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This study aims to demonstrate similarities between two different forms of entrectinib (A and C) when administered under fasted conditions in healthy subjects.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Form A to Form C Crossover | Experimental | Participants first randomized to this arm will receive a single oral dose of entrectinib form A (reference form) under fasted conditions on Day 1 of each Period. This dose will be followed by a minimum 14-day washout period, after which participants will receive 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). |
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| Form C to Form A Crossover | Experimental | Participants first randomized to this arm will receive a single oral dose of entrectinib form C (test form) under fasted conditions on Day 1 of each Period. This dose will be followed by a minimum 14-day washout period, after which participants will receive 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). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Entrectinib Form A | Drug | Participants will receive a single oral dose of entrectinib form A under fasted conditions. |
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| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Concentration-Time Curve (AUC0-t) of Entrectinib and M5 Metabolite | At pre-defined intervals from Hour 0 through Day 5 of each study Period (Periods 1 and 2 = 6 days) | |
| Maximum Observed Concentration (Cmax) of Entrectinib and M5 Metabolite | At pre-defined intervals from Hour 0 through Day 5 of each study 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 - Dallas | Dallas | Texas | 75247 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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). |
| 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 5, 2018 | Jan 27, 2020 |
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| Entrectinib Form C | Drug | Participants will receive a single oral dose of entrectinib form C under fasted conditions. |
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| Baseline through the end of study (up to clinical cut-off date 06 Feb 2019 [28 days]) |
| FG001 | 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). |
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| NOT COMPLETED |
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| Period 2 |
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| ID | Title | Description |
|---|---|---|
| BG000 | 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). |
| BG001 | 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). |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| 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 | ||||||||||||||||||||||||||||||
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| Primary | Area Under the Concentration-Time Curve (AUC0-t) of Entrectinib and M5 Metabolite | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | nmol*h/L | At pre-defined intervals from Hour 0 through Day 5 of each study Period (Periods 1 and 2 = 6 days) |
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| Primary | Maximum Observed Concentration (Cmax) of Entrectinib and M5 Metabolite | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | nmol/L | At pre-defined intervals from Hour 0 through Day 5 of each study 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 consisted of 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 06 Feb 2019 [28 days]) |
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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.
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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 | Form A Reference Formulation | 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). | 0 | 28 | 0 | 28 | 2 | 28 |
| EG001 | Form C Test Formulation | 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). | 0 | 28 | 0 | 28 | 0 | 28 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Arthropod bite | Injury, poisoning and procedural complications | MedDRA 21.1 | Non-systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Non-systematic Assessment |
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| Nasal congestion | Respiratory, thoracic and mediastinal 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 31, 2019 | Feb 25, 2020 | SAP_001.pdf |
| Male |
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| Black or African American |
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| Asian |
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| Multiple |
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| Not Hispanic or Latino |
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| Units | Counts |
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| Participants |
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