CGI-I

CGI-S

QIDS-SR-16

PGI-I

Statistically significant symptom improvement on the CGI-I scale as early as Week 1 and sustained at Week 6^1-4*^†

Symptom improvement on the CGI-I scale vs placebo^1-4*^†

Significantly more patients taking AUVELITY had symptoms that were
"very much improved"
or "much improved"
at Week 1 vs placebo (P=0.035).
This increase was sustained
at Week 6 (P=0.016).¹

P-values for Weeks 2 to 4 were not adjusted for multiplicity and are therefore not presented.

GEMINI Study Design

Footnotes and Definitions

References

Reduction on the CGI-S scale from Week 1 to Week 6^1-3*^†

Change in severity of symptoms
on the CGI-S scale vs placebo^1-3

Statistically significant
improvement in
symptom severity at
Week 6 vs placebo
(P=0.002)¹

P-values for Weeks 1 to 4 were not adjusted for multiplicity and are therefore not presented.

GEMINI Study Design

Footnotes and Definitions

References

QIDS-SR-16 scores decreased from Week 1 to Week 6^1-3

Change in QIDS-SR-16 score vs placebo^1-3*^†

Depressive symptom severity was measured based on domains such as sleep, mood, and suicidal ideation.³

P-values for comparisons were not adjusted for multiplicity and are therefore not presented.

GEMINI Study Design

Footnotes and Definitions

References

More patients reported being "very much improved" or "much improved" on the PGI-I scale from Week 1 through Week 6¹

PGI-I vs placebo^1-4*^†

Global improvement or worsening of mental illness was measured.⁴
P-values for comparisons were not adjusted for multiplicity and are therefore not presented.

GEMINI Study Design

Footnotes and Definitions

References

GEMINI Phase 3 Study Design¹

Primary Endpoint¹

LS mean change from baseline in MADRS total score at Week 6.

Key Secondary Endpoints¹

LS mean change in MADRS total score from baseline at Week 1
LS mean change in MADRS total score from baseline at Week 2
Percentage of patients achieving response (≥50% reduction in MADRS total score from baseline) at Week 6
Percentage of patients achieving remission (MADRS total score ≤10) at Week 2

Other Secondary Endpoints¹

Clinical Global Impression-Improvement (CGI-I)
Clinical Global Impression-Severity (CGI-S)
Quality of Life Enjoyment and Satisfaction Questionnaire‑Short Form (Q‑LES‑Q‑SF)
Sheehan Disability Scale (SDS)
Patient Global Impression of Improvement (PGI‑I)
Quick Inventory of Depressive Symptomatology‑Self‑Report (16 items) (QIDS‑SR‑16)

Efficacy Assessments

Efficacy assessments were performed at Weeks 1, 2, 3, 4, and 6 on the mITT population. The mITT population was defined as all randomized patients who took at least 1 dose of study drug and had at least 1 post-baseline assessment. Examination of demographic subgroups by age, sex, and race did not suggest differences on the primary endpoint.¹

Footnotes and Definitions

BID=twice a day; LS=least squares; MADRS=Montgomery-Åsberg Depression Rating Scale; mITT=modified intention-to-treat.

References

losifescu DV, Jones A, O'Gorman C, et al. Efficacy and safety of AXS-05 (dextromethorphan-bupropion) in patients with major depressive disorder: a phase 3 randomized clinical trial (GEMINI). J Clin Psychiatry. 2022;83(4):21ml4345.

Patients with moderate to severe MDD were evaluated in the GEMINI trial¹

Not actual patients.

Demographic and baseline disease characteristics were generally similar across both treatment groups

Footnotes and Definitions

AA=African American; BID=twice a day; BMI=body mass index; MADRS=Montgomery-Åsberg Depression Rating Scale; MDD=major depressive disorder; PHQ-9=Patient Health Questionnaire-9.

References

losifescu DV, Jones A, O'Gorman C, et al. Efficacy and safety of AXS-05 (dextromethorphan-bupropion) in patients with major depressive disorder: a phase 3 randomized clinical trial (GEMINI). J Clin Psychiatry. 2022;83(4):21ml4345.
Hawley CJ, Gale TM, Smith PS, et al. Equations for converting scores between depression scales (MADRS, SRS, PHQ-9 and BDI-II): good statistical, but weak idiographic, validity. Hum Psychopharmacol. 2013;28:544-551.

Statistically significant symptom improvement on the CGI-I scale as early as Week 1 and sustained at Week 61-4*†

Symptom improvement on the CGI-I scale vs placebo1-4*†

Reduction on the CGI-S scale from Week 1 to Week 61-3*†

Change in severity of symptomson the CGI-S scale vs placebo1-3

QIDS-SR-16 scores decreased from Week 1 to Week 61-3

Change in QIDS-SR-16 score vs placebo1-3*†

More patients reported being "very much improved" or "much improved" on the PGI-I scale from Week 1 through Week 61

PGI-I vs placebo1-4*†

Footnotes and Definitions

Footnotes and Definitions

Footnotes and Definitions

Footnotes and Definitions

References

References

References

References

CGI-I

CGI-S

QIDS-SR-16

PGI-I

GEMINI Phase 3 Study Design1

Efficacy Assessments

Footnotes and Definitions

References

Patients with moderate to severe MDD were evaluated in the GEMINI trial1

Footnotes and Definitions

References

Symptom improvement on the CGI-I scale vs placebo1-4*†

Change in severity of symptoms on the CGI-S scale vs placebo1-3*†

Change in QIDS-SR-16 score vs placebo1-3*†

PGI-I vs placebo1-4*†

Statistically significant symptom improvement on the CGI-I scale as early as Week 1 and sustained at Week 6^1-4*^†

Symptom improvement on the CGI-I scale vs placebo^1-4*^†

Reduction on the CGI-S scale from Week 1 to Week 6^1-3*^†

Change in severity of symptoms
on the CGI-S scale vs placebo^1-3

QIDS-SR-16 scores decreased from Week 1 to Week 6^1-3

Change in QIDS-SR-16 score vs placebo^1-3*^†

More patients reported being "very much improved" or "much improved" on the PGI-I scale from Week 1 through Week 6¹

PGI-I vs placebo^1-4*^†

GEMINI Phase 3 Study Design¹

Patients with moderate to severe MDD were evaluated in the GEMINI trial¹

Symptom improvement on the CGI-I
scale vs placebo^1-4*^†

Change in severity of symptoms
on the CGI-S scale vs placebo^1-3*^†

Change in QIDS-SR-16 score vs placebo^1-3*^†

PGI-I vs placebo^1-4*^†