A Study to Investigate the Bioequivalence of Two Different Forms of Entrectinib (Forms A and C) Under Fasted Conditions in Healthy Subjects

Phase 1

Completed

Conditions: Healthy Volunteers

Interventions: Drug: Entrectinib Form A
Drug: Entrectinib Form C

Registration Number: NCT03796013

Lead Sponsor: Genentech, Inc.

Brief Summary: This study aims to demonstrate similarities between two different forms of entrectinib (A and C) when administered under fasted conditions in healthy subjects.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 28

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
Form C to Form A Crossover	Entrectinib Form A	Participants first randomized to this arm will receive a single oral dose of entrectinib form C (test form) under fasted conditions on Day 1 of each Period. This dose will be followed by a minimum 14-day washout period, after which participants will receive a single oral dose of entrectinib form A (reference form) under fasted conditions on Day 1 of Period 2 (Periods 1 and 2 = 6 days).
Form C to Form A Crossover	Entrectinib Form C	Participants first randomized to this arm will receive a single oral dose of entrectinib form C (test form) under fasted conditions on Day 1 of each Period. This dose will be followed by a minimum 14-day washout period, after which participants will receive a single oral dose of entrectinib form A (reference form) under fasted conditions on Day 1 of Period 2 (Periods 1 and 2 = 6 days).
Form A to Form C Crossover	Entrectinib Form A	Participants first randomized to this arm will receive a single oral dose of entrectinib form A (reference form) under fasted conditions on Day 1 of each Period. This dose will be followed by a minimum 14-day washout period, after which participants will receive a single oral dose of entrectinib form C (test form) under fasted conditions on Day 1 of Period 2 (Periods 1 and 2 = 6 days).
Form A to Form C Crossover	Entrectinib Form C	Participants first randomized to this arm will receive a single oral dose of entrectinib form A (reference form) under fasted conditions on Day 1 of each Period. This dose will be followed by a minimum 14-day washout period, after which participants will receive a single oral dose of entrectinib form C (test form) 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 (AUC0-t) of Entrectinib and M5 Metabolite	At pre-defined intervals from Hour 0 through Day 5 of each study Period (Periods 1 and 2 = 6 days)
Maximum Observed Concentration (Cmax) of Entrectinib and M5 Metabolite	At pre-defined intervals from Hour 0 through Day 5 of each study Period (Periods 1 and 2 = 6 days)

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 06 Feb 2019 [28 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.