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The study is being conducted to evaluate the effect of rifampin (a strong CYP3A4 inducer) and rabeprazole (a pH elevating agent) on the PK of dabrafenib (a CYP3A4/CYP2C8 substrate). The study will be conducted in subjects with BRAF V600 mutation-positive tumors. Data collected from this study will be used to inform recommendations regarding use of concomitant medications with dabrafenib and future clinical pharmacologic evaluation of dabrafenib.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm A | Experimental | Subjects will administer Dabrafenib from Day 1 to Day 15, Dabrafenib and Rabeprazole from Day 16 to Day 19, Dabrafenib and Rifampin from Day 20 to Day 29. The serial PK samples will be collected for 12 hours following dosing on Day 15 (Dabrafenib alone), Day 19 (Dabrafenib and Rabeprazole), and Day 29 (Dabrafenib and Rifampin). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Dabrafenib 150 mg twice a day (BID) | Drug | Dabrafenib dosed at 150mg twice a day from Day 1 to the morning of Day 29 |
|
| Measure | Description | Time Frame |
|---|---|---|
| PK assessment (Cmax) of Dabrafenib with and without Rabeprazole or Rifampin | Blood samples will be collected to assess PK parameters including: maximum observed concentration (Cmax) | Day 15, 19 and Day 29 |
| PK assessment (tmax) of Dabrafenib with and without Rabeprazole or Rifampin | Blood samples will be collected to assess PK parameters including: time to Cmax (tmax) | Day 15, 19 and Day 29 |
| PK assessment (AUC[0-tau]) of Dabrafenib with and without Rabeprazole or Rifampin | Blood samples will be collected to assess PK parameters including: area under the concentration-time curve over the dosing interval (AUC[0-tau]) | Day 15, 19 and Day 29 |
| Measure | Description | Time Frame |
|---|---|---|
| PK assessment of Dabrafenib co administered with rabeprazole or rifampin | Blood samples will be collected to assess PK parameters including: Pre-dose concentration (Ctau) after administration of Dabrafenib co-administered with rabeprazole or rifampin | Day 15, 19 and Day 29 |
| PK assessment (AUC[0-tau]) of hydroxy-dabrafenib, carboxy-dabrafenib, and desmethyl-dabrafenib |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Goodyear | Arizona | 85338 | United States | ||
| GSK Investigational Site |
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| Label | URL |
|---|---|
| Results for study 200072 can be found on the GSK Clinical Study Register. | View source |
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| Rabeprazole 40 mg once daily (OD) | Drug | Rabeprazole dosed at 40mg each morning on Days 16 to 19 |
|
| Rifampin 600 mg OD | Drug | Rifampin dosed at 600mg each morning on Days 20 to 29 |
|
Blood samples will be collected to assess PK parameter (AUC[0-tau]) after administration of Dabrafenib co-administered with rabeprazole or rifampin |
| Day 15, 19 and Day 29 |
| PK assessment (Cmax and Ctau,) of hydroxy-dabrafenib, carboxy-dabrafenib, and desmethyl-dabrafenib | Blood samples will be collected to assess PK parameters including: Cmax and Ctau, after administration of Dabrafenib co-administered with rabeprazole or rifampin | Day 15, 19 and Day 29 |
| PK assessment (tmax) of hydroxy-dabrafenib, carboxy-dabrafenib, and desmethyl-dabrafenib | Blood samples will be collected to assess PK parameter (tmax), after administration of Dabrafenib co-administered with rabeprazole or rifampin | Day 15, 19 and Day 29 |
| Ratio of metabolite to Dabrafenib | Blood samples will be collected for AUC(0 tau) to estimate ratio of Dabrafenib metabolites to parent Dabrafenib co-administered with rabeprazole or rifampin | Day 15, 19 and Day 29 |
| Safety and tolerability assessment to measure vital signs | Safety and tolerability assessment for vital signs including systolic and diastolic blood pressure, temperature, and pulse rate for dabrafenib in combination with rabeprazole or rifampin | Day 15, 19 and Day 29 |
| Safety and tolerability assessment for 12-lead ECG | A single 12-lead ECG will be obtained to assess safety and tolerability of dabrafenib in combination with rabeprazole or rifampin | From Screening up to follow up visit within 7-10 days of the last dose of study medication |
| Safety and tolerability assessment for laboratory tests | Safety and tolerability assessment for clinical laboratory tests including hematology, clinical chemistry and other tests for dabrafenib in combination with rabeprazole or rifampin | From Screening up to follow up visit within 7-10 days of the last dose of study medication |
| Safety and tolerability assessment of dabrafenib in combination with rabeprazole or rifampin | Safety and tolerability assessment includes adverse events (AEs) and serious adverse events (SAEs) | From Screening up to follow up visit within 7-10 days of the last dose of study medication |
| Concentrations of Rabeprazole in the presence of Dabrafenib | Blood sample will be collected to measure concentration of Rabeprazole in the presence of Dabrafenib | Predose, 1, 2, 3 and 12 hours postdose on Day 19 |
| Concentrations of Rifampin in the presence of Dabrafenib | Blood sample will be collected to measure concentration of Rifampin in the presence of Dabrafenib | Predose, 1, 2, 3 and 12 hours postdose on Day 29 |
| Dallas |
| Texas |
| 75201 |
| United States |
| GSK Investigational Site | Tacoma | Washington | 98405 | United States |
| GSK Investigational Site | Heidelberg | Victoria | 3084 | Australia |
| GSK Investigational Site | Melbourne | Victoria | 3004 | Australia |
| GSK Investigational Site | London | W1G 6AD | United Kingdom |
| ID | Term |
|---|---|
| D009369 | Neoplasms |
| D008545 | Melanoma |
| ID | Term |
|---|---|
| D018358 | Neuroendocrine Tumors |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009380 | Neoplasms, Nerve Tissue |
| D018326 | Nevi and Melanomas |
| D012878 | Skin Neoplasms |
| D009371 | Neoplasms by Site |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
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| ID | Term |
|---|---|
| C561627 | dabrafenib |
| D064750 | Rabeprazole |
| D012293 | Rifampin |
| ID | Term |
|---|---|
| D053799 | 2-Pyridinylmethylsulfinylbenzimidazoles |
| D013454 | Sulfoxides |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D001562 | Benzimidazoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D012294 | Rifamycins |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D047029 | Lactams, Macrocyclic |
| D047028 | Macrocyclic Compounds |
| D011083 | Polycyclic Compounds |
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