Trial Outcomes & Findings for A Study to Investigate the Relative Bioavailability of Entrectinib Capsule Formulations F1 and F06 Under Fed Conditions in Healthy Participants (NCT NCT03796260)
NCT ID: NCT03796260
Last Updated: 2020-02-26
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
14 participants
Primary outcome timeframe
At pre-defined intervals from study Day 1 through Day 5 of each Period (Periods 1 and 2 = 6 days)
Results posted on
2020-02-26
Participant Flow
Participant milestones
| Measure |
F1 to F06 Crossover
Participants first randomized to F1/F06 arm and received a single oral dose of entrectinib F1 (test formulation) on Day 1 of Period 1 after a standardized meal. This dose was followed by a minimum 14-day washout period, after which participants received a single oral dose of entrectinib F06 (reference formulation) under fed conditions on Day 1 of Period 2 (Periods 1 and 2 = 6 days).
|
F06 to F1 Crossover
Participants first randomized to this arm received a single oral dose of entrectinib F06 (reference formulation) on Day 1 of Period 1 after a standardized meal. This dose was followed by a minimum 14-day washout period, after which participants received a single oral dose of entrectinib F1 (test formulation) under fed conditions on Day 1 of Period 2 (Periods 1 and 2 = 6 days).
|
|---|---|---|
|
Period 1
STARTED
|
7
|
7
|
|
Period 1
COMPLETED
|
7
|
7
|
|
Period 1
NOT COMPLETED
|
0
|
0
|
|
Period 2
STARTED
|
7
|
7
|
|
Period 2
COMPLETED
|
7
|
7
|
|
Period 2
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Study to Investigate the Relative Bioavailability of Entrectinib Capsule Formulations F1 and F06 Under Fed Conditions in Healthy Participants
Baseline characteristics by cohort
| Measure |
F1 to F06 Crossover
n=7 Participants
Participants first randomized to F1/F06 arm and received a single oral dose of entrectinib F1 (test formulation) on Day 1 of Period 1 after a standardized meal. This dose was followed by a minimum 14-day washout period, after which participants received a single oral dose of entrectinib F06 (reference formulation) under fed conditions on Day 1 of Period 2 (Periods 1 and 2 = 6 days).
|
F06 to F1 Crossover
n=7 Participants
Participants first randomized to this arm received a single oral dose of entrectinib F06 (reference formulation) on Day 1 of Period 1 after a standardized meal. This dose was followed by a minimum 14-day washout period, after which participants received a single oral dose of entrectinib F1 (test formulation) under fed conditions on Day 1 of Period 2 (Periods 1 and 2 = 6 days).
|
Total
n=14 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
37.3 Years
STANDARD_DEVIATION 11.7 • n=99 Participants
|
33.3 Years
STANDARD_DEVIATION 10.5 • n=107 Participants
|
36 Years
STANDARD_DEVIATION 11.6 • n=206 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
7 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
7 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
White
|
5 Participants
n=99 Participants
|
7 Participants
n=107 Participants
|
12 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Multiple
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Hispanic or Latino
|
4 Participants
n=99 Participants
|
6 Participants
n=107 Participants
|
10 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Not Hispanic or Latino
|
3 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
4 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: At pre-defined intervals from study Day 1 through Day 5 of each Period (Periods 1 and 2 = 6 days)Population: The PK Population included all participants who received at least 1 dose of study drug and had at least 1 evaluable postdose pharmacokinetic (PK) sample.
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.
Outcome measures
| Measure |
F1 Test Formulation
n=14 Participants
Participants who received a single oral dose of entrectinib F1 (test formulation) on Day 1 of Period 1 and Day 1 of Period 2 after a standardized meal (Periods 1 and 2 = 6 days).
|
F06 Reference Formulation
n=14 Participants
Participants who received a single oral dose of entrectinib F06 (reference formulation) on Day 1 of Period 1 and Day 1 of Period 2 after a standardized meal (Periods 1 and 2 = 6 days).
|
|---|---|---|
|
Area Under the Concentration-Time Curve Extrapolated to Infinity (AUC0-inf) of Entrectinib and M5 Metabolite
Entrectinib
|
44000 nmol*h/L
Geometric Coefficient of Variation 52.0
|
44900 nmol*h/L
Geometric Coefficient of Variation 50.1
|
|
Area Under the Concentration-Time Curve Extrapolated to Infinity (AUC0-inf) of Entrectinib and M5 Metabolite
M5 Metabolite
|
14400 nmol*h/L
Geometric Coefficient of Variation 51.09
|
15000 nmol*h/L
Geometric Coefficient of Variation 50.8
|
PRIMARY outcome
Timeframe: At pre-defined intervals from study Day 1 through Day 5 of each Period (Periods 1 and 2 = 6 days)Population: The PK Population included all participants who received at least 1 dose of study drug and had at least 1 evaluable postdose PK sample.
