TY - JOUR
T1 - Evaluation of diazepam nasal spray in patients with epilepsy concomitantly using maintenance benzodiazepines
T2 - An interim subgroup analysis from a phase 3, long-term, open-label safety study
AU - The DIAZ.001.05 Study Group
AU - Segal, Eric B.
AU - Tarquinio, Daniel
AU - Miller, Ian
AU - Wheless, James W.
AU - Dlugos, Dennis
AU - Biton, Victor
AU - Cascino, Gregory D.
AU - Desai, Jay
AU - Hogan, R. Edward
AU - Liow, Kore
AU - Sperling, Michael R.
AU - Vazquez, Blanca
AU - Cook, David F.
AU - Rabinowicz, Adrian L.
AU - Carrazana, Enrique
N1 - Funding Information:
Dr. Segal has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Eisai, Lundbeck, Nutricia, Novartis, Greenwich, Epitel, Encoded Therapeutics, and Qbiomed, and is an advisor for Neurelis, Inc. Dr. Tarquinio has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Marinus and Avexis. Dr. Miller has served as a consultant/advisor to GW Pharmaceuticals, Insys Therapeutics, Visualase, and NeuroPace, and as a study investigator for GW Pharmaceuticals. Dr. Wheless has served as an advisor or consultant for: CombiMatrix; Eisai Inc.; GW Pharmaceuticals; Lundbeck, Inc.; Neurelis, Inc; NeuroPace, Inc.; Supernus Pharmaceuticals, Inc.; and Upsher‐Smith Laboratories, Inc. Dr. Wheless has served as a speaker or a member of a speakers bureau for: Cyberonics, Inc.; Eisai Inc.; Lundbeck, Inc.; Mallinckrodt; Neurelis, Inc; Supernus Pharmaceuticals, Inc.; Upsher‐Smith Laboratories, Inc., and has received grants for clinical research from: Acorda Therapeutics; GW Pharmaceuticals; INSYS Therapeutics, Inc.; Lundbeck, Inc.; Mallinckrodt; Neurelis, Inc.; NeuroPace, Inc.; Upsher‐Smith Laboratories, Inc.; and Zogenix, Inc. Dr. Dlugos receives salary support from NIH/NINDS, Commonwealth of Pennsylvania Department of Health, Pediatric Epilepsy Research Foundation, and The Epilepsy Study Consortium. His institution receives research support for protocol development or studies from NIH; Commonwealth of PA Department of Health; Zogenix; GW Pharma; Greenwich Biosciences; UCB; Brain Sentinel; Neurelis, Inc.; Pfizer; Q‐State; USL; Aquestive; Sage; Bio‐Pharm; Insys; SK Life Sciences; Encoded Therapeutics; CURE; Rett Syndrome Research Trust. He received travel expenses for protocol development or investigator meetings from Marinus, Ovid/Takeda, Ultragenyx, USL, Pfizer, Zogenix. Dr. Biton has nothing to disclose. Dr. Cascino has nothing to disclose. Dr. Desai has received research funding from the Epilepsy Foundation of Greater Los Angeles; Neurelis, Inc.; Novartis; Ovid; Aquestive; and UCB. Dr. Hogan has received research support from UCB Pharmaceuticals, Neurelis, Inc; and Biogen Inc, and is an advisor for Neurelis, Inc. Dr. Liow has received research support from Intracellular Therapies, SK Life Sciences, Genentech, Biotie Therapies, Monosol, Aquestive Therapeutics, Engage Therapeutics, Xenon, Lundbeck, Biogen, Eli Lilly, Pfizer, Novartis, Sunovion, Acorda, Eisai, UCB, Livanova, Axsome, and Acadia. Dr. Sperling has received personal compensation for speaking from Neurology Live and Eisai, is an advisor for Neurelis, Inc, and consulting with payments to Thomas Jefferson University from Medtronic. Dr. Sperling has received research support from Eisai; Medtronic; Neurelis, Inc.; SK Life Science; Takeda; Sunovion; UCB Pharma; Xenon; and Engage Pharmaceuticals. Dr. Vazquez is an advisor for Neurelis, Inc. Dr. Cook and Dr. Rabinowicz are employees of and have received stock options from Neurelis, Inc. Dr. Carrazana is an employee of and has received stock and stock options from Neurelis, Inc. Dr. Carrazana has received compensation for serving on the boards of directors of Marinus and Hawaii‐Biotech.
Publisher Copyright:
© 2021 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.
