Authors :
Pavel Klein, MD – Mid-Atlantic Epilepsy and Sleep Center, Bethesda, MD, USA
Nico Poppert, MD – Christian Doppler University Hospital, Paracelsus Medical University and Centre for Cognitive Neuroscience, Member of the European Reference Network EpiCARE
Aljoscha Thomschewski, PhD – Christian Doppler University Hospital, Paracelsus Medical University and Centre for Cognitive Neuroscience, Member of the European Reference Network EpiCARE
Sandra Lafenthaler, PhD – Christian Doppler University Hospital, Paracelsus Medical University and Centre for Cognitive Neuroscience, Member of the European Reference Network EpiCARE
Detlev Boison, PhD – Ruttgers University
Presenting Author: Matthias Koepp, MD PhD – UCL Queen Square Institute of Neurology/NHNN
Christine Lemke, PhD – PrevEp, Inc.
Wolfgang Löscher, PhD – 1Translational Epilepsy Research Group, Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine, Hannover, Germany
Alexander Rotenberg, MD, PhD – PrevEp, Inc.
Chris Rundfeldt, PhD – PrevEp, Inc.
Eugen Trinka, MD, MSc, FRCP – Christian Doppler University Hospital, Member of the European Reference Network EpiCARE, and Centre for Cognitive Neuroscience, Paracelsus Medical University, Salzburg, Austria
Rationale:
Currently available acute repetitive seizure rescue therapy includes only benzodiazepines, with potential for sedation, respiratory depression and addiction which restricts their repeated use. A non-sedating, fast-acting effective non-benzodiazepine medication is needed.
Seletracetam (SEL) is a levetiracetam analogue with~100- and~10 greater potency than levetiracetam and brivaracetam, respectively, developed by UCB pharma to Phase 2 clinical stage, with good efficacy and safety profiles.[1] PrevEp, Inc. has developed intranasal SEL for acute rescue therapy. Here, we report the first in human nasal spray administration of SEL to a patient with reflex reading epilepsy.
Methods:
A 42-year-old male with reading epilepsy, as described previously[2], suffering from predictable reading-induced focal aware seizures with oro-facial clicking sensation and from focal-to-bilateral tonic-clonic seizures with continued reading in the past, incompletely controlled with levetiracetam 3000mg daily, was treated with intranasal SEL at the Christian Dopper University Hospital Salzburg under the Austrian regulation of a “Named Patient Use” according to Article 83 of Regulation 726/2004/EC and § 8 Abs. 1 Z 2 Austrian Medicinal Products Act 2009. SEL was formulated for intranasal spray administration at a concentration of 200 mg/ml, and administered as 30 mg in 150 µl mucoadhesive aqueous nasal spray solution via a syringe with attached vaporizer [3].
Once a text was identified which provoked three unequivocal seizures, we administered first saline, then after the 3rd unequivocal seizure 30 mg nasal SEL. If reading-induced seizures still occurred after the 1st SEL dose, a 2nd dose of 30mg nasal SEL was administered. Magnetic encephalogram (MEG) was recorded continuously.
Results:
After saline treatment, the first reading-induced seizure occurred after 1:56 minutes of reading (Fig 1). After 30 mg SEL, seizure onset was delayed to 4:17 minutes. Following a second 30 mg dose, no further seizures occurred despite continuing to read the same material for a further 25 minutes. MEG spike frequency was 3.1/min during after saline, declining to 1.9/min after the first, and to 1.6/min after the second 30 mg SEL doses.
A mild transient bitter taste after the first SEL dose was the only adverse event, with no sedation.
Conclusions:
In this compassionate use case report, intranasal administration of a total of 60mg seletracetam fully prevented reflex seizures. A bitter taste after the first administration, but not the second, suggest that part of first 30mg dose was swallowed, and possibly explains that reading-induced seizures still occurred albeit with delayed onset and reduced spike-frequency. This case supports SEL’s potential as the first non-benzodiazepine acute seizure treatment.
Funding: PrevEp, Inc