Safety of Diazepam Nasal Spray in Children and Adolescents With Epilepsy: Results From a Long-Term Phase 3 Safety Study.


Journal

Pediatric neurology
ISSN: 1873-5150
Titre abrégé: Pediatr Neurol
Pays: United States
ID NLM: 8508183

Informations de publication

Date de publication:
07 2022
Historique:
received: 03 02 2022
revised: 04 04 2022
accepted: 18 04 2022
pubmed: 1 6 2022
medline: 22 6 2022
entrez: 31 5 2022
Statut: ppublish

Résumé

To evaluate safety and tolerability of long-term treatment with diazepam nasal spray (Valtoco) for seizure clusters in patients aged six to 17 years. The study enrolled patients aged six to 65 years with frequent seizure clusters. Age- and weight-based doses of diazepam nasal spray were administered; second doses were permitted if needed. Safety assessments included treatment-emergent adverse events (TEAEs). Of 163 treated patients, 45 (27.6%) were aged six to 11 years and 33 (20.2%) were aged 12 to 17 years. Mean doses per month were 2.1 in the 6 to 11 subgroup and 2.4 in the 12 to 17 subgroup. Of 1634 seizure clusters in pediatric patients, 186 (11.4%) required a second dose of diazepam nasal spray within 24 hours of the first dose. Similar proportions of TEAEs and serious TEAEs were reported in 6 to 11 (91.1%, 40.0%) and 12 to 17 subgroups (81.8%, 30.3%), respectively. No serious TEAEs were considered treatment related, and no patients discontinued because of TEAEs. Treatment-related TEAEs were more frequent in the 12 to 17 subgroup; only epistaxis and somnolence occurred in two or more patients overall. TEAE rates were similar across subgroups that received concomitant clobazam (90.0%), received prior diazepam rectal gel (90.9%), and were administered less than two versus greater than or equal to two doses per month (87.2% for both) of diazepam nasal spray. Most survey respondents (88%) were satisfied or very satisfied with treatment. In this long-term safety analysis in pediatric patients with seizure clusters, repeated doses of diazepam nasal spray demonstrated a safety profile consistent across subgroups. These data support the dosing guidelines for diazepam nasal spray according to age and weight for pediatric patients.

Sections du résumé

BACKGROUND
To evaluate safety and tolerability of long-term treatment with diazepam nasal spray (Valtoco) for seizure clusters in patients aged six to 17 years.
METHODS
The study enrolled patients aged six to 65 years with frequent seizure clusters. Age- and weight-based doses of diazepam nasal spray were administered; second doses were permitted if needed. Safety assessments included treatment-emergent adverse events (TEAEs).
RESULTS
Of 163 treated patients, 45 (27.6%) were aged six to 11 years and 33 (20.2%) were aged 12 to 17 years. Mean doses per month were 2.1 in the 6 to 11 subgroup and 2.4 in the 12 to 17 subgroup. Of 1634 seizure clusters in pediatric patients, 186 (11.4%) required a second dose of diazepam nasal spray within 24 hours of the first dose. Similar proportions of TEAEs and serious TEAEs were reported in 6 to 11 (91.1%, 40.0%) and 12 to 17 subgroups (81.8%, 30.3%), respectively. No serious TEAEs were considered treatment related, and no patients discontinued because of TEAEs. Treatment-related TEAEs were more frequent in the 12 to 17 subgroup; only epistaxis and somnolence occurred in two or more patients overall. TEAE rates were similar across subgroups that received concomitant clobazam (90.0%), received prior diazepam rectal gel (90.9%), and were administered less than two versus greater than or equal to two doses per month (87.2% for both) of diazepam nasal spray. Most survey respondents (88%) were satisfied or very satisfied with treatment.
CONCLUSIONS
In this long-term safety analysis in pediatric patients with seizure clusters, repeated doses of diazepam nasal spray demonstrated a safety profile consistent across subgroups. These data support the dosing guidelines for diazepam nasal spray according to age and weight for pediatric patients.

Identifiants

pubmed: 35636283
pii: S0887-8994(22)00063-7
doi: 10.1016/j.pediatrneurol.2022.04.011
pii:
doi:

Substances chimiques

Anticonvulsants 0
Nasal Sprays 0
Diazepam Q3JTX2Q7TU

Types de publication

Clinical Trial, Phase III Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

50-55

Informations de copyright

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Auteurs

Daniel Tarquinio (D)

Center for Rare Neurological Diseases, Norcross, Georgia. Electronic address: daniel@rareneuro.com.

Dennis Dlugos (D)

Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.

James W Wheless (JW)

Le Bonheur Children's Hospital and University of Tennessee Health Science Center, Memphis, Tennessee.

Jay Desai (J)

Children's Hospital Los Angeles, Los Angeles, California.

Enrique Carrazana (E)

Neurelis, Inc., San Diego, California; John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii.

Adrian L Rabinowicz (AL)

Neurelis, Inc., San Diego, California.

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Classifications MeSH