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

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

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

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Entrectinib Form A; Drug: Entrectinib Form C

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75247
      • Covance Research Unit - Dallas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 56 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Form A to Form C Crossover; 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; Participants will receive a single oral dose of entrectinib form A under fasted conditions.; Drug: Entrectinib Form C; Participants will receive a single oral dose of entrectinib form C under fasted conditions.
Experimental: Form C to Form A Crossover; 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; Participants will receive a single oral dose of entrectinib form A under fasted conditions.; Drug: Entrectinib Form C; Participants will receive a single oral dose of entrectinib form C under fasted conditions.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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])

Collaborators and Investigators

• Sponsor: Genentech, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): January 10, 2019
• Primary Completion (Actual): February 6, 2019
• Study Completion (Actual): February 6, 2019

Study Registration Dates

• First Submitted: January 4, 2019
• First Submitted That Met QC Criteria: January 4, 2019
• First Posted (Actual): January 8, 2019

Study Record Updates

• Last Update Posted (Actual): March 9, 2020
• Last Update Submitted That Met QC Criteria: February 25, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Entrectinib
• Other Study ID Numbers: GP41049

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No