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)
- Conditions
- Partial onset seizuresMedDRA version: 9.1Level: LLTClassification code 10034091Term: Partial seizures, simple
- Registration Number
- EUCTR2007-002929-78-CZ
- 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
- 600
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 epilepsy characterized by partial onset seizures, including simple partial motor, complex partial, or secondarily generalized seizures
4. Must have had since the diagnosis of epilepsy and within the past 5 years a neuroimaging procedure, including a computed tomography (CT) scan or magnetic resonance imaging (MRI), that excluded a progressive neurologic disorder; these procedures may be performed within the 21-day screening phase (prior to
randomization)
5. At least 1 partial onset seizure, but no more than 120 partial seizures during the 3-month retrospective baseline period prior to screening despite adequate AED treatment
6. AED treatment with at least 1, and no more than 2, AEDs given at stable dosage(s) 30 days prior to screening, and throughout the double-blind phase.
7. History of AED treatment failure (due to lack of efficacy or tolerability) to at least 2 but not more than 4 AEDs in the past. Note: The current (baseline) AED treatment should be counted among the previous AED treatment failures.
- Treatment failure due to lack of efficacy is defined as persistence of seizures at the highest tolerated dose of at least one AED, excluding those cases in which the efficacy of a dose within usually effective range could not be assessed due to occurrence of an idiosyncratic adverse reaction.
- The occasional use of rescue medication is not considered prior AED use
8. 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.
9. Negative urine drug screen (except for prescription benzodiazepines, prescription barbiturates, or prescription narcotics) at screening
10. Willing to adhere to the prohibitions and restrictions as specified in Section 4.4, Prohibitions and Restrictions
11. Willing to allow the investigator (if not the treating physician) to contact the treating physician to discuss the subject’s participation in the trial. Subjects will only be eligible if the treating physician agrees that their participation is appropriate
12. 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.)
13. 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
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. Any previous and/or current treatment with TPM or LEV (or other medications with equivalent international non-proprietary names)
9. More than 3 days of sedative or benzodiazepine use to treat breakthrough seizures in the 3 months prior to screening. Note: The use of benzodiazepines as daily, stably dosed AED treatment is permitted and should be counted among baseline AEDs.
10. 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
11. History of nephrolithiasis with symptomatic renal stones within the last 2 years prior to screening
12. Diagnosis of autism and/or pervasive developmental disability not otherwise specified (NOS) and/or mental retardation or evidence of an intelligence quotient (IQ) =70
13. ALT greater than 1.5 times the ULN or total bilirubin above the ULN at screening
14. History of drug-induced liver injury (ie, history of ALT elevation 3 times ULN from prior drug exposure) or severe drug-induced, hypersensitivity reactions
15. History of Steven Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), a drug-related exfoliative rash, or any drug-related rash requiring hospitalization, or rash associated with an AED that involved conjunctiva or mucosa, or a maculopapular rash
that requires discontinuation of an AED.
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 participation in a clinical trial of CRS or any 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 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 significant shortening or lengthening of QTcF int
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