E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Lennox–Gastaut syndrome (LGS) is a form of childhood-onset epilepsy. |
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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 | 13.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10048816 |
E.1.2 | Term | Lennox-Gastaut syndrome |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To compare the effect of 2 drug regimens consisting of either rufinamide or any other approved AED of the investigator’s choice as an add-on to the subject’s existing regimen of 1-3 AEDs on the overall safety and tolerability of rufinamide in subjects aged 1 to less than 4 years of age with inadequately controlled LGS
To characterize the age group specific pharmacokinetics of rufinamide in a pediatric population, 1 to less than 4 years of age, with inadequately controlled LGS, using
the population approach
To evaluate the effect of rufinamide as adjunctive treatment on the cognitive development and behavioral effects in a pediatric population, 1 to less than 4 years of age, with inadequately controlled LGS. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Age ≥ 1 and < 4 years
Clinical diagnosis of LGS at screening, which might include the presence of a slow background EEG rhythm, slow spikes-waves pattern (less than 3 Hz), the presence of polyspikes; care should be taken not to include benign myoclonic epilepsy of infancy, subjects with a diagnosis of atypical benign partial epilepsy (pseudo-Lennox syndrome), or continuous spike-waves of slow sleep (CSWS)
On a fixed dose of one to three concomitant regionally approved antiepileptic drugs (AEDs) for a minimum of 8 weeks prior to randomization with an inadequate response to treatment
Consistent seizure documentation (i.e., no uncertainty of the presence of seizures) and AED treatment documentation during the 8 week prerandomization period
Written informed consent provided by parent(s)/legal representative(s)
Are able to comply with all aspects of the protocol |
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E.4 | Principal exclusion criteria |
Familial short QT syndrome
Prior treatment with rufinamide
Evidence of clinically significant disease (e.g., cardiac, respiratory, gastrointestinal,
renal disease) that in the opinion of the investigator(s) could affect the subject’s safety or study conduct
Subject with hypersensivity to rufinamide and /or triazole or any of the excipients
Any history of or concomitant medical condition that, in the opinion of the
Investigator, would compromise the subject’s ability to safely complete the study
Scheduled for surgery during the projected course of the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary efficacy variable:
Change from baseline in CBCL Total Problems Score to the end of the 2-year (106 weeks) treatment period |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline to end of 2 year treatment period. Physical and neurological examinations (the latter only if possible) will be
performed at screening, baseline, Visits 3, 4, 5, 7, 10, 12, 13, 14, and follow up/final visit. |
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | 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 | 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 | Yes |
E.8.1.1 | Randomised | Yes |
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 | Yes |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Investigators Choice of Approved AED |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 14 |
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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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 | 1 |
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 | 1 |
E.8.9.2 | In all countries concerned by the trial days | 0 |