E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Epilepsy
Partial Seizures |
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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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10015037 |
E.1.2 | Term | Epilepsy |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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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 |
First Period:
The primary objective was to evaluate the efficacy of Levetiracetam (LEV) dry syrup at doses up to a maximum of 60 mg/kg/day or 3000 mg/day used as an adjunctive therapy in Japanese pediatric subjects aged ≥4 to <16 years and with uncontrolled partial seizures despite treatment with 1 or 2 anti-epileptic drugs (AEDs).
Second Period:
To provide LEV treatment to subjects who were judged by the investigators to benefit
from long-term treatment and who are willing to continuously receive this drug and to continuously evaluate the safety of long-term administration of LEV at doses ranging from 20 mg/kg/day or 1000 mg/day to 60 mg/kg/day or 3000 mg/day in subjects who completed the First Period of this study.
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E.2.2 | Secondary objectives of the trial |
First Period:
The secondary objective was to evaluate the safety and pharmacokinetics of LEV dry syrup (up to 60 mg/kg/day or 3000 mg/day).
Second Period:
The secondary objective was to continuously evaluate the efficacy and pharmacokinetics of long-term administration of LEV at doses ranging from 20 mg/kg/day to 60 mg/kg/day or 1000 mg/day to 3000 mg/day in subjects who completed the First Period of this study.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- The patient has partial Epilepsy and the diagnosis must be confirmed in the last 6 months
- The patients must be on a stable 1 or 2 anti-epileptic drug(s) treatment during the 4 weeks prior to Baseline and must have at least 8 partial seizures during the 8-week prospective Baseline Period
- Patient at the age of 4 to 16 years, and at the body weight of 11 to 82 kg
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E.4 | Principal exclusion criteria |
- The patient has a treatable seizure etiology
- The patient has Epilepsy secondary to a progressive cerebral disease or any other progressively neurodegenerative disease, including Rasmussen and Landau-Kleffner diseases
- The patient has a history of status Epilepticus during the 3 months prior to Visit 1
- The patient has a past and present history of pseudo seizures
- The patient has a current diagnosis of Lennox-Gastaut syndrome
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E.5 End points |
E.5.1 | Primary end point(s) |
- Change From Baseline in Partial Seizure Frequency Per Week Over the 14-weeks Treatment Period
- Incidence of Treatment-Emergent Adverse Events (TEAEs) During the Second Period (up to Three Years Until the Time of Approval Granted)
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
- From Baseline (Week 0-8) to the 14-weeks Treatment Period (First Period: 4 weeks Up-titration (Week 8-12) and 10 weeks Evaluation (Week 12-22))
- During the Second Period from Visit 8 (Week 22) to the end of the Follow-up Period (up to three years until the time of approval granted)
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E.5.2 | Secondary end point(s) |
- Change From Baseline in Partial Seizure Frequency Per Week Over the 10-week Evaluation Period
- Partial Seizure Frequency Per Week Over the 14-weeks Treatment Period
- Partial Seizure Frequency Per Week Over the 10-weeks Evaluation Period
- Percentage of Partial Seizures 50 % Responders Over the 14-weeks Treatment Period
- Percentage of Partial Seizures 50 % Responders Over the 10-weeks Evaluation Period
- Number of Seizure-free Subjects Over the 14-weeks Treatment Period
- Number of Seizure-free Subjects Over the 10-weeks Evaluation Period
- Incidence of Treatment-emergent Adverse Drug Reactions (ADRs) During the Second Period (up to Three Years Until the Time of Approval Granted)
- Change From Baseline in Partial Seizure Frequency Per Week for the Second Period (up to Three Years From Informed Consent Until the Time of Approval Granted)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- From Baseline (Week 0-8) to the 10-weeks Evaluation Period (Part of the first Period: Week 12 to Week 22)
- 14-weeks Treatment Period (First Period: 4 weeks Up-titration (Week 8-12) and 10 weeks Evaluation (Week 12-22))
- During the second Period from Visit 8 (Week 22) to the end of the Follow-up Period (up to three years until the time of approval granted)
- From Baseline (Week 0-8) until the time of approval granted (up to three years from date of informed consent (Week 0); without 6-weeks Withdrawal Period)
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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 | No |
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 | Yes |
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.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA 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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 9 |