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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| F1 to F06 Crossover | Experimental | 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). |
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| F06 to F1 Crossover | Experimental | 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). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Entrectinib Test Formulation (F1) | Drug | Participants will receive a single oral dose of entrectinib F1 after completion of a standardized meal. |
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| Measure | Description | Time Frame |
|---|---|---|
| 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. | At pre-defined intervals from study Day 1 through Day 5 of each Period (Periods 1 and 2 = 6 days) |
| 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. | At pre-defined intervals from study Day 1 through Day 5 of each Period (Periods 1 and 2 = 6 days) |
| 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. | At pre-defined intervals from study Day 1 through Day 5 of each Period (Periods 1 and 2 = 6 days) |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Hoffmann-La Roche | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Covance Research Unit - Daytona | Daytona Beach | Florida | 32117 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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). |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Period 1 |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Nov 2, 2018 | Jan 27, 2020 |
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| Entrectinib Reference Formulation (F06) | Drug | Participants will receive a single oral dose of entrectinib F06 after completion of a standardized meal. |
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| Baseline through the end of study (up to clinical cut-off date 04 Feb 2019 [27 days]) |
| FG001 | 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). |
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| NOT COMPLETED |
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| Period 2 |
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| ID | Title | Description |
|---|---|---|
| BG000 | 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). |
| BG001 | 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). |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | nmol*h/L | At pre-defined intervals from study Day 1 through Day 5 of each Period (Periods 1 and 2 = 6 days) |
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| Primary | 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. | The PK Population included all participants who received at least 1 dose of study drug and had at least 1 evaluable postdose PK sample. | Posted | Geometric Mean | Geometric Coefficient of Variation | nmol*h/L | At pre-defined intervals from study Day 1 through Day 5 of each Period (Periods 1 and 2 = 6 days) |
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| Primary | 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. | The PK Population included all participants who received at least 1 dose of study drug and had at least 1 evaluable postdose PK sample. | Posted | Geometric Mean | Geometric Coefficient of Variation | nmol/L | At pre-defined intervals from study Day 1 through Day 5 of each Period (Periods 1 and 2 = 6 days) |
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| Secondary | 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. | The Safety Population included all participants who received at least 1 dose of study drug and had at least 1 postdose safety assessment. | Posted | Number | Percentage of Participants | Baseline through the end of study (up to clinical cut-off date 04 Feb 2019 [27 days]) |
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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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | F1 Test Formulation | 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). | 0 | 14 | 0 | 14 | 4 | 14 |
| EG001 | F06 Reference Formulation | 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). | 0 | 14 | 0 | 14 | 3 | 14 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | MedDRA 21.1 | Non-systematic Assessment |
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| Paraesthesia | Nervous system disorders | MedDRA 21.1 | Non-systematic Assessment |
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| Cognitive disorder | Nervous system disorders | MedDRA 21.1 | Non-systematic Assessment |
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| Parosmia | Nervous system disorders | MedDRA 21.1 | Non-systematic Assessment |
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| Paraesthesia oral | Gastrointestinal disorders | MedDRA 21.1 | Non-systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | MedDRA 21.1 | Non-systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 21.1 | Non-systematic Assessment |
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| Fatigue | General disorders | MedDRA 21.1 | Non-systematic Assessment |
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| Decreased appetite | Metabolism and nutrition disorders | MedDRA 21.1 | Non-systematic Assessment |
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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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Communications | Hoffmann-La Roche | 800 821-8590 | genentech@druginfo.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jan 28, 2019 | Jan 27, 2020 | SAP_001.pdf |
| Male |
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| Black or African American |
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| Multiple |
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| Not Hispanic or Latino |
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