E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Refractory partial-onset seizures with or without secondary generalization |
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E.1.1.1 | Medical condition in easily understood language |
Study to examine if USL255 is effective in patients with refractory partial-onset seizures
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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 | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10056209 |
E.1.2 | Term | Partial seizures with secondary generalisation |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10040703 |
E.1.2 | Term | Simple partial seizures |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10034090 |
E.1.2 | Term | Partial seizures, complex |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10048674 |
E.1.2 | Term | Partial seizures with secondary generalization |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10010145 |
E.1.2 | Term | Complex partial seizures |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10034091 |
E.1.2 | Term | Partial seizures, simple |
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 |
To assess the efficacy of USL255 compared to placebo in subjects with refractory partial-onset seizures with or without secondary generalization. |
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E.2.2 | Secondary objectives of the trial |
To assess the safety of USL255 compared to placebo in subjects with refractory partial-onset seizures with or without secondary generalization. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Subject has a confirmed diagnosis of partial-onset seizures with or without secondary generalization for at least 12 months prior to Visit 1. The diagnosis of partial-onset seizures with or without secondary generalized seizure is defined by the ILAE commission in 1981.
•Currently on a stable dosing regimen of 1 to 3 AEDs for at least 4-weeks prior to Visit 1 (12 weeks for phenobarbital and primidone).
oNote: VNS can be counted as one of the AEDs provided the VNS has been in place for at least 6 months and on a stable setting for at least 1 month prior to Visit 1. The VNS settings must not change throughout the course of the study (baseline, titration, and maintenance phases).
oNote: Benzodiazepines (BZD) taken more than once per week, for any indication, will be counted as one of the AEDs.
•Male or female, aged 18 to 75 years, inclusive.
•Can safely be treated, in the opinion of the investigator, with topiramate
•Have a minimum of 8 partial-onset seizures and no more than 21 consecutive seizure free days, during the 8-week baseline.
oNote: Only simple partial seizures with motor signs, complex partial seizures, and partial seizures with secondary generalization are counted toward this inclusion.
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E.4 | Principal exclusion criteria |
•Have a predisposing condition or medications that may interfere with the absorption of USL255. For example, Crohn’s disease, ileostomy, short bowel syndrome, chronic diarrhea.
•Have a history of seizure episodes 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, within 3 months prior to Visit 1.
•Have a history of pseudoseizures, or status epilepticus, within 3 months prior to Visit 1.
•Have a history of metabolic acidosis, nephrolithiasis, ureterolithiasis, or narrow angle glaucoma.
•Have a history of suicidal attempts, suicidal ideation, or uncontrolled psychiatric illness within 2 years of Visit 1.
•Have taken topiramate within the past 6 months.
•History of lack of efficacy to topiramate, for epilepsy, despite adequate exposure (200mg/day)
•History of safety or tolerability issues to topiramate not related to dosage titration
•Currently taking, or have taken felbamate within the past 18 months, or have taken vigabatrin in the past.
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary efficacy end point:
•Percent reduction from baseline in weekly (7 day) partial-onset seizure frequency during the titration plus maintenance phase.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Seizure Diary Data will be used for analysis of the primary study endpoint. |
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E.5.2 | Secondary end point(s) |
Key Secondary Efficacy Endpoint
•Proportion of subjects with ≥50% reduction (responder rate) in weekly (7 day) partial-onset seizure frequency during the titration plus maintenance phase compared to baseline. (This could become a primary endpoint to meet country specific regulatory requirements for approval outside the United States.)
Other Secondary Efficacy Endpoints
•Proportions of subjects with ≥50% reduction (responder rate) in weekly (7 day) partial-onset seizure frequency during the titration and maintenance phases, separately.
•Percent reductions from baseline in weekly (7 day) partial-onset seizure frequency during the titration and maintenance phases, separately.
•Percent reduction from baseline in weekly (7 day) all seizure frequency during the titration plus maintenance phase.
•Proportions of subjects with ≥25%, ≥75%, and 100% reduction in weekly (7 day) partial-onset seizure frequency during the titration, maintenance and titration plus maintenance phases, separately. |
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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 | 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 | 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 | No |
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.8.2.4 | 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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
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 |
Argentina |
Australia |
Belgium |
Canada |
Chile |
Germany |
Greece |
India |
Israel |
New Zealand |
Poland |
Russian Federation |
South Africa |
Spain |
United States |
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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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Last Patient Last Visit defines the end of 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 | 10 |
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 | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |