Consistent safety and tolerability of Valtoco ® (diazepam nasal spray) in relationship to usage frequency in patients with seizure clusters: Interim results from a phase 3, long‐term, open‐label, repeat‐dose safety study

Objective Need for rescue therapy differs among patients with seizure clusters. Diazepam nasal spray is approved to treat seizure clusters in patients with epilepsy ≥6 years of age. This analysis used interim data from a phase 3 safety study to assess safety profile and effectiveness of diazepam nasal spray using average number of doses/month as a proxy measurement. Methods This phase 3, open-label, repeat-dose, safety study of diazepam nasal spray enrolled patients (6-65 years) with epilepsy and need of benzodiazepine rescue. Patients were stratified by average number of doses/month ( 5, very-high frequency). Safety was evaluated based on treatment-emergent adverse events (TEAEs), assessed nasal irritation, and olfaction. The proportion of treatments given as a second dose was used as an exploratory proxy for effectiveness. Results Of 175 enrolled patients (data cutoff, October 31, 2019), 158 received ≥1 dose of diazepam nasal spray. Frequency of use was moderate in 43.7% of patients, high in 50.6% of patients, and very high in 5.7% of patients. Patients treated 3397 seizure episodes (moderate frequency, 14.2%; high frequency, 59.9%; very high frequency, 25.8%). Nasal discomfort was the most common treatment-related TEAE in all groups. No notable changes in nasal irritation or olfaction were observed. Second doses represented only 2.5%, 7.5%, and 17.2% of all doses in the moderate-, high-, and very-high-frequency groups, respectively. Overall retention rate was 82.9%, without an observed relationship to frequency of use. Significance Frequency of dosing diazepam nasal spray had little impact on the safety/tolerability profile across a range of 5 doses/month. Effectiveness was suggested for all dosing frequencies by the high proportion of seizure clusters not treated with a second dose. These results support the utility, safety profile, and effectiveness of diazepam nasal spray across frequencies of seizure cluster burden.