The ARISE study is investigating whether Padsevonil—when taken with current anti-epileptic medicine—helps decrease the number of seizures patients with drug-resistant epilepsy experience. This study enrolls adults who are at least 18 years or older, have drug-resistant epilepsy that has not been controlled with four or more anti-epileptic drugs (AEDs), and are currently treated with between one and three AEDs. Patients have a 20% chance of receiving placebo; they have the opportunity to receive Padsevonil for another two years afterwards in an open-label extension study. The study is running in a total of 15 countries, including the US.
Eligibility Criteria:
Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
Sexes Eligible for Study: All
Accepts Healthy Volunteers: No
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
- History of status epilepticus or hospitalization for status epilepticus in the previous 6 months before study entry
- 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 1 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