An Open-label, Randomised, Parallel-group, Fixed-sequence Study to Assess the Effect of Oral Ticagrelor on the Pharmacokinetics of Oral Rosuvastatin in Healthy Participants
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 28
- 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 measure the effect of ticagrelor on the pharmacokinetics (PK) of rosuvastatin in healthy participants.
详细描述
This study will be conducted at a single Clinical Unit. It includes 2 parallel arms (one for each rosuvastatin dose) and 2 treatment periods.
The study will comprise:
- A Screening Period of maximum 28 days.
- Period 1: It will start on Day -1. A single dose of rosuvastatin (dose 1 or dose 2) will be administered on Day 1 followed by PK sampling of rosuvastatin for 96 hours. Participants will be admitted to the Clinical Unit on Study Day -1. Period 1 will end on Study Day 5.
- Period 2: It will start on Study Day 6. A second single dose of rosuvastatin (dose 1 or dose 2) will be administered on Day 6 followed by PK sampling of rosuvastatin for 120 hours. Ticagrelor 90 mg, twice a day will be started on Day 6 (administered concomitantly with rosuvastatin) and administered through Day 10. Period 2 will end on Study Day 12.
- A Follow-up Visit, 4 to 7 days after discharge.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 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 participants with suitable veins for cannulation or repeated venipuncture.
- •All females must have a negative pregnancy test at the Screening Visit and on admission to the Clinical Unit.
- •Females of childbearing potential must not be lactating and if heterosexually active must agree to use an approved method of highly effective contraception, to avoid pregnancy from the time of first administration of study intervention until 1 month after the study Follow-up Visit.
- •Females of non-childbearing potential must be confirmed at the Screening Visit by fulfilling one of the following criteria:
- •Postmenopausal defined as amenorrhea for at least 12 months following cessation of all exogenous hormonal treatments and follicle-stimulating hormone (FSH) levels in the postmenopausal range.
- •Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy but not tubal ligation or tubal occlusion.
- •Sexually active fertile male participants with partners of childbearing potential must adhere to the specified contraception methods from the time of first administration of study intervention administration until 2 weeks after the study Follow-up Visit.
- •Have a BMI between 18 and 30 kg/m2 inclusive and weigh at least 50 kg and no more than 100 kg inclusive.
排除标准
- •History of any clinically important disease or disorder which may either put the participant at risk or influence the results or the participant's ability to participate in the study.
- •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 within 4 weeks of the first administration of study intervention.
- •Any clinically important abnormal laboratory values or vital signs.
- •Any positive result on Screening for serum HBsAg OR anti-HBc antibody, indicative of active hepatitis B (i.e., participants with positive anti HBc antibody result are acceptable if anti HBc IgM antibodies are negative).
- •Current smokers or those who have smoked or used nicotine products (including e-cigarettes) within the previous 3 months prior to screening.
- •Known or suspected history of alcohol or drug abuse or excessive intake of alcohol. Excessive intake of alcohol defined as the regular consumption of more than 24 g of alcohol per day for men or 12 g of alcohol per day for females.
- •Positive screen for drugs of abuse, or alcohol or cotinine at screening or on admission to the Clinical Unit.
研究组 & 干预措施
Rosuvastatin (Dose 1) + Ticagrelor
Participants will receive rosuvastatin (dose 1) orally as a single dose on Day 1 in Period 1 and Day 6 in Period 2. During Period 2, participants will also receive ticagrelor 90 mg BID (twice a day) on Day 6 through Day 10.
干预措施: Rosuvastatin (Drug)
Rosuvastatin (Dose 1) + Ticagrelor
Participants will receive rosuvastatin (dose 1) orally as a single dose on Day 1 in Period 1 and Day 6 in Period 2. During Period 2, participants will also receive ticagrelor 90 mg BID (twice a day) on Day 6 through Day 10.
干预措施: Ticagrelor (Drug)
Rosuvastatin (Dose 2) + Ticagrelor
Participants will receive rosuvastatin (dose 2) orally as a single dose on Day 1 in Period 1 and Day 6 in Period 2. During Period 2, participants will also receive ticagrelor 90 mg BID on Day 6 through Day 10.
干预措施: Rosuvastatin (Drug)
Rosuvastatin (Dose 2) + Ticagrelor
Participants will receive rosuvastatin (dose 2) orally as a single dose on Day 1 in Period 1 and Day 6 in Period 2. During Period 2, participants will also receive ticagrelor 90 mg BID on Day 6 through Day 10.
干预措施: Ticagrelor (Drug)
结局指标
主要结局
Area under concentration-time curve from time 0 to infinity (AUCinf)
时间窗: From Day 1 to Day 11
To assess the effect of ticagrelor on plasma PK (AUCinf) of rosuvastatin dose 1 and dose 2 separately, in healthy participants.
Area under concentration-curve from time 0 to the last quantifiable concentration (AUClast)
时间窗: From Day 1 to Day 11
To assess the effect of ticagrelor on plasma PK (AUClast) of rosuvastatin dose 1 and dose 2 separately, in healthy participants.
Maximum observed drug concentration (Cmax)
时间窗: From Day 1 to Day 11
To assess the effect of ticagrelor on plasma PK (Cmax) of rosuvastatin dose 1 and dose 2 separately, in healthy participants.
次要结局
- Terminal elimination half-life (t1/2)(From Day 1 to Day 11)
- Terminal rate constant (parent only) (λz)(From Day 1 to Day 11)
- Number of participants with adverse events (AEs)(Approximately 7 weeks)
- Time to reach maximum observed concentration (tmax)(From Day 1 to Day 11)
- Percent of dose excreted(From Day 1 to Day 11)
- Amount of drug excreted (Ae)(From Day 1 to Day 11)
- Renal clearance (Clrenal)(From Day 1 to Day 11)