Anhedonia, Major Depressive Disorder
Conditions
Keywords
Anhedonia, Major Depressive Disorder, MDD, NBI-1065846, TERPSIS, Neurocrine, Antidepressant, Depression, TAK-041
Brief summary
To evaluate the efficacy of NBI-1065846 compared with placebo on improving symptoms of anhedonia in participants with major depressive disorder (MDD).
Interventions
DRUGPlacebo
Tablets for oral administration
DRUGNBI-1065846
Tablets for oral administration
Sponsors
Neurocrine Biosciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: Participants must meet all of the following key inclusion criteria: 1. Completed written informed consent. 2. Aged 18 to 65 years, inclusive, at the time of informed consent. 3. Primary diagnosis of MDD. 4. 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. 5. 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: 1. Any psychiatric disorder disallowed per protocol and electroconvulsive therapy (ECT) within 6 months prior to screening. Comorbid anxiety disorders are not exclusionary. 2. Have a significant risk of suicidal or violent behavior. 3. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Puerto Rico, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participant follows placebo schedule (57 days). | 47 |
| NBI-1065846 Participant follows NBI-1065846 schedule (57 days). | 46 |
| Total | 93 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 2 |
| Overall Study | Other Than Specified | 0 | 1 |
| Overall Study | Withdrawal by Subject | 5 | 1 |
Baseline characteristics
| Characteristic | NBI-1065846 | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 43.8 years STANDARD_DEVIATION 14 | 42.3 years STANDARD_DEVIATION 12.8 | 43.1 years STANDARD_DEVIATION 13.4 |
| Clinical Global Impression - Severity (CGI-S) | 4.8 units on a scale STANDARD_DEVIATION 0.6 | 4.7 units on a scale STANDARD_DEVIATION 0.7 | 4.8 units on a scale STANDARD_DEVIATION 0.7 |
| Dimensional Anhedonia Rating Scale (DARS) Score | 18.7 units on a scale STANDARD_DEVIATION 12.8 | 15.1 units on a scale STANDARD_DEVIATION 10.5 | 16.9 units on a scale STANDARD_DEVIATION 11.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants | 7 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 37 Participants | 40 Participants | 77 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Asian | 2 Participants | 3 Participants | 5 Participants |
| Race/Ethnicity, Customized Race Black or African American | 6 Participants | 4 Participants | 10 Participants |
| Race/Ethnicity, Customized Race Multiple | 2 Participants | 2 Participants | 4 Participants |
| Race/Ethnicity, Customized Race Other | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Race White | 35 Participants | 36 Participants | 71 Participants |
| Sex: Female, Male Female | 32 Participants | 31 Participants | 63 Participants |
| Sex: Female, Male Male | 14 Participants | 16 Participants | 30 Participants |
| Total Montgomery Åsberg Depression Rating Scale (MADRS) Score | 31.0 units on a scale STANDARD_DEVIATION 5.5 | 30.8 units on a scale STANDARD_DEVIATION 6.6 | 30.9 units on a scale STANDARD_DEVIATION 6.1 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 47 | 0 / 46 |
| other Total, other adverse events | 4 / 47 | 3 / 46 |
| serious Total, serious adverse events | 1 / 47 | 0 / 46 |
Outcome results
Primary
Change in Anhedonia Severity, as Measured by Change in DARS Score From Baseline to 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.
Time frame: Baseline, Day 57
Population: Full Analysis Set (FAS): All randomized participants. Here, 'Overall number of participants analyzed' = participants evaluable for specified outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Anhedonia Severity, as Measured by Change in DARS Score From Baseline to Day 57 | 17.4 units on a scale | Standard Error 3.7 |
| NBI-1065846 | Change in Anhedonia Severity, as Measured by Change in DARS Score From Baseline to Day 57 | 13.5 units on a scale | Standard Error 3.6 |
p-value: 0.8663ANCOVA
Secondary
CGI-S Scores
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.
