OBJECTIVES : Patient reported outcomes (PROs) are directly reported by the patient, without interpretation of patient response by a clinician. Incorporation of PROs into clinical trials allows for a more complete assessment of investigational therapies. This analysis evaluates the antidepressant effects of AXS-05 compared to placebo using PROs.

METHODS : GEMINI (N=327) was a randomized, double-blind, placebo-controlled, multi-center trial, in which adults with moderate-severe MDD were randomized 1:1 to AXS-05 (dextromethorphan HBr 45 mg-bupropion HCl 105 mg) or placebo, twice daily for 6 weeks. The primary efficacy outcome, change from baseline in MADRS total score, demonstrated a rapid and statistically significant improvement starting at Week 1, which was maintained through Week 6 (primary timepoint). PROs for depression used in this trial were: the Quick Inventory of Depressive Symptomatology (Self-Report) (QIDS-SR-16) and the Patient Global Impression of Improvement (PGI-I) for depression. Clinician-reported measures in GEMINI included the MADRS and CGI-I.

RESULTS : Improvements from baseline on the QIDS-SR-16, were statistically significant for AXS-05 vs. placebo beginning at Week 1 (3.7 vs. 2.5, p=0.010) and at every timepoint thereafter: Week 2 (5.6 vs. 3.6, respectively, p<0.001), Week 3 (6.5 vs 4.1, respectively, p<0.001), Week 4 (7.5 vs 4.9, p<0.001), and Week 6 (7.7 vs 5.7, respectively, p=0.001).

Percentages of patients reporting very much/much improved on the PGI-I were statistically significant for AXS-05 vs. placebo beginning at Week 1 (13.5% vs. 4.9%, p=0.008) and at every timepoint thereafter: Week 2 (30.0% vs. 18.2%, p=0.015), Week 3 (43.2% vs. 18.2%, p<0.001), Week 4 (46.9% vs. 28.0%, p=0.001), and Week 6 (47.2% vs. 31.3%, p=0.007).

CONCLUSIONS : Patients self-reported that treatment with AXS-05 resulted in rapid, substantial, and statistically significant improvements in depressive symptoms consistent with clinician-reported measures (MADRS, CGI-I), starting at Week 1 and sustained through Week 6.