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| ID | Type | Description | Link |
|---|---|---|---|
| 2019-000783-15 | EudraCT Number |
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This study will evaluate the bioavailability, palatability, safety and tolerability of entrectinib in healthy volunteers. Part 1 of the study will explore the performance of entrectinib multi-particle formulation. Part 2 will evaluate the effect of drug substance particle size on entrectinib bioavailability.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part 1 | Experimental | Participants will be randomly assigned to one of the three treatment sequences (T1T2R, T2RT1, RT1T2). In each treatment sequences, participants will cross-over to three periods taking different formulations of entrectinib. Entrectinib will be administered as a single 600 milligram (mg) oral dose under fed condition in three different formulations. Test formulation 1 (T1): film-coated mini-tablet; Test formulation 2 (T2): film-coated mini-tablet; Reference formulation (R): hard capsule. |
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| Part 2 | Experimental | Participants will be randomly assigned to one of the two treatment sequences (TR, RT). In each treatment sequences, participants will cross-over to two periods taking different formulations of entrectinib. Entrectinib will be administered as a single 200 mg oral dose under fasted condition in two different formulations. Test formulation (T): hydroxypropyl methylcellulose (HPMC) capsule; Reference formulation (R): hard capsule. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Entrectinib 600 mg (T1) | Drug | Test formulation 1 (T1): Multi-particulate formulation 1: entrectinib film-coated mini-tablets |
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| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC0-inf) of Entrectinib | At pre-defined intervals from study Day 1 to Day 5 of each periods (each period=7 days) | |
| AUC0-inf of Entrectinib Active Metabolite M5 | At pre-defined intervals from study Day 1 to Day 5 of each periods (each period=7 days) | |
| Maximum Plasma Concentration (Cmax) of Entrectinib | At pre-defined intervals from study Day 1 to Day 5 of each periods (each period=7 days) | |
| Cmax of Entrectinib Active Metabolite M5 | At pre-defined intervals from study Day 1 to Day 5 of each periods (each period=7 days) |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) | An adverse event (AE) 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. Treatment-emergent adverse events (TEAEs) are AEs that were not present before the first dose of study drug or that were present before the first dose of study drug but worsened in intensity during exposure to study drug. |
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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 |
|---|---|---|---|---|---|---|
| Quotient Clinical Ltd, Clinical Research Unit | Nottingham | NG11 6JS | United Kingdom |
Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research\_and\_development/who\_we\_are\_how\_we\_work/clinical\_trials/our\_commitment\_to\_data\_sharing.htm).
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| ID | Title | Description |
|---|---|---|
| FG000 | Part 1 T1T2R Sequence | Participants were randomly assigned to one of the three treatment sequences (T1T2R, T2RT1, RT1T2). In each treatment sequences, participants crossed over to three periods (each period=7 days) taking different formulations of entrectinib. Entrectinib was administered as a single 600 milligram (mg) oral dose under fed condition in three different formulations. Test formulation 1 (T1): film-coated mini-tablet; Test formulation 2 (T2): film-coated mini-tablet; Reference formulation (R): hard capsule. The washout period between entrectinib doses was at least 14 days. |
| FG001 | Part 1 T2RT1 Sequence | Participants were randomly assigned to one of the three treatment sequences (T1T2R, T2RT1, RT1T2). In each treatment sequences, participants crossed over to three periods (each period=7 days) taking different formulations of entrectinib. Entrectinib was administered as a single 600 milligram (mg) oral dose under fed condition in three different formulations. Test formulation 1 (T1): film-coated mini-tablet; Test formulation 2 (T2): film-coated mini-tablet; Reference formulation (R): hard capsule. The washout period between entrectinib doses was at least 14 days. |
