Clinical trial NCT03961100: A Performance and Bioavailability Study of Entrectinib in Healthy Volunteers.
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumor
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2019-05-23
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC0-inf) of Entrectinib
timeFrame: At pre-defined intervals from study Day 1 to Day 5 of each periods (each period=7 days)
measure: AUC0-inf of Entrectinib Active Metabolite M5
timeFrame: At pre-defined intervals from study Day 1 to Day 5 of each periods (each period=7 days)
measure: Maximum Plasma Concentration (Cmax) of Entrectinib
timeFrame: At pre-defined intervals from study Day 1 to Day 5 of each periods (each period=7 days)
measure: Cmax of Entrectinib Active Metabolite M5
timeFrame: At pre-defined intervals from study Day 1 to Day 5 of each periods (each period=7 days)
Secondary outcomes:
measure: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: From Day -1 to Day 5 of each periods (each period=7 days)
Other outcomes:
Locations:
city: Nottingham
country: United Kingdom
facility: Quotient Clinical Ltd, Clinical Research Unit
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical trials
role: STUDY_DIRECTOR
References: