An Open-label, Randomized, 2-period, 2-sequence Study to Evaluate the Single-dose Pharmacokinetics of Milademetan When Administered Alone or Concomitantly With Itraconazole or Posaconazole in Healthy Subjects
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- Maximum plasma concentration (Cmax) of milademetan
研究概览
简要总结
This will be an open-label, randomized, 3-treatment, 2-period, 2-sequence study in healthy subjects to evaluate the single-dose PK of milademetan when given as monotherapy and when administered with steady-state levels of the strong CYP3A4 inhibitors itraconazole or posaconazole.
The duration of the study for each individual subject will be approximately 49 days from the start of Screening through Study Discharge. Subjects will remain in-house for up to 23 days, including 22 overnight stays.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Basic Science
- 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
- •Has negative urine test for drugs of abuse, alcohol and tobacco
- •If female, is surgically sterile or postmenopausal
- •If male, agrees to protocol-defined contraceptive methods
- •Has adequate hematologic, hepatic, and renal function as defined by the protocol
- •Is able and willing to follow all study procedures
- •Has provided a signed informed consent
排除标准
- •Is female who is pregnant or breastfeeding
- •Is unable to swallow oral medication
- •Is unable to follow study procedures
- •Has creatinine clearance < 90 mL/min at screening
- •Is taking or has taken any medications or therapies outside of protocol-defined parameters
- •Has history of or a known allergic reaction to azole antifungal agents
- •Has any disease or condition that, per protocol or in the opinion of the investigator, might affect:
- •safety and well-being of the participant or offspring
- •safety of study staff
研究组 & 干预措施
Milademetan alone (A)
During Period 1, participants receive a single 100 mg milademetan oral dose on Study Day 1, with PK sampling to 168 hours post-dose (during the following 7-day washout period)
干预措施: Milademetan (Drug)
Milademetan with itraconazole (AB)
During Period 2, participants receive itraconazole, 200 mg twice daily (BID) on Study day 8 and 200 mg once daily (QD) on Study Days 9 through 20, along with a single 100 mg milademetan dose on Day 14
干预措施: Milademetan (Drug)
Milademetan with itraconazole (AB)
During Period 2, participants receive itraconazole, 200 mg twice daily (BID) on Study day 8 and 200 mg once daily (QD) on Study Days 9 through 20, along with a single 100 mg milademetan dose on Day 14
干预措施: Itraconazole (Drug)
Milademetan with posaconazole (AC)
During Period 2, participants receive 200 mg posaconazole three times daily (TID) on Study Days 8 through 20, along with a single 100 mg milademetan dose on Day 14
干预措施: Milademetan (Drug)
Milademetan with posaconazole (AC)
During Period 2, participants receive 200 mg posaconazole three times daily (TID) on Study Days 8 through 20, along with a single 100 mg milademetan dose on Day 14
干预措施: Posaconazole (Drug)
结局指标
主要结局
Maximum plasma concentration (Cmax) of milademetan
时间窗: pre-dose and then at 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose
Categories: alone (A), in sequence AB, in sequence AC
Area under the plasma concentration-time curve extrapolated to infinity (AUCinf) of milademetan
时间窗: within 168 hours postdose
Categories: alone (A), in sequence AB, in sequence AC
次要结局
- Apparent volume of distribution (Vz/F)(within 168 hours postdose)
- Time to reach maximum plasma concentration (Tmax) of milademetan(pre-dose and then at 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose)
- Area under the plasma concentration-time curve from time 0 to the time of last measurable concentration (AUC0-t) for milademetan(within 168 hours postdose)
- Terminal elimination half-life (t½) of milademetan(within 168 hours postdose)
- Apparent total body clearance (CL/F) of milademetan(within 168 hours postdose)