An analysis of 2 different doses of intranasal diazepam showed consistent safety and tolerability results for repeat dosing
An interim analysis of a study of intranasal diazepam (Valtoco; Neurelis) demonstrated a safety and tolerability profile consistent with what is expected for diazepam, regardless of usage frequency. The results were presented at the 2019 American Epilepsy Society Annual Meeting, December 6-10, 2019 in Baltimore, Maryland.
In October, Neurelis reported that intranasal diazepam was safe and tolerable for the treatment of cluster or acute, repetitive seizures in pediatric patients with epilepsy.
This analysis included data from 132 patients (6-65 years; 53.8% female; 82.6% white) and 2485 seizure episodes from the open-label, repeat dose, phase 3 study of intranasal diazepam. Over 1-year follow-up, patients received either 5, 10, 15, or 20 mg of intranasal diazepam based on weight, with a second dose administered 4 to 12 hours later, if needed.
To better understand whether the safety and tolerability of intranasal diazepam would remain consistent with its previous safe and tolerable profile, investigators assessed patients based on how frequently they used the drug per month, noting “moderate” if a patient averaged 1-2 doses per month or “frequent” if a patient averaged >2 doses per month. Investigators used a 6-point scale and olfactory changes on the National Institute of Health (NIH) Toolbox Odor Identification Test to document nasal irritation and tolerability. Patients were observed on treatment-emergent adverse events (TEAEs) as well.
Among the 132 patients assessed, 65 (49.2%) recorded moderate use of intranasal diazepam, compared to 67 (50.8%) patients who reported using the drug frequently. Overall, 91 (68.9%) patients reported a TEAE: 40 (61.5%) patients who used intranasal diazepam moderately, and 51 (76.1%) who used the drug on a frequent basis.
The most common TEAEs observed in the study (>5%) were seizure, naspharyngitis, influenza, nasal discomfort, upper respiratory tract infection, headache, pyrexia, dizziness, and contusion. Moderate users more often experienced seizure, upper respiratory tract infection, and dizziness compared to frequent users who more often experienced nasopharyngitis, influenza, nasal discomfort, headache, pyrexia, and contusion. Serious TEAEs occurred in 37 patients, 18 (27.7%) of whom were using intranasal diazepam moderately, and 19 (28.4%) who were using it frequently. The most common treatment-related TEAEs (>2%) were nasal discomfort, headache, epistaxis, and rhinalgia
Overall, the investigators did not report any trends for usage frequency effects on clinical or laboratory parameters, as well as olfactory changes. There was a slightly higher incidence of mild nasal irritation in frequent users, as well as one TEAE-related discontinuation in a frequent user due to major depression and anxiety.
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Miller I, Wheless JW, Hogan RE, et al. Safety and tolerability of NRL-1, an intranasal formulation of diazepam, in relationship to usage frequency in subjects with epilepsy: interim results from a phase 3, open-label, repeat dose study. Presented at: 2019 American Epilepsy Society Annual Meeting. December 6-10, 2019; Baltimore, Maryland. Abstract 1.22.