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

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT01844674
• Date of registration: 29/04/2013
• Prospective Registration: Yes
• Primary sponsor: Hoffmann-La Roche
• Public title: A Study on the Effect of Vemurafenib on the Pharmacokinetics of a Single Dose of Tizanidine in Patients With BRAFV600 Mutation-Positive Metastatic Malignancies
• Scientific title: A Phase I, Open-Label, Multicenter, 3- Period, Fixed-Sequence Study to Investigate the Effect of Vemurafenib on the Pharmacokinetics of a Single Dose of Tizanidine (a CYP1A2 Substrate) in Patients With BRAFV600 Mutation-Positive Metastatic Malignancy
• Date of first enrolment: September 2, 2013
• Target sample size: 18
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01844674
• Study type: Interventional
• Study design: Intervention model: Single Group Assignment. Primary purpose: Other. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

Argentina, Brazil, Canada, Cyprus, Korea, Republic of, United States

Contacts

• Name: Clinical Trials
• Affiliation: Hoffmann-La Roche

Key inclusion & exclusion 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



Age minimum: 18 Years
Age maximum: 70 Years
Gender: All

Health Condition(s) or Problem(s) studied

Malignant Melanoma, Neoplasms

Intervention(s)

Drug: Vemurafenib

Drug: Tizanidine

Primary Outcome(s)

Pharmacokinetics of tizanidine under conditions of vemurafenib steady-state exposure: Apparent clearance (CL/F) [Time Frame: Pre-dose and up to 12 hours post-dose]

Pharmacokinetics of tizanidine under conditions of vemurafenib steady-state exposure: Terminal half-life (t1/2) [Time Frame: Pre-dose and up to 12 hours post-dose]

Pharmacokinetics of tizanidine under conditions of vemurafenib steady-state exposure: Area under the concentration-time curve (AUC) [Time Frame: Pre-dose and up to 12 hours post-dose]

Pharmacokinetics of tizanidine under conditions of vemurafenib steady-state exposure: Maximum plasma concentration (Cmax) [Time Frame: Pre-dose and up to 12 hours post-dose]

Pharmacokinetics of tizanidine under conditions of vemurafenib steady-state exposure: Time to maximum plasma concentration (Tmax) [Time Frame: Pre-dose and up to 12 hours post-dose]

Secondary Outcome(s)

Safety: Incidence, nature and severity of adverse events and serious adverse events, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0 [Time Frame: Up to approximately 9 months]

Secondary ID(s)

2012-003705-94

GO28396

Source(s) of Monetary Support

Please refer to primary and secondary sponsors