Anhedonia, Depressive Disorder, Major
Conditions
Brief summary
The purpose of this study is to evaluate how well aticaprant works as compared with placebo when given along with an antidepressant therapy in improving the depressive symptoms in adult participants with major depressive disorder (MDD) with moderate to severe anhedonia (ANH+) who have not responded well to current antidepressant therapy with a selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor (SSRI or SNRI).
Interventions
DRUGAticaprant
Aticaprant tablet will be administered orally.
OTHERPlacebo
Placebo tablet will be administered orally.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
* Be medically stable based on physical examination (including a brief neurologic examination), medical history, vital signs (including blood pressure), and 12-lead electrocardiogram (ECG) performed at screening and double blind (DB) baseline * Meet diagnostic and statistical manual of mental disorders-5th edition (DSM-5) diagnostic criteria for recurrent or single episode major depressive disorder (MDD), without psychotic features (DSM-5 296.22, 296.23, 296.32, or 296.33), based upon clinical assessment and confirmed by the structured clinical interview for DSM-5 axis I disorders-clinical trials version (SCID-CT) * 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 * Have had an inadequate response to at least 1 and up to 5 (inclusive) oral antidepressant treatments, administered at an adequate dose * Is currently receiving and tolerating well any one of the following selective serotonin reuptake inhibitor or serotonin-norepinephrine reuptake inhibitor (SSRI or SNRI) antidepressants at screening, in any approved formulation and available in the participating country/territory: citalopram, duloxetine, escitalopram, fluvoxamine, fluoxetine, milnacipran, levomilnacipran, paroxetine, sertraline, venlafaxine, or desvenlafaxine at a stable dose (at or above the minimum therapeutic dose per Massachusetts general hospital antidepressant treatment response questionnaire (MGH ATRQ) for at least 6 weeks. The current antidepressant cannot be the first antidepressant treatment for the first lifetime episode of depression
Exclusion criteria
* 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 (that is the one to be continued in the treatment phases) assessed using the MGH ATRQ * Has one or more of the following diagnoses: (1) a current or prior (lifetime) DSM-5 diagnosis of: (a) a psychotic disorder or MDD with psychotic features, (b) bipolar or related disorders, (c) intellectual disability, (d) autism spectrum disorder, (e) borderline personality disorder, (f) antisocial personality disorder, (g) histrionic personality disorder, (h) narcissistic personality disorders, (i) somatoform disorders; (2) A primary DSM-5 diagnosis (which has been the primary focus of psychiatric treatment within the past 2 years) of: (a) panic disorder, (b) generalized anxiety disorder, (c) social anxiety disorder, (d) specific phobia; (3) A current (in the past year) DSM-5 diagnosis of: (a) obsessive-compulsive disorder, (b) post-traumatic stress disorder, (c) anorexia nervosa, (d) bulimia nervosa * Has a history or evidence of clinically meaningful noncompliance with current antidepressant therapy * Has a history of moderate-to-severe substance use disorder including alcohol use disorder according to DSM-5 criteria within 6 months before screening * Has in the current depressive episode had vagal nerve stimulation or deep brain stimulation device in the current episode or has had an inadequate response to an adequate course of intravenous or intranasal ketamine or esketamine (greater than \[\>\] 2 treatments), or electroconvulsive therapy (that is at least 7 treatments) * Has homicidal ideation/intent, per the investigator's clinical judgment, or has suicidal ideation with some intent to act within 3 months prior to the start of the screening phase, per the investigator's clinical judgment or based on the columbia suicidality severity rating scale (C-SSRS), corresponding to a response of "Yes" on Item 4 (active suicidal ideation with some intent to act, without specific plan) or Item 5 (active suicidal ideation with specific plan and intent) for suicidal ideation on the C-SSRS, or a history of suicidal behavior within the past 6 months prior to the start of the screening phase. Participants reporting suicidal ideation with intent to act or suicidal behavior at DB baseline should be excluded
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Day 43 in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | Baseline to Day 43 | Change from baseline to Day 43 in MADRS total score will be reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Day 43 in Dimensional Anhedonia Rating Scale (DARS) Total Score | Baseline to Day 43 | Change from baseline to Day 43 in DARS total score will be reported. |
| Change From Baseline to Day 43 in Changes in Sexual Function Questionnaire - 14 items (CSFQ-14) Total Score | Baseline to Day 43 | Change from baseline to Day 43 in CSFQ-14 total score will be reported. |
| Change From Baseline Over Time in MADRS Total Score | For double-blind (DB) treatment phase: Baseline (Day 1), Up to Day 43; For open-label (OL) treatment phase: Baseline (Day 43), Up to Week 31 | Change from baseline over time in the MADRS total score will be reported. |
| Percentage of responders on Depressive Symptoms Scale, Defined as a Greater Than or Equal to (>=) 50 Percent (%) Improvement in MADRS Total Score From Baseline to Day 43 | Baseline to Day 43 | Percentage of responders on depressive symptoms scale, defined as a \>= 50 % improvement in MADRS total score from baseline to Day 43 will be reported. |
| Percentage of Participants With Remission of Depressive Symptoms, Defined as a MADRS Total Score Less Than or Equal to (<=)10 at Day 43 | Day 43 | Percentage of participants with remission of depressive symptoms, defined as a MADRS total score \<=10 at Day 43 will be reported. |
| Change From Baseline to Day 43 in Patient Health Questionnaire, 9-item (PHQ-9) Total Score | Baseline to Day 43 | Change from baseline to Day 43 in the PHQ-9 total score will be reported. |
| Change From Baseline Over Time in DARS Total score. | For DB treatment phase: Baseline (Day 1), Up to Day 43; For OL treatment phase: Baseline (Day 43), Up to Week 31 | Change from baseline over time in DARS total score will be reported. |
| Change From Baseline Over Time in the PHQ-9 Anhedonia-Specific Item (PHQ-9, item 1). | For DB treatment phase: Baseline (Day 1), Up to Day 43; For OL treatment phase: Baseline (Day 43), Up to Week 31 | Change from baseline over time in the PHQ-9 Anhedonia-specific item (PHQ-9, Item 1) will be reported. |
| Percentage of Participants With a Score Less than (<) 2 in the PHQ-9 Anhedonia-specific Item (PHQ-9, Item 1) at Day 43 | Day 43 | Percentage of participants with a score \< 2 in the PHQ-9 Anhedonia-specific Item (PHQ-9, Item 1) at Day 43 will be reported. |
Countries
Belgium, Brazil, Bulgaria, Finland, Hungary, Poland, Spain, Sweden, United States
Contacts
STUDY_DIRECTORJanssen Research & Development, LLC Clinical Trial
Janssen Research & Development, LLC
Outcome results
None listed