| FG002 | Part 1 RT1T2 Sequence | Participants were randomly assigned to one of the three treatment sequences (T1T2R, T2RT1, RT1T2). In each treatment sequences, participants crossed over to three periods (each period=7 days) taking different formulations of entrectinib. Entrectinib was administered as a single 600 milligram (mg) oral dose under fed condition in three different formulations. Test formulation 1 (T1): film-coated mini-tablet; Test formulation 2 (T2): film-coated mini-tablet; Reference formulation (R): hard capsule. The washout period between entrectinib doses was at least 14 days. |
| FG003 | Part 2 TR Sequence | Participants were randomly assigned to one of the two treatment sequences (TR, RT). In each treatment sequences, participants crossed over to two periods (each period=7 days) taking different formulations of entrectinib. Entrectinib was administered as a single 200 mg oral dose under fasted condition in two different formulations. Test formulation (T): hydroxypropyl methylcellulose (HPMC) capsule; Reference formulation (R): hard capsule. The washout period between entrectinib doses was at least 14 days. |
| FG004 | Part 2 RT Sequence | Participants were randomly assigned to one of the two treatment sequences (TR, RT). In each treatment sequences, participants crossed over to two periods (each period=7 days) taking different formulations of entrectinib. Entrectinib was administered as a single 200 mg oral dose under fasted condition in two different formulations. Test formulation (T): hydroxypropyl methylcellulose (HPMC) capsule; Reference formulation (R): hard capsule. The washout period between entrectinib doses was at least 14 days. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part 1 |
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| Part 2 |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Part 1 T1T2R Sequence | Participants were randomly assigned to one of the three treatment sequences (T1T2R, T2RT1, RT1T2). In each treatment sequences, participants crossed over to three periods (each period=7 days) taking different formulations of entrectinib. Entrectinib was administered as a single 600 milligram (mg) oral dose under fed condition in three different formulations. Test formulation 1 (T1): film-coated mini-tablet; Test formulation 2 (T2): film-coated mini-tablet; Reference formulation (R): hard capsule. The washout period between entrectinib doses was at least 14 days. |
| 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 |
| 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 From Time 0 to Infinity (AUC0-inf) of Entrectinib | The analysis population included all participants in Part 1 and Part 2, who received at least one dose of entrectinib. Only participants for whom data were collected are included in the analysis. | Posted | Geometric Mean | Geometric Coefficient of Variation | nmol*h/L | At pre-defined intervals from study Day 1 to Day 5 of each periods (each period=7 days) |
|
Day -1 through Day 5 of each period in both Part 1 and Part 2 (one period=7 days)
The analysis population included all participants in Part 1 and Part 2, who received at least one dose of entrectinib.
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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 | Part 1 T1/F15 (Test Formulation 1) | Participants who received a single oral dose of 600 mg (240 × 2.5 mg) entrectinib film-coated mini-tablets in each period (one period=7 days) sprinkled on to, and mixed with, one tablespoon (15 mL) of yoghurt within 30 minutes of consumption of a standardized light "pediatric" breakfast. The washout period between entrectinib doses was at least 14 days. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Constipation | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Communications | Hoffmann-La Roche | 800 821-8590 | genentech@druginfo.com |
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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 | Jul 11, 2019 | Aug 6, 2020 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jul 8, 2019 | Aug 6, 2020 | SAP_001.pdf |
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| ID | Term |
|---|---|
| C000607349 | entrectinib |
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| Entrectinib 600 mg (T2) | Drug | Test formulation 2 (T2): Multi-particulate formulation 2: entrectinib film-coated mini-tablets |
|
| Entrectinib 200 mg (R) | Drug | Reference formulation (R): entrectinib hard capsules |
|
| Entrectinib 200 mg (T) | Drug | Test formulation (T): entrectinib HPMC capsules |
|
| From Day -1 to Day 5 of each periods (each period=7 days) |
| COMPLETED |
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| NOT COMPLETED |
|
