Pediatric Neurology Center, Dana-Dwek Children's Hospital, Tel Aviv Medical Center, Israel; Sackler Faculty of Medicine, Tel Aviv University, Israel.
Pediatric Neurology Center, Dana-Dwek Children's Hospital, Tel Aviv Medical Center, Israel; Sackler Faculty of Medicine, Tel Aviv University, Israel.
Epilepsy Behav. 2019 Sep;98(Pt A):233-237. doi: 10.1016/j.yebeh.2019.07.007. Epub 2019 Aug 5.
Several works have reported on the antiepileptic impact of cannabis-based preparations in patients with treatment-resistant epilepsy (TRE). However, current formulations suffer from low bioavailability and side effects. PTL-101, an oral formulation containing highly purified cannabidiol (CBD) embedded in seamless gelatin matrix beadlets was designed to enhance bioavailability and maintain a constant gastrointestinal transit time.
This phase II, prospective study was open to pediatric patients with TRE on stable antiepileptic drugs' (AEDs) doses, who experienced ≥4 seizures within four weeks of enrolment and with a history of ≥4 AEDs failing to provide seizure control. Following a 4-week observation period, patients began a 2-week dose-titration phase (up to ≤25mg/kg or 450mg, the lower of the two), followed by a 10-week maintenance treatment period. Caregivers recorded seizure frequency, type, and severity and ranked their global impressions after 7 and 12weeks of treatment. Responders were those showing a ≥50% reduction from baseline monthly seizure frequency. Safety assessments monitored vital signs, adverse effects, physical and neurological exams, and laboratory tests.
Sixteen patients (age: 9.1±3.4) enrolled in the study; 11 completed the full treatment program. The average maintenance dose was 13.6±4.2mg/kg. Patient adherence to treatment regimens was 96.3±9.9%. By the end of the treatment period, 81.9% and 73.4±24.6% (p<0.05) reductions from baseline median seizure count and monthly seizure frequency, respectively, were recorded. Responders' rate was 56%; two patients became fully seizure-free. By study end, 8 (73%) caregivers reported an improved/very much improved condition, and 9 (82%) reported reduced/very much reduced seizure severity. Most commonly reported treatment-related adverse effects were sleep disturbance/insomnia, (4 (25.0%) patients), followed by somnolence, increased seizure frequency, and restlessness (3 patients each (18.8%)). None were serious or severe, and all resolved.
PTL-101 was safe and tolerable for use and demonstrated a potent seizure-reducing effect among pediatric patients with TRE.
几项研究报告了大麻制剂在治疗抵抗性癫痫（TRE）患者中的抗癫痫作用。然而，目前的制剂存在生物利用度低和副作用的问题。PTL-101 是一种口服制剂，含有高度纯化的大麻二酚（CBD）嵌入无缝明胶基质珠粒中，旨在提高生物利用度并保持恒定的胃肠道转运时间。
这是一项 II 期、前瞻性研究，对正在接受稳定剂量抗癫痫药物（AEDs）治疗的 TRE 儿科患者开放，这些患者在入组四周内有≥4 次发作，且有≥4 种 AEDs 治疗失败未能控制发作的病史。在 4 周观察期后，患者开始进行 2 周的剂量滴定期（最高可达≤25mg/kg 或 450mg，以两者中较低者为准），然后进行 10 周的维持治疗期。照顾者在治疗 7 周和 12 周后记录癫痫发作的频率、类型和严重程度，并对其总体印象进行排名。反应者是指与基线每月发作频率相比减少≥50%的患者。安全性评估监测生命体征、不良反应、身体和神经检查以及实验室检查。
16 名患者（年龄：9.1±3.4）入组该研究；11 名患者完成了完整的治疗方案。维持治疗的平均剂量为 13.6±4.2mg/kg。患者对治疗方案的依从性为 96.3±9.9%。治疗期末，中位发作次数和每月发作频率分别较基线降低了 81.9%和 73.4±24.6%（p<0.05）。反应者的比例为 56%；两名患者完全无癫痫发作。研究结束时，8 名（73%）照顾者报告病情改善/大大改善，9 名（82%）报告癫痫发作严重程度减轻/大大减轻。最常见的与治疗相关的不良反应是睡眠障碍/失眠（4 名（25.0%）患者），其次是嗜睡、发作频率增加和不安（各 3 名患者（18.8%））。均不严重或严重，且均已解决。
PTL-101 对 TRE 儿科患者使用安全且耐受良好，并显示出强大的抗癫痫作用。
