Abstract Details

Title Safety and Tolerability of NRL-1, an Intranasal Formulation of Diazepam, in Subjects with Epilepsy in a Phase 1, Open-Label Study: Focus on Adverse Events Relevant to Clinicians and Patients

Topic Epilepsy/Clinical Neurophysiology (EEG)

Presentation(s) P3 - Poster Session 3 (12:00 PM-1:00 PM)

Poster/Presentation
Number 12-004

Objective To evaluate the tolerability of NRL-1 (Valtoco^®) with a focus on adverse events that are especially likely to be relevant to clinicians and patients.

Background NRL-1 (diazepam nasal spray formulated with Intravail A3) provides a rapid, non-invasive route of diazepam administration for individuals with epilepsy who experience seizure emergencies despite stable antiepileptic drug regimens.

Design/Methods

Patients were diagnosed with partial or generalized epilepsy with motor seizures or seizures with clear alteration of awareness. Open-label intranasal NRL-1 was administered during 2 periods (ictal/peri-ictal and inter-ictal) ≥14 days apart. In both periods, one dose was administered (5, 10, 15, or 20 mg; based on body weight). Safety and tolerability included treatment-emergent adverse events (TEAEs), clinical laboratory tests, vital signs, and electrocardiograms. AEs of relevance to clinicians and patients included nasal irritation and sedation, both measured using 6-point scales, and olfactory changes on the NIH Toolbox Odor Identification Test.

Results A total of 57 subjects (54.4% female; median age 31 years; 80.7% white) received ≥1 dose of NRL-1. Seventeen subjects (29.8%) reported TEAEs; none resulted in discontinuation, and there were no treatment-related serious TEAEs. Eight patients (14%) had treatment-related TEAEs, with those reported in ≥2 patients being dysgeusia (n=3; 5.3%) and nasal discomfort (n=2; 3.5%). The reports of nasal irritation were mild (score of 0 or 1A). There were no reported TEAEs of somnolence; sedation scores indicated small increases overall compared with baseline, with variability among the patients. No clinically significant abnormalities were noted for vital signs (eg, no changes in respiratory rate in the ictal/peri-ictal or inter-ictal period). Smell tests showed no clinically relevant olfactory changes.

Conclusions

NRL-1 was generally well tolerated. Adverse events of specific relevance to clinicians or patients were generally minor and transient. Changes in respiratory rate and heart rate were not observed.

Authors/Disclosures
Daniel C. Tarquinio, DO PRESENTER	The institution of Dr. Tarquinio has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurelis.
	No disclosure on file
Michael R. Sperling, MD, FAAN (Thomas Jefferson University)	Dr. Sperling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurelis. The institution of Dr. Sperling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medtronic. Dr. Sperling has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for UCB Pharma. Dr. Sperling has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Medscape. Dr. Sperling has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for International Medical Press. Dr. Sperling has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Projects for Knowledge. The institution of Dr. Sperling has received research support from SK Life Science. The institution of Dr. Sperling has received research support from UCB Pharma . The institution of Dr. Sperling has received research support from Takeda. The institution of Dr. Sperling has received research support from Neurelis. The institution of Dr. Sperling has received research support from Engage Therapeutics . The institution of Dr. Sperling has received research support from Medtronic. The institution of Dr. Sperling has received research support from Cavion. The institution of Dr. Sperling has received research support from Xenon Pharma. The institution of Dr. Sperling has received research support from Cerevel. The institution of Dr. Sperling has received research support from National Institutes of Health . The institution of Dr. Sperling has received research support from DARPA. Dr. Sperling has received publishing royalties from a publication relating to health care. Dr. Sperling has received publishing royalties from a publication relating to health care. Dr. Sperling has received personal compensation in the range of $500-$4,999 for serving as a Vice President with Epilepsy Consortium .
James W. Wheless, MD, FAAP, FACP, FAES, FCNS, FAAN (UTHSC-Pediatric Neurology)	Dr. Wheless has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Jazz. Dr. Wheless has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurelis. Dr. Wheless has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Azurity. Dr. Wheless has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB. Dr. Wheless has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biocodex. Dr. Wheless has received personal compensation in the range of $500-$4,999 for serving as a Consultant for LivaNova. Dr. Wheless has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Stoke. Dr. Wheless has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for LivaNova. Dr. Wheless has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Jazz. Dr. Wheless has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for UCB. Dr. Wheless has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for UCB. Dr. Wheless has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Neurelius.
Dennis J. Dlugos, MD	Dr. Dlugos has received research support from NIH. The institution of Dr. Dlugos has received research support from The Epilepsy Study Consortium.
Ian Miller, MD	Dr. Miller has received personal compensation for serving as an employee of Marinus Pharmaceuticals. Dr. Miller has stock in Marinus Pharmaceuticals.
Adrian L. Rabinowicz, MD, FAAN (Neurelis, Inc.; Center for Molecular Biology and Biotechnology, Charles E. Schmidt College of Science, Florida Atlantic University)	Dr. Rabinowicz has received personal compensation for serving as an employee of Neurelis, Inc. Dr. Rabinowicz has stock in Neurelis, Inc.
Enrique J. Carrazana, MD	No disclosure on file
	No disclosure on file

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