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

Study Overview
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Brief Summary
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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).

Official Title
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A Phase I, Open-Label, Multicenter, Three-Period, One-Sequence Study to Investigate the Effect of Rifampin on the Pharmacokinetics of a Single Oral Dose of 960 mg of Vemurafenib

Conditions
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Malignant Melanoma, Neoplasms

Intervention / Treatment
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* Drug: Rifampin
* Drug: Vemurafenib


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vemurafenib + Rifampin<br>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). | Drug: Rifampin<br>* Rifampin at a dose of 600 mg as capsules orally once daily will be administered from Days 8 through 23 (Periods B and C).<br>Drug: Vemurafenib<br>* Participants, after an overnight fast of at least 10 hours, will receive vemurafenib at a dose of 960 mg as film-coated tablets orally on Day 1 (Period A) and on Day 17 (Period C).<br>* Other names: RO5185426, Zelboraf;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Plasma Concentration Time-curve From Zero to the Last Measurable Concentration Time Point (AUClast) of Vemurafenib | 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). | 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) | 
| Area Under the Plasma Concentration Time-curve From Zero to Extrapolated Infinite Time (AUC[0-inf]) of Vemurafenib | 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. | 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) | 
| Maximum Observed Plasma Concentration (Cmax) of Vemurafenib | Cmax is the maximum observed plasma vemurafenib concentration, presented in microgram per milliliter (mcg/mL). | 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) |