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

UCB

Status and phase: Completed; Phase 2

Conditions: Focal-Onset Seizures; Drug-resistant Epilepsy

Treatments: Other: Placebo; Drug: Padsevonil

Study type: Interventional

Funder types: Industry

Identifiers

NCT03373383

EP0091

2017-003200-48 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 411 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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411 participants in 5 patient groups, including a placebo group

Padsevonil dosing regimen 1

Experimental group

Description:

Subjects will be randomized to receive a combination of tablets of Padsevonil and Placebo (as appropriate) to maintain the blinding.

Treatment:

Drug: Padsevonil

Other: Placebo

Padsevonil dosing regimen 2

Experimental group

Description:

Subjects will be randomized to receive a combination of tablets of Padsevonil and Placebo (as appropriate) to maintain the blinding.

Treatment:

Drug: Padsevonil

Other: Placebo

Padsevonil dosing regimen 3

Experimental group

Description:

Subjects will be randomized to receive a combination of tablets of Padsevonil and Placebo (as appropriate) to maintain the blinding.

Treatment:

Drug: Padsevonil

Other: Placebo

Padsevonil dosing regimen 4

Experimental group

Description:

Subjects will be randomized to receive a combination of tablets of Padsevonil and Placebo (as appropriate) to maintain the blinding.

Treatment:

Drug: Padsevonil

Other: Placebo

Placebo

Placebo Comparator group

Description:

Subjects randomized to the placebo group will receive a combination of several Placebo tablets to maintain the blinding.

Treatment:

Other: Placebo