Patients treated with intranasal midazolam who were on enzyme-inducing AEDs experienced numerically lower treatment-emergent adverse events.
James Wheless, MD
Results from a study of midazolam nasal spray (MDZ-NS) in outpatient treatment of patients with seizure clusters (SC) demonstrated similar seizure-free outcomes post-administration regardless of enzyme-inducing antiepileptic drugs (EIAEDs) and number of concomitant AEDs. The results were presented at the 2019 American Epilepsy Society Annual Meeting
, December 6-10, 2019 in Baltimore, Maryland.
In November, UCB announced the availability of midazolam nasal spray
, marketed under the brand name Nayzilam, for the treatment of intermittent, stereotypic episodes of frequent seizure activity, including seizure clusters and acute repetitive seizures. The drug was proven to be effective and well-tolerated for the acute treatment of status epilepticus and is expected to be available in retail pharmacies in December 2019.
The placebo-controlled study contained a test dose phase followed by an outpatient double-blind comparative phase (CP) where patients were randomized 2:1 to 5 mg of MDZ-NS or placebo. Patients were evaluated on TEAEs and treatment success (seizure termination within 10 minutes and no recurrence 10 minutes-6 hours after trial drug administration). Additionally, the investigators stratified patients by EIAEDs or non-enzyme-inducing AEDs (NEIADs), as well as subgroups of patients on <2, 2-3, or >
4 concomitant AEDs, and evaluated their return to full baseline functionality within 24 hours during the CP, no seizure recurrence 10 minutes- 24 hours after trial drug administration.
Patients on EIAEDs who received >1 MDZ-NS dose had a lower number of overall incidences of TEAEs than those on NEIAEDs during the CP. Notably, the number of TEAEs continued to rise with the number of concomitant AEDs. Somnolence, the most common TEAE, was present in 4.5%, 8%, 16.1% of patients on <2, 2-3, or >
4 concomitant AEDs, respectively. Additional TEAEs noted in the trial included nasal discomfort, headache, product taste abnormalities, throat irritation, dysarthria, rhinorrhea.
As for seizure freedom, 56.3%, 56.4%, and 48.9% of patients who received treatment with MDZ-NS 5 mg who were on <2, 2-3, >
4 number of concomitant AEDS, respectively, had treatment success. Notably, 87.2% of patients who remained seizure free 10 minutes to 6 hours following one MDZ-NS 5 mg dose remained seizure free over 24 hours. Similarly, 88.9% and 84.8% of patients on EIAEDs and NEIADs, respectively, remained seizure free over 24 hours after remaining seizure free during the 10 minute to 6-hour evaluation period.
Among patients on EIAEDs and NEIAEDs, 96.2% and 97.4% who received one 5 mg dose of MDZ-NS, respectively, returned to full baseline functionality within 24 hours of administration. Additionally, 100%, 94.3% and 97.2% of patients taking <2, 2-3, or >
4 AEDs also returned to full baseline functionality within 24 hours of treatment administration, respectively.
"We’ve always known that we needed a treatment for seizure clusters at home and the key was trying to develop a product that would do what we wanted it to do—that it was safe, but would also interrupt the seizure cluster—and was one that the patient could use at home. Nayzilam represents an option that fills all of those criteria," study investigator James Wheless, MD, told NeurologyLive
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Chung SS, Wheless JW, Dimova S. Tolerability and efficacy of midazolam nasal spray in outpatient treatment of patients with seizure clusters by concomitant AEDs: post-hoc analysis of randomized, double-blind, placebo-controlled trial. Presented at: 2019 American Epilepsy Society Annual Meeting. December 6-10, 2019; Baltimore, Maryland. Abstract 1.308.