Concomitant Cannabidiol Does Not Impact Safety and Effectiveness of Diazepam Nasal Spray for Seizure Clusters: Post Hoc Analysis of a Phase 3 Safety Study
Jurriaan Peters1, Vinay Puri2, Eric Segal3, Richard Gustin4, Sunita Misra4, Adrian Rabinowicz4, Enrique Carrazana5
1Harvard Medical School and Boston Children’s Hospital, Boston, MA, 2Norton Children’s Neuroscience Institute, University of Louisville, Louisville, KY, 3Hackensack University Medical Center and Northeast Regional Epilepsy Group, Hackensack, NJ, 4Neurelis, Inc., San Diego, CA, 5Neurelis, Inc., San Diego, CA and John A. Burns School of Medicine, University of Hawaii, Honolulu, HI
Objective:
To examine potential effects of concomitant cannabidiol on safety and effectiveness of diazepam nasal spray (Valtoco®).
Background:
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.
Design/Methods:
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.
Results:
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%).
Conclusions:
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.