A Performance and Bioavailability Study of Entrectinib in Healthy Volunteers.

NCT03961100 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: GP413412019-000783-15
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

This study will evaluate the bioavailability, palatability, safety and tolerability of entrectinib in healthy volunteers. Part 1 of the study will explore the performance of entrectinib multi-particle formulation. Part 2 will evaluate the effect of drug substance particle size on entrectinib bioavailability.

Conditions

Solid Tumor

Outcome Measures

Primary Outcomes (4)

• Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC0-inf) of Entrectinib

  At pre-defined intervals from study Day 1 to Day 5 of each periods (each period=7 days)

• AUC0-inf of Entrectinib Active Metabolite M5

  At pre-defined intervals from study Day 1 to Day 5 of each periods (each period=7 days)

• Maximum Plasma Concentration (Cmax) of Entrectinib

  At pre-defined intervals from study Day 1 to Day 5 of each periods (each period=7 days)

• Cmax of Entrectinib Active Metabolite M5

  At pre-defined intervals from study Day 1 to Day 5 of each periods (each period=7 days)

Secondary Outcomes (1)

• Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)

  From Day -1 to Day 5 of each periods (each period=7 days)

Study Arms (2)

Part 1

EXPERIMENTAL

Participants will be randomly assigned to one of the three treatment sequences (T1T2R, T2RT1, RT1T2). In each treatment sequences, participants will cross-over to three periods taking different formulations of entrectinib. Entrectinib will be administered as a single 600 milligram (mg) oral dose under fed condition in three different formulations. Test formulation 1 (T1): film-coated mini-tablet; Test formulation 2 (T2): film-coated mini-tablet; Reference formulation (R): hard capsule.

Drug: Entrectinib 600 mg (T1); Drug: Entrectinib 600 mg (T2); Drug: Entrectinib 200 mg (R)

Part 2

EXPERIMENTAL

Participants will be randomly assigned to one of the two treatment sequences (TR, RT). In each treatment sequences, participants will cross-over to two periods taking different formulations of entrectinib. Entrectinib will be administered as a single 200 mg oral dose under fasted condition in two different formulations. Test formulation (T): hydroxypropyl methylcellulose (HPMC) capsule; Reference formulation (R): hard capsule.

Drug: Entrectinib 200 mg (R); Drug: Entrectinib 200 mg (T)

Interventions

Entrectinib 600 mg (T1) DRUG

Test formulation 1 (T1): Multi-particulate formulation 1: entrectinib film-coated mini-tablets

Part 1

Entrectinib 600 mg (T2) DRUG

Test formulation 2 (T2): Multi-particulate formulation 2: entrectinib film-coated mini-tablets

Part 1

Entrectinib 200 mg (R) DRUG

Reference formulation (R): entrectinib hard capsules

Part 1; Part 2

Entrectinib 200 mg (T) DRUG

Test formulation (T): entrectinib HPMC capsules

Part 2

Eligibility Criteria

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

You may qualify if:

• A body mass index (BMI) between 18.0 and 32.0 kilogram per square meter (kg/m2), inclusive, and weighing \>/=50 kg.
• Agreement to comply with measures to prevent pregnancy and restrictions on egg and sperm donation

You may not qualify if:

• Women of childbearing potential, women who are pregnant or breastfeeding, or intending to become pregnant during the study or within 14 days after the final dose of entrectinib or have a pregnant partner
• A clinical significant medical history of gastrointestinal surgery (e.g., gastric bypass) or other gastrointestinal disorder (e.g., malabsorption syndrome) 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
• Clinically significant change in health status, or any major illness, or clinically significant acute infection or febrile illness
• Use of moderate or potent inhibitors or inducers of CYP P450 3A4 enzyme or P-gp transporter, or use of other prohibited medications
• Participation in any other clinical study involving an investigational medicinal product (IMP) or device
• A positive test result for hepatitis B, hepatitis C (HCV), or human immunodeficiency virus (HIV)
• Current smokers and those who have smoked, or users of e-cigarettes and nicotine replacement products within the last 12 months
• Known history of clinically significant hypersensitivity, or severe allergic reaction, to entrectinib or related compounds

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (1)

Quotient Clinical Ltd, Clinical Research Unit

Nottingham, NG11 6JS, United Kingdom

Location

MeSH Terms

Interventions

entrectinib

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: May 22, 2019
• First Posted: May 23, 2019
• Study Start: June 6, 2019
• Primary Completion: August 9, 2019
• Study Completion: August 9, 2019
• Last Updated: September 7, 2020
• Results First Posted: September 7, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)