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
Conditions:Skin Cancer
Therapuetic Areas:Oncology
Healthy:No
Age Range:18 - 70
Updated:4/21/2016
Start Date:September 2013
End Date:August 2014

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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

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).


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
We found this trial at
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Durham, NC
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Pleasant Hill, California 94522
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Rio de Janeiro,
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