| BG001 | Part 1 T2RT1 Sequence | Participants were randomly assigned to one of the three treatment sequences (T1T2R, T2RT1, RT1T2). In each treatment sequences, participants crossed over to three periods (each period=7 days) taking different formulations of entrectinib. Entrectinib was administered as a single 600 milligram (mg) oral dose under fed condition in three different formulations. Test formulation 1 (T1): film-coated mini-tablet; Test formulation 2 (T2): film-coated mini-tablet; Reference formulation (R): hard capsule. The washout period between entrectinib doses was at least 14 days. |
| BG002 | Part 1 RT1T2 Sequence | Participants were randomly assigned to one of the three treatment sequences (T1T2R, T2RT1, RT1T2). In each treatment sequences, participants crossed over to three periods (each period=7 days) taking different formulations of entrectinib. Entrectinib was administered as a single 600 milligram (mg) oral dose under fed condition in three different formulations. Test formulation 1 (T1): film-coated mini-tablet; Test formulation 2 (T2): film-coated mini-tablet; Reference formulation (R): hard capsule. The washout period between entrectinib doses was at least 14 days. |
| BG003 | Part 2 TR Sequence | Participants were randomly assigned to one of the two treatment sequences (TR, RT). In each treatment sequences, participants crossed over to two periods (each period=7 days) taking different formulations of entrectinib. Entrectinib was administered as a single 200 mg oral dose under fasted condition in two different formulations. Test formulation (T): hydroxypropyl methylcellulose (HPMC) capsule; Reference formulation (R): hard capsule. The washout period between entrectinib doses was at least 14 days. |
| BG004 | Part 2 RT Sequence | Participants were randomly assigned to one of the two treatment sequences (TR, RT). In each treatment sequences, participants crossed over to two periods (each period=7 days) taking different formulations of entrectinib. Entrectinib was administered as a single 200 mg oral dose under fasted condition in two different formulations. Test formulation (T): hydroxypropyl methylcellulose (HPMC) capsule; Reference formulation (R): hard capsule. The washout period between entrectinib doses was at least 14 days. |
| BG005 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| OG001 |
| Part 1 T2/F16 (Test Formulation 2) |
Participants who received a single oral dose of 600 mg (240 × 2.5 mg) entrectinib film-coated mini-tablets in each period (one period=7 days) sprinkled on to, and mixed with, one tablespoon (15 mL) of yoghurt within 30 minutes of consumption of a standardized light "pediatric" breakfast. The washout period between entrectinib doses was at least 14 days. |
| OG002 | Part 1 R/F06 (Reference Formulation) | Participants who received a single oral dose of 600 mg (3 × 200 mg) entrectinib hard capsule in each period (one period=7 days) swallowed whole with approximately 240 mL of water within 30 minutes of consumption of a standardized light "pediatric" breakfast. The washout period between entrectinib doses was at least 14 days. |
| OG003 | Part 2 T/F06 Coarse (Test Formulation) | Participants who received a single oral dose of 1 x 200 mg entrectinib hydroxypropyl methylcellulose (HPMC) capsule in each period (one period=7 days) swallowed whole with approximately 240 mL of water after an overnight fast (minimum 8 hours). The washout period between entrectinib doses was at least 14 days. |
| OG004 | Part 2 R/F06 Fine (Reference Formulation) | Participants who received a single oral dose of 1 x 200 mg entrectinib hard capsule in each period (one period=7 days) swallowed whole with approximately 240 mL of water after an overnight fast (minimum 8 hours). The washout period between entrectinib doses was at least 14 days. |
|
|
| Primary | AUC0-inf of Entrectinib Active Metabolite M5 | The analysis population included all participants in Part 1 and Part 2, who received at least one dose of entrectinib. Only participants for whom data were collected are included in the analysis. | Posted | Geometric Mean | Geometric Coefficient of Variation | nmol*h/L | At pre-defined intervals from study Day 1 to Day 5 of each periods (each period=7 days) |
|
|
|
| Primary | Maximum Plasma Concentration (Cmax) of Entrectinib | The analysis population included all participants in Part 1 and Part 2, who received at least one dose of entrectinib. Only participants for whom data were collected are included in the analysis. | Posted | Geometric Mean | Geometric Coefficient of Variation | nmol/L | At pre-defined intervals from study Day 1 to Day 5 of each periods (each period=7 days) |
|
|
|
