A Randomized, Double-blind, Multicenter, Placebo-controlled Study to Evaluate the Efficacy, Safety, and Tolerability of Aticaprant 10 mg as Adjunctive Therapy in Adult Participants with Major Depressive Disorder (MDD) with Moderate-to-Severe Anhedonia and Inadequate Response to Current Antidepressant Therapy and an Open- labeled Long-term Extension Treatment with Aticaprant

Prior treatment

• Has one or more of the following diagnoses: A current or prior (lifetime) DSM-5 diagnosis of: a psychotic disorder or MDD with psychotic features; bipolar or related disorders; intellectual disability; autism spectrum disorder; personality disorders (borderline, antisocial, histrionic, narcissistic); somatoform disorders A primary DSM-5 diagnosis (which has been the primary focus of psychiatric treatment within the past 2 years) of: panic disorder; generalized anxiety disorder; social anxiety disorder; specific phobia (allowed as secondary diagnosis); A current (in the past year) DSM-5 diagnosis of:obsessive-compulsive disorder (OCD),post-traumatic stress disorder (PTSD),anorexia nervosa, bulimia nervosa (allowed if stable for 1 year)
• Has a history of moderate-to-severe substance use disorder including alcohol use disorder according to DSM-5 criteria within 6 months before screening

Other illness

• Has had no response (treatment failure) to 2 or more consecutive antidepressant treatments administered at an adequate dose (at or above the minimum therapeutic dose) and duration (at least 6 weeks) in the current episode of depression including the current SSRI/SNRI (ie, the one to be continued in the treatment phases) assessed using the MGH-ATRQ.

Other

• Has current suicidal risk, per investigator’s clinical judgment or based on the C-SSRS.

• Adults aged 18 (or the legal age of consent in the jurisdiction in which the study is taking place) to 64 years, inclusive.
• Meet DSM-5 diagnostic criteria for recurrent or single episode MDD, without psychotic features, based upon clinical assessment and confirmed by the SCID-CT
• Moderate to severe depressive episode: MADRS ≥25 at Screening and Baseline Stable symptom severity - no clinically significant improvement (ie, >25%) between 2 the site-rater assessments
• Have symptoms of anhedonia based on clinical assessment and confirmed by presence of anhedonia (positive response to MDE module symptom Item 2) on the SCID-CT at screening and have a SHAPS total score.
• Have had an inadequate response to at least 1 and up to 5 (inclusive) oral antidepressant treatments, administered at an adequate dose (at or above the minimum therapeutic dose per MGH ATRQ) and duration (at least 6 weeks) in the current episode of depression, including current SSRI/SNRI treatment
• Be medically stable based on clinical assessment , vital signs and ECG and laboratory assessments