Concomitant Cannabidiol Does Not Impact Safety and Effectiveness of Diazepam Nasal Spray for Seizure Clusters: Post Hoc Analysis of a Phase 3 Safety Study (P9-1.012)

Abstract

<h3>Objective:</h3> To examine potential effects of concomitant cannabidiol on safety and effectiveness of diazepam nasal spray (Valtoco^®). <h3>Background:</h3> Cannabidiol (CBD) is used as an antiseizure drug with multiple mechanisms of action. In clinical studies, the FDA-approved oral solution of CBD (Epidiolex^®) has altered the safety and effectiveness of benzodiazepines, especially clobazam. Diazepam nasal spray is approved for acute treatment of seizure clusters in patients with epilepsy aged ≥6 years. This post hoc analysis from a long-term, open-label safety study examines safety and effectiveness of diazepam nasal spray in patients also receiving CBD treatment. <h3>Design/Methods:</h3> Patients (6–65 years) received age- and weight-based doses of diazepam nasal spray to treat seizure clusters. Seizures and drug administration were recorded in patient diaries. CBD use and treatment-emergent adverse events (TEAEs) were collected. Diazepam nasal spray second dose usage within 24 hours of the first was a proxy for effectiveness. <h3>Results:</h3> Of 163 patients treated with ≥1 dose of diazepam nasal spray, 119 (73.0%) did not receive CBD, 23 (14.1%) received oral-solution CBD, and 21 (12.9%) received other CBD. Patients receiving any CBD were more likely to have epileptic encephalopathies than patients with no CBD (63.6% vs 30.3%). Rates of TEAEs and serious TEAEs were higher in patients receiving CBD (90.9%, 45.5%) than no CBD (79.0%, 25.2%); treatment-related TEAEs were similar (18.2% vs 17.7%). Effectiveness measured by second dose use was similar between the CBD (14.7%) and no CBD groups (11.5%). <h3>Conclusions:</h3> CBD does not appear to influence the safety of diazepam nasal spray. In this cohort, incidence of epileptic encephalopathies in patients receiving CBD may underlie the overall rates of TEAEs in this population. Treatment-related TEAEs were similar across groups. These results suggest that CBD does not alter safety/effectiveness of diazepam nasal spray and support concomitant use in appropriate patients. <b>Disclosure:</b> Dr. Peters has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurelis. Dr. Peters has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Neurelis. Dr. Peters has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Neurelis. Dr. Puri has received personal compensation for serving as an employee of neurelis. Dr. Puri has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Neurelis. Dr. Puri has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Neurelis. Dr. Puri has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Eisai. Dr. Segal has received personal compensation for serving as an employee of Lundbeck. Dr. Segal has received personal compensation for serving as an employee of Eisai. Dr. Segal has received personal compensation for serving as an employee of Neurelis. Dr. Segal has received personal compensation for serving as an employee of Zogenix. Dr. Segal has received personal compensation for serving as an employee of Aquestive. Dr. Segal has received personal compensation for serving as an employee of Greenwich Biosciences. Dr. Segal has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Aquestive. Dr. Segal has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurelis. Dr. Segal has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Greenwhich Bioscience. Dr. Segal has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Greenwhich Bioscience. Dr. Segal has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Neurelis. Dr. Gustin has received personal compensation for serving as an employee of Neurelis. Dr. Gustin has received personal compensation in the range of $500-$4,999 for serving as an officer or member of the Board of Directors for The Recovery Research Network Foundation. Dr. Misra has received personal compensation for serving as an employee of Neurelis, Inc. An immediate family member of Dr. Misra has received personal compensation for serving as an employee of Neurocrine Biosciences. Dr. Misra has received personal compensation in the range of $500-$4,999 for serving as a Consultant for RubiconMD. Dr. Misra has received intellectual property interests from a discovery or technology relating to health care. Dr. Rabinowicz has received personal compensation for serving as an employee of Neurelis, Inc. Dr. Rabinowicz has stock in Neurelis, Inc. Enrique Carrazana has received personal compensation for serving as an employee of Neurelis. Enrique Carrazana has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Neurelis, Alexza, Zogenix. Enrique Carrazana has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Hawaii-Biotech, CND Life Sciences. Enrique Carrazana has stock in Neurelis, Marinus, .