Pharmacokinetic Drug-drug Interaction Study of Encorafenib and Binimetinib on Probe Drugs in Patients With BRAF V600-mutant Melanoma or Other Advanced Solid Tumors
Pharmacokinetic Drug-drug Interaction Study of Encorafenib and Binimetinib on Probe Drugs in Patients With BRAF V600-mutant Melanoma or Other Advanced Solid Tumors
NCT ID: NCT03864042 Phase: PHASE1 Status: COMPLETED Enrollment: 56 Completion: 2023-05-29
Conditions
Advanced Solid Tumors, Metastatic Melanoma
Interventions
losartan, dextromethorphan, caffeine, omeprazole, midazolam, rosuvastatin, bupropion immediate release (IR), encorafenib, binimetinib, modafinil
Summary
This is an open-label, 3-arm, fixed-sequence study to evaluate the effect of single and multiple oral doses of encorafenib in combination with binimetinib on the single oral dose pharmacokinetics (PK) of cytochrome P450 (CYP) enzyme probe substrates using a probe cocktail, on an organic anion-transporting polypeptide/breast cancer resistance protein (OATP/BCRP) substrate using rosuvastatin and on a CYP2B6 substrate using bupropion. The effect of multiple oral doses of the moderate cytochrome P450 (CYP) inhibitor modafinil on encorafenib in combination with binimetinib will also be assessed. The study will have 2 treatment phases, a drug-drug interaction (DDI) phase followed by a post-DDI phase.
Primary Outcome
Maximum Concentration (Cmax) of Plasma Midazolam on Day -7, Day 1, and Day 14