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Abstract Details

Intra-nasal Seletracetam for Reading Epilepsy: A First in Human Proof-of-concept Case Study
Epilepsy/Clinical Neurophysiology (EEG)
P5 - Poster Session 5 (11:45 AM-12:45 PM)
11-001

To determine if  intranasal seletracetam treatment prevents seizures in a patient drug resistant reflex epilepsy.

Acute rescue therapy for repetitive seizures relies on benzodiazepines, whose sedation, respiratory depression, and addiction risks limit repeated use. A fast-acting, effective, non-sedating non-benzodiazepine is needed. Seletracetam (SEL), a levetiracetam analogue ~100-fold and ~10-fold more potent than levetiracetam and brivaracetam, respectively, showed favorable efficacy and safety to Phase 2 at UCB Pharma. PrevEp has developed intranasal SEL for acute rescue. We report the first human nasal-spray administration of SEL in reflex reading epilepsy.

A 42-year-old man with reading epilepsy, with predictable reading-induced focal aware seizures (orofacial clicking) and prior focal-to-bilateral tonic-clonic seizures during continued reading, inadequately controlled on levetiracetam 3000 mg/day, was treated under Austria’s “Named Patient Use” (Article 83, Regulation 726/2004/EC; §8 Abs.1 Z2, Medicinal Products Act 2009). SEL (200 mg/mL) was given as 30 mg in 150 µL mucoadhesive aqueous solution via a syringe-mounted vaporizer. After identifying text provoking three unequivocal seizures, saline was given first; after the third, 30 mg intranasal SEL was administered. If seizures persisted, a second 30 mg dose followed. Magnetoencephalography (MEG) was recorded continuously.

After saline, the first reading-induced seizure occurred at 1:56 (Figure 1). After 30 mg SEL, onset was delayed to 4:17. Following a second 30 mg dose, no further seizures occurred despite 25 additional minutes of reading. MEG spike frequency was 3.1/min after saline, decreasing to 1.9/min after the first and 1.6/min after the second 30 mg dose. The only adverse event was a mild transient bitter taste after the first dose; no sedation occurred.

In this compassionate-use case, 60 mg intranasal SEL fully prevented reflex seizures. Bitter taste after first, not second, dose suggests partial swallowing, explaining residual seizures and reduced spike frequency. Data support SEL’s potential as the first non-benzodiazepine acute seizure treatment.

Authors/Disclosures
Pavel Klein, MD, FAAN (Mid-atlantic Epilepsy and Sleep Center)
PRESENTER
The institution of Dr. Klein has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Aquestive. The institution of Dr. Klein has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Neurelis. The institution of Dr. Klein has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for UCB Pharma. The institution of Dr. Klein has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for SK Life Sience. The institution of Dr. Klein has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Eisai. The institution of Dr. Klein has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. The institution of Dr. Klein has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Alliance. The institution of Dr. Klein has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Arvelle Therapeutics. Dr. Klein has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Aquestive. Dr. Klein has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Eisai. Dr. Klein has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for UCB Pharma. Dr. Klein has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for SK Life Sciences. Dr. Klein has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Sunovion. Dr. Klein has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for PrevEp. Dr. Klein has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Fenwick . Dr. Klein has received research support from DOD/CURE.
Kai-Nicolas J. Poppert, MD (Christian-Doppler Klinik Salzburg) Dr. Poppert has stock in Eli Lilly. An immediate family member of Dr. Poppert has stock in Novo Nordisk.
Aljoscha Thomschewski, PhD The institution of Dr. Thomschewski has received research support from European Union.
Sandra Lafenthaler Dr. Lafenthaler has received research support from Austrian Alzheimer Society.
Matthias J. Koepp, MD, PhD Dr. Koepp has stock in PrevEp. The institution of Dr. Koepp has received research support from Wellcome Trust.
Christine Lemke, DVM Dr. Lemke has received personal compensation for serving as an employee of Absci GmbH. Dr. Lemke has received personal compensation in the range of $100,000-$499,999 for serving as an officer or member of the Board of Directors for Acousia Therapeutics GmbH. Dr. Lemke has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Melius Pharma AB. Dr. Lemke has stock in PrevEP Inc..
Wolfgang Löscher, PhD Prof. Löscher has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Lundbeck. Prof. Löscher has stock in PrevEp, Inc..
Chris Rundfeldt, PhD, Dr med vet Prof. Rundfeldt has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Multiple companies . Prof. Rundfeldt has stock in PrevEp, Inc. .
Eugen Trinka Eugen Trinka has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB. Eugen Trinka has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eisai. Eugen Trinka has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bial. Eugen Trinka has received personal compensation in the range of $500-$4,999 for serving as a Consultant for GW Pharmaceuticals. The institution of Eugen Trinka has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Rapport. The institution of Eugen Trinka has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbott. The institution of Eugen Trinka has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB. Eugen Trinka has received research support from European Union. Eugen Trinka has received publishing royalties from a publication relating to health care.