A Study to Investigate the Relative Bioavailability of Entrectinib Capsule Formulations F1 and F06 Under Fed Conditions in Healthy Participants

Phase 1

Completed

Conditions: Healthy Volunteers

Interventions: Drug: Entrectinib Test Formulation (F1)
Drug: Entrectinib Reference Formulation (F06)

Registration Number: NCT03796260

Lead Sponsor: Genentech, Inc.

Brief Summary: This study aims to investigate the relative bioavailability, safety, and tolerability of entrectinib capsule formulations F1 and F06 under fed conditions in healthy adult male and female participants.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 14

Inclusion Criteria

Healthy in the opinion of the investigator. Healthy is defined by the absence of evidence of any active disease or clinically significant medical condition based on a detailed medical history and examination
Negative test results for Hepatitis B, Hepatitis C, and Human Immunodeficiency Virus (HIV)
Females must not be pregnant or breastfeeding, and females of childbearing potential will agree to use highly-effective contraception. Females of childbearing potential must also agree to refrain from donating eggs during the treatment period and for 6 weeks after the final dose of study drug
Males must agree to use contraception and to refrain from sperm donation from check-in (Day -1 of Period 1) to 90 days after the final dose of study drug

Exclusion Criteria

History of gastrointestinal surgery or other gastrointestinal disorder 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. Ongoing chronic disorders which are not considered clinically significant are permissible providing they are stable
Clinically significant change in health status, as judged by the investigator, or any major illness within the 4 weeks before screening, or clinically significant acute infection or febrile illness within the 14 days before screening
Participation in any other clinical study involving an investigational medicinal product (IMP) or device within 30 days or 5 half-lives (if known), whichever is longer, before screening

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
F1 to F06 Crossover	Entrectinib Test Formulation (F1)	Participants first randomized to this arm will receive a single oral dose of entrectinib F1 (test formulation) on Day 1 of Period 1 after a standardized meal. This dose will be followed by a minimum 14-day washout period, after which participants will receive a single oral dose of entrectinib F06 (reference formulation) under fasted conditions on Day 1 of Period 2 (Periods 1 and 2 = 6 days).
F1 to F06 Crossover	Entrectinib Reference Formulation (F06)	Participants first randomized to this arm will receive a single oral dose of entrectinib F1 (test formulation) on Day 1 of Period 1 after a standardized meal. This dose will be followed by a minimum 14-day washout period, after which participants will receive a single oral dose of entrectinib F06 (reference formulation) under fasted conditions on Day 1 of Period 2 (Periods 1 and 2 = 6 days).
F06 to F1 Crossover	Entrectinib Test Formulation (F1)	Participants first randomized to this arm will receive a single oral dose of entrectinib F06 (reference formulation) on Day 1 of Period 1 after a standardized meal. This dose will be followed by a minimum 14-day washout period, after which participants will receive a single oral dose of entrectinib F1 (test formulation) under fasted conditions on Day 1 of Period 2 (Periods 1 and 2 = 6 days).
F06 to F1 Crossover	Entrectinib Reference Formulation (F06)	Participants first randomized to this arm will receive a single oral dose of entrectinib F06 (reference formulation) on Day 1 of Period 1 after a standardized meal. This dose will be followed by a minimum 14-day washout period, after which participants will receive a single oral dose of entrectinib F1 (test formulation) under fasted conditions on Day 1 of Period 2 (Periods 1 and 2 = 6 days).

Primary Outcome Measures

Name	Time	Method
Area Under the Concentration-Time Curve Extrapolated to Infinity (AUC0-inf) of Entrectinib and M5 Metabolite	At pre-defined intervals from study Day 1 through Day 5 of each Period (Periods 1 and 2 = 6 days)	The area under the concentration-time curve extrapolated to infinity is calculated using the formula: AUC0-inf = AUC0-t + (Ct/λz) where Ct is the last measurable concentration and λz is the apparent terminal elimination rate constant. The presented values in the table are based on all 14 participants receiving the F1 formulation in a 2-way crossover pattern.
Area Under the Concentration-Time Curve (AUC0-t) of Entrectinib and M5 Metabolite	At pre-defined intervals from study Day 1 through Day 5 of each Period (Periods 1 and 2 = 6 days)	The area under the concentration-time curve calculated from Hour 0 to the last measurable concentration, calculated using the linear trapezoidal rule for increasing concentrations and the logarithmic rule for decreasing concentrations. The presented values in the table are based on all 14 participants receiving the F1 formulation in a 2-way crossover pattern.
Maximum Observed Concentration (Cmax) of Entrectinib and M5 Metabolite	At pre-defined intervals from study Day 1 through Day 5 of each Period (Periods 1 and 2 = 6 days)	The presented values in the table are based on all 14 participants receiving the F1 formulation in a 2-way crossover pattern.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)	Baseline through the end of study (up to clinical cut-off date 04 Feb 2019 [27 days])	An adverse event 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.