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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
23
Dabrafenib dosed at 150mg twice a day from Day 1 to the morning of Day 29
Rabeprazole dosed at 40mg each morning on Days 16 to 19
Rifampin dosed at 600mg each morning on Days 20 to 29
GSK Investigational Site
Goodyear, Arizona, United States
GSK Investigational Site
Dallas, Texas, United States
GSK Investigational Site
Tacoma, Washington, United States
GSK Investigational Site
Heidelberg, Victoria, Australia
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)
Time frame: 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)
Time frame: 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\[0-tau\])
Time frame: Day 15, 19 and Day 29
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
Time frame: Day 15, 19 and Day 29
PK assessment (AUC[0-tau]) of hydroxy-dabrafenib, carboxy-dabrafenib, and desmethyl-dabrafenib
Blood samples will be collected to assess PK parameter (AUC\[0-tau\]) after administration of Dabrafenib co-administered with rabeprazole or rifampin
Time frame: 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
Time frame: Day 15, 19 and Day 29
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GSK Investigational Site
Melbourne, Victoria, Australia
GSK Investigational Site
London, United Kingdom
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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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)
Time frame: 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
Time frame: 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
Time frame: Predose, 1, 2, 3 and 12 hours postdose on Day 29