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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT01844674
Registration number
NCT01844674
Ethics application status
Date submitted
29/04/2013
Date registered
1/05/2013
Date last updated
20/03/2017
Titles & IDs
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
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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
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Secondary ID [1]
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2012-003705-94
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Secondary ID [2]
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GO28396
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Malignant Melanoma, Neoplasms
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Condition category
Condition code
Cancer
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Malignant melanoma
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - Tizanidine
Treatment: Drugs - Vemurafenib
Experimental: Pharmacokinetic Population - 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: Drugs: Tizanidine
Participants will receive tizanidine as single oral doses, 2 milligrams (mg) on Day 1 and repeated on Day 22, each following an overnight fast >/= 10 hours.
Treatment: Drugs: Vemurafenib
Participants will receive vemurafenib as multiple oral doses, 960 mg twice daily on Days 2 to 22.
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Pharmacokinetics of tizanidine under conditions of vemurafenib steady-state exposure: Area under the concentration-time curve (AUC)
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Assessment method [1]
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Timepoint [1]
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Pre-dose and up to 12 hours post-dose
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Primary outcome [2]
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Pharmacokinetics of tizanidine under conditions of vemurafenib steady-state exposure: Maximum plasma concentration (Cmax)
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Assessment method [2]
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Timepoint [2]
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Pre-dose and up to 12 hours post-dose
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Primary outcome [3]
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Pharmacokinetics of tizanidine under conditions of vemurafenib steady-state exposure: Time to maximum plasma concentration (Tmax)
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Assessment method [3]
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Timepoint [3]
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Pre-dose and up to 12 hours post-dose
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Primary outcome [4]
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Pharmacokinetics of tizanidine under conditions of vemurafenib steady-state exposure: Terminal half-life (t1/2)
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Assessment method [4]
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Timepoint [4]
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Pre-dose and up to 12 hours post-dose
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Primary outcome [5]
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Pharmacokinetics of tizanidine under conditions of vemurafenib steady-state exposure: Apparent clearance (CL/F)
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Assessment method [5]
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Timepoint [5]
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Pre-dose and up to 12 hours post-dose
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Secondary outcome [1]
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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
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Assessment method [1]
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Timepoint [1]
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Up to approximately 9 months
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Eligibility
Key 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
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Minimum age
18
Years
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Maximum age
70
Years
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key 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
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Study design
Purpose of the study
Other
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Allocation to intervention
N/A
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Single group
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Other design features
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Phase
Phase 1
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
2/09/2013
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
26/08/2014
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Sample size
Target
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Accrual to date
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Final
18
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Recruitment in Australia
Recruitment state(s)
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Recruitment outside Australia
Country [1]
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United States of America
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State/province [1]
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California
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Country [2]
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United States of America
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State/province [2]
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Michigan
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United States of America
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North Carolina
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Country [4]
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Brazil
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State/province [4]
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RJ
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Country [5]
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Brazil
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State/province [5]
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RS
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Country [6]
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Canada
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State/province [6]
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Quebec
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Country [7]
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Cyprus
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State/province [7]
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Nicosia
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Country [8]
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Korea, Republic of
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State/province [8]
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Seoul
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
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Name
Hoffmann-La Roche
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Address
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Ethics approval
Ethics application status
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Summary
Brief 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).
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Trial website
https://clinicaltrials.gov/ct2/show/NCT01844674
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Trial related presentations / publications
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Public notes
This record is viewable in the ANZCTR as it had previously listed Australia and/or New Zealand as a recruitment site, however these sites have since been removed
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Contacts
Principal investigator
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Address
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Hoffmann-La Roche
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Phone
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Fax
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Email
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Contact person for public queries
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Address
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Country
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Fax
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT01844674
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