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

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

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

Study Overview

• Status: Completed
• Conditions: Photosensitive Epilepsy
• Intervention / Treatment: Drug: ACT-709478 for oral use; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Le Kremlin-Bicêtre, France, 94275
    • HOSP - Bicêtre Neurologie
• Germany
  • Bielefeld, Germany, 33617
    • Bethel Epilepsy Center, Mara Hospital
  • Frankfurt, Germany, 60528
    • Epilepsy Center Frankfurt
  • Kehl, Germany, 77694
    • Epilepsiezentrum Kork
  • Radeberg, Germany, 01454
    • Kleinwachau, Sächsisches Epilepsiezentrum Radeberg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ACT-709478 - Single dose administration; 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; Hard gelatin capsules for oral administration formulated at strengths of 10 mg and 100 mg
Placebo Comparator: Placebo; Placebo will be administered on two study days	Drug: Placebo; Matching placebo available as matching capsules for oral administration

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Idorsia Pharmaceuticals Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): October 6, 2017
• Primary Completion (Actual): April 25, 2018
• Study Completion (Actual): April 25, 2018

Study Registration Dates

• First Submitted: August 2, 2017
• First Submitted That Met QC Criteria: August 2, 2017
• First Posted (Actual): August 4, 2017

Study Record Updates

• Last Update Posted (Actual): August 31, 2018
• Last Update Submitted That Met QC Criteria: August 30, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy; Epilepsy, Reflex; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; ACT-709478
• Other Study ID Numbers: AC-083-103

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No