Trial Outcomes & Findings for A Study to Investigate the Bioequivalence of Two Different Forms of Entrectinib (Forms A and C) Under Fasted Conditions in Healthy Subjects (NCT NCT03796013)
NCT ID: NCT03796013
Last Updated: 2020-03-09
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
28 participants
Primary outcome timeframe
At pre-defined intervals from Hour 0 through Day 5 of each study Period (Periods 1 and 2 = 6 days)
Results posted on
2020-03-09
Participant Flow
Participant milestones
| Measure |
Form A to Form C Crossover
Participants first randomized to this arm received a single oral dose of entrectinib form A (reference form) under fasted conditions on Day 1 of Period 1. This dose was followed by a minimum 14-day washout period, after which participants received a single oral dose of entrectinib form C (test form) under fasted conditions on Day 1 of Period 2 (Periods 1 and 2 = 6 days).
|
Form C to Form A Crossover
Participants first randomized to this arm received a single oral dose of entrectinib form C (test form) under fasted conditions on Day 1 of Period 1. This dose was followed by a minimum 14-day washout period, after which participants received a single oral dose of entrectinib form A (reference form) under fasted conditions on Day 1 of Period 2 (Periods 1 and 2 = 6 days).
|
|---|---|---|
|
Period 1
STARTED
|
14
|
14
|
|
Period 1
COMPLETED
|
14
|
14
|
|
Period 1
NOT COMPLETED
|
0
|
0
|
|
Period 2
STARTED
|
14
|
14
|
|
Period 2
COMPLETED
|
14
|
14
|
|
Period 2
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Study to Investigate the Bioequivalence of Two Different Forms of Entrectinib (Forms A and C) Under Fasted Conditions in Healthy Subjects
Baseline characteristics by cohort
| Measure |
Form A to Form C Crossover
n=14 Participants
Participants first randomized to this arm received a single oral dose of entrectinib form A (reference form) under fasted conditions on Day 1 of Period 1. This dose was followed by a minimum 14-day washout period, after which participants received a single oral dose of entrectinib form C (test form) under fasted conditions on Day 1 of Period 2 (Periods 1 and 2 = 6 days).
|
Form C to Form A Crossover
n=14 Participants
Participants first randomized to this arm received a single oral dose of entrectinib form C (test form) under fasted conditions on Day 1 of Period 1. This dose was followed by a minimum 14-day washout period, after which participants received a single oral dose of entrectinib form A (reference form) under fasted conditions on Day 1 of Period 2 (Periods 1 and 2 = 6 days).
|
Total
n=28 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
43.9 Years
STANDARD_DEVIATION 8.4 • n=5 Participants
|
44.4 Years
STANDARD_DEVIATION 11.7 • n=7 Participants
|
44 Years
STANDARD_DEVIATION 10.4 • n=5 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
8 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
5 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Multiple
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Hispanic or Latino
|
5 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Not Hispanic or Latino
|
9 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: At pre-defined intervals from Hour 0 through Day 5 of each study Period (Periods 1 and 2 = 6 days)Population: The PK Population consisted of all participants who received at least 1 dose of study drug and had at least 1 evaluable postdose pharmacokinetic (PK) sample.
Outcome measures
| Measure |
Form A Reference Formulation
n=28 Participants
Participants who received a single oral dose of entrectinib form A (reference form) under fasted conditions on Day 1 of Period 1 and Day 1 of Period 2 (Periods 1 and 2 = 6 days).
|
Form C Test Formulation
n=28 Participants
Participants who received a single oral dose of entrectinib form C (test form) under fasted conditions on Day 1 of Period 1 and Day 1 of Period 2 (Periods 1 and 2 = 6 days).
|
|---|---|---|
|
Area Under the Concentration-Time Curve (AUC0-t) of Entrectinib and M5 Metabolite
Entrectinib
|
18500 nmol*h/L
Geometric Coefficient of Variation 37.9
|
16600 nmol*h/L
Geometric Coefficient of Variation 30.7
|
|
Area Under the Concentration-Time Curve (AUC0-t) of Entrectinib and M5 Metabolite
M5 metabolite
|
3610 nmol*h/L
Geometric Coefficient of Variation 37.0
|
3070 nmol*h/L
Geometric Coefficient of Variation 36.9
|
PRIMARY outcome
Timeframe: At pre-defined intervals from Hour 0 through Day 5 of each study Period (Periods 1 and 2 = 6 days)Population: The PK Population consisted of all participants who received at least 1 dose of study drug and had at least 1 evaluable postdose PK sample.
