A Multi-Center, Open-Label, Single 60 mg Dose, Two Period, Two Sequence Cross-Over Trial to Investigate the Relative Bioavailability of Two Solid Oral Pimasertib Formulations in Cancer Patients
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- EMD Serono
- 入组人数
- 38
- 试验地点
- 1
- 主要终点
- Maximum Observed Plasma Concentration (Cmax)
研究概览
简要总结
This is a Phase 1, multi-center, open-label, single-dose, 2 period, 2 sequence cross-over trial to investigate the relative bioavailability of 2 solid oral pimasertib formulations in cancer subjects (Part A), followed by open-label pimasertib administration (Part B and trial extension phase).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Pathologically confirmed solid tumors, either refractory to standard therapy or for which no effective standard therapy is available, with a measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
- •An Eastern Cooperative Oncology Group Performance Status (ECOG PS) of less than or equal to (<=) 1
- •Other protocol defined inclusion criteria could apply
排除标准
- •Disease conditions or concomitant medication that may significantly influence the conduct of the trial or an abnormal electrocardiogram (ECG) or blood pressure at Screening as defined in the protocol
- •Treatment with strong inhibitors or inducers of cytochrome P450 2C19 (CYP2C19) and CYP3A4 including fruit juices or beverages containing these substances
- •History of prior mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) kinase (MEK) inhibitor exposure (including, pimasertib) or progression of disease on MEK inhibitors
- •Evidence of a retinal vein occlusion (RVO) on fluorescein angiogram or a history of RVO
- •Life expectancy of less than 12 weeks
- •Other protocol defined exclusion criteria could apply
研究组 & 干预措施
Pimasertib Capsule/Pimasertib Tablet
干预措施: Pimasertib Capsule (Part A) (Drug)
Pimasertib Capsule/Pimasertib Tablet
干预措施: Pimasertib Tablet (Part A) (Drug)
Pimasertib Capsule/Pimasertib Tablet
干预措施: Pimasertib Capsule (Part B and trial extension phase) (Drug)
Pimasertib Tablet/Pimasertib Capsule
干预措施: Pimasertib Tablet (Part A) (Drug)
Pimasertib Tablet/Pimasertib Capsule
干预措施: Pimasertib Capsule (Part A) (Drug)
Pimasertib Tablet/Pimasertib Capsule
干预措施: Pimasertib Capsule (Part B and trial extension phase) (Drug)
结局指标
主要结局
Maximum Observed Plasma Concentration (Cmax)
时间窗: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 8, and 24 hours post-dose on Day 1 and 3
Maximum observed plasma concentration (Cmax) was calculated for Part A Pimasertib 60 mg Capsule and tablet.
Area Under the Plasma Concentration-time Curve From Zero to the Last Quantifiable Concentration (AUC 0-t)
时间窗: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 8, and 24 hours post-dose on Day 1 and 3
Area under the plasma concentration-time curve from time zero to the last sampling time (AUC0-t) at which the concentration was at or above the lower limit of quantification.
次要结局
- Time to Reach Maximum Observed Plasma Concentration (Tmax)(Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 8, and 24 hours post-dose on Day 1 and 3)
- Apparent Terminal Half-life (t1/2)(Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 8, and 24 hours post-dose on Day 1 and 3)
- Area Under the Plasma Concentration-time Curve From Zero to Infinity (AUC0-inf)(Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 8, and 24 hours post-dose on Day 1 and 3)
- Apparent Volume of Distribution (Vz/f)(Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 8, and 24 hours post-dose on Day 1 and 3)
- Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation(From the first dose of study drug administration until 30 days after the last dose of study drug administration, assessed up to 14 Months)
- Terminal Rate Constant (λz)(Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 8, and 24 hours post-dose on Day 1 and 3)
- Part B: Number of Subjects Who Experienced Complete Response (CR)(Screening to Day 1 of each cycle (21 day in each cycle) until disease progression, intolerable toxicity, withdrawal of consent or death; assessed up to 14 Months)
- Part B: Number of Subjects Who Experienced Stable Disease (SD)(Screening to Day 1 of each cycle (21 day in each cycle) until disease progression, intolerable toxicity, withdrawal of consent or death; assessed up to 14 Months)
- Part B: Number of Subjects Who Experienced Progressive Disease (PD)(Screening to Day 1 of each cycle (21 day in each cycle) until disease progression, intolerable toxicity, withdrawal of consent or death; assessed up to 14 Months)
- Apparent Total Body Clearance (CL/f)(Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 8, and 24 hours post-dose on Day 1 and 3)
- Part B: Number of Subjects Who Experienced Partial Response (PR)(Screening to Day 1 of each cycle (21 day in each cycle) until disease progression, intolerable toxicity, withdrawal of consent or death; assessed up to 14 Months)