BACKGROUND Fragile X syndrome (FXS) is characterized by a range of developmental, neuropsychiatric, and behavioral symptoms that cause significant impairment in those with the disorder. Cannabidiol (CBD) holds promise as a potential treatment for FXS symptoms due to its safety profile and positive effects on a number of emotional and behavioral symptoms associated with FXS. The aim of the current study was to evaluate the safety, tolerability, and initial efficacy of ZYN002, a transdermal CBD gel, in a pediatric population with FXS. METHODS Twenty children and adolescents (aged 6-17 years) with a diagnosis of FXS (confirmed through molecular documentation of FMR1 full mutation) were enrolled in an open-label, multi-site, trial of ZYN002. Transdermal CBD gel was administered twice daily for 12 weeks, titrated from 50 mg to a maximum daily dose of 250 mg. The primary efficacy endpoint was change from screening to week 12 on the Anxiety, Depression, and Mood Scale (ADAMS). Secondary endpoint measures included the Aberrant Behavior Checklist-Community for FXS (ABC-CFXS), Pediatric Anxiety Rating Scale (PARS-R), Pediatric Quality of Life Inventory (PedsQL™), three Visual Analogue Scales (VAS), and the Clinical Global Impression Scale-Severity (CGI-S) and Improvement (CGI-I). RESULTS The majority of treatment-emergent AEs (reported by 85% of participants) were mild in severity (70%), and no serious adverse events were reported. There was a statistically significant reduction in ADAMS total score from screening to week 12 and significant reductions on nearly all other secondary endpoints, including all ADAMS subscales (except depressed mood), all ABC-CFXS subscale scores (e.g., social avoidance, irritability), PARS-R total severity score, and PedsQL total score. CONCLUSIONS ZYN002 was well tolerated and produced clinically meaningful reductions in anxiety and behavioral symptoms in children and adolescents with FXS. These findings support further study of ZYN002 in a randomized, well-controlled trial for the treatment of behavioral symptoms of FXS. TRIAL REGISTRATION ANZCTR, ACTRN12617000150347 Registered 27 January 2017.

中文翻译：

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1/2期开放标签评估经皮大麻素（ZYN002）在治疗儿童脆性X综合征中的安全性，耐受性和有效性。

背景技术脆性X综合征（FXS）的特征在于一系列发展，神经精神病学和行为症状，这些症状导致患有该疾病的人明显受损。卡纳比多醇（CBD）由于其安全性和对与FXS相关的许多情绪和行为症状的积极影响，有望成为FXS症状的潜在治疗方法。本研究的目的是评估经皮CBD凝胶剂ZYN002在有FXS患儿的人群中的安全性，耐受性和初始疗效。方法将20名诊断为FXS的儿童和青少年（6-17岁）（通过FMR1全突变的分子文件确认）纳入ZYN002的开放标签，多站点试验。每天两次经皮CBD凝胶给药，持续12周，从50毫克滴定至每日最大250毫克剂量。主要功效终点是焦虑，抑郁和情绪量表（ADAMS）从筛查到第12周的变化。次要终点指标包括FXS的异常行为清单-社区（ABC-CFXS），小儿焦虑评分量表（PARS-R），小儿生活质量量表（PedsQL™），三个视觉类比量表（VAS）和临床全球量表印象量表严重性（CGI-S）和改善（CGI-1）。结果大多数出现治疗的AE（由85％的参与者报告）严重程度较轻（70％），并且未报告严重的不良事件。从筛查到第12周，ADAMS总分在统计学上显着降低，并且几乎所有其他次要终点（包括所有ADAMS分量表（情绪低落除外））均显着降低，所有ABC-CFXS子量表得分（例如，社交回避，烦躁不安），PARS-R总严重程度得分和PedsQL总得分。结论ZYN002具有良好的耐受性，并在具有FXS的儿童和青少年中产生了临床上有意义的减轻焦虑和行为症状的方法。这些发现为ZYN002在FXS行为症状治疗的随机对照试验中的进一步研究提供了支持。ANZCTR审判注册号ACTRN12617000150347,2017年1月27日注册。FXS行为症状治疗的对照试验。ANZCTR审判注册号ACTRN12617000150347,2017年1月27日注册。FXS行为症状治疗的对照试验。ANZCTR审判注册号ACTRN12617000150347,2017年1月27日注册。