Trial results for a Phase 3 study evaluating seltorexant as adjunctive therapy for Major Depressive Disorder with Insomnia Symptoms (MDDIS) were posted on ClinicalTrials.gov on 2023-04-25. The study demonstrated a statistically significant improvement in depressive symptoms, with seltorexant 20 mg showing a least square (LS) mean difference of -2.6 in Montgomery-Asberg Depression Rating Scale (MADRS) total score compared to placebo (p=0.007).
Background
The study investigated seltorexant as an adjunctive therapy for adult and elderly participants diagnosed with Major Depressive Disorder with Insomnia Symptoms (MDDIS). These participants had previously shown an inadequate response to current antidepressant therapy, specifically selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs).
Trial design
The Phase 3 study (NCT04533529) was completed with an enrollment of 588 participants. The trial's primary purpose was to assess the efficacy of seltorexant compared with placebo as adjunctive therapy in improving depressive symptoms in participants with MDDIS. The study included a double-blind treatment phase followed by a long-term safety extension treatment phase.
Key results
In the double-blind treatment phase, the change from baseline to Day 43 in the Montgomery-Asberg Depression Rating Scale (MADRS) total score was measured:
- Participants receiving seltorexant 20 mg as adjunctive therapy showed a mean change of -12.9 (Standard Deviation 9.63) units on the scale.
- Participants receiving placebo as adjunctive therapy showed a mean change of -10.5 (Standard Deviation 10.26) units on the scale.
A mixed model repeated measures (MMRM) analysis indicated a statistically significant least square (LS) mean difference of -2.6 (95% CI -4.53 to -0.74) between seltorexant 20 mg and placebo, with a p-value of 0.007. Additional MMRM analyses also showed LS mean differences of -2.0 (95% CI -3.75 to -0.28, p=0.023) and -3.7 (95% CI -5.48 to -2.0, p=0.001).
Safety outcomes from the open-label (OL) treatment phase included:
- Treatment Emergent Adverse Events (TEAEs): 167 participants in the group that switched from placebo to seltorexant 20 mg, and 163 participants in the group that continued seltorexant 20 mg.
- Treatment-Emergent Adverse Events of Special Interest (AESI): 10 participants in the group that switched from placebo to seltorexant 20 mg, and 8 participants in the group that continued seltorexant 20 mg.
- Changes in vital signs (blood pressure) from baseline ranged from mean changes of 0.1 (SD 8.22) to 0.9 (SD 8.38) mmHg, and 0.5 (SD 10.38) to -0.5 (SD 11.29) mmHg.
- Changes in Body Mass Index (BMI) from baseline were mean changes of 0.44 (SD 1.589) and 0.67 (SD 1.673) kg/m2.
What this means
The results from this Phase 3 study indicate that seltorexant 20 mg, when used as an adjunctive therapy, significantly improved depressive symptoms in patients with MDDIS who had not adequately responded to prior antidepressant treatment. The observed reduction in MADRS total score suggests a clinically meaningful effect. The open-label safety data provides initial insights into the tolerability profile of seltorexant, showing adverse events but no substantial changes in vital signs or BMI.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for the study NCT04533529, titled "A Study of Seltorexant as Adjunctive Therapy to Antidepressants in Adult and Elderly Participants With Major Depressive Disorder With Insomnia Symptoms Who Have Responded Inadequately to Antidepressant and Long-term Safety Extension Treatment With Seltorexant", were posted on 2023-04-25 on clinicaltrials.gov.