Carisbamate Retention Study (CaReS): Comparative Study on the Long Term Effectiveness, Safety and Tolerability of Carisbamate Compared to Two Other Frequently Prescribed Anti-Epileptic Drugs (AEDs) in Patients With Epilepsy.
A Randomized, Double-Blind, Parallel-Group, Multicenter Study to Evaluate the Retention Rate, Efficacy, Safety, and Tolerability of Carisbamate, Topiramate and Levetiracetam as Adjunctive Therapy in Subjects With Partial Onset Seizures
Ortho-McNeil Janssen Scientific Affairs, LLC
600 participants
Nov 15, 2007
Interventional
Conditions
Summary
This study has resumed recruitment following a protocol amendment. This is a randomized, double-blind, parallel-group, active-comparator, multi-center study. The study consists of 5 phases: pretreatment (screening), double-blind titration phase, double blind maintenance phase, a transition phase, and an open-label phase. Patients who are not eligible or choose not to enter the transition and open-label phases of the study will complete an exit phase following double-blind treatment.The primary outcome variable is long term retention rate and safety of adjunctive therapy with carisbamate vs. topiramate and levetiracetam over a six month period. This primary endpoint is a clinically meaningful measure of efficacy, safety and tolerability over time, reflecting the therapeutic effectiveness of antiepileptic drugs (AEDs). Safety evaluations including adverse event monitoring, blood tests, and vital signs will be conducted throughout the study.The hypothesis is that the 3 study medications at a minimum will have similar treatment retention rates, but based on their distinct efficacy and side effect profiles, will have discernible differences in the rates of selected adverse events and reasons for treatment discontinuation in patients with partial onset seizures. Patients must be on at least 1, but not more than 2, baseline AEDs for 30 days prior to screening. By end of week 8 patients must have reached the following minimum dosages of study drug to be permitted to continue: carisbamate 400 mg/day, topiramate 200 mg/day, or levetiracetam 1000 mg/day. Double-blind phases last approximately 12 months. Carisbamate 800 mg/day, topiramate 300 mg/day and levetiracetam 2000mg/day will be administered orally in two equally divided doses.
Eligibility
Inclusion Criteria8
- Patients must weigh >= 45 kg (~100lbs)
- Established diagnosis, for at least 3 months prior to screening, of partial onset seizures, including simple partial motor, complex partial, or secondarily generalized seizures
- At least 1 but no more than 120 partial onset seizures during the 3-month retrospective baseline period prior to screening
- History of monotherapy Anti Epileptic Drug (AED) treatment failure at at least 1 but not more than 4 AEDs in the past
- Females must be postmenopausal for at least 2 years, surgically sterile, abstinent, or, if sexually active, practicing an acceptable method of birth control (eg, intrauterine device, double barrier method, male partner sterilization) before entry and throughout the study
- Females must have a negative serum beta chorionic gonadotropin pregnancy test result at screening/randomization
- Current AED treatment with at least 1 and no more than 2 AEDs given at a stable dose 30 days prior to screening
- For adolescents (as defined by local regulations), a responsible person must be available to accompany the patient to the study center at each visit, to provide reliable information for the safety and effectiveness evaluations, and to accurately and reliably dispense the study drug as directed, if required in the opinion of the investigator
Exclusion Criteria11
- Must not have a generalized epileptic syndrome, primary generalized seizures, atonic seizures, typical or atypical absence seizures nor only simple partial type seizures with manifestations other than motor symptoms (i.e, simple partial sensory)
- No history of unprovoked status epilepticus in the last 6 months prior to screening nor history of Lennox-Gastaut or West Syndrome
- More than 3 days of sedative or benzodiazepine use for seizures in the 3 months months prior to screening
- No clinical evidence of significant cardiac disease
- Alanine transaminase (ALT) > 1.5 times the upper limit of normal or total bilirubin above the upper limit of normal at screen
- No history of drug-induced liver injury, diagnosis of any form of chronic liver disease, cirrhosis, or liver cancer nor positive hepatitis serology as determined by multiantigen enzyme immunoassay (EIA)
- No past or current treatment with topiramate or levetiracetam for any reason
- No current use of vagal nerve stimulator
- No diagnosis of psychotic disorder, bipolar disease, or major depression or other neurologic conditions, serious or medically unstable systemic disease, suicidal ideation or attempts, or homicide attempts at any time in the past 2 years
- Unable to swallow solid oral dosage forms whole with the aid of water (patients may not chew, divide, dissolve, or crush the study drug)
- Anyone who falls under the precautions, warnings or contraindications outlined in the local topiramate and/or local levetiracetam package insert
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Interventions
carisbamate oral capsule, daily dose range 400mg to 1200mg in 2 equally divided daily doses for twelve months. Actual dose is determined by the investigator on a case by case basis depending on participant tolerability and efficacy. If the patient then enters the open label carisbamate phase, treatment will continue until registration in Australia.
Locations(19)
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ACTRN12609000600246