Pharmacokinetic Drug-drug Interaction Study of Encorafenib and Binimetinib on Probe Drugs in Patients With BRAF V600-mutant Melanoma or Other Advanced Solid Tumors

Phase 1 Completed 56 enrolled Pfizer Pierre Fabre Laboratories · collab

Non-randomizedSequentialOpen-labelTreatment

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.

Timeline

Start: 2018-01-02
Primary completion: 2022-07-11
Completion: 2023-05-29

Publications

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Bupropion	Small molecule	75 mg	Oral
Subject	Caffeine	Small molecule	50 mg	Oral
Subject	Dextromethorphan	Unknown	30 mg	Oral
Subject	Encorafenib	Small molecule	450 mg	Oral
Subject	Losartan	Other / unclassified	25 mg	Oral
Subject	Midazolam	Small molecule	2 mg	Oral
Subject	Modafinil	Small molecule	400 mg	Oral
Subject	Omeprazole	Other / unclassified	20 mg	Oral
Subject	Rosuvastatin	Small molecule	10 mg	Oral
Background	Binimetinib	Small molecule	45 mg	Oral

Pharmacokinetic Drug-drug Interaction Study of Encorafenib and Binimetinib on Probe Drugs in Patients With BRAF V600-mutant Melanoma or Other Advanced Solid Tumors

Summary

Timeline

Publications

Drugs

Indications