Back to resultsA Study to Investigate the Relative Bioavailability of Entrectinib Capsule Formulations F1 and F06 Under Fed Conditions in Healthy Participants
Primary Purpose
Healthy Volunteers
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Entrectinib Test Formulation (F1)
Entrectinib Reference Formulation (F06)
Sponsored by
About this trial
This is an interventional treatment trial for Healthy Volunteers
Eligibility Criteria
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
Sites / Locations
- Covance Research Unit - Daytona
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
F1 to F06 Crossover
F06 to F1 Crossover
Arm Description
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).
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).
Outcomes
Primary Outcome Measures
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.
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.
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.
Secondary Outcome Measures
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03796260
Brief Title
A Study to Investigate the Relative Bioavailability of Entrectinib Capsule Formulations F1 and F06 Under Fed Conditions in Healthy Participants
Official Title
A Randomized, Open-Label, Two-Treatment, Two-Period, Two-Way Crossover Study to Investigate the Relative Bioavailability of Entrectinib Capsule Formulations F1 and F06 Under Fed Conditions in Healthy Subjects
Study Type
Interventional
2. Study Status
Record Verification Date
February 2020
Overall Recruitment Status
Completed
Study Start Date
January 9, 2019 (Actual)
Primary Completion Date
February 4, 2019 (Actual)
Study Completion Date
February 4, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Genentech, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Healthy Volunteers
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
14 (Actual)
8. Arms, Groups, and Interventions
Arm Title
F1 to F06 Crossover
Arm Type
Experimental
Arm Description
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).
Arm Title
F06 to F1 Crossover
Arm Type
Experimental
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
Entrectinib Test Formulation (F1)
Intervention Description
Participants will receive a single oral dose of entrectinib F1 after completion of a standardized meal.
Intervention Type
Drug
Intervention Name(s)
Entrectinib Reference Formulation (F06)
Intervention Description
Participants will receive a single oral dose of entrectinib F06 after completion of a standardized meal.
Primary Outcome Measure Information:
Title
Area Under the Concentration-Time Curve Extrapolated to Infinity (AUC0-inf) of Entrectinib and M5 Metabolite
Description
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.
Time Frame
At pre-defined intervals from study Day 1 through Day 5 of each Period (Periods 1 and 2 = 6 days)
Title
Area Under the Concentration-Time Curve (AUC0-t) of Entrectinib and M5 Metabolite
Description
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.
Time Frame
At pre-defined intervals from study Day 1 through Day 5 of each Period (Periods 1 and 2 = 6 days)
Title
Maximum Observed Concentration (Cmax) of Entrectinib and M5 Metabolite
Description
The presented values in the table are based on all 14 participants receiving the F1 formulation in a 2-way crossover pattern.
Time Frame
At pre-defined intervals from study Day 1 through Day 5 of each Period (Periods 1 and 2 = 6 days)
Secondary Outcome Measure Information:
Title
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)
Description
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.
Time Frame
Baseline through the end of study (up to clinical cut-off date 04 Feb 2019 [27 days])
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
Covance Research Unit - Daytona
City
Daytona Beach
State/Province
Florida
ZIP/Postal Code
32117
Country
United States
12. IPD Sharing Statement
Learn more about this trial
A Study to Investigate the Relative Bioavailability of Entrectinib Capsule Formulations F1 and F06 Under Fed Conditions in Healthy Participants
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