A Randomized, Open-Label, Two Part Study to Explore the Performance of Entrectinib Prototype Mini-Tablet Formulations and the Effect of Drug Substance Particle Size On Entrectinib Bioavailability in Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 31
- 试验地点
- 1
- 主要终点
- AUC0-inf of Entrectinib Active Metabolite M5
研究概览
简要总结
This study will evaluate the bioavailability, palatability, safety and tolerability of entrectinib in healthy volunteers. Part 1 of the study will explore the performance of entrectinib multi-particle formulation. Part 2 will evaluate the effect of drug substance particle size on entrectinib bioavailability.
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 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •A body mass index (BMI) between 18.0 and 32.0 kilogram per square meter (kg/m2), inclusive, and weighing >/=50 kg.
- •Agreement to comply with measures to prevent pregnancy and restrictions on egg and sperm donation
排除标准
- •Women of childbearing potential, women who are pregnant or breastfeeding, or intending to become pregnant during the study or within 14 days after the final dose of entrectinib or have a pregnant partner
- •A clinical significant medical history of gastrointestinal surgery (e.g., gastric bypass) or other gastrointestinal disorder (e.g., malabsorption syndrome) that might affect absorption of medicines from the gastrointestinal tract
- •Presence of a clinically significant disease, illness, medical condition or disorder, or any other medical history determined by the investigator to be clinically significant and relevant
- •Clinically significant change in health status, or any major illness, or clinically significant acute infection or febrile illness
- •Use of moderate or potent inhibitors or inducers of CYP P450 3A4 enzyme or P-gp transporter, or use of other prohibited medications
- •Participation in any other clinical study involving an investigational medicinal product (IMP) or device
- •A positive test result for hepatitis B, hepatitis C (HCV), or human immunodeficiency virus (HIV)
- •Current smokers and those who have smoked, or users of e-cigarettes and nicotine replacement products within the last 12 months
- •Known history of clinically significant hypersensitivity, or severe allergic reaction, to entrectinib or related compounds
研究组 & 干预措施
Part 1
Participants will be randomly assigned to one of the three treatment sequences (T1T2R, T2RT1, RT1T2). In each treatment sequences, participants will cross-over to three periods taking different formulations of entrectinib. Entrectinib will be administered as a single 600 milligram (mg) oral dose under fed condition in three different formulations. Test formulation 1 (T1): film-coated mini-tablet; Test formulation 2 (T2): film-coated mini-tablet; Reference formulation (R): hard capsule.
干预措施: Entrectinib 600 mg (T2) (Drug)
Part 1
Participants will be randomly assigned to one of the three treatment sequences (T1T2R, T2RT1, RT1T2). In each treatment sequences, participants will cross-over to three periods taking different formulations of entrectinib. Entrectinib will be administered as a single 600 milligram (mg) oral dose under fed condition in three different formulations. Test formulation 1 (T1): film-coated mini-tablet; Test formulation 2 (T2): film-coated mini-tablet; Reference formulation (R): hard capsule.
干预措施: Entrectinib 200 mg (R) (Drug)
Part 2
Participants will be randomly assigned to one of the two treatment sequences (TR, RT). In each treatment sequences, participants will cross-over to two periods taking different formulations of entrectinib. Entrectinib will be administered as a single 200 mg oral dose under fasted condition in two different formulations. Test formulation (T): hydroxypropyl methylcellulose (HPMC) capsule; Reference formulation (R): hard capsule.
干预措施: Entrectinib 200 mg (T) (Drug)
Part 1
Participants will be randomly assigned to one of the three treatment sequences (T1T2R, T2RT1, RT1T2). In each treatment sequences, participants will cross-over to three periods taking different formulations of entrectinib. Entrectinib will be administered as a single 600 milligram (mg) oral dose under fed condition in three different formulations. Test formulation 1 (T1): film-coated mini-tablet; Test formulation 2 (T2): film-coated mini-tablet; Reference formulation (R): hard capsule.
干预措施: Entrectinib 600 mg (T1) (Drug)
Part 2
Participants will be randomly assigned to one of the two treatment sequences (TR, RT). In each treatment sequences, participants will cross-over to two periods taking different formulations of entrectinib. Entrectinib will be administered as a single 200 mg oral dose under fasted condition in two different formulations. Test formulation (T): hydroxypropyl methylcellulose (HPMC) capsule; Reference formulation (R): hard capsule.
干预措施: Entrectinib 200 mg (R) (Drug)
结局指标
主要结局
AUC0-inf of Entrectinib Active Metabolite M5
时间窗: At pre-defined intervals from study Day 1 to Day 5 of each periods (each period=7 days)
Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC0-inf) of Entrectinib
时间窗: At pre-defined intervals from study Day 1 to Day 5 of each periods (each period=7 days)
Maximum Plasma Concentration (Cmax) of Entrectinib
时间窗: At pre-defined intervals from study Day 1 to Day 5 of each periods (each period=7 days)
Cmax of Entrectinib Active Metabolite M5
时间窗: At pre-defined intervals from study Day 1 to Day 5 of each periods (each period=7 days)
次要结局
- Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)(From Day -1 to Day 5 of each periods (each period=7 days))