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

Roche

Status and phase: Completed; Phase 1

Conditions: Malignant Melanoma, Neoplasms

Treatments: Drug: Tizanidine; Drug: Vemurafenib

Study type: Interventional

Funder types: Industry

Identifiers

NCT01844674

GO28396

2012-003705-94 (EudraCT Number)

Details and patient eligibility

About

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).

Enrollment: 18 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Other

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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18 participants in 1 patient group

Pharmacokinetic Population

Experimental group

Description:

All participants will receive a 3-period treatment including single-dose tizanidine on Day 1, twice-daily vemurafenib on Days 2 to 21, and both agents together on Day 22.

Treatment:

Drug: Tizanidine

Drug: Vemurafenib