This open-label, multicenter, parallel study will evaluate the effect of multiple doses of vemurafenib on the pharmacokinetics of a single dose of phenprocoumon in patients with BRAFV600 mutation-positive metastatic malignancies. Patients will be randomized to receive either treatment A: a single oral dose of phenprocoumon 6 mg on Day 1 (Eligible patients will have the option to continue treatment with vemurafenib as part of an extension study (NCT01739764).), or treatment B: vemurafenib 960 mg orally twice daily on Days 1-29 plus a single oral dose of phenprocoumon 6 mg on Day 22 (with the option to receive vemurafenib in the extension study after completion of pharmacokinetic assessments).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Masking
NONE
Enrollment
2
6 mg oral single dose
960 mg bid orally
Unnamed facility
Brussels, Belgium
Unnamed facility
Edegem, Belgium
Unnamed facility
Ghent, Belgium
Unnamed facility
Wilrijk, Belgium
Unnamed facility
Helsinki, Finland
Unnamed facility
Heidelberg, Germany
Unnamed facility
Mainz, Germany
Unnamed facility
Amsterdam, Netherlands
Unnamed facility
Maastricht, Netherlands
Unnamed facility
Utrecht, Netherlands
...and 7 more locations
Pharmacokinetics of single-dose phenprocoumon under conditions of vemurafenib steady-state exposure: Area under the concentration-time curve (AUC)
Time frame: Pre-dose and up to 168 hours post-dose
Pharmacokinetics of single-dose phenprocoumon under conditions of vemurafenib steady-state exposure: Maximum plasma concentration (Cmax)
Time frame: Pre-dose and up to 168 hours post-dose
Pharmacokinetics of single-dose phenprocoumon under conditions of vemurafenib steady-state exposure: Time to maximum plasma concentration (Tmax)
Time frame: Pre-dose and up to 168 hours post-dose
Pharmacokinetics of single-dose phenprocoumon under conditions of vemurafenib steady-state exposure: Terminal half-life (t1/2)
Time frame: Pre-dose and up to 168 hours post-dose
Pharmacokinetics of single-dose phenprocoumon under conditions of vemurafenib steady-state exposure: Apparent clearance (CL/F)
Time frame: Pre-dose and up to 168 hours post-dose
Safety: Incidence, nature and severity of adverse events (AEs) and serious AEs, graded according to NCI CTCAE Version 4.0
Time frame: approximately 1.5 years
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