TY - JOUR
T1 - Consistent safety and tolerability of Valtoco® (diazepam nasal spray) in relationship to usage frequency in patients with seizure clusters
T2 - Interim results from a phase 3, long-term, open-label, repeat-dose safety study
AU - The DIAZ.001.05 Study Group
AU - Miller, Ian
AU - Wheless, James W.
AU - Hogan, Robert E.
AU - Dlugos, Dennis
AU - Biton, Victor
AU - Cascino, Gregory D.
AU - Sperling, Michael R.
AU - Liow, Kore
AU - Vazquez, Blanca
AU - Segal, Eric B.
AU - Tarquinio, Daniel
AU - Mauney, Weldon
AU - Desai, Jay
AU - Rabinowicz, Adrian L.
AU - Carrazana, Enrique
N1 - Publisher Copyright:
© 2021 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy
PY - 2021/9
Y1 - 2021/9
N2 - 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.
AB - 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.
KW - acute repetitive seizure
KW - diazepam
KW - dosing frequency
KW - intranasal
KW - nasal spray
KW - seizure cluster
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U2 - 10.1002/epi4.12494
DO - 10.1002/epi4.12494
M3 - Article
C2 - 34033266
AN - SCOPUS:85105749995
SN - 2470-9239
VL - 6
SP - 504
EP - 512
JO - Epilepsia Open
JF - Epilepsia Open
IS - 3
ER -