Safety and effectiveness of diazepam nasal spray in patients with Rett syndrome and seizure clusters: post hoc analyses from a long-term safety study and survey of severity and burden.

INTRODUCTION: Rett syndrome is a neurodevelopmental disorder associated with epilepsy that influences motor/communication skills, behavior, and other systems. Clinical experiences for these patients are not well described.

METHODS: This post hoc analysis consists of a patient subgroup with Rett syndrome enrolled in an open-label, single-arm, safety study. Age- and weight-based doses of diazepam nasal spray (5-20 mg) were administered to patients (aged 6-65 years) for seizure clusters. Treatment-emergent adverse events (TEAEs) were recorded, and days between seizure clusters (SEIzure interVAL [SEIVAL]) from Period 1 (P1; days 1-90) to Period 4 (P4; days 271-360) were calculated. Caregivers completed surveys describing experiences with diazepam nasal spray and Rett syndrome.

RESULTS: Rates of TEAEs (87.5%), serious TEAEs (12.5%), and treatment-related TEAEs (18.8%) in patients with Rett syndrome (n = 16) who received diazepam nasal spray were comparable to the overall pediatric safety population (87.2, 35.9, and 14.1%, respectively; n = 78), as was use of second doses (proxy for effectiveness) (18.4 and 11.4%). Increase in SEIVAL was also similar (P1 = 7.6, P4 = 25.0 days and P1 = 13.0, P4 = 25.9 days). Most (n = 12; 75.0%) remained in the study ≥12 months. All caregivers felt diazepam nasal spray was very/extremely easy to use; 63.6% were able to return to normal activities within an hour of administration. Caregiver perceptions of clinical severity and caregiver affect were stable from baseline to final visits; scores for individuals using diazepam nasal spray were numerically higher.

CONCLUSION: Diazepam nasal spray has safety and effectiveness profiles consistent with the full study population and was easy to use.

CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02721069.