Le Bonheur Comprehensive Epilepsy Program & Neuroscience Institute, Le Bonheur Children's Hospital, Memphis, Tennessee.
Pediatric Neurology, University of Tennessee Health Science Center, Memphis, Tennessee.
Epilepsia. 2019 Sep;60(9):1809-1819. doi: 10.1111/epi.16300. Epub 2019 Jul 29.
To evaluate safety- and seizure-related outcomes with repeated intermittent use of a novel formulation of midazolam administered as a single-dose nasal spray (MDZ-NS) in the outpatient treatment of patients experiencing seizure clusters (SCs).
In this open-label extension trial (ClinicalTrials.gov NCT01529034), patients aged ≥12 years and on a stable regimen of antiepileptic drugs who completed the original phase III, randomized controlled trial were enrolled. Caregivers administered MDZ-NS 5 mg when patients experienced SCs; a second dose could be given if seizures did not terminate within 10 minutes or recurred within 10 minutes-6 hours. Patients were monitored for treatment-emergent adverse events (TEAEs) throughout, and the main seizure-related outcome was treatment success, defined as seizure termination within 10 minutes and no recurrence 10 minutes-6 hours after drug administration.
Of 175 patients enrolled, 161 (92.0%) received ≥1 MDZ-NS dose, for a total of 1998 SC episodes. Median time spent by patients in the trial was 16.8 months (range = 1-55.7 months). TEAEs were experienced by 40.4% of patients within 2 days of drug administration and 57.1% overall. TEAEs reported by most patients (within 2 days and overall) were nasal discomfort (12.4%) and somnolence (9.3%). One patient each discontinued due to treatment-related nasal discomfort and somnolence. There were no patients with treatment-related respiratory depression, and none with TEAEs indicative of drug abuse or dependence. Treatment success criteria were met in 55% (1108/1998) of SC episodes after administration of a single 5-mg dose and in 80.2% (617/769) with the second dose. Treatment success was consistent over treated episode number.
Repeated, intermittent, acute treatment of patients experiencing SCs with MDZ-NS in the outpatient setting was well tolerated over an extended period, with maintenance of efficacy suggesting lack of development of tolerance.
评估在门诊治疗癫痫发作群（SCs）患者中，使用新型咪达唑仑鼻喷雾剂（MDZ-NS）单次剂量重复间歇性使用的安全性和与癫痫发作相关的结果。
在这项开放标签扩展试验（ClinicalTrials.gov NCT01529034）中，纳入了完成原始 III 期、随机对照试验且年龄≥12 岁、正在使用稳定抗癫痫药物的患者。当患者出现 SCs 时，护理人员给予 MDZ-NS 5mg；如果癫痫发作在 10 分钟内未终止或在 10 分钟至 6 小时内复发，则可以给予第二剂。整个过程中，患者均接受治疗出现的不良事件（TEAEs）监测，主要的癫痫发作相关结局是治疗成功，定义为在给药后 10 分钟内终止癫痫发作，且在给药后 10 分钟至 6 小时内无复发。
175 名入组患者中，161 名（92.0%）患者接受了≥1 次 MDZ-NS 剂量，共发生 1998 次 SC 发作。患者在试验中的中位时间为 16.8 个月（范围=1-55.7 个月）。给药后 2 天内，40.4%的患者发生 TEAEs，总体发生率为 57.1%。大多数患者（给药后 2 天内和总体）报告的 TEAEs 为鼻不适（12.4%）和嗜睡（9.3%）。各有 1 名患者因与治疗相关的鼻不适和嗜睡而停药。无患者出现与治疗相关的呼吸抑制，也无患者出现与药物滥用或依赖相关的 TEAEs。单次 5mg 剂量给药后，1998 次 SC 发作中有 55%（1108/1998）符合治疗成功标准，第二次剂量后有 80.2%（617/769）符合治疗成功标准。随着治疗发作次数的增加，治疗成功率保持一致。
在门诊环境中，使用新型咪达唑仑鼻喷雾剂（MDZ-NS）对出现 SCs 的患者进行重复、间歇性、急性治疗，在延长的时间内具有良好的耐受性，疗效维持表明不存在耐药性的发展。
