86: Brexanolone iv efficacy in postpartum depression in three pivotal trials: montgomery-åsberg depression rating scale assessment

Abstract

The investigational, positive allosteric modulator of ɣ-aminobutyric acid A (GABAA) receptors, brexanolone iv (BRX), was evaluated for efficacy and safety in women with postpartum depression (PPD) in 3 double-blind, placebo-controlled, randomized trials. BRX met the primary efficacy endpoint with a significantly greater change from baseline in Hamilton Rating Scale for Depression (HAM-D) total score at Hour 60 than placebo (PBO). This abstract presents the results of a secondary measure, the Montgomery-Åsberg Depression Rating Scale (MADRS). An umbrella protocol for the 3 studies allowed integrated dataset analysis. Women aged 18-45 years, ≤ 6 months postpartum, with PPD (i.e. major depressive episode no earlier than third trimester and no later than 4 weeks post-delivery) and a qualifying 17-item HAM-D total score (≥ 26 in Studies A and B; 20-25 in Study C) were enrolled. Randomized subjects received a single, continuous 60-hour infusion of PBO, BRX 60 μg/kg/hour (BRX60), or 90 μg/kg/hour (BRX90) and were followed through Day 30. Change from baseline in MADRS total score (MADRSts) was a secondary endpoint, analyzed by a mixed effects model for repeated measures (BRX90). Safety and tolerability were assessed by adverse event (AE) reporting and clinical laboratory testing (BRX60 and BRX90). Least squares mean (SE) change from baseline in MADRSts at Hour 60 in the PBO (N=107) or BRX90 (N=102) groups was -17.7 (1.2) or -23.5 (1.2) respectively. A significantly greater mean reduction versus PBO was achieved with BRX90 starting at Hour 24 and maintained through Day 7 (Figure). At Day 30, the mean reduction of BRX90 versus PBO was numerically greater. The most common AEs (≥ 10%) reported in all BRX subjects included headache, dizziness, and somnolence. Brexanolone iv was generally well tolerated and showed statistically significant greater reductions of depressive symptoms in women with PPD compared to PBO, as measured by MADRSts. The proposed mechanism of action of brexanolone iv (i.e., positive allosteric modulation of GABAA receptors) is a novel approach in the development of a therapeutic agent for PPD and, if regulatory approval is obtained, has the potential to provide meaningful new treatment options for women with PPD.