A Pharmacokinetics (PK) Study to Investigate the Effect of Rifampin on PK of Vemurafenib (Zelboraf)

Phase 1

Completed

Brief Summary: This open-label, multi-center, three-period, one-sequence study will investigate the effect of rifampin on the PK of vemurafenib in participants with unresectable BRAFV600-mutation positive metastatic melanoma or other malignant tumor type that harbors a V600-activating mutation of BRAF without acceptable standard treatment options. Eligible participants will have the option to continue treatment with vemurafenib as part of an extension study GO28399 (NCT01739764).

Recruitment & Eligibility

Inclusion Criteria

Participants with either unresectable Stage IIIc or Stage IV metastatic melanoma positive for the BRAF V600 mutation or other malignant tumor type that harbors a V600-activating mutation of BRAF, as determined by results of cobas® 4800 BRAF V600 mutation test or a Deoxyribonucleic acid (DNA) sequencing method, and who have no acceptable standard treatment options
Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
Life expectancy of greater than or equal to (>/=) 12 weeks
Full recovery from the effects of any major surgery or significant traumatic injury within 14 days prior to the first dose of study treatment
Adequate hematologic and end organ function
Female participants of childbearing potential and male participants with partners of childbearing potential must agree to always use 2 effective methods of contraception
Negative serum pregnancy test within 7 days prior to commencement of dosing in women of childbearing potential

Exclusion Criteria

Prior treatment with vemurafenib or other BRAF inhibitor within 42 days of first dose of study drug
Requirement for immediate or urgent treatment with daily vemurafenib and for whom the intermittent schedule of vemurafenib employed during the 24-day period for this trial is not clinically acceptable
Allergy or hypersensitivity to components of the vemurafenib formulation
Experimental therapy within 4 weeks prior to first dose of study drug
Major surgical procedure or significant traumatic injury within 14 days prior to first dose of study drug, or anticipation of the need for major surgery during study treatment
Prior anti-cancer therapy within 28 days before the first dose of study drug
History of clinically significant cardiac or pulmonary dysfunction
History of symptomatic congestive heart failure of any New York Heart Association class or serious cardiac arrhythmia requiring treatment
History of myocardial infarction within 6 months prior to first dose of study drug
Current dyspnea at rest, owing to complications of advanced malignancy or any requirement for supplemental oxygen to perform activities of daily living
History of congenital long QT syndrome or corrected QT interval (QTc) greater than (>) 450 milliseconds
Active central nervous system lesions
Uncontrolled or poorly controlled diabetes
Current severe, uncontrolled systemic disease

Arm && Interventions

Group	Intervention	Description
Vemurafenib + Rifampin	Vemurafenib	There will be 3 intervention periods in the study: Period A (Days 1 to 7), Period B (Days 8 to 16), and Period C (Days 17 to 24). Participants, after an overnight fast of at least 10 hours, will receive vemurafenib at a dose of 960 milligrams (mg) as film-coated tablets orally alone on Day 1 (Period A); with rifampin (at a dose of 600 mg as capsules orally) on Day 17 (Period C); and rifampin alone at a dose of 600 mg as capsules orally once daily will be administered from Days 8 through 16 (Period B) and from Days 18 through 23 (Period C).
Vemurafenib + Rifampin	Rifampin	There will be 3 intervention periods in the study: Period A (Days 1 to 7), Period B (Days 8 to 16), and Period C (Days 17 to 24). Participants, after an overnight fast of at least 10 hours, will receive vemurafenib at a dose of 960 milligrams (mg) as film-coated tablets orally alone on Day 1 (Period A); with rifampin (at a dose of 600 mg as capsules orally) on Day 17 (Period C); and rifampin alone at a dose of 600 mg as capsules orally once daily will be administered from Days 8 through 16 (Period B) and from Days 18 through 23 (Period C).

Primary Outcome Measures

Name	Time	Method
Area Under the Plasma Concentration Time-curve From Zero to the Last Measurable Concentration Time Point (AUClast) of Vemurafenib	Predose (0 hour), 1, 2, 4, 6, 8, 12, 24, 30-32, 48, 72, 96, 120, 168 hours post vemurafenib-dose on Day 1 (Period A) and Day 17 (Period C)	AUClast is the area under the vemurafenib plasma concentration versus time curve from time zero to the time of last measured concentration of vemurafenib (Tlast). Area under the curve (AUC) is a measure of the plasma concentration of a drug over time. AUClast is presented in micrograms times (\) hour per milliliter (mcg\h/mL).
Area Under the Plasma Concentration Time-curve From Zero to Extrapolated Infinite Time (AUC[0-inf]) of Vemurafenib	Predose (0 hour), 1, 2, 4, 6, 8, 12, 24, 30-32, 48, 72, 96, 120, 168 hours post vemurafenib-dose on Day 1 (Period A) and Day 17 (Period C)	AUC(0-inf) is the AUC from time zero (pre-dose) to extrapolated infinite time (0-inf). AUC is a measure of the plasma concentration of a drug over time. AUC(0-inf) is presented in mcg\*h/mL.
Maximum Observed Plasma Concentration (Cmax) of Vemurafenib	Predose (0 hour), 1, 2, 4, 6, 8, 12, 24, 30-32, 48, 72, 96, 120, 168 hours post vemurafenib-dose on Day 1 (Period A) and Day 17 (Period C)	Cmax is the maximum observed plasma vemurafenib concentration, presented in microgram per milliliter (mcg/mL).

Secondary Outcome Measures

Name	Time	Method