Trial results for a Phase 3 study (NCT04532749) investigating Seltorexant as adjunctive therapy for Major Depressive Disorder with Insomnia Symptoms were posted on ClinicalTrials.gov on 2025-06-04. The study found that the least square mean difference for change in Montgomery-Asberg Depression Rating Scale (MADRS) total score from baseline to Day 43 was -1.2 (95% CI: -4.0 to 1.64) for Seltorexant versus placebo, with a p-value of 0.411, indicating it did not meet statistical significance.
Background
The study investigated Seltorexant as an adjunctive therapy to antidepressants for adult and elderly participants with Major Depressive Disorder with Insomnia Symptoms (MDDIS) who had an inadequate response to current antidepressant therapy with a selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI).
Trial design
The study (NCT04532749) was a Phase 3, randomized, placebo-controlled trial that enrolled 212 participants. It investigated Seltorexant as adjunctive therapy in participants with Major Depressive Disorder with insomnia symptoms. Participants received either Seltorexant or placebo. The trial's overall status is TERMINATED. The primary endpoint, as indicated by the analysis, was the change from baseline to Day 43 in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score.
Key results
Key results from the trial included changes from baseline to Day 43 across several depression and sleep scales. For the primary outcome, the change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score:
- Participants receiving Seltorexant showed a mean change of -14.0 units on a scale (Standard Deviation: 10.46).
- Participants receiving placebo showed a mean change of -13.1 units on a scale (Standard Deviation: 9.51).
The Mixed Model Repeated Measures (MMRM) analysis for this outcome reported a least square (LS) mean difference of -1.2 (95.0% CI: -4.0 to 1.64) with a p-value of 0.411.
Other key measurements included:
- Change in MADRS Without Sleep Item (MADRS-WOSI) Total Score: Seltorexant mean change -12.0 units on a scale (SD: 9.27) vs. placebo mean change -11.3 units on a scale (SD: 8.44). The LS mean difference was -0.9 (95.0% CI: -3.41 to 1.59) with a p-value of 0.473. Formal statistical testing was not performed for this secondary endpoint as the primary endpoint did not achieve significance.
- Change in PROMIS-SD (Short Form 8a) T-score for Sleep Disturbance: Seltorexant mean change -13.7 T-score (SD: 11.06) vs. placebo mean change -11.9 T-score (SD: 11.83). The LS mean difference was -2.0 (95.0% CI: -4.87 to 0.85) with a p-value of 0.167. Formal statistical testing was not performed for this secondary endpoint.
- Change in 6-item MADRS (MADRS-6) Total Score: Seltorexant mean change -9.1 units on a scale (SD: 6.86) vs. placebo mean change -8.1 units on a scale (SD: 6.37).
- Percentage of Participants Achieving Response on Depressive Symptoms Scale (MADRS Total Score) at Day 43: 42.9% for Seltorexant vs. 36.3% for placebo.
- Change in Patient Health Questionnaire, 9-item (PHQ-9) Total Score: Seltorexant mean change -8.8 units on a scale (SD: 6.44) vs. placebo mean change -8.1 units on a scale (SD: 6.27).
What this means
The results indicate that Seltorexant, when used as adjunctive therapy, did not achieve statistical significance compared to placebo for its primary endpoint of improving depressive symptoms as measured by the MADRS Total Score. Due to the hierarchical testing sequence, formal statistical testing was not performed for the secondary endpoints, including MADRS-WOSI and PROMIS-SD scores. These findings suggest that Seltorexant did not demonstrate a statistically significant clinical benefit in this Phase 3 trial for Major Depressive Disorder with Insomnia Symptoms.
Source
The information for these trial results was sourced from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT04532749, titled "A Study of Seltorexant as Adjunctive Therapy to Antidepressants in Adult and Elderly Participants With Major Depressive Disorder With Insomn," were posted on 2025-06-04 on clinicaltrials.gov.