A phase 3, multicenter, double-blind, randomized, placebo-controlled clinical trial to verify the efficacy and safety of ansofaxine (LY03005) for major depressive disorder

Abstract

Major depressive disorder (MDD) is the most prevalent form of depression and is becoming a great challenge for public health and medical practice. Although first-line antidepressants offer therapeutic benefits, about 35% of depressed patients are not adequately treated, creating a substantial unmet medical need. A multicenter, double-blind, randomized, placebo-controlled phase 3 clinical trial was conducted in patients with MDD in China to assess the efficacy and safety of ansofaxine (LY03005), a potential triple reuptake inhibitor of serotonin, norepinephrine, and dopamine. Eligible 588 MDD patients were included and randomly assigned (1:1:1) to 8-week treatment with ansofaxine 80 mg/day(n = 187), ansofaxine 160 mg/day(n = 186), or placebo(n = 185). The primary efficacy endpoint was the Montgomery-Åsberg Depression Rating Scale (MADRS) total score change from baseline to the end of the study. Safety indexes included adverse events, vital signs, physical examination, laboratory tests, 12-lead electrocardiogram (ECG), and evaluation of suicide tendency and sexual function. Significant differences were found in mean changes in MADRS total score at week 8 in the two ansofaxine groups (80 mg, −20.0; 160 mg, −19.9) vs. placebo (−14.6; p < 0.0001). All doses of ansofaxine were generally well-tolerated. Treatment-emergent adverse events (TEAEs) were reported by 137 (74.46%) patients in ansofaxine 80 mg group, 144 (78.26%) patients in ansofaxine 160 mg and 125 (67.93%) patients in the placebo group. The incidence of treatment-related adverse events (TRAEs) was 59.2% (109 patients), 65.22% (120 patients) in the 80, 160 mg ansofaxine groups, and 45.11% (83 patients) in the placebo group. The initial results of this trial indicate that ansofaxine at both the 80 mg/day and 160 mg/day was effective and safe in adult patients with MDD. ClinicalTrials.gov Identifier: NCT04853407.

A 6-week, phase IIb, randomized, double-blind, placebo-controlled trial of Anyu Peibo capsules for the treatment of major depressive disorder in adults

“…These rates were comparable to those reported in a previous study including SSRIs, SNRIs and the novel antidepressants vortioxetine and vilazodone (the response rate was 53–74%, and the remission rate was 31–46%). 29–31 However, the improvements in the placebo group (least-squares mean difference in change, 14.51) were higher than those seen in another study (least-squares mean difference in change: −11.0, 32 −10.3, 33 respectively), suggesting a slightly stronger placebo effect.…”

“…35 In contrast, the 1.23% rate of discontinuation due to AEs for the placebo group in our trial was lower than the 4% average reported for the placebo arms in that same meta-analysis. Additionally, when comparing Anyu Peibo capsules to other commonly prescribed antidepressants, the discontinuation rate for venlafaxine (37.5–225 mg/day) was 12%, while for desvenlafaxine, the discontinuation rates were 4.1% 31 at 50 mg/day and 8.5% at 100 mg/day. For vortioxetine, the discontinuation rates were 5%, 6%, 8%, and 8% for doses of 5, 10, 15, and 20 mg/day, respectively.…”

“…34 Specifically, for the medication escitalopram, the incidence of TEAEs ranged from 73.3% to 73.6%, while that of other SSRIs such as citalopram, fluoxetine, paroxetine, and sertraline was 78.2%. 31 Additionally, SNRIs (venlafaxine and duloxetine) had a TEAE incidence rate of 77.4%. 31 In comparison, the AE incidence rate of 48.15% for the placebo group in this trial was lower than the 63.0% average reported for the placebo arms in a meta-analysis.…”

“…31 Additionally, SNRIs (venlafaxine and duloxetine) had a TEAE incidence rate of 77.4%. 31 In comparison, the AE incidence rate of 48.15% for the placebo group in this trial was lower than the 63.0% average reported for the placebo arms in a meta-analysis. 34 In terms of discontinuation rates due to TEAEs, the Anyu Peibo capsule group exhibited favorable results.…”

“…The incidence rate of treatment-emergent adverse events (TEAEs) observed in this study was 52.44%, which was lower than the findings of some meta-analyses. 31 An average incidence rate of 76.4% was reported for antidepressant arms in a large meta-analysis of placebo-controlled depression trials. 34 Specifically, for the medication escitalopram, the incidence of TEAEs ranged from 73.3% to 73.6%, while that of other SSRIs such as citalopram, fluoxetine, paroxetine, and sertraline was 78.2%.…”