A Performance and Bioavailability Study of Entrectinib in Healthy Volunteers.

Genentech

Status and phase: Completed; Phase 1

Conditions: Solid Tumor

Treatments: Drug: Entrectinib 200 mg (T); Drug: Entrectinib 600 mg (T1); Drug: Entrectinib 600 mg (T2); Drug: Entrectinib 200 mg (R)

Study type: Interventional

Funder types: Industry

Identifiers

NCT03961100

GP41341

2019-000783-15 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 31 patients

Sex: All

Ages: 18 to 60 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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31 participants in 2 patient groups

Part 1

Experimental group

Description:

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.

Treatment:

Drug: Entrectinib 200 mg (R)

Drug: Entrectinib 600 mg (T2)

Drug: Entrectinib 600 mg (T1)

Part 2

Experimental group

Description:

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.

Treatment:

Drug: Entrectinib 200 mg (R)

Drug: Entrectinib 200 mg (T)