Supernus Pharmaceuticals, Inc., 9715 Key West Ave, Rockville, MD 20850.
Supernus Pharmaceuticals, Inc, Rockville, Maryland, USA.
J Clin Psychiatry. 2020 Oct 13;81(6):20m13395. doi: 10.4088/JCP.20m13395.
To assess the effects of a supratherapeutic dose of SPN-812, a drug currently under investigation as a treatment for attention-deficit/hyperactivity disorder, on cardiac repolarization (QTc) in healthy adults.
The study was conducted from June 27, 2018, to July 10, 2018. It had a double-blind, randomized, crossover design in which subjects received a 3-treatment sequence-placebo, 400 mg moxifloxacin, and 1,800 mg SPN-812 for 2 consecutive days (separated by at least a 3-day washout). The primary endpoint was the correlation between the change from baseline (CFB) in individual heart rate corrected QT interval (QTcI) (ΔQTcI) and viloxazine and 5-hydroxyviloxazine glucuronide (5-OH-VLX-gluc) plasma concentrations (Cps). The secondary endpoint was the time point placebo-adjusted CFB in QTcI (ΔΔQTcI) for viloxazine. For assay sensitivity, the correlations between moxifloxacin Cp and the ΔQTcI, and moxifloxacin and time point ΔΔQTcI were evaluated. Additional evaluations included Fridericia's formula QT correction, heart rate, and the PR and QRS intervals. Changes in electrocardiogram (ECG) morphology along with other safety parameters were also analyzed and reported.
The correlation between ΔQTcI and viloxazine Cp demonstrated a statistically significant negative slope (P = .0012). 5-OH-VLX-gluc Cp and ΔQTcI also demonstrated a statistically significant negative slope (P = .0007). Secondary time point analyses showed no effect of SPN-812 on QTcI. Assay sensitivity with moxifloxacin was confirmed. Safety parameters were acceptable.
This study demonstrated that SPN-812 had no effect on cardiac repolarization or other ECG parameters in healthy adults, suggesting that it is not associated with a risk for cardiac arrhythmias or other electrocardiographic parameters.
评估 SPN-812 超治疗剂量对健康成年人心脏复极化（QTc）的影响，SPN-812 是一种目前正在研究用于治疗注意缺陷/多动障碍的药物。
该研究于 2018 年 6 月 27 日至 7 月 10 日进行，采用双盲、随机、交叉设计，受试者接受 3 种治疗顺序（安慰剂、400mg 莫西沙星和 1800mg SPN-812，连续 2 天，间隔至少 3 天洗脱期）。主要终点是个体心率校正 QT 间期（QTcI）的基线变化（CFB）（ΔQTcI）与维拉佐酮和 5-羟基维拉佐酮葡萄糖醛酸（5-OH-VLX-gluc）血浆浓度（Cp）之间的相关性。次要终点是维拉佐酮校正的 QTcI（ΔΔQTcI）的安慰剂调整 CFB 时间点。为了评估检测灵敏度，还评估了莫西沙星 Cp 与 ΔQTcI 之间的相关性，以及莫西沙星与时间点 ΔΔQTcI 之间的相关性。其他评估包括 Fridericia 公式 QT 校正、心率以及 PR 和 QRS 间隔。还分析和报告了心电图（ECG）形态变化以及其他安全性参数。
ΔQTcI 与维拉佐酮 Cp 的相关性显示出统计学上显著的负斜率（P=.0012）。5-OH-VLX-gluc Cp 和 ΔQTcI 也显示出统计学上显著的负斜率（P=.0007）。次要时间点分析显示 SPN-812 对 QTcI 没有影响。莫西沙星的检测灵敏度得到确认。安全性参数是可以接受的。
这项研究表明，SPN-812 对健康成年人的心脏复极化或其他心电图参数没有影响，这表明它与心律失常或其他心电图参数无关。