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.
Outcome measures
| Measure |
F1 Test Formulation
n=14 Participants
Participants who received a single oral dose of entrectinib F1 (test formulation) on Day 1 of Period 1 and Day 1 of Period 2 after a standardized meal (Periods 1 and 2 = 6 days).
|
F06 Reference Formulation
n=14 Participants
Participants who received a single oral dose of entrectinib F06 (reference formulation) on Day 1 of Period 1 and Day 1 of Period 2 after a standardized meal (Periods 1 and 2 = 6 days).
|
|---|---|---|
|
Area Under the Concentration-Time Curve (AUC0-t) of Entrectinib and M5 Metabolite
Entrectinib
|
41200 nmol*h/L
Geometric Coefficient of Variation 50.9
|
42100 nmol*h/L
Geometric Coefficient of Variation 48.5
|
|
Area Under the Concentration-Time Curve (AUC0-t) of Entrectinib and M5 Metabolite
M5 Metabolite
|
11600 nmol*h/L
Geometric Coefficient of Variation 49.4
|
12600 nmol*h/L
Geometric Coefficient of Variation 48.2
|
PRIMARY outcome
Timeframe: At pre-defined intervals from study Day 1 through Day 5 of each Period (Periods 1 and 2 = 6 days)Population: The PK Population included all participants who received at least 1 dose of study drug and had at least 1 evaluable postdose PK sample.
The presented values in the table are based on all 14 participants receiving the F1 formulation in a 2-way crossover pattern.
Outcome measures
| Measure |
F1 Test Formulation
n=14 Participants
Participants who received a single oral dose of entrectinib F1 (test formulation) on Day 1 of Period 1 and Day 1 of Period 2 after a standardized meal (Periods 1 and 2 = 6 days).
|
F06 Reference Formulation
n=14 Participants
Participants who received a single oral dose of entrectinib F06 (reference formulation) on Day 1 of Period 1 and Day 1 of Period 2 after a standardized meal (Periods 1 and 2 = 6 days).
|
|---|---|---|
|
Maximum Observed Concentration (Cmax) of Entrectinib and M5 Metabolite
Entrectinib
|
1870 nmol/L
Geometric Coefficient of Variation 49.4
|
2000 nmol/L
Geometric Coefficient of Variation 37.6
|
|
Maximum Observed Concentration (Cmax) of Entrectinib and M5 Metabolite
M5 Metabolite
|
427 nmol/L
Geometric Coefficient of Variation 60.8
|
487 nmol/L
Geometric Coefficient of Variation 50.6
|
SECONDARY outcome
Timeframe: Baseline through the end of study (up to clinical cut-off date 04 Feb 2019 [27 days])Population: The Safety Population included 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 |
F1 Test Formulation
n=14 Participants
Participants who received a single oral dose of entrectinib F1 (test formulation) on Day 1 of Period 1 and Day 1 of Period 2 after a standardized meal (Periods 1 and 2 = 6 days).
|
F06 Reference Formulation
n=14 Participants
Participants who received a single oral dose of entrectinib F06 (reference formulation) on Day 1 of Period 1 and Day 1 of Period 2 after a standardized meal (Periods 1 and 2 = 6 days).
|
|---|---|---|
|
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)
|
28.6 Percentage of Participants
|
21.4 Percentage of Participants
|
Adverse Events
F1 Test Formulation
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
F06 Reference Formulation
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
F1 Test Formulation
n=14 participants at risk
Participants who received a single oral dose of entrectinib F1 (test formulation) on Day 1 of Period 1 and Day 1 of Period 2 after a standardized meal (Periods 1 and 2 = 6 days).
|
F06 Reference Formulation
n=14 participants at risk
Participants who received a single oral dose of entrectinib F06 (reference formulation) on Day 1 of Period 1 and Day 1 of Period 2 after a standardized meal (Periods 1 and 2 = 6 days).
