Kerrigan J F, Shields W D, Nelson T Y, Bluestone D L, Dodson W E, Bourgeois B F, Pellock J M, Morton L D, Monaghan E P
Barrow Neurological Institute, 500 W. Thomas Road, S-930, Phoenix, AZ 85013, USA.
Epilepsy Res. 2000 Dec;42(2-3):133-9. doi: 10.1016/s0920-1211(00)00170-4.
This is a multicenter, open-label, add-on trial, investigating the safety and efficacy of ganaxolone (GNX) in a population of children with refractory infantile spasms, or with continuing seizures after a prior history of infantile spasms. A total of 20 children aged 7 months to 7 years were enrolled in this dose-escalation study, after baseline seizure frequencies were established. Concomitant antiepilepsy drugs were maintained throughout the study period. The dose of GNX was progressively increased to 36 mg/kg/d (or to the maximally tolerated dose) over a period of 4 weeks, then maintained for 8 weeks before tapering and discontinuation. Seizure diaries were maintained by the families, and spasm frequency was compared with the baseline period. The occurrence of adverse events was clinically monitored, and global evaluations of seizure severity and response to treatment were obtained. A total of 16 of the 20 subjects completed the study, 15 of whom had refractory infantile spasms at the time of study enrollment. Spasm frequency was reduced by at least 50% in 33% of these subjects, with an additional 33% experiencing some improvement (25-50% reduction in spasm frequency). Ganaxolone was well tolerated, and adverse events attributed to GNX were generally mild. Ganaxolone was safe and effective in treating this group of refractory infantile spasms patients in an open-label, add-on trial. Further investigation with randomized, controlled study design is warranted.
这是一项多中心、开放标签、附加试验，旨在研究加奈索酮（GNX）在难治性婴儿痉挛症患儿群体或有婴儿痉挛症既往史且仍有癫痫发作的患儿中的安全性和有效性。在确定基线癫痫发作频率后，共有20名7个月至7岁的儿童参加了这项剂量递增研究。在整个研究期间维持使用抗癫痫药物。加奈索酮的剂量在4周内逐步增加至36mg/kg/d（或至最大耐受剂量），然后维持8周，之后逐渐减量并停药。家庭记录癫痫发作日记，并将痉挛频率与基线期进行比较。临床监测不良事件的发生情况，并对癫痫发作严重程度和治疗反应进行整体评估。20名受试者中有16名完成了研究，其中15名在研究入组时患有难治性婴儿痉挛症。这些受试者中有33%的痉挛频率降低了至少50%，另有33%有一定改善（痉挛频率降低25%-50%）。加奈索酮耐受性良好，归因于GNX的不良事件通常较轻。在一项开放标签、附加试验中，加奈索酮治疗这组难治性婴儿痉挛症患者安全有效。有必要采用随机对照研究设计进行进一步研究。