Time frame: Baseline and Day 57
Population: FAS: All randomized participants. Here, 'Overall number of participants analyzed' = participants evaluable for specified outcome measure. Number analyzed = number of participants with evaluable data at the specified timepoint.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | CGI-S Scores | Baseline: Normal, not at all ill (1) | 0 Participants |
| Placebo | CGI-S Scores | Baseline: Borderline ill (2) | 0 Participants |
| Placebo | CGI-S Scores | Baseline: Mildly ill (3) | 1 Participants |
| Placebo | CGI-S Scores | Baseline: Moderately ill (4) | 16 Participants |
| Placebo | CGI-S Scores | Baseline: Markedly ill (5) | 23 Participants |
| Placebo | CGI-S Scores | Baseline: Severely ill (6) | 6 Participants |
| Placebo | CGI-S Scores | Baseline: Extremely ill (7) | 0 Participants |
| Placebo | CGI-S Scores | Day 57: Normal, not at all ill (1) | 6 Participants |
| Placebo | CGI-S Scores | Day 57: Borderline ill (2) | 7 Participants |
| Placebo | CGI-S Scores | Day 57: Mildly ill (3) | 12 Participants |
| Placebo | CGI-S Scores | Day 57: Moderately ill (4) | 10 Participants |
| Placebo | CGI-S Scores | Day 57: Markedly ill (5) | 9 Participants |
| Placebo | CGI-S Scores | Day 57: Severely ill (6) | 0 Participants |
| Placebo | CGI-S Scores | Day 57: Extremely ill (7) | 0 Participants |
| NBI-1065846 | CGI-S Scores | Day 57: Moderately ill (4) | 12 Participants |
| NBI-1065846 | CGI-S Scores | Baseline: Normal, not at all ill (1) | 0 Participants |
| NBI-1065846 | CGI-S Scores | Day 57: Normal, not at all ill (1) | 7 Participants |
| NBI-1065846 | CGI-S Scores | Baseline: Borderline ill (2) | 0 Participants |
| NBI-1065846 | CGI-S Scores | Day 57: Severely ill (6) | 1 Participants |
| NBI-1065846 | CGI-S Scores | Baseline: Mildly ill (3) | 1 Participants |
| NBI-1065846 | CGI-S Scores | Day 57: Borderline ill (2) | 7 Participants |
| NBI-1065846 | CGI-S Scores | Baseline: Moderately ill (4) | 11 Participants |
| NBI-1065846 | CGI-S Scores | Day 57: Markedly ill (5) | 7 Participants |
| NBI-1065846 | CGI-S Scores | Baseline: Markedly ill (5) | 26 Participants |
| NBI-1065846 | CGI-S Scores | Day 57: Mildly ill (3) | 11 Participants |
| NBI-1065846 | CGI-S Scores | Baseline: Severely ill (6) | 4 Participants |
| NBI-1065846 | CGI-S Scores | Day 57: Extremely ill (7) | 0 Participants |
| NBI-1065846 | CGI-S Scores | Baseline: Extremely ill (7) | 0 Participants |
Comparison: CGI-S scores at Day 57 for NBI-1065846 compared to placebo.p-value: 0.9051Cochran-Mantel-Haenszel Chi-square test
Secondary
Change in Total MADRS Score From Baseline to Day 57 in Participants With Moderate or Higher Severity Depression
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.
Time frame: Baseline, Day 57
Population: FAS: All randomized participants. Here, 'Overall number of participants analyzed' = participants evaluable for specified outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Total MADRS Score From Baseline to Day 57 in Participants With Moderate or Higher Severity Depression | -13.9 units on a scale | Standard Error 3.4 |
| NBI-1065846 | Change in Total MADRS Score From Baseline to Day 57 in Participants With Moderate or Higher Severity Depression | -15.1 units on a scale | Standard Error 3 |
p-value: 0.700895% CI: [-7.1, 4.8]ANCOVA