In short
Clinical trials are investigating Aticaprant in people with major depressive disorder, including those with moderate-to-severe anhedonia. These studies look at whether Aticaprant can help improve depressive symptoms, prevent relapse, and assess long-term safety when used with antidepressants.
Key points
- Clinical trials of Aticaprant are focused mainly on major depressive disorder, especially in adults with moderate-to-severe anhedonia. Three phase 3 studies tested Aticaprant as an add-on to antidepressants, looking at symptom improvement, relapse prevention, and long-term safety. One phase 1 study in healthy adults examined how the drug is absorbed and processed in the body. The trials were completed and included both people with depression and healthy volunteers. Key outcomes included depression rating scores, time to relapse, and safety measures such as lab tests, ECG, weight, and suicidality checks.
Clinical trial overview
Aticaprant was studied in four interventional trials, and all were completed. Most trials focused on major depressive disorder (MDD), especially in adults with moderate-to-severe anhedonia, which means a strong loss of interest or pleasure.
Phase 3 studies in major depressive disorder
Three studies were in Phase 3, which is a late stage of research that usually tests whether a treatment works and how safe it is in a larger group of people.
One phase 3 trial studied Aticaprant as adjunctive therapy, meaning it was added to a current antidepressant, in adults with MDD and moderate-to-severe anhedonia who had an inadequate response to an SSRI or SNRI. This study compared Aticaprant 10 mg with placebo and measured change in the MADRS depression score from baseline to Day 43.
Another phase 3 trial studied Aticaprant plus an antidepressant for relapse prevention in adults with MDD and moderate-to-severe anhedonia who had already achieved a stable response. The main goal was to see how long it took before a relapse event happened during the maintenance phase.
A third phase 3 study looked at the long-term safety and tolerability of Aticaprant when added to a current antidepressant in people with MDD. This study followed participants for up to one year and included an open-label extension, which means some participants could continue treatment in a part of the study where the treatment was known rather than blinded.
Phase 1 study in healthy adults
One Phase 1 study enrolled healthy adult participants, not people with depression. The purpose was to evaluate the absolute bioavailability and metabolic profile of Aticaprant, which means how much of the drug reaches the body and how it is processed after taking it by mouth and by intravenous infusion.
This study was small, with 10 participants, and it used oral Aticaprant together with a microdose intravenous infusion.
Main endpoints and safety measures
The phase 3 relapse-prevention study measured the time from randomization to the first documented relapse event. This endpoint helps show whether the treatment can keep symptoms from returning for longer.
The phase 3 symptom-improvement study measured change in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score from baseline to Day 43. A change in this score helps show whether depression symptoms got better or worse during the study.
The long-term safety study tracked several safety outcomes, including adverse events, vital signs, weight and body mass index, suicidality using the Columbia Suicidality Severity Rating Scale (C-SSRS), laboratory tests, 12-lead ECG, withdrawal symptoms using the Physician Withdrawal Checklist (PWC-20), and sexual function using the Arizona Sexual Experiences Scale (ASEX).
The healthy adult study measured absolute bioavailability (Fabs) as its primary outcome.
Who took part in the studies
The phase 3 studies enrolled adults with MDD, and two of them specifically required moderate-to-severe anhedonia. One study also required an inadequate response to current antidepressant therapy with an SSRI or SNRI.
The relapse-prevention study focused on adults who had already achieved a stable response before entering the maintenance phase. The phase 1 study was different because it included healthy adults rather than people with depression.
What the trial program shows
The Aticaprant trial program is centered on depression research, especially MDD with anhedonia. The main questions were whether Aticaprant could improve symptoms, help prevent relapse, and remain safe when used with antidepressants.
In healthy volunteers, the research also asked how the body absorbs and processes Aticaprant. Together, these studies provide a clinical picture of Aticaprant research across early and late development stages.