A study to test the efficacy and safety of padsevonil as treatment of focal-onset seizures in adult subjects with drug-resistant epilepsy
- Conditions
- Focal-Onset SeizuresMedDRA version: 21.1Level: LLTClassification code 10065337Term: Focal epilepsySystem Organ Class: 100000004852Therapeutic area: Diseases [C] - Nervous System Diseases [C10]
- Registration Number
- EUCTR2018-002303-33-BE
- Lead Sponsor
- CB Biopharma SR
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 625
- 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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 600
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 25
- 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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objective is to evaluate the efficacy of the 3 selected dose regimens of padsevonil (PSL) administered concomitantly with up to 3 anti-epileptic drugs (AEDs) compared with placebo for treatment of observable focal-onset seizures in subjects with drug-resistant epilepsy.<br>;Secondary Objective: The secondary objective is to assess the safety and tolerability of padsevonil (PSL) in relation to placebo.<br>;Primary end point(s): 1. 75% responder rate from Baseline over the 12-week Maintenance Period<br>2. Incidence of Treatment-Emergent Adverse Events (TEAEs)<br>3. Incidence of Treatment-Emergent Adverse Events (TEAEs) leading to study withdrawal<br>4. Incidence of treatment-emergent serious adverse events (SAEs)<br>;Timepoint(s) of evaluation of this end point: 1: From Baseline over the 12 Week Maintenance Period (up to Week 16)<br>2-4: From Baseline until Safety Follow-Up (up to Week 23)<br>
- Secondary Outcome Measures
Name Time Method Secondary end point(s): 1. Change in log-transformed observable focal-onset seizure frequency from Baseline over the 12-week Maintenance Period<br>2. 50% responder rate status, from Baseline, over the 12-week Maintenance Period<br>3. Percent reduction in observable focal-onset seizure frequency from Baseline over the 12-week Maintenance Period<br><br>;Timepoint(s) of evaluation of this end point: 1 - 3: From Baseline until Safety Follow-Up (up to Week 23)<br>