Abstracts

Rationale: The results of a Phase 3, randomized, double-blind, parallel, placebo-controlled, multicenter study (Part 1) of IM diazepam auto-injector (AI) administered by a patient s family or caregiver to treat acute repetitive seizures (ARS) showed the diazepam AI to be well-tolerated and significantly more effective than placebo AI in delaying the time to next seizure or rescue. Here we report the results of the Part 2 open-label continuation of the study. The rationale was to evaluate the effectiveness and safety of diazepam AI administered by family or caregivers, for the management of patients with ARS who require additional intermittent treatment of seizures. Methods: In Part 1 of the study, 234 subjects were randomized to diazepam or placebo AI, with 161 subjects continuing into Part 2, all of whom were provided with open-label diazepam AI. Rescue medication could be given at any time if needed. Effectiveness was measured by evaluation of time to next seizure or rescue, frequency of rescue events, numbers of seizures, and caregiver and physician global treatment assessments. Safety data (adverse events and respirations <8/min) were also collected. Results: In Part 2, 128 subjects were treated with diazepam AI at least once (median 4.5; range 1 118), with a total of 1,380 diazepam AI treatments administered during the approximate 6-year duration of the open-label phase. Overall, 78% of treatments in Part 2 were effective; no subsequent seizure or rescue event occurred in the 12-hour post-treatment follow-up period. These results are consistent with those observed in Part 1 (65%). The mean caregiver and physician global assessment scores trended in a positive direction (6.8 and 6.9, respectively). The most common treatment emergent adverse events reported over the course of the study were headache (17.2%), injection site pain and worsening epilepsy (both 11.7%), injection site hemorrhage (9.4%) and vomiting and pyrexia (both 7.8%). Conclusions: The open-label continuation of diazepam AI for the treatment of ARS demonstrated effectiveness and was well tolerated.