 2: Maximum observed plasma drug concentration (Cmax)
时间窗: Day 1 through Day 3 of each treatment period
Relative bioavailability of zibotentan and dapagliflozin after dosing with two different FDC formulations and dosing with separate formulations of zibotentan and dapagliflozin will be evaluated.
Part 2: Area under plasma concentration time curve from zero to infinity (AUCinf)
时间窗: Day 1 through Day 3 of each treatment period
Relative bioavailability of zibotentan and dapagliflozin after dosing with two different FDC formulations and dosing with separate formulations of zibotentan and dapagliflozin will be evaluated.
Part 2: Area under the plasma concentration curve from zero to the last quantifiable concentration (AUClast)
时间窗: Day 1 through Day 3 of each treatment period
Relative bioavailability of zibotentan and dapagliflozin after dosing with two different FDC formulations and dosing with separate formulations of zibotentan and dapagliflozin will be evaluated.
Part 2: Observed concentration at 24 hours post-dose (C24)
时间窗: Day 1 through Day 3 of each treatment period
Relative bioavailability of zibotentan and dapagliflozin after dosing with two different FDC formulations and dosing with separate formulations of zibotentan and dapagliflozin will be evaluated.
次要结局
- Part 2: Time to reach peak or maximum observed concentration (tmax)(Day 1 through Day 3 of each treatment period)
- Part 2: Terminal rate constant (λz)(Day 1 through Day 3 of each treatment period)
- Part 2: Half life associated with λz (t½λz)(Day 1 through Day 3 of each treatment period)
- Part 2: Apparent total body clearance of drug from plasma after extravascular administration (CL/F)(Day 1 through Day 3 of each treatment period)
- Part 2: Volume of distribution at steady state following extravascular administration (Vz/F)(Day 1 through Day 3 of each treatment period)
- Part 1 and Part 2: Number of adverse events and serious adverse events(From Sceerning to Follow-up Visit approximately 40 days for Part 1 and 49 days for Part 2)