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, Followed by an Open-Label Extension Study

• Register: EUCTR
• Last refreshed on: 11 February 2013
• Main ID: EUCTR2008-005098-37-DE
• Date of registration: 26/09/2008
• Prospective Registration: Yes
• Primary sponsor: Janssen Cilag International, NV
• Public 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, Followed by an Open-Label Extension Study
• Scientific 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, Followed by an Open-Label Extension Study
• Date of first enrolment: 16/01/2009
• Target sample size: 600
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-005098-37
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Finland, Germany, Italy, Netherlands, Spain, Sweden

Key inclusion & exclusion criteria

Inclusion criteria:
-Male or female 16 years of age or older
-Weight of at least 40 kg
-Established diagnosis of partial onset seizures, including simple partial motor, complex partial, or secondarily generalized seizures, for at least 1 year using the International League Against Epilepsy (ILAE) criteria (ILAE 1989) Note: Seizures must be adequately classified as partial onset seizures.
-Must have had a neuroimaging procedure within 5 years, including a computed tomography (CT) scan or magnetic resonance imaging (MRI), that excluded a progressive neurologic disorder; these procedures may be performed within the 56-day baseline period
-History of inadequate response to at least 1 AED, administered at the appropriate dosage(s) and for a sufficient treatment period, based on the judgment of the investigator (subject may be currently treated with this therapy). Subjects with a history of 10 or more generalized seizures (of any type) per month should have exhibited inadequate response to at least 3 prior AEDs.
-Current treatment with at least 1 and up to 3 AEDs, administered at stable dosage(s) for at least 1 month before screening, and no new AEDs added for the previous 2 months; these AEDs must remain unchanged throughout the pretreatment and double-blind treatment phases (with the exception of dosage reductions of concomitant AEDs because of suspected elevated AED levels or side effects) Note: One-time changes in AED dosages do not represent a change in the daily AED regimen. For example, if the subject took an extra dose of an AED on one day, this would not represent a change in the daily AED regimen. Benzodiazepines received on a continuing basis at stable dosages for 1 month before screening should be considered as concomitant AEDs.
-Females must be: Postmenopausal (for at least 2 years), Surgically sterile (have had a hysterectomy or bilateral oophorectomy, tubal ligation, or otherwise be incapable of pregnancy), Abstinent (at the discretion of the investigator/per local regulations), or if sexually active, be practicing an effective method of birth control
-All women must have a negative urine pregnancy test at screening and at the time of randomization on Day 1.
-Negative urine drug screen (except for prescription benzodiazepines, prescription barbiturates, or prescription narcotics) at screening
-Negative urine alcohol test at screening
-Willing/able to follow the prohibitions and restrictions specified in this protocol
-Willing/able to complete the subject diaries correctly (subjects or legally acceptable representatives)
-Subjects (or their legally acceptable representatives) must have signed an informed consent form indicating that they understand the purpose of and the procedures required for the study and are willing to participate in this study. Assent is also required of adolescents capable of understanding the nature of the study, as described in the protocol. Note: Subjects with cognitive impairment may be enrolled in this study. The investigator will determine each subject’s capacity to provide informed consent. When cognitive impairment brings a subject’s capacity into question, the investigator will obtain informed consent and assent from the cognitively impaired subject, and consent from the legally acceptable representative(s) in accordance with all applicable local regulations.
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
Exclusion criteria:
-History of status epilepticus or epilepsia partialis continua in the 6 months before study entry. Status epilepticus is defined as sequential seizures without full recovery of consciousness between seizures, or more than 30 minutes of continuous seizure activity
-Have a generalized epileptic syndrome
-Diagnosis of Lennox-Gastaut Syndrome
-Currently experiencing seizures that cannot be counted accurately, for example, because of the following reasons: Extreme frequency or clustering, Lack of clear onset and cessation between seizures, Lack of informant to provide a seizure count when the subject is unable to independently recall
-Have experienced rates of 100 or more partial onset seizures in any monthly period in the 6 months before study entry
-History of any current or past nonepileptic seizures, including psychogenic seizures
-History of or current serious or medically unstable systemic disease, including clinically apparent liver disease, renal insufficiency, a malignant neoplasm (except treated non-melanoma skin cancer), diabetes requiring insulin, or any disorder which in the judgment of the investigator will place the subject at excessive risk if participating in a controlled study.
-Clinical 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 QTcF (Fridericia’s correction) intervals (<330 ms or >500 ms)
-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, such as schizophrenia, bipolar disorder, or other psychotic conditions, recent (within the past 6 months) interictal psychosis, and Major Depressive Disorder with psychotic features
-Exacerbation of Major Depressive Disorder within the past 6 months; antidepressant use is allowed
-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
-History of drug or alcohol abuse within the past year
-Current treatment with vagus nerve stimulation (VNS) for 1 year or less duration
-Planned epilepsy surgery within the next 6 months
-Currently on a ketogenic diet


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Epilepsy
MedDRA version: 9.1 Level: LLT Classification code 10015037 Term: Epilepsy

Intervention(s)

Product Name: Carisbamate
Product Code: RWJ-333369
Pharmaceutical Form: Film-coated tablet
Current Sponsor code: RWJ-333369
Other descriptive name: Carisbamate
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 100-600
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: The primary objectives of this study are to compare the efficacy, safety, and tolerability of carisbamate as adjunctive treatment of partial onset seizures, relative to placebo, as measured by the:
-Percent reduction in partial onset seizure frequency from baseline relative to the entire double blind treatment phase.
-Responder rate from baseline relative to the entire double-blind treatment phase.

Primary end point(s): Responder rate:

The primary efficacy endpoint is the responder rate, the proportion of subjects with 50% reduction in partial onset seizure frequency (average seizure rate per 28 days of all simple partial motor, complex partial, or secondarily generalized seizures) from baseline relative to the entire double-blind treatment phase.

Secondary Objective: The secondary objectives of this study are:
-To evaluate the effect of carisbamate on percent reduction in partial onset seizure frequency from baseline relative to the entire double blind treatment phase for registration in the countries of Europe, Australia, New Zealand, and South Africa
-To evaluate the effect of carisbamate on percent reduction in secondarily generalized seizures from baseline relative to the entire double blind treatment phase
-To evaluate the time to onset of treatment effect of carisbamate on partial onset seizure frequency reduction
-To characterize the pharmacokinetics of carisbamate using a limited sampling strategy, in which all subjects will participate, followed by population pharmacokinetic (PK) analyses. The potential impact of carisbamate on the trough concentrations of select concomitant AEDs will also be assessed.

Overall safety and tolerability of carisbamate will be evaluated.

Secondary ID(s)

CARISEPY3013/3014

2008-005098-37-FI