Major Depressive Disorder
Conditions
Keywords
Major Depressive Disorder, Anhedonia, antidepressant, Nociceptin, NOPR
Brief summary
This study will determine the efficacy, safety, and tolerability of a once-daily (QD) dose of up to 80 mg of BTRX-246040 for 8 weeks in participants with MDD.
Interventions
DRUGBTRX-246040 oral capsule(s)
BTRX-246040 administered once daily to patients with MDD for 8 weeks
DRUGPlacebo oral capsule(s)
administered once daily to patients with MDD for 8 weeks
Sponsors
BlackThorn Therapeutics, Inc.
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
* Patients with a diagnosis of MDD as defined by DSM-5 criteria and have had at least 1 prior major depressive episode in the past 10 years * Patients must present with a new current episode of MDD and the duration of the current episode must be at least 4 weeks but not longer than 18 months. * At Visit 1 (screening) and Visit 2 (baseline), patients must have clinically significant depressive symptoms defined by tandem (investigator- and computer-administered) Montgomery-Asberg Depression Rating Scale (MADRS) total scores ≥ 26 with a difference of ≤ 7 points between the Investigator- and computer-administered MADRS total scores * Patients must have a CGI-S score ≥ 4 at Visit 2 (baseline).
Exclusion criteria
* Patients who present with any current DSM-5 disorder other than MDD which is the focus of treatment. * Patients who are homicidal in the opinion of the Investigator or are at suicidal risk (any suicide attempts within 12 months prior to Visit 1 \[screening\] or any suicidal intent, including a plan, within 3 months prior to Visit 1 \[screening\]; C-SSRS answer of YES on item 4 or 5 \[suicidal ideation\]; Investigator- or computer-administered MADRS score of ≥ 5 on item 10 \[suicidal thoughts\]; by Investigator clinical evaluation). * Patients cannot have any history of substance or alcohol use disorder within 12 months prior to Visit 1 (screening) per DSM-5 criteria * Patients must not have a clinically significant comorbid disease.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Investigator-administered MADRS Total Score From Baseline BTRX-246040 and Placebo | Week 8 | The Investigator-administered MADRS includes 10 items assessing the following symptoms: apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. Each item is scored from 0 (absence of symptom) to 6 (severe symptom); the overall score ranges from 0 to 60. MADRS total scores from 0 to 6 indicate normal/symptom absent, from 7 to 19 indicate mild depression, from 20 to 34 indicate moderate depression, and from 35 to 60 indicate severe depression. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Investigator-administered MADRS-6 Total Score | Week 8 | The Investigator-administered MADRS-6 subscale focuses on the core symptoms of depression and assesses the following symptoms: apparent sadness, reported sadness, inner tension, lassitude, inability to feel, and pessimistic thoughts. Each item is scored from 0 (absence of symptom) to 6 (severe symptom); the overall score ranges from 0 to 36. The change from baseline in the Investigator-administered MADRS-6 subscale was analyzed using the same method as the MADRS efficacy endpoint, substituting the baseline MADRS-6 subscale as the covariate in place of the MADRS total score. |
| Change From Baseline in Investigator-administered HADS-A (Hospital Anxiety and Depression Scale - Anxiety Subscale) Score | Week 8 | The Investigator-administered Hospital Anxiety and Depression Scale (HADS) subscales comprises of 7 questions regarding Depression and 7 questions regarding Anxiety. Each question is rated on a scale from 0 - 3. The outcome of the HADS questionnaire is two total scores, the HADS-A (for anxiety) and the HADS-D (for depression). Both total scores are graded on a scale of 0 - 21 and can be categorized as Normal (0 - 7), Borderline Abnormal (8 - 10) and Abnormal (11 - 21). Higher scores indicate higher levels of anxiety and depression. |
| Change From Baseline in Investigator-administered HADS-D (Hospital Anxiety and Depression Scale - Depression Subscale) Score | Week 8 | The Investigator-administered Hospital Anxiety and Depression Scale (HADS) subscales comprises of 7 questions regarding Depression and 7 questions regarding Anxiety. Each question is rated on a scale from 0 - 3. The outcome of the HADS questionnaire is two total scores, the HADS-A (for anxiety) and the HADS-D (for depression). Both total scores are graded on a scale of 0 - 21 and can be categorized as Normal (0 - 7), Borderline Abnormal (8 - 10) and Abnormal (11 - 21). Higher scores indicate higher levels of anxiety and depression. |
| Change From Baseline in Investigator-administered Dimensional Anhedonia Rating Scale (DARS) | Week 8 | The Investigator-administered Dimensional Anhedonia Rating Scale (DARS) is a 17-item questionnaire with each answer between 0 and 4 on a Likert scale grading (0=Not at all, 1=Slightly, 2=Moderately, 3=Mostly, 4=Very Much). Therefore, the DARS total score is on a scale of 0 - 68. The DARS Total score is broken down into four dimensions; Hobbies, Food/Drink, Social Activities and Sensory Experience. |
| Change From Baseline in Investigator-administered Snaith-Hamilton Pleasure Scale (SHAPS) Score | Week 8 | The Investigator-administered Snaith Hamilton Pleasure Scale (SHAPS) is a 14-item questionnaire. The SHAPS is scored two different ways. Under the original scoring method, each question has 4 responses, 2 of which imply agreement (Definitely Agree, Agree; each scored as 0) and 2 which imply disagreement (Disagree, Strongly Disagree; each scored as 1). Therefore, the SHAPS total score ranges 0 - 14. In this study, in addition to the traditional scoring method, an alternative scoring method will assign 1 - Strongly Agree, 2 - Agree, 3 - Disagree, and 4 - Strongly Disagree. Using this alternative scoring method, the total score ranges 14-56. In both scoring systems, higher scores indicate greater anhedonia. |
Countries
United States
Participant flow
Recruitment details
Total of 104 subjects were randomized for the study NEP-MDD-201
Participants by arm
| Arm | Count |
|---|---|
| BTRX-246040 40 mg administered orally as 1 capsule QD for 1 week, followed by 80 mg as 2 capsules QD for 7 weeks.
