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.

Sponsor

SK Life Science, Inc. (Industry)

Overall Status

Terminated

CT.gov ID

NCT00563459

Collaborator

(none)

Enrollment

Arms

Duration (Months)

Study Details

Study Description

Brief Summary

The purpose of this research study is to compare the long term effectiveness, safety and tolerability of carisbamate compared to two other frequently prescribed anti-epileptic drugs (AEDs) in patients with epilepsy.

Condition or Disease	Intervention/Treatment	Phase
Epilepsy Seizures	Drug: carisbamate Drug: topiramate Drug: levetiracetam	Phase 3

Detailed Description

Following a protocol amendment, this study resumed recruitment from April 10 to September 4, 2009. 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 siezures. 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.

Study Design

Study Type:

Interventional

Actual Enrollment :

89 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Nov 1, 2007

Actual Primary Completion Date :

Apr 1, 2010

Actual Study Completion Date :

Apr 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 001 carisbamate 400-1200 mg/day for 12 months	Drug: carisbamate 400-1200 mg/day for 12 months
Active Comparator: 002 topiramate 200-400mg/day for 12 months	Drug: topiramate 200-400mg/day for 12 months
Active Comparator: 003 levetiracetam 1000-3000mg/day for 12 months	Drug: levetiracetam 1000-3000mg/day for 12 months

Arm

Intervention/Treatment

Experimental: 001

carisbamate 400-1200 mg/day for 12 months

Drug: carisbamate

400-1200 mg/day for 12 months

Active Comparator: 002

topiramate 200-400mg/day for 12 months

Drug: topiramate

200-400mg/day for 12 months

Active Comparator: 003

levetiracetam 1000-3000mg/day for 12 months

Drug: levetiracetam

1000-3000mg/day for 12 months

Outcome Measures

Primary Outcome Measures

The primary efficacy endpoint is time from the first intake of study medication to discontinuation (all causes) of study medication during the 6 month core double-blind phase. [A six month period]

Secondary Outcome Measures

Cognitive side effect profiles of CRS and TPM [At 6 and 12 month periods]
Neuropsychiatric side effect profiles of CRS and LEV [At 6 and 12 month periods]
Reasons for discontinuation among the 3 treatment arms [At 6 and 12 month periods]
Seizures rates among the 3 treatment arms [At 6 and 12 month periods]
Subject reported mood states, behavioral and cognitive side effect changes among the 3 treatment arms [At 6 and 12 month periods]

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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 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 Criteria:

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
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 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.