19 Dec Efficacy of Midazolam Nasal Spray For Outpatient Treatment of Seizure Clusters
MedicalResearch.com Interview with:
Steve S. Chung MD
Banner University Medical Center
University of Arizona, Phoenix, AZ
MedicalResearch.com: What is the background for this study?
Response: Prior studies have shown that midazolam nasal spray (MDZ-NS) is superior to placebo in providing rapid, sustained seizure control and a favorable safety profile when administered to patients experiencing seizure clusters, a type of seizure emergency impacting an estimated 150,000 patients in the U.S. with uncontrolled epilepsy.
To explore the influence of concomitant antiepileptic drugs (AEDs) on treatment outcomes, we conducted a post hoc analysis of a Phase III trial to evaluate the tolerability and efficacy of midazolam nasal spray in patients 12 years of age and older with seizure clusters, according to concomitant enzyme-inducing AED (EIAED)/non-enzyme-inducing AED (NEIAED) status and by the number of concomitant AEDs.
MedicalResearch.com: What are the main findings?
- During the comparative phase, the overall incidence of TEAEs in patients with ≥1 MDZ-NS dose was numerically lower in patients on EIAEDs vs. NEIAEDs and increased with the number of concomitant AEDs.
- Most patients (87.2%) randomized to MDZ-NS who did not have a seizure 10 minutes to 6 hours after one MDZ-NS 5 mg dose remained seizure free over 24 hours.
- This proportion was generally similar in patients on EIAEDs (88.9%) and NEIAEDs (84.8%), and across patient subgroups by number of concomitant AEDs (95.0%, 78.8%, and 92.0% in patients on <2, 2–3, and ≥4 AEDs).
- Amongst patients randomized to MDZ-NS who received only one MDZ-NS 5 mg dose, 96.2% on EIAEDs (n=53), 97.4% on NEIAEDs (n=38), and 100%, 94.3%, and 97.2% on <2 (n=20), 2–3 (n=35), and ≥4 (n=36) AEDs returned to full baseline functionality within 24h of trial drug administration (median time to return: 1.25h, 1.00h, 0.95h, 1.25h, and 1.23h, respectively).
MedicalResearch.com: What should readers take away from your report?
Response: The incidence of somnolence (sleepiness or drowsiness) after midazolam nasal spray administration was low and if somnolence was reported, the median duration was approximately 4 hours. Additionally, the proportion of patients returning to full baseline functionality within 24 hours after taking midazolam nasal spray was not affected by the occurrence of somnolence. As somnolence is a common adverse event after rescue treatment with benzodiazepines in patients with seizure clusters, this data is important as it shows somnolence after midazolam nasal spray administration was low and return to full baseline functionality happened shortly after administration.
Additionally, the study showed that regardless of enzyme-inducing anti-epileptic drug (AED) use and number of concomitant AEDs, most patients returned to full baseline functionality within 24 hours of taking midazolam nasal spray. As patients with seizure clusters require medications beyond a rescue medication, this data is important as it shows midazolam nasal spray is still effective and tolerable with concomitant use of AEDs.
The main clinical utility of midazolam nasal spray is to prevent adverse consequences from prolonged or cluster seizures such as head trauma, bodily injury, mood or cognitive impairment.
Please see full Prescribing Information, including boxed warning. Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death.
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
Response: The main benefits of midazolam nasal spray include rapid onset of action, availability of effective treatment outside hospitals, ease of use and portability. Consequently, it would be great if we can show improved health outcome, reduced hospitalization and incurred costs, as well as quality of life.
Disclosures: This was a UCB, Inc. sponsored study.
Dr. Chung is a consultant and speaker for UCB. He also received a research grant for midazolam nasal spray clinical trials.
AES 2019 Abstract 1.308), 2019
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
Authors: Steve S. Chung, Banner University Medical Center, University of Arizona, Phoenix, AZ, USA; James W. Wheless, Division of Pediatric Neurology, University of Tennessee Health Science Center; Le Bonheur Comprehensive Epilepsy Program & Neuroscience Institute, LeBonHeur Children’s Hospital, Memphis TN, USA; Svetlana Dimova, UCB Pharma, Brussels, Belgium; Eun Jung Choi, UCB Pharma, Smyrna, GA, USA; Aliceson King, UCB Pharma, Smyrna, GA, USA; Jody Cleveland, UCB Pharma, Raleigh NC, USA
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