Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Melanoma

Gastrointestinal Agents

All Drugs and Chemicals

Anti-Infective Agents

Antineoplastic Agents

Rabeprazole

Rifampin

Dabrafenib

Antacids

Anti-Ulcer Agents

Proton Pump Inhibitors

Enzyme Inhibitors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Antitubercular Agents

Protein Kinase Inhibitors

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).

Dabrafenib dosed at 150mg twice a day from Day 1 to the morning of Day 29

Dabrafenib 150 mg twice a day (BID)

Rabeprazole dosed at 40mg each morning on Days 16 to 19

Rabeprazole 40 mg once daily (OD)

Rifampin dosed at 600mg each morning on Days 20 to 29

Rifampin 600 mg OD

GSK Clinical Trials

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.

A Pharmacokinetics (PK) Study of the Effects Rabeprazole and Rifampin on Dabrafenib in Subjects With BRAF V600 Mutation Positive Tumors

An Open-label Study to Evaluate the Effects of a Potent CYP3A4 Inducer and the Effects of a pH Elevating Agent on the Repeat Dose Pharmacokinetics of Dabrafenib (GSK2118436) in Subjects With BRAF V600 Mutation Positive Tumors

Blood samples will be collected to assess PK parameters including: maximum observed concentration (Cmax)

Blood samples will be collected to assess PK parameters including: time to Cmax (tmax)

Blood samples will be collected to assess PK parameters including: area under the concentration-time curve over the dosing interval (AUC\[0-tau\])

Blood samples will be collected to assess PK parameters including: Pre-dose concentration (Ctau) after administration of Dabrafenib co-administered with rabeprazole or rifampin

Blood samples will be collected to assess PK parameter (AUC\[0-tau\]) after administration of Dabrafenib co-administered with rabeprazole or rifampin

Blood samples will be collected to assess PK parameters including: Cmax and Ctau, after administration of Dabrafenib co-administered with rabeprazole or rifampin

Blood samples will be collected to assess PK parameter (tmax), after administration of Dabrafenib co-administered with rabeprazole or rifampin

Blood samples will be collected for AUC(0 tau) to estimate ratio of Dabrafenib metabolites to parent Dabrafenib co-administered with rabeprazole or rifampin

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

A single 12-lead ECG will be obtained to assess safety and tolerability of dabrafenib in combination with rabeprazole or rifampin

Safety and tolerability assessment for clinical laboratory tests including hematology, clinical chemistry and other tests for dabrafenib in combination with rabeprazole or rifampin

Safety and tolerability assessment includes adverse events (AEs) and serious adverse events (SAEs)

Blood sample will be collected to measure concentration of Rabeprazole in the presence of Dabrafenib

Blood sample will be collected to measure concentration of Rifampin in the presence of Dabrafenib

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
A Pharmacokinetics (PK) Study of the Effects Rabeprazole and Rifampin on Dabrafenib in Subjects With BRAF V600 Mutation Positive Tumors	NCT01954043	Cancer	Dabrafenib 150 ... Rabeprazole 40 ... Rifampin 600 mg...	18 Years -	GlaxoSmithKline
A Pharmacokinetics (PK) Study of the Effects Rabeprazole and Rifampin on Dabrafenib in Subjects With BRAF V600 Mutation Positive Tumors	NCT01954043	Cancer	Dabrafenib 150 ... Rabeprazole 40 ... Rifampin 600 mg...	18 Years -	GlaxoSmithKline

Spots Global Cancer Trial Database for rifampin 600 mg od