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. Issue 3 (13th May 2021)

• Record Type: Journal Article
• Authors: Miller, Ian; Wheless, James W.; Hogan, Robert E.; Dlugos, Dennis; Biton, Victor; Cascino, Gregory D.; Sperling, Michael R.; Liow, Kore; Vazquez, Blanca; Segal, Eric B.; Tarquinio, Daniel; Mauney, Weldon; Desai, Jay; Rabinowicz, Adrian L.; Carrazana, Enrique
• Is Part Of: Epilepsia open. Volume 6:Issue 3(2021)
• Page Start: 504
• Page End: 512
• Publication Date: 2021-05-13
• Subjects: acute repetitive seizure -- diazepam -- dosing frequency -- intranasal -- nasal spray -- seizure cluster; Epilepsy -- Periodicals; Epilepsy -- Research -- Periodicals; Epilepsy; Periodicals; Fulltext; Internet Resources; Periodicals; 616.853005
• DOI: 10.1002/epi4.12494
• Languages: English
• ISSNs: 2470-9239

Abstract

Abstract: 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.