Efficacy, Safety, and Tolerability of Ansofaxine (Ly03005) Extended-Release Tablet for Major Depressive Disorder: A Randomized, Double-Blind, Placebo Controlled, Dose-Finding, Phase 2 Clinical Trial

BACKGROUND Ansofaxine (LY03005) extended-release (ER) tablet is a potential triple reuptake inhibitor of serotonin, norepinephrine, and dopamine. This study assessed the efficacy, safety, and appropriate dosage of ansofaxine for the treatment of major depressive disorder (MDD). METHOD A multicenter, randomized, double-blind, placebo-controlled, dose-finding, Phase 2 clinical trial was conducted in China. Eligible patients with MDD (18-65 years) were randomly assigned to receive fixed-dose ansofaxine ER tablets (40, 80, 120, or 160 mg/day) or placebo for 6 weeks. The primary outcome measure was a change in the total score on the 17-item Hamilton Depression Rating Scale (HAMD17) from baseline to week 6. RESULT A total of 260 patients were recruited from October 2015 to September 2017. 255 patients received the study drug as the following: 40 mg (n = 52), 80 mg (n = 52), 120 mg (n = 51), and 160 mg (n = 51) ansofaxine and placebo (n = 49). Significant differences were found in mean changes in HAMD17 total scores at week 6 in the four ansofaxine groups vs. placebo (-12.46; χ  2 = -9.71, p = 0.0447). All doses of ansofaxine were generally well-tolerated. Treatment-related adverse events (TRAEs) occurred in 141 patients (303 cases), giving TRAEs incidence rates of 51.92%, 65.38%, 56.86%, and 62.75%in the 40, 80, 120, and 160 mg ansofaxine groups and 38.78% in the placebo group. CONCLUSION Active doses (40, 80, 120, and 160 mg per day) of ansofaxine in a controlled setting were safe, tolerated, and effective in improving depression symptoms in MDD patients.