Evidence map›Paper›PMID 34418086›Full record

Trial reportEpilepsia2021

Final results from a Phase 3, long-term, open-label, repeat-dose safety study of diazepam nasal spray for seizure clusters in patients with epilepsy.

James W Wheless, Ian Miller, R Edward Hogan, Dennis Dlugos, Victor Biton, Gregory D Cascino, Michael R Sperling, Kore Liow, Blanca Vazquez, Eric B Segal and 6 more

Registry-linked trialOpen access · hybridAbstract readClinical Trial, Phase III
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Epilepsia, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02721069 (A 12-Month Open-Label, Repeat-Dose Safety Study of NRL-1 in Epilepsy Subjects), which is not on this map. Cited by 38 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed, 1 pooled it
8.7field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02721069 phase3completednot on this map

A 12-Month Open-Label, Repeat-Dose Safety Study of NRL-1 in Epilepsy Subjects (DIAZ.001.05)

TypeinterventionalSponsorNeurelis, Inc.Ran2016 to 2020Enrolled175ConditionsAcute Repetitive Seizures, Breakthrough SeizuresArmsNRL-1
3 · Its place in the literature

Who cites it

38 citing papers in PubMed, 1 synthesis or guideline pooled it, 65 citations in OpenAlex.

  1. Short-Term Impact of Seizures and Mitigation Opportunities.Current neurology and neuroscience reports · 2024
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors at 13 institutions in 2 countries.

James W WhelessLe Bonheur Children's Hospital, University of Tennessee Health Science Center, Memphis, Tennessee, USA.ORCID 0000-0002-4735-3431
Ian MillerFormerly Nicklaus Children's Hospital, Miami, Florida, USA.ORCID 0000-0003-0416-1015
R Edward HoganWashington University in St. Louis, St. Louis, Missouri, USA.ORCID 0000-0003-2272-5005
Dennis DlugosChildren's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Victor BitonArkansas Epilepsy Program, Little Rock, Arkansas, USA.
Gregory D CascinoMayo Clinic, Rochester, Minnesota, USA.
Michael R SperlingThomas Jefferson University, Philadelphia, Pennsylvania, USA.ORCID 0000-0003-0708-6006
Kore LiowHawaii Pacific Neuroscience, Honolulu, Hawaii, USA.
Blanca VazquezNew York University, Comprehensive Epilepsy Center, New York, New York, USA.
Eric B SegalHackensack University Medical Center and Northeast Regional Epilepsy Group, Hackensack, New Jersey, USA.
Daniel TarquinioCenter for Rare Neurological Diseases, Atlanta, Georgia, USA.
Weldon MauneyNorthwest Florida Clinical Research Group, Gulf Breeze, Florida, USA.
Jay DesaiChildren's Hospital of Los Angeles, Los Angeles, California, USA.
Adrian L RabinowiczNeurelis, San Diego, California, USA.
Enrique CarrazanaNeurelis, San Diego, California, USA.ORCID 0000-0001-8788-0722
DIAZ.001.05 Study Group
Neurelis (United States) · USArkansas Cardiology · USChildren's Hospital of Los Angeles · USChildren's Hospital of Philadelphia · USEpilepsy Action · GBGulf Marine Institute of Technology · USHackensack University Medical Center · USHawaii Pacific University · USMayo Clinic · USMiami Children's Hospital · USThomas Jefferson University · USUniversity of Tennessee Health Science Center · USWashington University in St. Louis · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveA Phase 3 open-label safety study (NCT02721069) evaluated long-term safety of diazepam nasal spray (Valtoco) in patients with epilepsy and frequent seizure clusters.

methodsPatients were 6-65 years old with diagnosed epilepsy and seizure clusters despite stable antiseizure medications. The treatment period was 12 months, with study visits at Day 30 and every 60 days thereafter, after which patients could elect to continue. Doses were based on age and weight. Seizure and treatment information was recorded in diaries. Treatment-emergent adverse events (TEAEs), nasal irritation, and olfactory changes were recorded.

resultsOf 163 patients in the safety population, 117 (71.8%) completed the study. Duration of exposure was ≥12 months for 81.6% of patients. There was one death (sudden unexpected death in epilepsy) and one withdrawal owing to a TEAE (major depression), both considered unlikely to be related to treatment. Diazepam nasal spray was administered 4390 times for 3853 seizure clusters, with 485 clusters treated with a second dose within 24 h; 53.4% of patients had monthly average usage of one to two doses, 41.7% two to five doses, and 4.9% more than five doses. No serious TEAEs were considered to be treatment related. TEAEs possibly or probably related to treatment (n = 30) were most commonly nasal discomfort (6.1%); headache (2.5%); and dysgeusia, epistaxis, and somnolence (1.8% each). Only 13 patients (7.9%) showed nasal irritation, and there were no relevant olfactory changes. The safety profile of diazepam nasal spray was generally similar across subgroups based on age, monthly usage, concomitant benzodiazepine therapy, or seasonal allergy/rhinitis. SIGNIFICANCE: In this large open-label safety study, the safety profile of diazepam nasal spray was consistent with the established profile of rectal diazepam, and the high retention rate supports effectiveness in this population. A second dose was used in only 12.6% of seizure clusters.

Indexed as

EpilepsyEpilepsy, GeneralizedOlfaction DisordersAdministration, IntranasalAdolescentAdultAgedAnticonvulsantsBrain Damage, ChronicChildDeath, SuddenDiazepamHumansMiddle AgedNasal SpraysSeizuresAnticonvulsantsDiazepamNasal Spraysacute repetitive seizurediazepamintranasalrescuestereotypic episodes of frequent seizure activity

Identifiers

PMID34418086
PMCPMC9290500
OpenAlexW3195873071

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.