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. - Full Text View

Sponsor:	Ortho-McNeil Janssen Scientific Affairs, LLC
Information provided by:	Ortho-McNeil Janssen Scientific Affairs, LLC
ClinicalTrials.gov Identifier:	NCT00563459

Purpose

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	Intervention	Phase
Epilepsy Seizures	Drug: carisbamate Drug: topiramate Drug: levetiracetam	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Single Group Assignment, Safety Study
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

Resource links provided by NLM:

Genetics Home Reference related topics: pyridoxal 5'-phosphate-dependent epilepsy pyridoxine-dependent epilepsy

MedlinePlus related topics: Epilepsy Seizures

Drug Information available for: Topiramate Levetiracetam Carisbamate

U.S. FDA Resources

Further study details as provided by Ortho-McNeil Janssen Scientific Affairs, LLC:

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. [ Time Frame: A six month period ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Cognitive side effect profiles of CRS and TPM [ Time Frame: At 6 and 12 month periods ] [ Designated as safety issue: No ]
Neuropsychiatric side effect profiles of CRS and LEV [ Time Frame: At 6 and 12 month periods ] [ Designated as safety issue: No ]
Reasons for discontinuation among the 3 treatment arms [ Time Frame: At 6 and 12 month periods ] [ Designated as safety issue: Yes ]
Seizures rates among the 3 treatment arms [ Time Frame: At 6 and 12 month periods ] [ Designated as safety issue: Yes ]
Subject reported mood states, behavioral and cognitive side effect changes among the 3 treatment arms [ Time Frame: At 6 and 12 month periods ] [ Designated as safety issue: No ]

Estimated Enrollment:	600
Estimated Study Completion Date:	December 2011
Estimated Primary Completion Date:	July 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
001: Experimental	Drug: carisbamate 400-1200 mg/day for 12 months
002: Active Comparator	Drug: topiramate 200-400mg/day for 12 months
003: Active Comparator	Drug: levetiracetam 1000-3000mg/day for 12 months

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.

Eligibility

Ages Eligible for Study:	16 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00563459

Show 187 Study Locations

Sponsors and Collaborators

Ortho-McNeil Janssen Scientific Affairs, LLC

Investigators

Study Director:

Ortho-McNeil Janssen Scientific Affairs, LLC Clinical Trial

Ortho-McNeil Janssen Scientific Affairs, LLC

More Information

No publications provided

Responsible Party:	Ortho-McNeil Janssen Scientific Affairs, LLC ( Vice President, Medical Affairs, CNS )
Study ID Numbers:	CR014317, Carisbamate Retention Study, CaReS, EudraCT # 2007-02929-78, CARISEPY3007
Study First Received:	November 21, 2007
Last Updated:	November 5, 2009
ClinicalTrials.gov Identifier:	NCT00563459 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by Ortho-McNeil Janssen Scientific Affairs, LLC:

Epilepsy, seizures
partial onset seizures
anti-epileptic drugs (AED)

carisbamate
topiramate
levetiracetam

Additional relevant MeSH terms:

Nootropic Agents
Physiological Effects of Drugs
Seizures
Nervous System Diseases
Central Nervous System Diseases
Brain Diseases
Protective Agents
Neuroprotective Agents
Pharmacologic Actions

Anti-Obesity Agents
Signs and Symptoms
Epilepsy
Therapeutic Uses
Neurologic Manifestations
Topiramate
Etiracetam
Central Nervous System Agents
Anticonvulsants

ClinicalTrials.gov processed this record on February 04, 2010