A Randomized, Single Dose, Crossover Study to Assess the Effect of Food on the Pharmacokinetics of Single Dose, Orally Administered, Combined Zibotentan/Dapagliflozin in Healthy Participants
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 26
- 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 investigate the concentrations of zibotentan and dapagliflozin in blood when given with and without food in healthy participants.
详细描述
This is a Phase I, open-label, randomized, 2-period, 2-treatment, crossover study in healthy participants.
This study will measure the impact of food on the pharmacokinetics (PK) of combined zibotentan/dapagliflozin for the to be marketed fixed-dose combination (FDC) formulation (study intervention).
The study will comprise of, (i) A screening period (ii) 2 treatment periods (iii) A final follow-up visit.
All participants will receive a single dose of the study intervention once under fasted condition (Treatment A) and once under fed condition (Treatment B).
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 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy male and/or female of non-childbearing potential. Participants with suitable veins for cannulation or repeated venipuncture.
- •Have a body mass index (BMI) between 18 and 32 kg/m2 inclusive and weigh at least 50 kg and no more than 100 kg (inclusive) at Screening.
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.
- •Any clinically important illness, medical/surgical procedure, or trauma.
- •Any clinically important abnormalities in clinical chemistry, hematology, or urinalysis results or other laboratory values or vital signs.
- •Any positive result on screening for serum Hepatitis B surface antigen (HBsAg), Hepatitis B core antibody (HBcAb), Hepatitis C virus (HCV) antibody, or Human immunodeficiency virus (HIV) (Type 1 and 2) antibodies.
- •Known or suspected history of alcohol or drug abuse or excessive intake of alcohol.
- •History or ongoing allergy/hypersensitivity, to Sodium-Glucose Cotransporter-2 Inhibitors (SGLT2i- eg, dapagliflozin, empagliflozin), or zibotentan or other Endothelin Receptor Antagonist (ERAs- eg, ambrisentan, atrasentan,bosentan), or any of the excipients in the zibotentan/dapagliflozin tablets.
- •Participants who have previously received zibotentan.
研究组 & 干预措施
Treatment AB
Participants will receive single dose of Zibotentan/Dapagliflozin FDC after an overnight fast of at least 10 hours (Treatment A). After a washout period, participants will receive another single dose of Zibotentan/Dapagliflozin FDC 30 minutes after having a high-fat, high-calorie standardized meal (Treatment B).
干预措施: Zibotentan/Dapagliflozin FDC (Drug)
Treatment BA
Participants will receive single dose of Zibotentan/Dapagliflozin FDC 30 minutes after having a high-fat high-calorie standardized meal (Treatment B). After a washout period, participants will receive another single dose of Zibotentan/Dapagliflozin FDC after an overnight fast of at least 10 hours (Treatment A).
干预措施: Zibotentan/Dapagliflozin FDC (Drug)
结局指标
主要结局
Area under concentration-time curve from time 0 to infinity (AUCinf)
时间窗: At predefined intervals from Day 1 to Day 4 for both treatment periods
To investigate the effect of a high fat, high calorie meal, in comparison to fasting conditions, on the PK of zibotentan/dapagliflozin FDC after a single oral dose in healthy participants.
Area under concentration-curve from time 0 to the last quantifiable concentration (AUClast)
时间窗: At predefined intervals from Day 1 to Day 4 for both treatment periods
To investigate the effect of a high fat, high calorie meal, in comparison to fasting conditions, on the PK of zibotentan/dapagliflozin FDC after a single oral dose in healthy participants.
Maximum observed drug concentration (Cmax)
时间窗: At predefined intervals from Day 1 to Day 4 for both treatment periods
To investigate the effect of a high fat, high calorie meal, in comparison to fasting conditions, on the PK of zibotentan/dapagliflozin FDC after a single oral dose in healthy participants.
次要结局
- Number of participants with adverse events (AEs) and serious adverse events (SAEs)(Up to end of study visit, for a total of approximately 5 weeks)
- Apparent total body clearance (CL/F)(At predefined intervals from Day 1 to Day 4 for both treatment periods)
- Apparent volume of distribution based on the terminal phase (Vz/F)(At predefined intervals from Day 1 to Day 4 for both treatment periods)
- Time to reach maximum observed concentration (tmax)(At predefined intervals from Day 1 to Day 4 for both treatment periods)
- Terminal elimination half-life (t½λz)(At predefined intervals from Day 1 to Day 4 for both treatment periods)