Study to Evaluate the Efficacy and Safety of Once-Weekly Oral NBI-1065846 in the Treatment of Anhedonia in MDD

Phase 2

Completed

Brief Summary: To evaluate the efficacy of NBI-1065846 compared with placebo on improving symptoms of anhedonia in participants with major depressive disorder (MDD).

Recruitment & Eligibility

Inclusion Criteria

Participants must meet all of the following key inclusion criteria:

Completed written informed consent.
Aged 18 to 65 years, inclusive, at the time of informed consent.
Primary diagnosis of MDD.
Participants must meet one of the following criteria:
- must have been taking ≥1 antidepressant medication(s) for ≥8 weeks prior to screening.
- must have received ≥1 antidepressant medication(s) for ≥8 weeks in the current or most recent episode of depression.
Snaith Hamilton Pleasure Scale (SHAPS) score is ≥30 at screening and Day 1.

Key

Exclusion Criteria

Participants will be excluded from the study if they meet any of the following key criteria:

Any psychiatric disorder disallowed per protocol and electroconvulsive therapy (ECT) within 6 months prior to screening. Comorbid anxiety disorders are not exclusionary.
Have a significant risk of suicidal or violent behavior.
A history of seizure disorder, stroke, Alzheimer disease, Parkinson disease, multiple sclerosis, head injury associated with loss of consciousness for more than 15 minutes, or other neurodegenerative disorder.

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Participant follows Placebo schedule (57 days)
Antidepressant	NBI-1065846	Participant follows NBI-1065846 schedule (57 days)

Primary Outcome Measures

Name	Time	Method
Change in Anhedonia Severity, as Measured by Change in DARS Score From Baseline to Day 57	Baseline, Day 57	The DARS is a dynamic scale that measured desire, motivation, effort and consummatory pleasure across hedonic domains. The DARS is a self-report questionnaire that measured anhedonia across 4 domains: hobbies/past-times, food/drinks, social activities, and sensory experiences. The DARs was rated on a five-point Likert scale from 0 (not at all) to 4 (very much), higher values indicating less anhedonia. All items were summed up to a total score in the range of 0 to 68.

Secondary Outcome Measures

Name	Time	Method
Change in Total MADRS Score From Baseline to Day 57 in Participants With Moderate or Higher Severity Depression	Baseline, Day 57	The MADRS is a validated rating scale designed to measure changes in the severity of depressive symptoms. The MADRS consists of 10 items scored on a 7-point scale (0 to 6). Higher MADRS scores indicate more severe depression. The MADRS total score was calculated as the sum of the 10 individual item scores which ranges from 0 to 60.
CGI-S Scores	Baseline and Day 57	The CGI-S scale, which is based on a 7-point scale (range: 1=normal, not at all ill, 2 = borderline ill, 3 = mildly ill, 4 = moderately ill, 5 = markedly ill, 6 = severely ill, and 7 = extremely ill), was used to rate the severity of the participants illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis.