| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
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| 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 | 10015037 |
| E.1.2 | Term | Epilepsy |
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| 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 |
The objective of this study is to evaluate the efficacy and safety of oral LCM as first add-on treatment in subjects with uncontrolled partial-onset seizures with or without secondary generalization after treatment with first adequate AED monotherapy regimen, compared to subjects with uncontrolled partial-onset seizures with or without secondary generalization despite prior adequate treatment with at least 2 AEDs (concurrently or sequentially).
|
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| E.2.2 | Secondary objectives of the trial |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Subject is informed and given ample time and opportunity to think about his/her
participation and has given his/her written informed consent.
2. Subject is willing and able to comply with all study requirements.
3. Subject is male or female, at least 16 (EU and the rest of the world), 17 (US), or
18 (Mexico and Bulgaria) years of age.
4. Group 1: Subject has a diagnosis of epilepsy with simple partial seizures (motor
component) and/or complex partial seizures with or without secondary generalization
according to the International Classification of Epileptic Seizures (1981) (see
Section 16.1), and subject is currently taking a first adequate monotherapy (defined as a single AED for at least 28 days prior to Screening) and has no history of AED
polytherapy. Prior use of rescue medication (short-term intermittent use) is acceptable. Epilepsy diagnosis should be ≤24 months at the time of the Screening Visit. OR Group 2: Subject has a diagnosis of epilepsy with simple partial seizures (motor component) and/or complex partial seizures with or without secondary generalization according to the International Classification of Epileptic Seizures (1981) (see Section 16.1), is currently taking 1 to 3 AEDs, and has tried at least 2 prior AED treatment regimens (concurrently or sequentially). Epilepsy diagnosis should be ≥5 years at the time of the Screening Visit.
5. The minimum required seizure frequency during the 12 weeks prior to the Screening Visit is ≥1 partial-onset seizure (IA, IB, or IC) per 28 days (based on investigator assessment of subject report). In the case of simple partial seizures, only those with motor signs (IA1) will be counted towards meeting this inclusion criterion.
6.The maximum allowed seizure frequency during the 12 weeks prior to the Screening Visit is 140 partial-onset seizures with motor and/or non-motor component per 28 days (based on investigator assessment of subject report).
7. Subject must be able to provide documented evidence of seizure count for the 4 weeks prior to the Screening Visit.
8. Subject has been maintained on a stable dose regimen of AED(s) for at least 28 days prior to Visit 1 and during the Screening Phase with or without additional concurrent stable VNS. The VNS must have been in place for at least 6 months prior to the Screening Visit with constant settings for at least 28 days prior to Visit 1 and during the Screening Phase. |
|
| E.4 | Principal exclusion criteria |
Subject : 1)has previously participated in this study or subject has previously been assigned to treatment in a LCM study or received treatment with LCM. 2)is currently participating or has participated within the last 2 months in any study of an investigational drug or experimental device. 3)has a seizure disorder characterized
primarily by isolated auras (ie, simple partial seizures without observable motor signs). 4)has a history of primary generalized seizures. 5)has a history of status epilepticus within the 12-month period prior to Visit1. 6)has seizures that are uncountable due to clustering (ie, an episode lasting less than 30 minutes in which
several seizures occur with such frequency that the initiation and completion of each individual seizure cannot be distinguished) during the 12-week period prior to Visit 1.
7)has a current or previous diagnosis of pseudoseizures, conversion disorders, or
other nonepileptic ictal events which could be confused with seizures. 8)has any medical or psychiatric condition, which in the opinion of the investigator, could jeopardize the subject’s health or would compromise the subject’s ability to participate in this study. 9)has a history of suicide attempt, has received professional counseling for suicidal ideation, or is currently experiencing active suicidal ideation. 10)has a known hypersensitivity to any component of LCM as stated in Section7.1. 11) has a medical condition that could reasonably be expected to interfere with drug absorption, distribution, metabolism, or excretion. 12)has any history of alcohol or drug abuse within the previous 2 years. 13)has an acute or subacutely progressive central nervous system disease. 14)has a known history of severe anaphylactic reaction or serious blood dyscrasias. 15)has alanine amino-transferase (ALT), aspartate aminotransferase (AST), or total bilirubin levels ≥2x the upper limit of normal (ULN) or has alkaline phosphatase levels≥3x the ULN at Visit 1. 16)has impaired renal function (ie, creatinine clearance [CLcr] is lower than
30mL/min) at Visit 1. Creatinine clearance will be estimated as follows: Adult males: CLcr = (140-age) x weight in kg/(72 x serum creatinine in mg/dL) Adult females: CLcr = [(140-age) x weight in kg/(72 x serum creatinine in mg/dL)] x 0.85. 17)has a sick sinus syndrome without a pacemaker, or second or third degree atrioventricular
(AV) block. 18)has experienced a myocardial infarction in the last 3 months. 19)has New York Heart Association Class III or Class IV heart failure. 20)is pregnant or nursing and/or a woman of childbearing potential who is not surgically sterile, 2 years postmenopausal, or does not practice 2 combined methods of contraception
(unless sexually abstinent) for the duration of the study. 21)with concomitant treatment of felbamate or previous felbamate therapy within the last 6 months prior to study entry. 22)has taken vigabatrin in the preceding 6 months. (Note: A subject with a history of vigabatrin treatment must have had a visual perimetry test at least
6 months following conclusion of treatment. The results of the visual perimetry test must have shown either no damage or a visual field defect associated with 1 of the following 2 conditions:a) there was no change from a visual field test done at some point while the subject was taking vigabatrin, or b) there was no change from
a visual field test done shortly after stopping vigabatrin administration.).
23.Subject has undergone cranial surgery within the last year prior to study entry.
24.Subject has a known sodium channelopathy, such as Brugada syndrome. |
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| E.5 End points |
| E.5.1 | Primary end point(s) |
1. efficacy variables : the primary efficacy variable is the proportion of subjects who achieve "seizure-free status" (yes/no) during the firts 12 weeks of the Maintenance Phase
1.1 Seizure frequency and seizure type
1.2 Clinical Global impression of change (improvement or change in the subject's clinical status) & Patient's Global Impression of Change.
1.3 Quality of life Inventory in Epilepsy-31-P
2. safety variables :
2.1 Adverse events and serious adverse events
2.2 Laboratory measurements :
• hematology, •clinical chemistry(including liver function test),•uranalysis, •pregnancy
2.3 Other safety measurements :
• Physical and Neurological examination, •vital signs - body weight and height,
• 12-lead ECG |
|
| 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 | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| 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 | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| 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 | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| 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 | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 75 |
| 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 | No |
| 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
|
| The end of the study is defined as the date of the last visit of the last subject in the study. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 2 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 2 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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