An Open-label, Fixed-sequence Study to Assess the Effect of Repeated Doses of Capivasertib on the Pharmacokinetics of Oral Midazolam (a CYP450 3A Probe) in Patients With Advanced Solid Tumours
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 21
- 试验地点
- 1
- 主要终点
- Midazolam AUCinf
研究概览
简要总结
This is an open-label, fixed-sequence study to evaluate the effect of capivasertib on the pharmacokinetics (PK) of midazolam, a sensitive CYP3A substrate. The PK of midazolam will be assessed when administered alone and in combination with repeated doses of capivasertib.
详细描述
This is 2 part study: Part A and Part B. Part A of the study consists of a screening period and 3 treatment periods (midazolam alone, capivasertib alone, and midazolam + capivasertib). During Part A, the PK profile of midazolam will be determined with and without capivasertib.All participants will receive capivasertib treatment (4 days on/3 days off); however, at the Investigator's discretion, ER positive breast cancer patients may also receive fulvestrant in addition to capivasertib and midazolam. Participants completing Part A without disease progression or unacceptable toxicity, who are considered likely to continue to benefit from further capivasertib treatment (with or without certain standard of care treatment) in the opinion of the Investigator will enter Part B. Part B of the study consists of an extended treatment period with capivasertib, with or without certain standard of care treatment, followed by a 30-day safety follow-up.
Part A of the study may be extended to allow the administration of midazolam on a rescheduled Cycle 1 Day 8(C1D8) and Cycle 1 Day 12(C1D12 ) visit.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 130 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants with documented evidence of locally advanced inoperable or metastatic solid tumours who may be suitable to receive capivasertib treatment.
- •Eastern Cooperative Oncology Group/World Health Organization performance status 0 to 1 and with minimum life expectancy for 12 weeks.
- •Participant should have at least one lesion that can be assessed by computed tomography/magnetic resonance imaging or plain X-ray at baseline.
- •Body mass index within the range 18 to 32 kg/m^2
排除标准
- •Participants are excluded from the study if any of the following criteria apply:
- •Radiotherapy with a wide field of radiation within 4 weeks of the first dose of capivasertib and/or radiotherapy with a limited field of radiation for palliation within 2 weeks prior to study intervention initiation.
- •Participants with diabetes mellitus type I or participants with diabetes mellitus type II requiring insulin treatment.
- •Undergone a major surgery within 4 weeks of the first dose of capivasertib.
- •Any unresolved toxicities from prior therapies higher than CTCAE grade 2 or any unresolved toxicity that may interfere with PK assessment at the time of study intervention initiation.
- •Participants with spinal cord compression or brain metastases.
- •Participants with severe or uncontrolled systemic diseases, active bleeding diatheses, or active infection.
- •Previous allogeneic bone marrow transplant or solid organ transplant.
- •Known immunodeficiency syndrome.
研究组 & 干预措施
Treatment (Midazolam + Capivasertib)
Midazolam will be administered on Cycle 1 Day 1 and Cycle 1 Day 8. Capivasertib will be administrated from Cycle 1 Day 2 as an intermittent schedule (4 days on/3 days off) until discontinuation. On Cycle 1 Day 12, Midazolam will be administrated with Capivasertib.
干预措施: Capivasertib (Drug)
Treatment (Midazolam + Capivasertib)
Midazolam will be administered on Cycle 1 Day 1 and Cycle 1 Day 8. Capivasertib will be administrated from Cycle 1 Day 2 as an intermittent schedule (4 days on/3 days off) until discontinuation. On Cycle 1 Day 12, Midazolam will be administrated with Capivasertib.
干预措施: Midazolam (Drug)
结局指标
主要结局
Midazolam AUCinf
时间窗: Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 8, Cycle 1 Day 9, Cycle 1 Day 12 and Cycle 1 Day 13 (Cycle 1 is 29 days)
Area under the plasma concentration-time curve from zero to infinity
Midazolam Cmax
时间窗: Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 8, Cycle 1 Day 9, Cycle 1 Day 12 and Cycle 1 Day 13 (Cycle 1 is 29 days)
Maximum observed plasma (peak) drug concentration
次要结局
- Midazolam AUClast(Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 8, Cycle 1 Day 9, Cycle 1 Day 12 and Cycle 1 Day 13 (Cycle 1 is 29 days))
- Capivasertib Ctrough(Cycle 1 Day 9 and Cycle 1 Day 13 (Cycle 1 is 29 days))
- Capivasertib AUCτ(Cycle 1 Day 12 and Cycle 1 Day 13 (Cycle 1 is 29 days))
- Capivasertib t½λz(Cycle 1 Day 12 and Cycle 1 Day 13 (Cycle 1 is 29 days))
- Capivasertib tmax(Cycle 1 Day 12 and Cycle 1 Day 13 (Cycle 1 is 29 days))
- Capivasertib CL/F(Cycle 1 Day 12 and Cycle 1 Day 13 (Cycle 1 is 29 days))
- Capivasertib metabolite AZ14102143 Ctrough(Cycle 1 Day 9 and Cycle 1 Day 13 (Cycle 1 is 29 days))
- Capivasertib metabolite AZ14102143 Cmax(Cycle 1 Day 12 and Cycle 1 Day 13 (Cycle 1 is 29 days))
- Capivasertib metabolite AZ14102143 AUCτ(Cycle 1 Day 12 and Cycle 1 Day 13 (Cycle 1 is 29 days))
- Capivasertib metabolite AZ14102143 t½λz(Cycle 1 Day 12 and Cycle 1 Day 13 (Cycle 1 is 29 days))
- Capivasertib metabolite AZ14102143 tmax(Cycle 1 Day 12 and Cycle 1 Day 13 (Cycle 1 is 29 days))
- Number of participants with adverse events and serious adverse events(From screening to disease progression or discontinuation from the study (up to 15 months))
- Midazolam t½λz(Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 8, Cycle 1 Day 9, Cycle 1 Day 12 and Cycle 1 Day 13 (Cycle 1 is 29 days))
- Midazolam tmax(Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 8, Cycle 1 Day 9, Cycle 1 Day 12 and Cycle 1 Day 13 (Cycle 1 is 29 days))
- Capivasertib Cmax(Cycle 1 Day 12 and Cycle 1 Day 13 (Cycle 1 is 29 days))