Midazolam nasal spray a promising treatment option in patients with seizure clusters
Midazolam nasal spray (MDZ-NS) delivers prompt and prolonged seizure control with a favourable safety profile in the outpatient treatment of patients experiencing a seizure cluster (SC), according to the results of the phase III ARTEMIS-1* trial.
“These results demonstrate the potential of MDZ–NS in addressing an important unmet clinical need,” the investigators said, adding that the conservative statistical approach used in the final analysis ensured integrity of the data, given that the trial was stopped early due to acquisition of the original sponsor company.
ARTEMIS-1 involved 292 patients aged ≥12 years (median, 33 years) on a stable regimen of antiepileptic drugs, of whom 262 were randomized and 201 received double-blind treatment (MDZ-NS, n=134; placebo, n=67). Treatment was administered by caregivers during a seizure attack.
The primary efficacy endpoint of treatment success (seizure termination within 10 minutes and no recurrence 10 minutes to 6 hours after drug administration) occurred with significantly greater frequency in the MDZ-NS vs placebo arm (53.7 percent vs 34.4 percent; p=0.0109). [Epilepsia 2019;doi:10.1111/epi.15159]
Results for the secondary efficacy endpoints were also significantly different, in favour of MDZ-NS. Specifically, the number of patients with seizure recurrence (within 10 minutes to 4 hours) were fewer (38.1 percent vs 59.7 percent; p=0.0043) and time-to-next seizure >10 minutes after double-blind drug administration was longer (58.3 percent vs 37.1 percent; p=0.0124) than with placebo.
“Throughout the trial, treatment-emergent adverse events (TEAEs) experienced by most patients were, not unexpectedly, sedation‐type events and, given the route of administration, nasal discomfort,” the investigators noted.
“The incidence of events considered likely indicative of clinically meaningful respiratory depression related to the trial drug was low (0.7 percent) and occurred only during [an in‐clinic test dose phase before patients underwent randomization],” they added.
During the randomization phase, 27.6 percent and 22.4 percent of patients in the MDZ-NS and placebo arms, respectively, had ≥1 TEAE. There were no reports of treatment‐related serious AEs, discontinuations due to TEAEs or AEs of special interest in the category of acute central respiratory depression. Neither there were any TEAEs in the category of depression and suicidality/self‐injury indicative of suicide or attempted suicide, or abuse.
“These results confirm the acceptable safety profile of MDZ–NS and support the feasibility of administration by nonhealthcare professionals (non-HCPs) in outpatient settings,” the investigators said.
“Antiseizure agents that can be administered rapidly and safely by non‐HCPs in the outpatient setting can help patients experiencing SCs achieve seizure cessation, reduce seizure‐related complications and prevent progression to more serious sequelae. Early intervention may help avoid emergency department visits and also provide a greater sense of control for patients and their caregivers, which may have a positive impact on their quality of life,” they added. [Epilepsy Behav 2015;49:303-306; CNS Drugs 2015;29:55-70; Seizure 2018;doi:10.1016/j.seizure.2018.05.013]
*Acute Rescue Therapy in Epilepsy with Midazolam Intranasal Spray