Child and Adolescent Psychiatry, Johannes Gutenberg University Mainz, Mainz, Germany.
Shire, Wayne, PA, USA.
Eur Child Adolesc Psychiatry. 2018 Oct;27(10):1283-1294. doi: 10.1007/s00787-018-1113-4. Epub 2018 Feb 13.
Data are reported from SPD503-318, a phase 3, open-label, safety study of guanfacine extended release (GXR) in European children and adolescents with attention-deficit/hyperactivity disorder (ADHD). Participants received dose-optimized GXR (1-7 mg/day) for up to 2 years. Of 215 enrolled participants, 214 were included in the safety population and 133 completed the study. Participants' mean age was 11.7 years and 73.8% were male. Overall, 177 participants (82.7%) experienced a treatment-emergent adverse event (TEAE). TEAEs reported in at least 10% of participants were somnolence (36.0%), headache (28.5%), fatigue (20.1%), and nasopharyngitis (11.7%). Serious TEAEs were reported in 4.7% of participants and TEAEs leading to discontinuation were reported in 3.3% of participants. There were no deaths. Mean z-scores for BMI were stable throughout the study. The incidence of sedative TEAEs (somnolence, sedation, and hypersomnia) peaked during week 3 and decreased thereafter. Small changes from baseline to the final assessment in mean supine pulse [- 5.5 bpm (standard deviation, 12.98)] and blood pressure [systolic, 0.6 mmHg (9.32); diastolic, 0.2 mmHg (9.17)] were reported. ADHD symptoms initially decreased and remained significantly lower than baseline at study endpoint. At the final assessment, the mean change in ADHD-RS-IV total score from baseline was - 19.8 (standard error of mean, 0.84; nominal p < 0.0001). In conclusion, GXR was well tolerated and more than 60% of participants completed the 2-year study.
数据来自 SPD503-318 研究，这是一项评估胍法辛缓释剂（GXR）在欧洲儿童和青少年注意力缺陷多动障碍（ADHD）中的安全性的 3 期、开放性标签研究。参与者接受了剂量优化的 GXR（1-7mg/天）治疗，时间长达 2 年。在 215 名入组的参与者中，214 名被纳入安全性人群，133 名完成了研究。参与者的平均年龄为 11.7 岁，73.8%为男性。总体而言，177 名参与者（82.7%）出现了治疗引起的不良事件（TEAE）。报告发生率至少为 10%的 TEAEs 包括嗜睡（36.0%）、头痛（28.5%）、疲劳（20.1%）和鼻咽炎（11.7%）。4.7%的参与者报告了严重的 TEAEs，3.3%的参与者报告了因 TEAEs 而停药。没有死亡报告。整个研究过程中，BMI 的平均 z 评分保持稳定。镇静性 TEAEs（嗜睡、镇静和催眠过度）的发生率在第 3 周达到峰值，此后逐渐下降。与基线相比，平均仰卧位脉搏（-5.5bpm，标准差 12.98）和血压（收缩压，0.6mmHg，9.32；舒张压，0.2mmHg，9.17）在最终评估时有较小的变化。ADHD 症状最初下降，在研究结束时仍显著低于基线。在最终评估时，ADHD-RS-IV 总分从基线的平均变化为-19.8（均数标准差，0.84；名义 p<0.0001）。总之，GXR 具有良好的耐受性，超过 60%的参与者完成了 2 年的研究。