Outcome measures
| Measure |
Form A Reference Formulation
n=28 Participants
Participants who received a single oral dose of entrectinib form A (reference form) under fasted conditions on Day 1 of Period 1 and Day 1 of Period 2 (Periods 1 and 2 = 6 days).
|
Form C Test Formulation
n=28 Participants
Participants who received a single oral dose of entrectinib form C (test form) under fasted conditions on Day 1 of Period 1 and Day 1 of Period 2 (Periods 1 and 2 = 6 days).
|
|---|---|---|
|
Maximum Observed Concentration (Cmax) of Entrectinib and M5 Metabolite
Entrectinib
|
796 nmol/L
Geometric Coefficient of Variation 35.6
|
726 nmol/L
Geometric Coefficient of Variation 28.9
|
|
Maximum Observed Concentration (Cmax) of Entrectinib and M5 Metabolite
M5 metabolite
|
138 nmol/L
Geometric Coefficient of Variation 47.9
|
114 nmol/L
Geometric Coefficient of Variation 50.3
|
SECONDARY outcome
Timeframe: Baseline through the end of study (up to clinical cut-off date 06 Feb 2019 [28 days])Population: The Safety Population consisted of all participants who received at least 1 dose of study drug and had at least 1 postdose safety assessment.
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.
Outcome measures
| Measure |
Form A Reference Formulation
n=28 Participants
Participants who received a single oral dose of entrectinib form A (reference form) under fasted conditions on Day 1 of Period 1 and Day 1 of Period 2 (Periods 1 and 2 = 6 days).
|
Form C Test Formulation
n=28 Participants
Participants who received a single oral dose of entrectinib form C (test form) under fasted conditions on Day 1 of Period 1 and Day 1 of Period 2 (Periods 1 and 2 = 6 days).
|
|---|---|---|
|
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)
|
7.1 Percentage of Participants
|
0 Percentage of Participants
|
Adverse Events
Form A Reference Formulation
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Form C Test Formulation
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Form A Reference Formulation
n=28 participants at risk
Participants who received a single oral dose of entrectinib form A (reference form) under fasted conditions on Day 1 of Period 1 and Day 1 of Period 2 (Periods 1 and 2 = 6 days).
|
Form C Test Formulation
n=28 participants at risk
Participants who received a single oral dose of entrectinib form C (test form) under fasted conditions on Day 1 of Period 1 and Day 1 of Period 2 (Periods 1 and 2 = 6 days).
|
|---|---|---|
|
Injury, poisoning and procedural complications
Arthropod bite
|
7.1%
2/28 • Baseline through the end of study (up to clinical cut-off date 06 Feb 2019 [28 days])
The Safety Population consisted of all participants who received at least 1 dose of study drug and had at least 1 postdose safety assessment.
|
0.00%
0/28 • Baseline through the end of study (up to clinical cut-off date 06 Feb 2019 [28 days])
The Safety Population consisted of all participants who received at least 1 dose of study drug and had at least 1 postdose safety assessment.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
3.6%
1/28 • Baseline through the end of study (up to clinical cut-off date 06 Feb 2019 [28 days])
The Safety Population consisted of all participants who received at least 1 dose of study drug and had at least 1 postdose safety assessment.
|
0.00%
0/28 • Baseline through the end of study (up to clinical cut-off date 06 Feb 2019 [28 days])
The Safety Population consisted of all participants who received at least 1 dose of study drug and had at least 1 postdose safety assessment.
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
3.6%
1/28 • Baseline through the end of study (up to clinical cut-off date 06 Feb 2019 [28 days])
The Safety Population consisted of all participants who received at least 1 dose of study drug and had at least 1 postdose safety assessment.
|
0.00%
0/28 • Baseline through the end of study (up to clinical cut-off date 06 Feb 2019 [28 days])
The Safety Population consisted of all participants who received at least 1 dose of study drug and had at least 1 postdose safety assessment.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER