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 - CaReS (Carisbamate Retention Study)

Phase 1

Conditions: Partial onset seizures
MedDRA version: 9.1Level: LLTClassification code 10034091Term: Partial seizures, simple

Registration Number: EUCTR2007-002929-78-FR

Lead Sponsor: Ortho-McNeil Janssen Scientific Affairs, LLC

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 89

Inclusion Criteria

1. Male or female aged 16 years or older
2. Subjects must weigh at least 45 kg (~100lbs)
3. Established diagnosis, for at least 3 months prior to screening, of partial onset seizures, including simple partial motor, complex partial, or secondarily generalized seizures
4. At least 1 partial onset seizure during the 3-month retrospective baseline period prior to screening
5. History of AED failure (due to lack of efficacy or tolerability) to at least 1 but not more than 4 AEDs in the past. The occasional use of rescue medication is not considered prior AED use
6. Current treatment with at least 1 and no more than 2 AEDs given at stable dosage(s) 30 days prior to screening. Additional infrequent (less than 3 days during the 3 month baseline) and occasional use of sedatives or benzodiazepines to prevent breakthrough seizures is permitted
7. 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
8. Negative urine drug screen (except for prescription benzodiazepines, prescription barbiturates, or prescription narcotics) at screening
9. Willing to adhere to the prohibitions and restrictions as specified in Section 4.4, Prohibitions and Restrictions
10. Must have signed an informed consent form document (subjects or their legally acceptable representatives) indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study. Assent is also required of adolescents as described in Section 16.2.3, Informed Consent. (Assent applies to adolescents only. Adults not competent to consent will not be allowed into the study.)
11. For adolescents (as defined by local regulations), a responsible person must be available to accompany the subject to the study center at each visit, to provide reliable information for the safety and efficacy evaluations, and to accurately and reliably dispense the study drug as directed, if in the opinion of the investigator, the subject cannot otherwise be compliant with study procedures and study drug

Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Have a generalized epileptic syndrome
2. Have primary generalized seizures
3. Have atonic seizures
4. Have typical or atypical absence seizures
5. Have only simple partial type seizures with manifestations other than motor symptoms (ie, simple partial sensory)
6. History of unprovoked status epilepticus in the last 6 months prior to screening
7. History of Lennox-Gastaut Syndrome
8. Failed, in the judgment of the investigator, an adequate treatment attempt (dose and duration) with TPM or LEV due to lack of efficacy or tolerability (or other medications with equivalent international nonproprietary names)
9. Currently (within the past 30 days prior to screening) taking TPM or LEV (or other medications with equivalent international non-proprietary names)
10. More than 3 days of sedative or benzodiazepine use for seizures in the 3 months prior to screening
11. 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
12. History of nephrolithiasis with symptomatic renal stones within the last 2 years prior to screening
13. Diagnosis of autism and/or pervasive developmental disability not otherwise specified (NOS) and/or mental retardation or evidence of an intelligence quotient (IQ) =70
14. ALT greater than 1.5 times the ULN or total bilirubin above the ULN at screening
15. History of drug-induced liver injury (ie, history of ALT elevation 3 times ULN from prior drug exposure) or severe drug-induced, hypersensitivity reactions
16. History of any medical conditions that could potentially disqualify the subject for medical or safety reasons (e.g., renal insufficiency; vascular, pulmonary, gastrointestinal, endocrine, hematologic, or metabolic disturbances)
17. Diagnosis of any form of chronic liver disease, cirrhosis, or liver cancer. Examples of chronic liver disease include autoimmune hepatitis, hemochromatosis, Wilson’s disease, primary biliary cirrhosis, sclerosing cholangitis
18. Positive hepatitis serology as determined by multiantigen enzyme immunoassay (EIA): includes Anti-HCV, HBsAg, Anti-HBc, HepBCoreM, and Anti-HBs. Subjects with positive Anti-HCV test results will be excluded from the study. Criteria for excluding subjects based on hepatitis B results are provided in Attachment 1
19. Known to be positive for human immunodeficiency virus/ acquired immunodeficiency syndrome (HIV/AIDS). Note: HIV testing is not required for this study
20. Clinically relevant abnormalities for laboratory test values at screening
21. History of experimental drug or medical device use within the 30 days prior to screening
22. History of prior exposure to CRS
23. Current treatment with a vagal nerve stimulator (VNS) or ketogenic diet
24. Planned epilepsy surgery within the next 12 months
25. Subjects who have a test score of less than 7 on the Non-Verbal Reasoning Test (NVRT) during visit 2, prior to randomization. Note: Such subjects may be retested once after 7 days if the investigator believes that the subject can read and comprehend instruction, is able to operate a computer mouse and a keyboard, and is assumed to have an IQ above 70.
26. Subjects with clinical evidence of significant cardiac disease, including unstable angina, myocardial infarction within the past 2 years, uncontrolled heart failure, congenital short QT syndrome, Brugada syndrome, major arrhythmias, or sig

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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