A Study of the Effectiveness, Safety, and Tolerability of Carisbamate as Add-On Therapy in Patients With Partial Onset Seizures.

Sponsor

SK Life Science, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT00740623

Collaborator

(none)

547

Enrollment

Arms

14.9

Duration (Months)

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the effectiveness, safety, and tolerability of carisbamate as add-on therapy for the treatment of partial onset seizures in patients with epilepsy.

Condition or Disease	Intervention/Treatment	Phase
Epilepsy, Partial, Motor Epilepsy, Complex Partial Epilepsy, Simple Partial Focal Motor Epilepsy	Drug: Carisbamate Drug: placebo Drug: Carisbamate	Phase 3

Detailed Description

According to the World Health Organization (WHO), epilepsy afflicts more than 50 million people worldwide. Older antiepileptic drugs are still commonly used, despite a diverse range of side effects. New AEDs approved since the early 1990s have shown an improved tolerability profile. Nonetheless, approximately 30% of patients, particularly those with partial onset seizures, are not well controlled even on the newer treatments or they experience significant side effects secondary to treatment. Therefore, the development of new drugs with effectiveness or safety and tolerability advantages over currently marketed antiepileptic drugs is needed. This is a randomized (study medication assigned by chance), double-blind (neither the physician nor the patient knows the name of the assigned study medication), placebo-controlled, parallel-group, multicenter study. The study has 3 phases: an 8-week pretreatment phase including screening and a baseline period, a 14-week double blind treatment phase, including a 2-week titration period and a 12-week maintenance period, and a 4 week posttreatment phase. During the 56-day baseline period, patients will be required to have at least 6 partial onset seizures, no more than >= 100 partial onset seizures per 28 days, and no seizure-free period for more than 3 weeks to be eligible to enter the double-blind treatment phase of the study. During the double-blind treatment phase of study CARISEPY3013, patients will be randomly assigned to receive 800 mg/day carisbamate, 1,200 mg/day carisbamate, or placebo for 14 weeks. The total duration of study CARISEPY3013 is approximately 26 weeks for each subject. Patients who complete the double-blind treatment phase will be eligible to enter the separate extension study CARISEPY3014. Safety assessments include the monitoring of the frequency, severity, and timing of adverse events, clinical laboratory test results, 12-lead electrocardiogram (ECG) recordings, vital signs measurements, physical and neurologic examinations, the Physician Withdrawal Checklist for symptoms of withdrawal for those patients who taper and/or discontinue study drug, and pregnancy tests for females of childbearing potential. Assessments of effectiveness include seizure counts at every visit and the Quality of Life in Epilepsy-31 Patient Inventory questionnaire. A Medical Resource utilization questionnaire will be used to obtain cost-effectiveness information on carisbamate. The study hypothesis is that carisbamate is superior to placebo as add-on therapy (i.e., in addition to the current antiepileptic drugs that patients are taking) for the treatment of partial onset seizures in patients with epilepsy. Carisbamate 800 mg/day, 1,200 mg/day, or placebo taken twice daily in 2 equally divided doses, with or without food, and taken with noncarbonated water. A double-dummy design will be used so that all patients will take the same number of active drug and placebo tablets each day during the 14 weeks of the double blind treatment phase. Patients will continue to take a stable dosage or dosages of up to 3 antiepileptic drugs that they are already taking for their seizures during the entire study.

Study Design

Study Type:

Interventional

Actual Enrollment :

547 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter Study to Evaluate the Efficacy, Safety, and Tolerability of Carisbamate as Adjunctive Therapy in Subjects With Partial Onset Seizures.

Study Start Date :

Jan 1, 2009

Actual Primary Completion Date :

Oct 1, 2009

Actual Study Completion Date :

Apr 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 001 Carisbamate 800 mg/day for 14 weeks	Drug: Carisbamate 800 mg/day for 14 weeks
Experimental: 002 Carisbamate 1,200 mg/day for 14 weeks	Drug: Carisbamate 1,200 mg/day for 14 weeks
Placebo Comparator: 003 placebo for 14 weeks	Drug: placebo placebo for 14 weeks

Arm

Intervention/Treatment

Experimental: 001

Carisbamate 800 mg/day for 14 weeks

Drug: Carisbamate

800 mg/day for 14 weeks

Experimental: 002

Carisbamate 1,200 mg/day for 14 weeks

Drug: Carisbamate

1,200 mg/day for 14 weeks

Placebo Comparator: 003

placebo for 14 weeks

Drug: placebo

placebo for 14 weeks

Outcome Measures

Primary Outcome Measures

Primary efficacy endpoints are percent reduction in partial onset seizure frequency in the US and the rest of the world (excluding Europe, Australia, New Zealand, S Africa), and responder rate for Europe, Australia, New Zealand, S Africa [from baseline relative to the entire double-blind treatment phase (14 weeks)]

Secondary Outcome Measures

Secondary endpoints are percent reduction in partial onset seizure frequency for EuropeAustraliaNew Zealand S Africa, percent reduction in secondarily generalized seizure and time to onset of treatment effect on partial onset seizure frequency reduction [from baseline relative to the entire double-blind treatment phase (14 weeks)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Diagnosis of partial onset seizures
had a neuroimaging procedure (computed tomography [CT] or magnetic resonance imaging [MRI] within the past 5 years that excluded a progressive neurologic disorder
History of inadequate response to at least 1 antiepileptic drug
Current treatment with at least 1 and up to 3 antiepileptic drugs. To be eligible for the double-blind treatment phase of study CARISEPY3013, patients must: have at least 6 partial onset seizures during the 56-day baseline period
Have not had > = 100 partial onset seizures per 28 days in the baseline period
And no seizure-free period of more than 3 weeks during the baseline period.

Exclusion Criteria:

History of status epilepticus or epilepsia partialis continua in the 6 months before study entry
Have a generalized epileptic syndrome
have a diagnosis of Lennox-Gastaut Syndrome
Currently experiencing seizures that cannot be counted accurately
have experienced rates of > = 100 partial onset seizures in any monthly period in the 6 months before study entry
Have a history of any current or past nonepileptic seizures, including psychogenic seizures
History of or current serious or medically unstable systemic disease
evidence of cardiac disease, including unstable angina, myocardial infarction, within the past 2 years, uncontrolled heart failure, major arrhythmias, congenital short QT syndrome, or significant shortening or lengthening of the QTc interval of the electrocardiogram
progressive neurologic disorder, such as a brain tumor, demyelinating disease, and degenerative CNS disease, or active CNS infection
current or past (within the past year) major psychotic disorder
History of suicidal or homicidal ideation within the past 2 years, or an episode of suicide attempt or homicide at any time in the past.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

SK Life Science, Inc.

Investigators

Study Director: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial, Johnson & Johnson Pharmaceutical Research & Development, L.L.C.