A Performance and Bioavailability Study of Entrectinib in Healthy Volunteers.

Solid Tumor Clinical Trial

Official title:

A Randomized, Open-Label, Two Part Study to Explore the Performance of Entrectinib Prototype Mini-Tablet Formulations and the Effect of Drug Substance Particle Size On Entrectinib Bioavailability in Healthy Volunteers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03961100
• Other study ID #: GP41341
• Secondary ID: 2019-000783-15
• Status: Completed
• Phase: Phase 1
• Start date: June 6, 2019
• Est. completion date: August 9, 2019

Study information

• Verified date: September 2020
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: August 9, 2019
• Est. primary completion date: August 9, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Solid Tumor

Intervention

Drug:
• Entrectinib 600 mg (T1)
Test formulation 1 (T1): Multi-particulate formulation 1: entrectinib film-coated mini-tablets
• Entrectinib 600 mg (T2)
Test formulation 2 (T2): Multi-particulate formulation 2: entrectinib film-coated mini-tablets
• Entrectinib 200 mg (R)
Reference formulation (R): entrectinib hard capsules
• Entrectinib 200 mg (T)
Test formulation (T): entrectinib HPMC capsules

Locations

Country	Name	City	State
United Kingdom	Quotient Clinical Ltd, Clinical Research Unit	Nottingham

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	Maximum Plasma Concentration (Cmax) of Entrectinib		At pre-defined intervals from study Day 1 to Day 5 of each periods (each period=7 days)
Primary	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	Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)	An adverse event (AE) 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. Treatment-emergent adverse events (TEAEs) are AEs that were not present before the first dose of study drug or that were present before the first dose of study drug but worsened in intensity during exposure to study drug.	From Day -1 to Day 5 of each periods (each period=7 days)