|
|---|---|---|
|
Nervous system disorders
Headache
|
7.1%
1/14 • Baseline through the end of study (up to clinical cut-off date 04 Feb 2019 [27 days])
The Safety Population included all participants who received at least 1 dose of study drug and had at least 1 postdose safety assessment.
|
7.1%
1/14 • Baseline through the end of study (up to clinical cut-off date 04 Feb 2019 [27 days])
The Safety Population included all participants who received at least 1 dose of study drug and had at least 1 postdose safety assessment.
|
|
Nervous system disorders
Paraesthesia
|
7.1%
1/14 • Baseline through the end of study (up to clinical cut-off date 04 Feb 2019 [27 days])
The Safety Population included all participants who received at least 1 dose of study drug and had at least 1 postdose safety assessment.
|
7.1%
1/14 • Baseline through the end of study (up to clinical cut-off date 04 Feb 2019 [27 days])
The Safety Population included all participants who received at least 1 dose of study drug and had at least 1 postdose safety assessment.
|
|
Nervous system disorders
Cognitive disorder
|
0.00%
0/14 • Baseline through the end of study (up to clinical cut-off date 04 Feb 2019 [27 days])
The Safety Population included all participants who received at least 1 dose of study drug and had at least 1 postdose safety assessment.
|
7.1%
1/14 • Baseline through the end of study (up to clinical cut-off date 04 Feb 2019 [27 days])
The Safety Population included all participants who received at least 1 dose of study drug and had at least 1 postdose safety assessment.
|
|
Nervous system disorders
Parosmia
|
7.1%
1/14 • Baseline through the end of study (up to clinical cut-off date 04 Feb 2019 [27 days])
The Safety Population included all participants who received at least 1 dose of study drug and had at least 1 postdose safety assessment.
|
0.00%
0/14 • Baseline through the end of study (up to clinical cut-off date 04 Feb 2019 [27 days])
The Safety Population included all participants who received at least 1 dose of study drug and had at least 1 postdose safety assessment.
|
|
Gastrointestinal disorders
Paraesthesia oral
|
14.3%
2/14 • Baseline through the end of study (up to clinical cut-off date 04 Feb 2019 [27 days])
The Safety Population included all participants who received at least 1 dose of study drug and had at least 1 postdose safety assessment.
|
0.00%
0/14 • Baseline through the end of study (up to clinical cut-off date 04 Feb 2019 [27 days])
The Safety Population included all participants who received at least 1 dose of study drug and had at least 1 postdose safety assessment.
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/14 • Baseline through the end of study (up to clinical cut-off date 04 Feb 2019 [27 days])
The Safety Population included all participants who received at least 1 dose of study drug and had at least 1 postdose safety assessment.
|
7.1%
1/14 • Baseline through the end of study (up to clinical cut-off date 04 Feb 2019 [27 days])
The Safety Population included all participants who received at least 1 dose of study drug and had at least 1 postdose safety assessment.
|
|
Gastrointestinal disorders
Nausea
|
7.1%
1/14 • Baseline through the end of study (up to clinical cut-off date 04 Feb 2019 [27 days])
The Safety Population included all participants who received at least 1 dose of study drug and had at least 1 postdose safety assessment.
|
0.00%
0/14 • Baseline through the end of study (up to clinical cut-off date 04 Feb 2019 [27 days])
The Safety Population included all participants who received at least 1 dose of study drug and had at least 1 postdose safety assessment.
|
|
General disorders
Fatigue
|
7.1%
1/14 • Baseline through the end of study (up to clinical cut-off date 04 Feb 2019 [27 days])
The Safety Population included all participants who received at least 1 dose of study drug and had at least 1 postdose safety assessment.
|
0.00%
0/14 • Baseline through the end of study (up to clinical cut-off date 04 Feb 2019 [27 days])
The Safety Population included all participants who received at least 1 dose of study drug and had at least 1 postdose safety assessment.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
7.1%
1/14 • Baseline through the end of study (up to clinical cut-off date 04 Feb 2019 [27 days])
The Safety Population included all participants who received at least 1 dose of study drug and had at least 1 postdose safety assessment.
|
0.00%
0/14 • Baseline through the end of study (up to clinical cut-off date 04 Feb 2019 [27 days])
The Safety Population included 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