The objective of this Phase 3, double-blind, randomized, placebo-controlled study was to evaluate the efficacy and safety of SAGE-217 in the treatment of adult subjects with major depressive disorder (MDD).

An estimated 300 million people worldwide are affected with MDD. Dysregulation of ?-aminobutyric acid (GABA) signaling has been associated with MDD. SAGE-217 is an investigational, oral, neuroactive steroid and GABA_A receptor positive allosteric modulator that has demonstrated reductions in depressive symptoms in a Phase 2 double-blind, randomized, placebo-controlled study in MDD.

Subjects with MDD were randomized 1:1:1 to SAGE-217 30 mg, 20 mg, or placebo capsules. Subjects were treated for 14 days, then followed weekly for 4-weeks, and then again after four more weeks, and then again every 8 weeks through 182-days. The primary endpoint was change from baseline in Hamilton Depression Rating Scale (HAM-D) total score at Day 15 compared with placebo, assessed by a statistical analysis using an MMRM. Safety and tolerability were assessed by standard clinical assessments.

The double-blind treatment and the initial 4-week follow-up periods of this Phase 3 study will be completed by the end of 2019. Change in HAM-D scores against placebo will be reported at all assessment points. Data will be reported on HAM-D time points at Days 3-42 (including Day 15), HAM-D response (≥50% reduction) and remission (≤7) rates, Montgomery–Åsberg Depression Rating Scale (MADRS), and Hamilton Anxiety Rating Scale (HAM-A) scores will be reported as secondary endpoints. Safety and tolerability data will also be presented.

This Phase 3 study aims to confirm and extend the previous results in a larger study population utilizing two dose groups versus placebo. These results have the potential to be an important milestone in the development of SAGE-217 in the treatment of individuals with MDD.