Evaluation of the Effect of SPN-812 (Viloxazine Extended-Release) on QTc Interval in Healthy Adults

Abstract

ABSTRACT Objective: To assess the effects of a supratherapeutic dose of SPN-812, a drug currently under investigation as a treatment for ADHD, on cardiac repolarization (QTc) in healthy adults. Methods: The study was conducted from 27 Jun 2018 to 10 Jul 2018. This was a double-blind, randomized, crossover design where subjects received a 3 treatment sequence—placebo, 400 mg moxifloxacin, and 1800 mg SPN-812 for 2 consecutive days (separated by at least a 3-day washout). The primary endpoint was the change from baseline (CFB) in QTcI (ΔQTcI) for 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 correlation between Cp of moxifloxacin ΔQTcI, and the time point ΔΔQTcI were tested. Additional evaluations included Fridericia's formula QT correction (QTcF), heart rate (HR), the PR, and QRS intervals. Changes in ECG morphology along with other safety parameters were also analyzed and reported. Results: The correlation between ΔQTcI and viloxazine Cp demonstrated a statistically significant negative slope (p=0.0012). 5-OH-VLX-gluc Cp and ΔQTcI also demonstrated a statistically significant negative slope (p=0.0007). Secondary time point analyses showed no effect of SPN-812 on QTcI. Assay sensitivity with moxifloxacin was confirmed. Safety parameters were acceptable. Conclusions: This study demonstrated that SPN-812 had no effect on cardiac repolarization or other ECG parameters in healthy adults, suggesting it is not associated with a risk for cardiac arrhythmias or other electrocardiographic parameters.