安非他明缓释剂治疗成人注意力缺陷多动障碍的安全性和有效性：2期研究结果

Safety and Efficacy of Centanafadine Sustained-Release in Adults With Attention-Deficit Hyperactivity Disorder: Results of Phase 2 Studies.

作者信息

Wigal Sharon B, Wigal Tim, Hobart Mary, Madera Jessica J, Baker Ross A, Kohegyi Eva, McKinney Anthony, Wilens Timothy E

机构信息

AVIDA Inc., Newport Beach, California, USA.

Otsuka Pharmaceutical Development & Commercialization, Inc., Rockville, Maryland, USA.

出版信息

Neuropsychiatr Dis Treat. 2020 Jun 8;16:1411-1426. doi: 10.2147/NDT.S242084. eCollection 2020.

PURPOSE

Two phase 2 studies evaluated the efficacy and tolerability of centanafadine sustained-release (SR) for adults with attention-deficit/hyperactivity disorder (ADHD).

PATIENTS AND METHODS

In a phase 2a, flexible-dose, single-blind study, 41 male patients (aged 18‒55 years) with a diagnosis of ADHD (based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) were titrated with centanafadine-SR 200‒300, 400, or 500 mg/d for 2 weeks, and then were treated with the titrated dose for 2 weeks. In a phase 2b, randomized, double-blind, placebo-controlled, crossover study, 85 male and female patients (aged 18‒60 years) with a diagnosis of ADHD (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition) were titrated to target doses of centanafadine-SR 400, 500, 600, or 800 mg/d over the course of 1 week, and then received their titrated dose for 3 weeks. The primary outcome in both studies was mean total ADHD Rating Scale-IV (ADHD-RS-IV) score.

RESULTS

In the phase 2a study, mean ADHD-RS-IV total score decreased by 21.41 (standard deviation 10.74) from the start of active centanafadine-SR treatment to the end of week 4 (<0.001). In the phase 2b study, centanafadine-SR treatment resulted in a statistically significant improvement in ADHD-RS-IV from baseline to week 3 compared with placebo (least-squares mean -16.5 vs -8.4; <0.001; effect size 0.66), with significant efficacy demonstrated as early as week 1. Centanafadine-SR was generally well tolerated at doses ≤400 mg. Most treatment-emergent adverse events (TEAEs) were mild or moderate; decreased appetite, headache, and nausea were the most frequently reported. In the 2 studies, 13 of 120 patients discontinued centanafadine-SR due to TEAEs; however, only 1 patient who received ≤400 mg discontinued due to a TEAE. No serious TEAEs were reported at any dose.

CONCLUSION

These results support the continued development of centanafadine-SR at doses up to 400 mg/d.

目的

两项2期研究评估了盐酸西他那非缓释片（SR）治疗成人注意力缺陷多动障碍（ADHD）的疗效和耐受性。

患者与方法

在一项2a期灵活剂量单盲研究中，41例诊断为ADHD（依据《精神疾病诊断与统计手册》第四版）的男性患者（年龄18 - 55岁）接受200 - 300、400或500 mg/d的盐酸西他那非缓释片滴定治疗2周，之后接受滴定剂量治疗2周。在一项2b期随机双盲安慰剂对照交叉研究中，85例诊断为ADHD（《精神疾病诊断与统计手册》第五版）的男性和女性患者（年龄18 - 60岁）在1周内滴定至目标剂量400、500、600或800 mg/d的盐酸西他那非缓释片，之后接受滴定剂量治疗3周。两项研究的主要结局均为ADHD评定量表-IV（ADHD-RS-IV）总分均值。

结果

在2a期研究中，从开始盐酸西他那非缓释片活性治疗至第4周结束，ADHD-RS-IV总分均值下降了21.41（标准差10.74）（<0.001）。在2b期研究中，与安慰剂相比，盐酸西他那非缓释片治疗从基线至第3周使ADHD-RS-IV有统计学显著改善（最小二乘均值-16.5对-8.4；<0.001；效应大小0.66），早在第1周即显示出显著疗效。剂量≤400 mg时，盐酸西他那非缓释片总体耐受性良好。大多数治疗中出现的不良事件（TEAE）为轻度或中度；食欲减退、头痛和恶心是最常报告的。在这两项研究中，120例患者中有13例因TEAE停用盐酸西他那非缓释片；然而，接受≤400 mg剂量治疗的患者中只有1例因TEAE停药。各剂量均未报告严重TEAE。