E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
E2007 is given as adjunctive, long-term treatment in patients with refractory partial onset seizures with or without secondary generalization |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
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 primary objective for this study is to evaluate the safety and tolerability of E2007 given as adjunctive, long-term treatment in patients with refractory partial onset seizures with or without secondary generalization that completed the E2007-A001-206 or the E2007-G000-208 study.(revised per Amendments 04, A, and 06) |
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E.2.2 | Secondary objectives of the trial |
The secondary objective for this study is to evaluate the long-term maintenance of E2007 efficacy for the control of partial onset seizures by the change in partial seizure frequency from Baseline in the E2007-A001-206 or E2007-G000-208 studies to the last efficacy collecting visit of the E2007-A001-207 study. (revised per Amendments 02, 04, A and 07) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Provide written informed consent signed by the patient or legal guardian prior to entering the OLE study or undergoing any study procedures.
2. Have completed all scheduled visits up to and including Visit 8 in the E2007-A001-206 study or Visit 9 of the E2007-G000-208 study (revised per Amendment 04 and A).
3. Are reliable and willing to make themselves available for the study period and are able to record seizures and report adverse events themselves or have a caregiver who can record and report the events.
4. Male and female patients will be eligible for enrollment. Females of childbearing potential must continue practicing a medically acceptable method of contraception (eg, abstinence, a barrier method plus spermicide, or IUD) and for 8 weeks after the end of the study. (revised per Amendment 06) Those women using hormonal contraceptives must also continue using an additional approved method of contraception (eg, a barrier method plus spermicide, or IUD) starting with the Titration Phase and continuing throughout the entire study period (revised per Amendments 02 and 06).
5. Are between the ages of 18 and 70 years of age, inclusive.
6. Are at least 40 kg (88 lb) in weight (revised per amendment 06).
7. Are currently being treated with a stable dose of one, or a maximum of three, marketed and approved AEDs and are known to take their medication(s) as directed (revised per Amendment 04 and A). |
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E.4 | Principal exclusion criteria |
1. Show evidence of clinically significant disease (cardiac, respiratory, gastrointestinal, renal disease, etc.) that in the opinion of the Investigator(s) could affect the patient’s safety or trial conduct.
2. Show evidence of significant active hepatic disease and/or bilirubin > 1.5 mg/dL. Stable elevations of liver enzymes, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) due to concomitant medication(s) will be allowed if they are less than two times the upper limit of normal (ULN).
3. Show evidence of significant active hematological disease. White blood cell (WBC) count cannot be <= 2500/microliter (2.50 1E+09/L) or an absolute neutrophil count <= 1000/microliter (1.00 1E+09/L) (revised per Amendment 01).
4. Clinically significant ECG abnormality, including prolonged QTc (defined as >= 450 msec). (revised per Amendments 03, 04 and A).
5. Presence of major active psychiatric disease. Patients taking a stable dose of selective serotonin reuptake inhibitor (SSRI) antidepressant will be allowed (revised per Amendment 03). |
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety of open-label study population exposed to E2007 in partial epilepsy patients with refractory seizures with or without secondary generalization will be examined based on nature, frequency, and severity of adverse events, vital signs, physical and neurological examination findings, 12-lead ECG abnormalities and chemistry and hematology laboratory test results. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Titration phase, maintenance phase up to week, end of trial/early termination, follow-up phase and unscheduled visit. |
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E.5.2 | Secondary end point(s) |
Proportion of patients with reduction in partial seizure frequency and median percentage change in partial seizure frequency from the baseline phase to the last efficacy collecting visit will be summarized (revised per amendment 07). Highest tolerated dose given to patients using a flexible titration schedule will be assessed. Highest tolerated dose will be defined as the maximum dose at which a maximum of 20% of the patients experience dose limiting adverse events.
To better interpret the results, this self-selecting cohort of patients entering the OLE will be characterized. Demographic variables, median percentage in partial seizures, and percentage of patients with abnormal labs and SAEs will be compared between the patients continuing OLE and patients who stop the study after completing the E2007 A001-206 or the E2007- G000-208 studies (revised per Amendments 04 and A).
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Baseline to last efficacy collecting visit. |
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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 | Yes |
E.6.13.1 | Other scope of the trial description |
Note: efficacy data not collected following implementation of Am07 |
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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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 36 |
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 | No |
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 |
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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
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End of study will be defined as database lock to ensure that all data is collected, verified, and cleaned thoroughly following last patient visit. (added per Amendment 06). |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 9 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 9 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |