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 (<2, moderate frequency; 2-5, high frequency; >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 <2 to >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.
['Miller|Ian|I|https://orcid.org/0000-0003-0416-1015', 'Wheless|James W|JW|', 'Hogan|Robert E|RE|https://orcid.org/0000-0003-2272-5005', 'Dlugos|Dennis|D|', 'Biton|Victor|V|', 'Cascino|Gregory D|GD|', 'Sperling|Michael R|MR|https://orcid.org/0000-0003-0708-6006', 'Liow|Kore|K|', 'Vazquez|Blanca|B|', 'Segal|Eric B|EB|', 'Tarquinio|Daniel|D|', 'Mauney|Weldon|W|', 'Desai|Jay|J|', 'Rabinowicz|Adrian L|AL|', 'Carrazana|Enrique|E|', '|||']
diazepam nasal spray seizure cluster dosing frequency acute repetitive seizure intranasal