Poster
117
(#117) Double-Blind and Open-Label Extension Results From a Phase 3 Trial of Seltorexant, Adjunctive to Antidepressants, in Adults With Major Depressive Disorder With Insomnia Symptoms
Psych Congress 2025
Abstract: Background: We report double-blind (DB) and open-label extension (OLE) results from a Phase-3 study (NCT04533529) of adjunctive seltorexant, a first-in-class, selective, orexin-2 receptor antagonist, in participants with major depressive disorder (MDD) with insomnia symptoms (IS) on background therapy with SSRI/SNRI.
Methods: Participants (18-74 years) had primary DSM-5 diagnosis of MDD without psychotic features and inadequate response to 1-2 antidepressants. Eligible DB-participants were randomized (1:1) to receive seltorexant-20mg or placebo for 6 weeks, while continuing baseline SSRI/SNRI. Primary endpoint was change from baseline to day-43 in MADRS score. Key secondary endpoints were changes from baseline to day-43 in MADRS without sleep item (MADRS-WOSI) score and Patient Reported Outcome Measurement Information System-Sleep Disturbance (PROMIS-SD-8a) T-score. Eligible participants from DB-phase received open-label seltorexant-20mg for 1 year in OLE.
Results: 586 participants with MDD received ≥1 study-drug dose (DB-safety-set); 419 with MDD with IS received ≥1 study-drug dose and had baseline MADRS score ≥24 (DB-efficacy set). Primary and key secondary endpoints significantly improved with seltorexant versus placebo at day-43; LS mean difference (95%CI;2-sided p) in MADRS: -2.6(-4.53,-0.74;p=0.007), MADRS-WOSI: -2.0(-3.75,-0.28;p=0.023), PROMIS-SD-8a: -3.7(-5.48,-2.00;p 0.001). TEAEs occurred in 104/283 (36.7%) seltorexant and 124/303 (40.9%) placebo recipients. 522 (96.7%) DB-participants entered OLE; 360 (69.0%) completed OLE. In OLE-participants who received ≥1 seltorexant dose, mean(SD) change in MADRS score from OLE-baseline to week-52: -11.0(10.55;n=359). No new safety concerns were identified.
Conclusions: Adjunctive seltorexant showed significant and clinically meaningful antidepressant effects, beyond improvement of IS, with safety profile similar to that of placebo. Depressive symptoms continued to improve in the OLE.
Short Description: We report double-blind (DB) and open-label extension (OLE) results from a Phase-3 trial (NCT04533529) of adjunctive seltorexant, in participants with major depressive disorder with insomnia symptoms on background SSRI/SNRI. Primary and key secondary efficacy endpoints significantly improved with seltorexant versus placebo at day-43 of DB phase, and depressive symptoms continued to improve in the OLE. The seltorexant safety profile was similar to that of placebo; no new safety concerns were identified with long-term seltorexant treatment.
Name of Sponsoring Organization(s): Johnson & Johnson
Methods: Participants (18-74 years) had primary DSM-5 diagnosis of MDD without psychotic features and inadequate response to 1-2 antidepressants. Eligible DB-participants were randomized (1:1) to receive seltorexant-20mg or placebo for 6 weeks, while continuing baseline SSRI/SNRI. Primary endpoint was change from baseline to day-43 in MADRS score. Key secondary endpoints were changes from baseline to day-43 in MADRS without sleep item (MADRS-WOSI) score and Patient Reported Outcome Measurement Information System-Sleep Disturbance (PROMIS-SD-8a) T-score. Eligible participants from DB-phase received open-label seltorexant-20mg for 1 year in OLE.
Results: 586 participants with MDD received ≥1 study-drug dose (DB-safety-set); 419 with MDD with IS received ≥1 study-drug dose and had baseline MADRS score ≥24 (DB-efficacy set). Primary and key secondary endpoints significantly improved with seltorexant versus placebo at day-43; LS mean difference (95%CI;2-sided p) in MADRS: -2.6(-4.53,-0.74;p=0.007), MADRS-WOSI: -2.0(-3.75,-0.28;p=0.023), PROMIS-SD-8a: -3.7(-5.48,-2.00;p 0.001). TEAEs occurred in 104/283 (36.7%) seltorexant and 124/303 (40.9%) placebo recipients. 522 (96.7%) DB-participants entered OLE; 360 (69.0%) completed OLE. In OLE-participants who received ≥1 seltorexant dose, mean(SD) change in MADRS score from OLE-baseline to week-52: -11.0(10.55;n=359). No new safety concerns were identified.
Conclusions: Adjunctive seltorexant showed significant and clinically meaningful antidepressant effects, beyond improvement of IS, with safety profile similar to that of placebo. Depressive symptoms continued to improve in the OLE.
Short Description: We report double-blind (DB) and open-label extension (OLE) results from a Phase-3 trial (NCT04533529) of adjunctive seltorexant, in participants with major depressive disorder with insomnia symptoms on background SSRI/SNRI. Primary and key secondary efficacy endpoints significantly improved with seltorexant versus placebo at day-43 of DB phase, and depressive symptoms continued to improve in the OLE. The seltorexant safety profile was similar to that of placebo; no new safety concerns were identified with long-term seltorexant treatment.
Name of Sponsoring Organization(s): Johnson & Johnson
