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

Study Overview
=================
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.

Official Title
-----------------
A Randomized, Open-Label, Two-Treatment, Two-Period, Two-Way Crossover Study to Investigate the Bioequivalence of Entrectinib Polymorph Forms A and C Under Fasted Conditions in Healthy Subjects

Conditions
-----------------
Healthy Volunteers

Intervention / Treatment
-----------------
* Drug: Entrectinib Form A
* Drug: Entrectinib Form C


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Form A to Form C Crossover<br>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). | Drug: Entrectinib Form A<br>* Participants will receive a single oral dose of entrectinib form A under fasted conditions.<br>Drug: Entrectinib Form C<br>* Participants will receive a single oral dose of entrectinib form C under fasted conditions.<br>|
| Experimental: Form C to Form A Crossover<br>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). | Drug: Entrectinib Form A<br>* Participants will receive a single oral dose of entrectinib form A under fasted conditions.<br>Drug: Entrectinib Form C<br>* Participants will receive a single oral dose of entrectinib form C under fasted conditions.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) | 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. | Baseline through the end of study (up to clinical cut-off date 06 Feb 2019 [28 days]) |