Phase 2
N=411
Study to Test the Efficacy and Safety of Padsevonil as Adjunctive Treatment of Focal-onset Seizures in Adults With Drug-resistant Epilepsy
Drug-resistant Epilepsy · Focal-Onset Seizures
Bottom Line
View on ClinicalTrials.gov: NCT03373383 ↗Enrolled (actual)
411
Serious AEs
3.0%
Results posted
Apr 2021
Primary outcome: Primary: Change in Log-transformed Observable Focal Onset Seizure Frequency From Baseline Over the 12 Week Maintenance Period — -0.27585; -0.46424; -0.48804; -0.48960 loge seizures per 28 days — p==0.102
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Padsevonil (Drug); Placebo (Other)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- UCB Biopharma S.P.R.L.
- Primary completion
- Jan 2020
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change in Log-transformed Observable Focal Onset Seizure Frequency From Baseline Over the 12 Week Maintenance Period |
-0.27585; -0.46424; -0.48804; -0.48960; -0.40831 | =0.102 |
| PRIMARY 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 |
78.3; 84.0; 80.7; 75.6; 92.6 | — |
| PRIMARY Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) Leading to Study Withdrawal |
8.4; 7.4; 12.0; 18.3; 25.9 | — |
| PRIMARY Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs) During the Entire Study |
4.8; 7.4; 4.8; 6.1; 6.2 | — |
| SECONDARY 75 % Responder Rate Over the 12 Week Maintenance Period |
6.2; 13.8; 12.2; 11.1; 16.0 | =0.081 |
| SECONDARY 50 % Responder Rate Over the 12 Week Maintenance Period |
21.0; 33.8; 31.7; 25.9; 32.1 | =0.045 sig |
| SECONDARY Percent Change in Observable Focal-onset Seizure Frequency From Baseline Over the 12 Week Maintenance Period |
12.49; 24.70; 25.25; 20.79; 15.79 | =0.316 |
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.
Eligibility 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
Data sourced from ClinicalTrials.gov (NCT03373383). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.