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 |
Seizure disorder with sensitivity to light |
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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 |
• To assess the pharmacodynamics by means of the change in intermittent photic stimulation (IPS)-induced photoparoxysmal response (PPR) in male and female subjects with photosensitive epilepsy following single dose administration of ACT-709478. |
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E.2.2 | Secondary objectives of the trial |
• To assess single-dose pharmacokinetics of ACT-709478 in male and female subjects with photosensitive epilepsy • To correlate plasma concentrations of ACT-709478 with the PD effect on the photosensitive range of IPS-induced PPR in subjects with photosensitive epilepsy • To assess the safety and tolerability of a single dose of ACT-709478 in subjects with photosensitive epilepsy |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Signed informed consent in the local language prior to any study-mandated procedure • Male and female subjects aged between 18 and 60 years (inclusive) at screening • Photosensitive epilepsy and a generalized PPR in response to IPS of at least 4 units on a standardized photosensitive range (SPR) in at least 1 condition (eye closure, eyes closed, or eyes open) on 2 occasions at screening with at least 1 hour interval and reproducible on Day -1 (less than 3 units difference in SPR between screening and Day -1) • Healthy on the basis of physical examination, cardiovascular assessments and laboratory tests • Women of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test on Day -1. They must consistently and correctly use a reliable method of contraception with a failure rate of <1% per year, be sexually inactive, or have a vasectomized partner. Hormonal contraceptives must be initiated at least 1 month before first study treatment administration. |
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E.4 | Principal exclusion criteria |
• Lactating women • Known hypersensitivity to any of the excipients of the study treatment formulation • History or clinical evidence of any disease other than epilepsy and/or existence of any surgical or medical condition, which might interfere with the absorption, distribution, metabolism, or excretion of the study treatment (appendectomy and herniotomy allowed, cholecystectomy not allowed) • Relevant history of a suicide attempt or suicidal behavior. Any recent suicidal ideation within the last 6 months (categories 4 or 5), or any suicidal behavior within the last 2 years, except for “Non-Suicidal Self-Injurious Behavior” (item also included in the Suicidal Behavior section), as judged by the investigator using the Columbia-Suicide Severity Rating Scale (C-SSRS) at screening • History of status epilepticus during the last 12 months • History of non-epileptic seizures that cannot be differentiated from the participant’s epileptic seizures • History of generalized tonic-clonic seizures triggered by IPS • Previous history of repeated fainting, syncope, orthostatic hypotension, or vasovagal reactions in the past 5 years • Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol |
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E.5 End points |
E.5.1 | Primary end point(s) |
Individual evaluation of the response to intermittent photic stimulation. Positive response described as complete suppression of photoparoxysmal response (PPR) or a clinically relevant reduction in the standardized photosensitive range (SPR). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• Time to onset of positive response, defined by the first time point after ACT-709478 administration at which complete suppression of PPR or clinically relevant reduction in SPR is achieved; • Duration of positive response, defined as the time elapsed between the time point of onset of the positive response and the last time point of the positive response after ACT-709478 administration; • Maximum SPR reduction, defined as the largest reduction in SPR achieved at any time point compared to baseline during the positive response after ACT-709478 administration; • Time to maximum SPR reduction. |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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 |
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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 | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 9 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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 | 1 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |