| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10065336 |
| E.1.2 | Term | Partial epilepsy |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| STUDY 3013 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, for registration in the United States and the rest of the world (excluding the countries of Europe, Australia, New Zealand, and South Africa) · Responder rate from baseline relative to the entire double-blind treatment phase, for registration in the countries of Europe, Australia, New Zealand, and South Africa CARISEPY3014 To obtain long-term safety and tolerability data on subjects with partial onset seizures treated with open-label carisbamate |
|
| E.2.2 | Secondary objectives of the trial |
| · 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 determine 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 antiepileptic drugs (AEDs) will also be assessed. Overall safety and tolerability of carisbamate will be evaluated. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
| STUDY 3013 1 Male or female 16 years of age or older 2 Weight of at least 40 kg 3 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) 4 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 5 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) ·6 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) 7 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. 8 Have had at least 6 simple partial motor, complex partial, or secondarily generalized seizures per 56 days 9 Have not had ³100 simple partial motor, complex partial, or secondarily generalized seizures per 28 days 10 No seizure-free interval for more than 3 weeks STUDY 3014 ·1 Must have completed the 14-week double-blind treatment phase of study CARISEPY3013 · 2 Willing/able to follow the prohibitions and restrictions specified in this protocol ·3 Willing/able to complete the subject diaries correctly (subjects or legally acceptable representatives) ·4 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 open-label extension study CARISEPY3014 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. |
|
| E.4 | Principal exclusion criteria |
| STUDY 3013 · 1 History of status epilepticus or epilepsia partialis continua in the 6 months before study entry. 2· Have a generalized epileptic syndrome 3· Diagnosis of Lennox-Gastaut Syndrome 4· Currently experiencing seizures that cannot be counted accurately ·5 Have experienced rates of ³100 partial onset seizures in any monthly period in the 6 months before study entry ·6 History of any current or past nonepileptic seizures, including psychogenic seizures 7 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. 8 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) 9 Progressive neurologic disorder, such as a brain tumor, demyelinating disease, and degenerative CNS disease, or active CNS infection 10 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 11 Exacerbation of Major Depressive Disorder within the past 6 months; antidepressant use is allowed 12 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 13 History of drug or alcohol abuse within the past year 14 Current treatment with vagus nerve stimulation (VNS) for 1 year or less duration 15 Planned epilepsy surgery within the next 6 months 16 Currently on a ketogenic diet 17 History of felbamate treatment within the past 3 months 18 Current treatment with vigabatrin. In the case of history of previous use of vigabatrin, a visual field examination must have been performed in the past after vigabatrin discontinuation. 19 History of prior exposure to carisbamate |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | Yes |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 44 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 0 |
| E.8.9.1 | In the Member State concerned months | 8 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 10 |
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