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

NCT03796260 | Completed Phase 1 Results FDA Drug

• 1 other identifier: GP41048
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (3)

• Area Under the Concentration-Time Curve Extrapolated to Infinity (AUC0-inf) of Entrectinib and M5 Metabolite

  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.

  At pre-defined intervals from study Day 1 through Day 5 of each Period (Periods 1 and 2 = 6 days)

• Area Under the Concentration-Time Curve (AUC0-t) of Entrectinib and M5 Metabolite

  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.

  At pre-defined intervals from study Day 1 through Day 5 of each Period (Periods 1 and 2 = 6 days)

• Maximum Observed Concentration (Cmax) of Entrectinib and M5 Metabolite

  The presented values in the table are based on all 14 participants receiving the F1 formulation in a 2-way crossover pattern.

  At pre-defined intervals from study Day 1 through Day 5 of each Period (Periods 1 and 2 = 6 days)

Secondary Outcomes (1)

• 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])

Study Arms (2)

F1 to F06 Crossover

EXPERIMENTAL

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).

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

F06 to F1 Crossover

EXPERIMENTAL

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).

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

Interventions

Entrectinib Test Formulation (F1) DRUG

Participants will receive a single oral dose of entrectinib F1 after completion of a standardized meal.

F06 to F1 Crossover; F1 to F06 Crossover

Entrectinib Reference Formulation (F06) DRUG

Participants will receive a single oral dose of entrectinib F06 after completion of a standardized meal.

F06 to F1 Crossover; F1 to F06 Crossover

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (1)

Covance Research Unit - Daytona

Daytona Beach, Florida, 32117, United States

Location

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 4, 2019
• First Posted: January 8, 2019
• Study Start: January 9, 2019
• Primary Completion: February 4, 2019
• Study Completion: February 4, 2019
• Last Updated: February 26, 2020
• Results First Posted: February 26, 2020

Record last verified: 2020-02

Locations

US (1)