| Primary | Cmax of Entrectinib Active Metabolite M5 | The analysis population included all participants in Part 1 and Part 2, who received at least one dose of entrectinib. Only participants for whom data were collected are included in the analysis. | Posted | Geometric Mean | Geometric Coefficient of Variation | nmol/L | At pre-defined intervals from study Day 1 to Day 5 of each periods (each period=7 days) |
|
|
|
| Secondary | Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) | An adverse event (AE) 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. Treatment-emergent adverse events (TEAEs) are AEs that were not present before the first dose of study drug or that were present before the first dose of study drug but worsened in intensity during exposure to study drug. | The analysis population included all participants in Part 1 and Part 2, who received at least one dose of entrectinib. | Posted | Number | Percentage of Participants | From Day -1 to Day 5 of each periods (each period=7 days) |
|
|
|
| 0 |
| 15 |
| 0 |
| 15 |
| 15 |
| 15 |
| EG001 | Part 1 T2/F16 (Test Formulation 2) | Participants who received a single oral dose of 600 mg (240 × 2.5 mg) entrectinib film-coated mini-tablets in each period (one period=7 days) sprinkled on to, and mixed with, one tablespoon (15 mL) of yoghurt within 30 minutes of consumption of a standardized light "pediatric" breakfast. The washout period between entrectinib doses was at least 14 days. | 0 | 15 | 0 | 15 | 14 | 15 |
| EG002 | Part 1 R/F06 (Reference Formulation) | Participants who received a single oral dose of 600 mg (3 × 200 mg) entrectinib hard capsule in each period (one period=7 days) swallowed whole with approximately 240 mL of water within 30 minutes of consumption of a standardized light "pediatric" breakfast. The washout period between entrectinib doses was at least 14 days. | 0 | 15 | 0 | 15 | 15 | 15 |
| EG003 | Part 2 T/F06 Coarse (Test Formulation) | Participants who received a single oral dose of 1 x 200 mg entrectinib hydroxypropyl methylcellulose (HPMC) capsule in each period (one period=7 days) swallowed whole with approximately 240 mL of water after an overnight fast (minimum 8 hours). The washout period between entrectinib doses was at least 14 days. | 0 | 16 | 0 | 16 | 5 | 16 |
| EG004 | Part 2 R/F06 Fine (Reference Formulation) | Participants who received a single oral dose of 1 x 200 mg entrectinib hard capsule in each period (one period=7 days) swallowed whole with approximately 240 mL of water after an overnight fast (minimum 8 hours). The washout period between entrectinib doses was at least 14 days. | 0 | 16 | 0 | 16 | 6 | 16 |
| Diarrhoea | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
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| Hyperaesthesia teeth | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
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| Hypoaesthesia oral | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
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| Lip dry | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
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| Paraesthesia oral | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
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| Toothache | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 22.0 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 22.0 | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 22.0 | Systematic Assessment |
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| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 22.0 | Systematic Assessment |
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| Pain in jaw | Musculoskeletal and connective tissue disorders | MedDRA 22.0 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 22.0 | Systematic Assessment |
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| Dysgeusia | Nervous system disorders | MedDRA 22.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 22.0 | Systematic Assessment |
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| Paraesthesia | Nervous system disorders | MedDRA 22.0 | Systematic Assessment |
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| Somnolence | Nervous system disorders | MedDRA 22.0 | Systematic Assessment |
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| Taste disorder | Nervous system disorders | MedDRA 22.0 | Systematic Assessment |
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| Tension headache | Nervous system disorders | MedDRA 22.0 | Systematic Assessment |
|
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.