Clinical trial · Interventional
A Study on the Effect of Vemurafenib on the Pharmacokinetics of a Single Dose of Tizanidine in Patients With BRAFV600 Mutation-Positive Metastatic Malignancies
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
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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).
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Malignant Melanoma, Neoplasms | Melanoma | ALIAS | 0.85 |
Interventions
Interventions (2)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Tizanidine | Drug | — | UNRESOLVED |
| Vemurafenib | Drug | Vemurafenib | ALIAS |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- Pharmacokinetic Population
- 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.
- interventionNames
- Drug: Tizanidine
- Drug: Vemurafenib
Primary outcomes (5)
- measure
- Pharmacokinetics of tizanidine under conditions of vemurafenib steady-state exposure: Area under the concentration-time curve (AUC)
- timeFrame
- Pre-dose and up to 12 hours post-dose
- measure
- Pharmacokinetics of tizanidine under conditions of vemurafenib steady-state exposure: Maximum plasma concentration (Cmax)
- timeFrame
- Pre-dose and up to 12 hours post-dose
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
- Maximum age
- 70 Years
Show eligibility criteria text
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
References
Publications (0)
Data not yet available