A Study to Evaluate the Effect of ACT-709478 in Photosensitive Epilepsy Patients

Study Overview
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Brief Summary
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The main study objective is to assess the effect of ACT-709478 in male and female subjects with photosensitive epilepsy following single dose administration

Official Title
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A Phase 2a, Multi-center, Single-blind, Within-subject, Placebo-controlled Study to Assess the Pharmacodynamics of ACT-709478 in Subjects With Photosensitive Epilepsy

Conditions
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Photosensitive Epilepsy

Intervention / Treatment
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* Drug: ACT-709478 for oral use
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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 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 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ACT-709478 - Single dose administration<br>Up to 16 subjects with photosensitive epilepsy will be studied across a maximum of 4 dose levels. Each dose level will initially be investigated in cohorts of 4 subjects undergoing a fixed sequence of study treatment administration in fed condition | Drug: ACT-709478 for oral use<br>* Hard gelatin capsules for oral administration formulated at strengths of 10 mg and 100 mg<br>|
| Placebo Comparator: Placebo<br>Placebo will be administered on two study days | Drug: Placebo<br>* Matching placebo available as matching capsules for oral administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | From Day 2 to Day 10 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | From Day 2 to Day 10 | 
| 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 | From Day 2 to Day 10 | 
| 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 | From Day 2 to Day 10 | 
| Time to maximum SPR reduction |  | From Day 2 to Day 10 |