E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Focal Onset Seizures (FOS) |
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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 | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10016843 |
E.1.2 | Term | Focal seizures |
E.1.2 | System Organ Class | 100000004852 |
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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 primary objective for this study is to evaluate the long-term safety and tolerability of NBI-921352 in subjects with FOS. |
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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 |
• Provided informed consent. • Completed at least 11 weeks of treatment in Study NBI-921352-FOS2021. • Anticipated use of stable treatment with at least 1 but not more than 4 ASMs during the Blinded Dose Conversion Period and for the first week of the Open-Label Treatment Period or for subjects that do not enrol directly from NBI-921352-FOS2021, for at least 1 month before screening and through the first week of the Open-Label Treatment Period. • At least 4 weeks of daily seizure diary data collected prior to Day 1 for subjects who do not enrol directly from NBI-921352-FOS2021. • Female subjects of childbearing potential must agree to use contraception consistently from Day 1 until the final study visit or 30 days after the last dose of study treatment, whichever is longer. • Male subjects must agree to use effective barrier contraception consistently from Day 1 until 30 days after the last dose of study treatment. • Be able to keep accurate seizure diaries • Willing and able to comply with all study procedures and restrictions. |
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E.4 | Principal exclusion criteria |
Subjects will be excluded from the study if they meet any of the following criteria: • Pregnant or breastfeeding or planning to become pregnant during the study. • Have developed any other disorder for which the treatment takes priority over the treatment of FOS or is likely to interfere with study treatment or impair treatment compliance. • Anticipated that the subject will require treatment with at least 1 of the disallowed concomitant medications (Section 7.1.1) during the study. • Plan to use any investigational drug (other than the study treatment) during the study. • Any medical condition or personal circumstance that in the opinion of the investigator exposes the subject to unacceptable risk by participating in the study or prevents adherence to the protocol. • In the investigator’s opinion, the subject is not capable of adhering to the protocol requirements, including the requirement to travel to the study sites for study visits, or is unsuitable for any reason. • For subjects who do not enrol directly from NBI-921352FOS2021, the following additional criteria apply: - A known history of clinically concerning cardiac arrhythmia (including long QT syndrome) or prolongation of screening (pre-treatment) QT interval corrected for heart rate. - Any suicidal behaviour or suicidal ideation of type 4 (active suicidal ideation with some intent to act, without specific plan) or type 5 (active suicidal ideation with specific plan and intent) based on the C-SSRS in the 2 years before screening, a history of suicide attempt in the last 2 years, or more than 1 lifetime suicide attempt. - History of resective neurosurgery for seizures <1 year before enrollment, or radiosurgery <2 years before enrollment (exceptions apply) - An implanted responsive neurostimulator system (RNS) - A VNS or DBS implanted <5 months before screening or have settings that are not stable <3 months before screening - Past use of vigabatrin =12 months before screening. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The occurrence of serious treatment-emergent adverse events (TEAEs). |
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E.5.1.1 | 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) | 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 | 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.8.3 |
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 | 26 |
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 |
Australia |
Belgium |
Czechia |
France |
Hungary |
Italy |
Spain |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | Yes |
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 | 11 |
E.8.9.1 | In the Member State concerned days | 21 |
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 | 1 |
E.8.9.2 | In all countries concerned by the trial days | 12 |