Skip to main content
OpenTrials
Completed

NCT Number: NCT03373383

Study to Test the Efficacy and Safety of Padsevonil as Adjunctive Treatment of Focal-onset Seizures in Adults With Drug-resistant Epilepsy

The purpose of the study is to characterize the dose-response relationship with respect to efficacy of Padsevonil administered concomitantly with up to 3 anti-epileptic drugs (AEDs) for treatment of observable focal-onset seizures in subjects with drug-resistant epilepsy.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Drug-resistant Epilepsy Brain Diseases Central Nervous System Diseases Drug Resistant Epilepsy Epilepsy Focal-Onset Seizures Nervous System Diseases Neurologic Manifestations Pathological Conditions, Signs and Symptoms Seizures Signs and Symptoms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Ep0091 855, Box Hill, Australia

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Diagnosis of focal epilepsy per 1989 International League Against Epilepsy (ILAE) criteria at least 3 years before study entry
  • Subject has failed to achieve seizure control with 4 tolerated and appropriately chosen prior antiepileptic drugs (AED), including past and ongoing treatment, that were individually optimized for adequate dose and duration. Prior discontinued AED treatment would need to be assessed by the Investigator considering the patient medical records and patient and/or caregiver interview. 'Prior AED' is defined as all past and ongoing AED treatments with a start date before the Screening Visit (Visit 1)
  • Average of >= 4 spontaneous and observable focal seizures (type IA1 (i.e. focal aware), IB (i.e. focal impaired awareness), IC (i.e. focal to bilateral tonic-clonic)) per month
  • Current treatment with an individually optimized and stable dose of at least 1 and up to 3 AEDs for the 8 weeks prior to the Screening Visit with or without additional Vagus Nerve Stimulation (VNS) or other neurostimulation treatments

Exclusion criteria

  • Subject has a history of or signs of generalized or combined generalized and focal epilepsy
  • Cluster seizures which are uncountable in the previous 8 weeks before study entry and during 4 weeks prospective baseline
  • Current treatment with carbamazepine, phenytoin, primidone, phenobarbital
  • Current treatment/ use of (non-AED) prescription, nonprescription, dietary (eg, grapefruit or passion fruit), or herbal products that are potent inducers or inhibitors of the CYP3A4 or 2C19 pathway for 2 weeks (or 5 half-lives, whichever is longer) prior to the Baseline Visit
  • Subjects taking sensitive substrates of CYP2C19 for 2 weeks (or 5 half-lives, whichever is longer) prior to the Baseline Visit
  • Subject has been taking vigabatrin less than 2 years at study entry
  • Subject has been taking felbamate for less than 12 months
  • Subject taking retigabine for less than 4 years
  • Current treatment with benzodiazepines (i.e. GABA-A-ergic drugs like zolpidem, zaleplon, or zopiclone, excluding GABA-A-ergic AEDs) <3 times per week for emergencies
  • Subject has a current medical condition that occurred within the last 12 months which, in the opinion of the investigator, could compromise his/her safety or ability to participate in this study

Treatment and study plan

Padsevonil

Drug

Padsevonil in different dosages.

Placebo

Other

Placebo will be provided matching Padsevonil.

Primary outcomes

  1. Change in Log-transformed Observable Focal Onset Seizure Frequency From Baseline Over the 12 Week Maintenance Period

    Time frame: From Baseline over the 12 Week Maintenance Period

    During the study, participants kept diaries to record daily seizure activity. Seizure frequency refers to 28-day adjusted frequency. Seizure frequency was based on investigator assessment of participants' reports of daily seizure type and frequency. Observable focal-onset seizures refer to Type IA1, IB, and IC (ILAE Classification of Epileptic Seizures, 1981). Based on ANCOVA on change in log-transformed, 28-day adjusted seizure frequency from Baseline with treatment group as the main factor, Baseline log-transformed seizure frequency as a continuous covariate, Baseline SV2A use (yes or no) and Region (Europe, Non-Europe) as categorical factors.

  2. Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) Reported by the Subject and/or Caregiver or Observed by the Investigator During the Entire Study

    Time frame: From Baseline until Safety Follow-Up (up to Week 23)

    An Adverse Event is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment.

  3. Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) Leading to Study Withdrawal

    Time frame: From Baseline until Safety Follow-Up (up to Week 23)

    An Adverse Event is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment.

  4. Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs) During the Entire Study

    Time frame: From Baseline until Safety Follow-Up (up to Week 23)

    A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose:

    • Results in death
    • Is life-threatening
    • Requires in patient hospitalization or prolongation of existing hospitalization
    • Is a congenital anomaly or birth defect
    • Is an infection that requires treatment parenteral antibiotics
    • Other important medical events which based on medical or scientific judgement may jeopardize the patients, or may require medical or surgical intervention to prevent any of the above.

Secondary outcomes

  1. 75 % Responder Rate Over the 12 Week Maintenance Period

    Time frame: End of Maintenance Period (Week 16) following 3 Weeks of titration and 1 Week stabilization

    The 75% responder rate, where a responder is a participant experiencing a ≥75% reduction in observable focal-onset seizure frequency from Baseline, over the 12-Week Maintenance Period.

  2. 50 % Responder Rate Over the 12 Week Maintenance Period

    Time frame: End of Maintenance Period (Week 16) following 3 Weeks of titration and 1 Week stabilization

    The 50% responder rate, where a responder was a participant experiencing a ≥50% reduction in observable focal-onset seizure frequency from Baseline, over the 12-Week Maintenance Period.

  3. Percent Change in Observable Focal-onset Seizure Frequency From Baseline Over the 12 Week Maintenance Period

    Time frame: End of Maintenance Period (Week 16) following 3 Weeks of titration and 1 Week stabilization

    During the study, participants kept diaries to record daily seizure activity. The percentage of participants who experienced a 50 % or greater reduction in seizure frequency per 28 days relative to Baseline (responders) was assessed.

Sponsors and collaborators

Lead sponsor

UCB Biopharma S.P.R.L.

Industry

Registry information

Official study title

A Randomized, Double-Blind, Placebo-Controlled, Dose Finding Study to Evaluate the Efficacy and Safety of Padsevonil as Adjunctive Treatment of Focal-Onset Seizures in Adult Subjects With Drug-Resistant Epilepsy

Acronym: ARISE

Important dates

Study start
2018
Primary completion
2020
Study completion
2020
First posted
Dec 14, 2017
Registry last updated
Dec 19, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.