PY - 2021/6
Y1 - 2021/6
N2 - Objective: Diazepam nasal spray (Valtoco), indicated for acute treatment of frequent seizure activity (seizure clusters) in patients with epilepsy ≥6 years of age, is designed to be a rapid, noninvasive, socially acceptable route of administration. This interim analysis evaluated the safety profile of diazepam nasal spray in patients with and without concomitant use of benzodiazepines, with use of a second dose for a seizure cluster as a proxy for effectiveness. Methods: A long-term, phase 3, open-label safety study enrolled patients with epilepsy who had seizures despite a stable antiseizure medication regimen. Results: Among 175 patients enrolled by October 31, 2019, a total of 158 were treated with diazepam nasal spray (aged 6–65 years; 53.8% female). Of those, 119 (75.3%) received concomitant benzodiazepines (60, chronic; 59, intermittent); 39 (24.7%) did not. Use of a second dose was similar in patients using chronic concomitant benzodiazepines (second dose in 11.1% [144/1299]) and those with no concomitant benzodiazepines (second dose in 10.3% [41/398]). Treatment emergent adverse events (TEAEs) occurred for 80.0% with chronic use of concomitant benzodiazepines and 61.5% without. Cardiorespiratory depression was not reported, and no serious TEAEs were treatment related. Study retention was high: 83.3% in the chronic benzodiazepine group and 76.9% in the no-benzodiazepine group. Findings were similar in a sub-analysis of patients who were (n = 44) or were not (n = 75) taking clobazam. Significance: This analysis of patients from a long-term study shows a similar safety profile of diazepam nasal spray in patients with and without concomitant benzodiazepines, and consistent with the established profile for diazepam. Use of a single dose of diazepam nasal spray and high study retention rates suggest the effectiveness of diazepam nasal spray in patients irrespective of chronic daily benzodiazepine use. Results were similar in the clobazam sub-analysis. These results support the safety and effectiveness of diazepam nasal spray in patients with concomitant benzodiazepine use.
AB - Objective: Diazepam nasal spray (Valtoco), indicated for acute treatment of frequent seizure activity (seizure clusters) in patients with epilepsy ≥6 years of age, is designed to be a rapid, noninvasive, socially acceptable route of administration. This interim analysis evaluated the safety profile of diazepam nasal spray in patients with and without concomitant use of benzodiazepines, with use of a second dose for a seizure cluster as a proxy for effectiveness. Methods: A long-term, phase 3, open-label safety study enrolled patients with epilepsy who had seizures despite a stable antiseizure medication regimen. Results: Among 175 patients enrolled by October 31, 2019, a total of 158 were treated with diazepam nasal spray (aged 6–65 years; 53.8% female). Of those, 119 (75.3%) received concomitant benzodiazepines (60, chronic; 59, intermittent); 39 (24.7%) did not. Use of a second dose was similar in patients using chronic concomitant benzodiazepines (second dose in 11.1% [144/1299]) and those with no concomitant benzodiazepines (second dose in 10.3% [41/398]). Treatment emergent adverse events (TEAEs) occurred for 80.0% with chronic use of concomitant benzodiazepines and 61.5% without. Cardiorespiratory depression was not reported, and no serious TEAEs were treatment related. Study retention was high: 83.3% in the chronic benzodiazepine group and 76.9% in the no-benzodiazepine group. Findings were similar in a sub-analysis of patients who were (n = 44) or were not (n = 75) taking clobazam. Significance: This analysis of patients from a long-term study shows a similar safety profile of diazepam nasal spray in patients with and without concomitant benzodiazepines, and consistent with the established profile for diazepam. Use of a single dose of diazepam nasal spray and high study retention rates suggest the effectiveness of diazepam nasal spray in patients irrespective of chronic daily benzodiazepine use. Results were similar in the clobazam sub-analysis. These results support the safety and effectiveness of diazepam nasal spray in patients with concomitant benzodiazepine use.
KW - antiseizure drug regimen
KW - benzodiazepine
KW - diazepam
KW - intranasal
KW - seizure cluster
UR - http://www.scopus.com/inward/record.url?scp=85105070968&partnerID=8YFLogxK
U2 - 10.1111/epi.16901
DO - 10.1111/epi.16901
M3 - Article
C2 - 33942315
AN - SCOPUS:85105070968
VL - 62
SP - 1442
EP - 1450
JO - Epilepsia
JF - Epilepsia
SN - 0013-9580
IS - 6
ER -