An Open-label, Fixed-sequence Study to Assess the Effect of Capivasertib on the Pharmacokinetics of Oral Rosuvastatin (a BCRP, OATP1B1 and OATP1B3 Sensitive Substrate) in Healthy Participants
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Area under concentration-time curve from time 0 to infinity (AUCinf) of rosuvastatin
研究概览
简要总结
The purpose of the study is to assess the effect of capivasertib on the pharmacokinetics (PK) of oral rosuvastatin in healthy participants.
详细描述
This study is an open-label, fixed-sequence, drug-drug interaction study of orally administered rosuvastatin in the presence and absence of capivasertib in healthy participants.
The study will comprise:
- A Screening Period of maximum 28 days.
- Two Treatment Periods
- Period 1: Participants will receive single oral dose of rosuvastatin.
- Period 2: Participants will receive two single oral doses of capivasertib administered 12 hours apart, with the first capivasertib dose being concomitantly administered with a single oral dose of rosuvastatin.
- A final Follow-up Visit within 7 to 10 days after the last study intervention administration.
There will be a minimum washout period of at least 7 days between the first dose of rosuvastatin (in Treatment Period 1) and the second dose of rosuvastatin (in Treatment Period 2).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Other
- 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 participants with suitable veins for cannulation or repeated venipuncture.
- •Body Mass Index (BMI) between 18 and 32 kg/m² inclusive and weigh at least 50 kg and no more than 150 kg inclusive.
- •All females must have a negative pregnancy test at the Screening Visit and on admission to the Clinical Unit and must not be lactating.
- •Females of non-childbearing potential must be confirmed at the Screening Visit by fulfilling one of the following criteria:
- •Postmenopausal (≥12 months of amenorrhea + hormone confirmation).
- •Irreversible surgical sterilization by hysterectomy and/or bilateral oophorectomy, and/or bilateral salpingectomy (excluding tubal ligation) at least 6 months prior to screening.
- •Male participants must be vasectomized (at least 6 months prior to screening), with documented post-procedural medical assessment of surgical success.
- •Participants must be willing to use study-specific contraceptive methods.
排除标准
- •History of any clinically important disease or disorder which may either put the participant at risk because of participation in the study 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.
- •Any clinically significant skin abnormalities that are chronic or currently active.
- •Any clinically important abnormalities in clinical chemistry, hematology, or urinalysis results.
- •Any positive result on screening for serum Hepatitis B surface antigen (HBsAg), Hepatitis B core antibody (HBcAb), Hepatitis C virus antibody (HCV antibody), or Human Immunodeficiency Virus (HIV).
- •Any clinically significant abnormalities in blood lipid profiles (triglycerides, high-density lipoprotein, low-density lipoprotein, and total cholesterol).
- •Any clinically significant abnormalities in glucose metabolism, including:
- •Diagnosis of type I or II diabetes mellitus (irrespective of management),
- •Fasting blood glucose ≥ 100 mg/dL, or
- •Hemoglobin A1c > 5.7% after at least 8 hours of fasting at screening.
- •Any clinically significant abnormal findings in vital signs.
- •Any clinically significant abnormalities on 12-lead electrocardiogram (ECG) and defined as Sick sinus syndrome, arrhythmia, prolonged QTcF > 450 ms, family history of long QT syndrome, persistent or intermittent bundle branch block, and atrio-ventricular block Grade II or III.
- •Current smokers or those who have smoked or used nicotine products (including e-cigarettes) within the previous 3 months.
- •Known or suspected history of alcohol or drug abuse or excessive intake of alcohol.
- •History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity or history of hypersensitivity to drugs with a similar chemical structure or class to capivasertib or rosuvastatin or history of hypersensitivity to any component of the finished dosage form of capivasertib.
- •Plasma donation or any blood donation/blood loss prior to the Screening Visit.
- •Participants who have previously received capivasertib.
研究组 & 干预措施
Rosuvastatin/Capivasertib+Rosuvastatin
Participants will receive a single dose of rosuvastatin in Period 1. After a minimum washout period of 7 days from the first dose of rosuvastatin, participants will receive the first dose of capivasertib, administered concomitantly with a single dose of rosuvastatin in Period 2, followed by a second dose of capivasertib after 12 hours.
干预措施: Capivasertib (Drug)
Rosuvastatin/Capivasertib+Rosuvastatin
Participants will receive a single dose of rosuvastatin in Period 1. After a minimum washout period of 7 days from the first dose of rosuvastatin, participants will receive the first dose of capivasertib, administered concomitantly with a single dose of rosuvastatin in Period 2, followed by a second dose of capivasertib after 12 hours.
干预措施: Rosuvastatin (Drug)
结局指标
主要结局
Area under concentration-time curve from time 0 to infinity (AUCinf) of rosuvastatin
时间窗: Period 1: Day 1 to Day 3 and Period 2: Day 1 to Day 3
To evaluate the PK (AUCinf) of rosuvastatin when administered orally alone and in combination with capivasertib.
Area under concentration-curve from time 0 to the last quantifiable concentration (AUClast) of rosuvastatin
时间窗: Period 1: Day 1 to Day 3 and Period 2: Day 1 to Day 3
To evaluate the PK (AUClast) of rosuvastatin when administered orally alone and in combination with capivasertib.
Maximum observed drug concentration (Cmax) of rosuvastatin
时间窗: Period 1: Day 1 to Day 3 and Period 2: Day 1 to Day 3
To evaluate the PK (Cmax) of rosuvastatin when administered orally alone and in combination with capivasertib.
次要结局
- Ratio of AUCinf (R AUCinf) of rosuvastatin(Period 1: Day 1 to Day 3 and Period 2: Day 1 to Day 3)
- Ratio of AUClast (R AUClast) of rosuvastatin(Period 1: Day 1 to Day 3 and Period 2: Day 1 to Day 3)
- Ratio of Cmax (R Cmax) of rosuvastatin(Period 1: Day 1 to Day 3 and Period 2: Day 1 to Day 3)
- Terminal elimination half-life (t½λz) of rosuvastatin(Period 1: Day 1 to Day 3 and Period 2: Day 1 to Day 3)
- Terminal elimination rate constant (λz) of rosuvastatin(Period 1: Day 1 to Day 3 and Period 2: Day 1 to Day 3)
- Time to reach maximum observed concentration (tmax) of rosuvastatin(Period 1: Day 1 to Day 3 and Period 2: Day 1 to Day 3)
- AUClast of capivasertib(Period 2: Day 1 to Day 3)
- Concentration at the end of a dosing interval (Ctrough) of capivasertib(Period 2: Day 1 to Day 3)
- Cmax of capivasertib(Period 2: Day 1 to Day 3)
- Number of participants with adverse events (AEs) and serious AEs(From Screening (Day -30 to Day -2) to follow-up visit (Day 10))
- Change in serum bilirubin levels(Day 1 (pre-capivasertib dose) to Day 3 (post-capivasertib dose))