Efficacy, safety, and tolerability of JNJ-61393215 (tebideutorexant), a selective orexin-1 receptor antagonist, as adjunctive treatment for major depressive disorder with anxious distress: A double-blind, placebo-controlled, randomized phase 2a study.

The selective orexin-1 receptor antagonist JNJ-61393215 (tebideutorexant) has shown anti-panic properties in rodent and human panic-anxiety models. This double-blind, placebo-controlled, randomized, parallel-group, multicenter, phase 2a study evaluated the efficacy, safety, and tolerability of JNJ-61393215 in 222 patients (18-64 years) with major depressive disorder (MDD) with anxious distress who had experienced a suboptimal response to standard antidepressants. Eligible patients were randomized (1:1) to receive either adjunctive JNJ-61393215 (135 mg) or placebo, once daily. The primary objective was to evaluate the efficacy of JNJ-61393215 versus placebo, as assessed by the change from baseline to week 6 on the 17-item Hamilton Depression Rating Scale (HDRS). The key secondary objective was to evaluate the impact of JNJ-61393215 versus placebo on the severity of anxiety as measured by the change in the Hamilton Anxiety Rating Scale (HAM-A) from baseline to week 6. The study results for the full intent-to-treat analysis dataset did not show significant treatment effects of adjunctive treatment with JNJ-61393215 on either the primary endpoint (the least squares mean difference [standard error]: -0.67 [0.893]; p=0.2227) or the key secondary endpoint (0.23 [1.007]; p=0.5889). The safety results were consistent with the known safety profile of JNJ-61393215 with no serious adverse events reported during the study. Overall, adjunctive treatment with an orexin-1 antagonist did not provide significant benefit relative to adjunctive placebo to patients with MDD and anxious distress. Trial registration number: ClinicalTrials.gov Identifier: NCT04080752.