A Performance and Bioavailability Study of Entrectinib in Healthy Volunteers.
Phase 1
Completed
- Conditions
- Solid Tumor
- Interventions
- Registration Number
- NCT03961100
- Lead Sponsor
- Genentech, Inc.
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 31
Inclusion Criteria
- 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
Exclusion Criteria
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Part 1 Entrectinib 600 mg (T2) 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. Part 1 Entrectinib 200 mg (R) 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. Part 2 Entrectinib 200 mg (T) 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. Part 1 Entrectinib 600 mg (T1) 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. Part 2 Entrectinib 200 mg (R) 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.
- Primary Outcome Measures
Name Time Method Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC0-inf) of Entrectinib At pre-defined intervals from study Day 1 to Day 5 of each periods (each period=7 days) AUC0-inf of Entrectinib Active Metabolite M5 At pre-defined intervals from study Day 1 to Day 5 of each periods (each period=7 days) Maximum Plasma Concentration (Cmax) of Entrectinib At pre-defined intervals from study Day 1 to Day 5 of each periods (each period=7 days) Cmax of Entrectinib Active Metabolite M5 At pre-defined intervals from study Day 1 to Day 5 of each periods (each period=7 days)
- Secondary Outcome Measures
Name Time Method Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) From Day -1 to Day 5 of each periods (each period=7 days) An adverse event (AE) is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. Treatment-emergent adverse events (TEAEs) are AEs that were not present before the first dose of study drug or that were present before the first dose of study drug but worsened in intensity during exposure to study drug.
Trial Locations
- Locations (1)
Quotient Clinical Ltd, Clinical Research Unit
🇬🇧Nottingham, United Kingdom