A Study on the Effect of Vemurafenib on the Pharmacokinetics of a Single Dose of Tizanidine in Patients With BRAFV600 Mutation-Positive Metastatic Malignancies

• Status: Completed
• Trial end date: 2014-08-26
• Target enrollment: 0
• Participant gender: All

Summary

This open-label, multicenter, 3-period, fixed-sequence study will evaluate the effect of multiple oral doses of vemurafenib on the pharmacokinetics of a single oral dose of tizanidine in participants with BRAFV600 mutation-positive metastatic malignancies. Participants will receive a single oral dose of tizanidine on Day 1, vemurafenib orally twice daily on Days 2 to 21, and tizanidine and vemurafenib on Day 22. Eligible participants will have the option to continue treatment with vemurafenib as part of an extension study (NCT01739764).

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Hoffmann-La Roche
• Treatments: Clonidine; Tizanidine; Vemurafenib

Criteria

Inclusion Criteria:

• Adults 18 to 70 years of age, inclusive

• Unresectable Stage IIIc or IV metastatic melanoma positive for the BRAFV600 mutation or other malignant tumor type which harbors a V600 activating mutation of BRAF, as determined by Cobas 4800 BRAFV600 Mutation Test or a DNA sequencing method

• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2

• Life expectancy greater than or equal to (>/=) 12 weeks

• Participant has not consumed tobacco or nicotine-containing products for 42 days prior to first dose of study drug, and must agree to refrain from such products while on study

• Adequate hematologic, renal and liver function

Exclusion Criteria:

• Prior treatment with vemurafenib or other BRAF inhibitor within 42 days of Day 1

• History of or current clinically significant cardiac or pulmonary dysfunction, including current uncontrolled Grade >/= 2 hypertension or unstable angina

• Current dyspnea at rest due to complications of advanced malignancy or any requirement for supplemental oxygen

• Active central nervous system lesions (participants with radiographically unstable, symptomatic lesions)

• Participants with CYP1A2 gene mutation (-3113G->A), either in one or two alleles

• Allergy or hypersensitivity to vemurafenib or tizanidine formulations

• Current severe uncontrolled systemic disease

• Inability or unwillingness to swallow pills

• History of malabsorption or other condition that would interfere with enteral absorption of study treatment

• History of clinically significant liver disease (including cirrhosis), current alcohol abuse, or human immunodeficiency (HIV) infection requiring antiretroviral treatment, acquired immune deficiency syndrome (AIDS)-related illness, or active hepatitis B or C

• Pregnant or breastfeeding women