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Trial record 1 of 1 for:    NCT03373383
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Study to Test the Efficacy and Safety of Padsevonil as Adjunctive Treatment of Focal-onset Seizures in Adults With Drug-resistant Epilepsy (ARISE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03373383
Recruitment Status : Completed
First Posted : December 14, 2017
Results First Posted : April 9, 2021
Last Update Posted : December 21, 2022
Sponsor:
Information provided by (Responsible Party):
UCB Pharma ( UCB Biopharma S.P.R.L. )

Study Description
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Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Drug-resistant Epilepsy Focal-Onset Seizures Drug: Padsevonil Other: Placebo Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 411 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : February 12, 2018
Actual Primary Completion Date : January 30, 2020
Actual Study Completion Date : January 30, 2020

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Padsevonil dosing regimen 1
Subjects will be randomized to receive a combination of tablets of Padsevonil and Placebo (as appropriate) to maintain the blinding.
 Drug: Padsevonil
Padsevonil in different dosages.

Other: Placebo
Placebo will be provided matching Padsevonil.
Experimental: Padsevonil dosing regimen 2
Subjects will be randomized to receive a combination of tablets of Padsevonil and Placebo (as appropriate) to maintain the blinding.
 Drug: Padsevonil
Padsevonil in different dosages.

Other: Placebo
Placebo will be provided matching Padsevonil.
Experimental: Padsevonil dosing regimen 3
Subjects will be randomized to receive a combination of tablets of Padsevonil and Placebo (as appropriate) to maintain the blinding.
 Drug: Padsevonil
Padsevonil in different dosages.

Other: Placebo
Placebo will be provided matching Padsevonil.
Experimental: Padsevonil dosing regimen 4
Subjects will be randomized to receive a combination of tablets of Padsevonil and Placebo (as appropriate) to maintain the blinding.
 Drug: Padsevonil
Padsevonil in different dosages.

Other: Placebo
Placebo will be provided matching Padsevonil.
Placebo Comparator: Placebo
Subjects randomized to the placebo group will receive a combination of several Placebo tablets to maintain the blinding.
 Other: Placebo
Placebo will be provided matching Padsevonil.


Outcome Measures
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Primary Outcome Measures :
  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 Outcome Measures :
  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.


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03373383


Locations
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Sponsors and Collaborators
UCB Biopharma S.P.R.L.
Investigators
Layout table for investigator information
Study Director: UCB Cares 001 844 599 2273 (UCB)
  Study Documents (Full-Text)

Documents provided by UCB Pharma ( UCB Biopharma S.P.R.L. ):
Study Protocol  [PDF] October 12, 2018
Statistical Analysis Plan  [PDF] February 12, 2020

More Information
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Publications of Results:

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Responsible Party: UCB Biopharma S.P.R.L.
ClinicalTrials.gov Identifier: NCT03373383    
Other Study ID Numbers: EP0091
2017-003200-48 ( EudraCT Number )
First Posted: December 14, 2017    Key Record Dates
Results First Posted: April 9, 2021
Last Update Posted: December 21, 2022
Last Verified: December 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Data from this trial may be requested by qualified researchers six months after product approval in the US and/or Europe, or global development is discontinued, and 18 months after trial completion. Investigators may request access to anonymized individual patient-level data and redacted trial documents which may include: analysis-ready datasets, study protocol, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.Vivli.org and a signed data sharing agreement will need to be executed. All documents are available in English only, for a prespecified time, typically 12 months, on a password protected portal. This plan may change if the risk of re-identifying trial participants is determined to be too high after the trial is completed; in this case and to protect participants, individual patient-level data would not be made available.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Time Frame: Data from this trial may be requested by qualified researchers six months after product approval in the US and/or Europe or global development is discontinued, and 18 months after trial completion.
Access Criteria: Qualified researchers may request access to anonymized IPD and redacted study documents which may include: raw datasets, analysis-ready datasets, study protocol, blank case report form, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.Vivli.org and a signed data sharing agreement will need to be executed. All documents are available in English only, for a pre-specified time, typically 12 months, on a password protected portal.
URL: http://www.Vivli.org

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by UCB Pharma ( UCB Biopharma S.P.R.L. ):
Epilepsy
Padsevonil
Additional relevant MeSH terms:
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Epilepsy
Seizures
Drug Resistant Epilepsy
Brain Diseases
Central Nervous System Diseases
 Nervous System Diseases
Neurologic Manifestations
Padsevonil
Anticonvulsants