An Open-label, Fixed-sequence Study to Assess the Effect of Capivasertib on the Pharmacokinetics of Oral Dextromethorphan (CYP2D6 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
- 42
- 试验地点
- 2
- 主要终点
- Area under concentration time curve from time 0 to infinity (AUCinf) of dextromethorphan
研究概览
简要总结
The purpose of this study is to assess the effect of capivasertib on the pharmacokinetics of oral dextromethorphan in healthy participants.
详细描述
This is an open-label, fixed sequence study conducted at a single study centre.
The study will comprise of:
- A Screening Period (from Day -28 to Day -2)
- In-house treatment period (from Day -1 to Day 8) Period 1 (from Day -1 to Day 3): Participants will receive single oral doses of dextromethorphan during this period.
Period 2 (from Day 4 to Day 8): Participants will receive 2 doses of capivasertib and a single dose of dextromethorphan during this period.
• Follow-up Visit within 7 to 10 days after the last administration of the Investigative Medical Products (from Day 13 to Day 16).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- •Main Inclusion Criteria:
- •Have a Body Mass Index (BMI) between 18 and 30 kg/m2 inclusive and weigh at least 50 kg.
- •All females must have a negative pregnancy test at the Screening Visit and on admission to the Clinical Unit.
- •Females of non-childbearing potential must be confirmed at the screening visit (postmenopausal or documentation of irreversible surgical sterilisation).
- •Male participants must have documentation of vasectomy done 6 months prior to screening visit. Participants must be willing to use one barrier method of contraception (condom) during sexual intercourse with a female partner of childbearing potential from the time of first study intervention administration until 16 weeks after the last dose of capivasertib.
排除标准
- •History of any clinically important disease or disorder
- •History or presence of gastrointestinal, hepatic or renal disease.
- •Any clinically important illness, medical/surgical procedure (excluding placement of vascular access), or significant traumatic injury within 4 weeks of the first administration of study intervention or an anticipated need for major surgery during the study.
- •Any clinically significant skin abnormalities that are chronic or currently active.
- •Abnormal hepato-renal and bone marrow organ function laboratory values.
- •Any clinically important abnormalities in clinical chemistry, haematology, or urinalysis.
- •Any clinically significant abnormalities in glucose metabolism.
- •Any positive result on screening for serum HBsAg OR anti-HBc antibody, indicative of active hepatitis B, hepatitis C, or human immunodeficiency virus (HIV)
- •Current smokers or those who have smoked or used other nicotine/nicotine-containing products within the previous 3 months prior to Screening Visit.
- •Known or suspected history of alcohol or drug abuse or excessive intake of alcohol.
- •Use of drugs with enzyme inducing properties 3 weeks prior to the first administration of study intervention.
- •Use of strong inhibitors of Cytochrome P450 3A4 (CYP3A4) or strong/moderate inducers of CYP3A4 within 2 weeks prior to first dose of capivasertib.
- •Concurrent use of herbal or natural products intended as treatment or prophylaxis that may interact with capivasertib.
- •Participants who have previously received capivasertib.
- •Any clinically significant abnormal findings in vital signs and 12-lead electrocardiogram (ECG).
- •History of severe allergy/hypersensitivity
研究组 & 干预措施
Dextromethorphan/ Dextromethorphan + Capivasertib
Participants will receive a single dose of dextromethorphan in Period 1. After a minimum washout period of 4 days from the first dose of dextromethorphan, participants will receive the first dose of capivasertib, followed by a second dose of capivasertib after 12 hours, administered concomitantly with a single dose of dextromethorphan in Period 2.
干预措施: Dextromethorphan (Drug)
Dextromethorphan/ Dextromethorphan + Capivasertib
Participants will receive a single dose of dextromethorphan in Period 1. After a minimum washout period of 4 days from the first dose of dextromethorphan, participants will receive the first dose of capivasertib, followed by a second dose of capivasertib after 12 hours, administered concomitantly with a single dose of dextromethorphan in Period 2.
干预措施: Capivasertib (Drug)
结局指标
主要结局
Area under concentration time curve from time 0 to infinity (AUCinf) of dextromethorphan
时间窗: Period 1: Day 1 to Day 3, Period 2: Day 6 to Day 8
To evaluate the PK (AUCinf) of dextromethorphan when administered orally alone and following oral dosing of capivasertib
Maximum observed drug concentration (Cmax) of dextromethorphan
时间窗: Period 1: Day 1 to Day 3, Period 2: Day 6 to Day 8
To evaluate the PK (Cmax) of dextromethorphan when administered orally alone and following oral dosing of capivasertib
Area under concentration curve from time 0 to the last quantifiable concentration (AUClast) of dextromethorphan
时间窗: Period 1: Day 1 to Day 3, Period 2: Day 6 to Day 8
To evaluate the PK (AUClast) of dextromethorphan when administered orally alone and following oral dosing of capivasertib
次要结局
- Area under concentration curve from time 0 to the last quantifiable concentration (AUClast) of capivasertib(Period 2: Day 5 to Day 8)
- Time to reach maximum observed concentration (tmax) of capivasertib(Period 2: Day 5 to Day 8)
- Ratio of AUClast following co-administration to AUClast following dosing alone (R AUClast) of dextromethorphan(Period 1: Day 1 to Day 3, Period 2: Day 6 to Day 8)
- Ratio of Cmax following co-administration to Cmax following dosing alone (R Cmax) of dextromethorphan(Period 1: Day 1 to Day 3, Period 2: Day 6 to Day 8)
- Time to reach maximum observed concentration (tmax) of dextromethorphan(Period 1: Day 1 to Day 3)
- Maximum observed drug concentration (Cmax) of metabolite (dextrorphan)(Period 1: Day 1 to Day 3)
- Maximum observed drug concentration (Cmax) of capivasertib(Period 2: Day 5 to Day 8)
- Terminal rate constant (λz) of dextromethorphan(Period 1: Day 1 to Day 3)
- Area under concentration curve from time 0 to the last quantifiable concentration (AUClast) of metabolite (dextrorphan)(Period 1: Day 1 to Day 3)
- Ratio of AUClast following co-administration to AUClast following dosing alone (R AUClast) of metabolite (dextrorphan)(Period 1: Day 1 to Day 3, Period 2: Day 6 to Day 8)
- Terminal elimination half-life (t1/2λz) of metabolite (dextrorphan)(Period 1: Day 1 to Day 3)
- Time to reach maximum observed concentration (tmax) of metabolite (dextrorphan)(Period 1: Day 1 to Day 3)
- Number of participants with adverse events (AEs) and serious AEs(Up to Day 16)
- Ratio of AUCinf following co-administration to AUCinf following dosing alone (R AUCinf) of dextromethorphan(Period 1: Day 1 to Day 3, Period 2: Day 6 to Day 8)
- Terminal elimination half-life (t1/2λz) of dextromethorphan(Period 1: Day 1 to Day 3)
- Area under concentration time curve from time 0 to infinity (AUCinf) of metabolite (dextrorphan)(Period 1: Day 1 to Day 3)
- Terminal rate constant (λz) of metabolite (dextrorphan)(Period 1: Day 1 to Day 3)
- Percentage change from baseline in bilirubin levels(Period 1: Day 1 to Day 2, Period 2: Day 4 to Day 7)