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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
411
Padsevonil in different dosages.
Placebo will be provided matching Padsevonil.
Change in Log-transformed Observable Focal Onset Seizure Frequency 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.
Time frame: From Baseline over the 12 Week Maintenance Period
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
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.
Time frame: From Baseline until Safety Follow-Up (up to Week 23)
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) Leading to Study Withdrawal
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.
Time frame: From Baseline until Safety Follow-Up (up to Week 23)
Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs) During the Entire Study
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.
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Ep0091 839
Chandler, Arizona, United States
Ep0091 810
Little Rock, Arkansas, United States
Ep0091 815
La Jolla, California, United States
Ep0091 801
San Francisco, California, United States
Ep0091 845
Washington D.C., District of Columbia, United States
Ep0091 809
Ocala, Florida, United States
Ep0091 823
Orlando, Florida, United States
Ep0091 825
Port Charlotte, Florida, United States
Ep0091 820
Tallahassee, Florida, United States
Ep0091 873
Atlanta, Georgia, United States
...and 138 more locations
Time frame: From Baseline until Safety Follow-Up (up to Week 23)
75 % Responder Rate Over the 12 Week Maintenance Period
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.
Time frame: End of Maintenance Period (Week 16) following 3 Weeks of titration and 1 Week stabilization
50 % Responder Rate Over the 12 Week Maintenance Period
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.
Time frame: End of Maintenance Period (Week 16) following 3 Weeks of titration and 1 Week stabilization
Percent Change in Observable Focal-onset Seizure Frequency From Baseline Over the 12 Week Maintenance Period
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.
Time frame: End of Maintenance Period (Week 16) following 3 Weeks of titration and 1 Week stabilization