BTRX-246040 oral capsule(s): BTRX-246040 administered once daily to patients with MDD for 8 weeks | 52 |
| Placebo administered orally as 1 capsule QD for 1 week, followed by 2 capsules QD for 7 weeks.
Placebo oral capsule(s): administered once daily to patients with MDD for 8 weeks | 50 |
| Total | 102 |
Baseline characteristics
| Characteristic | BTRX-246040 | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 39.3 years STANDARD_DEVIATION 12.29 | 42.6 years STANDARD_DEVIATION 15 | 40.9 years STANDARD_DEVIATION 13.72 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants | 9 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 43 Participants | 41 Participants | 84 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 3 Participants | 4 Participants |
| Race/Ethnicity, Customized Black or African American | 22 Participants | 19 Participants | 41 Participants |
| Race/Ethnicity, Customized Multiracial | 5 Participants | 1 Participants | 6 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islanders | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 24 Participants | 26 Participants | 50 Participants |
| Sex: Female, Male Female | 11 Participants | 13 Participants | 24 Participants |
| Sex: Female, Male Male | 41 Participants | 37 Participants | 78 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 53 | 0 / 51 |
| other Total, other adverse events | 34 / 53 | 27 / 51 |
| serious Total, serious adverse events | 0 / 53 | 1 / 51 |
Outcome results
Primary
Change in Investigator-administered MADRS Total Score From Baseline BTRX-246040 and Placebo
The Investigator-administered MADRS includes 10 items assessing the following symptoms: apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. Each item is scored from 0 (absence of symptom) to 6 (severe symptom); the overall score ranges from 0 to 60. MADRS total scores from 0 to 6 indicate normal/symptom absent, from 7 to 19 indicate mild depression, from 20 to 34 indicate moderate depression, and from 35 to 60 indicate severe depression.
Time frame: Week 8
Population: The full analysis set (FAS) contained all patients in the randomized set who received at least 1 dose of study medication and had at least 1 post-dose efficacy assessment
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BTRX-246040 | Change in Investigator-administered MADRS Total Score From Baseline BTRX-246040 and Placebo | -15.0 Change in score on a scale from baseline | Standard Error 1.73 |
| Placebo | Change in Investigator-administered MADRS Total Score From Baseline BTRX-246040 and Placebo | -13.6 Change in score on a scale from baseline | Standard Error 1.79 |
Comparison: Difference in LS Means (BTRX-246040 - Placebo)p-value: 0.593995% CI: [-6.3, 3.6]MMRM
Secondary
Change From Baseline in Investigator-administered Dimensional Anhedonia Rating Scale (DARS)
The Investigator-administered Dimensional Anhedonia Rating Scale (DARS) is a 17-item questionnaire with each answer between 0 and 4 on a Likert scale grading (0=Not at all, 1=Slightly, 2=Moderately, 3=Mostly, 4=Very Much). Therefore, the DARS total score is on a scale of 0 - 68. The DARS Total score is broken down into four dimensions; Hobbies, Food/Drink, Social Activities and Sensory Experience.
Time frame: Week 8
Population: The full analysis set (FAS) contained all patients in the randomized set who received at least 1 dose of study medication and had at least 1 post-dose efficacy assessment
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BTRX-246040 | Change From Baseline in Investigator-administered Dimensional Anhedonia Rating Scale (DARS) | 13.7 Change in score on a scale from baseline | Standard Error 16.7 |
| Placebo | Change From Baseline in Investigator-administered Dimensional Anhedonia Rating Scale (DARS) | 2.91 Change in score on a scale from baseline | Standard Error 3.04 |
p-value: 0.486995% CI: [-11.5, 5.5]MMRM
Secondary
Change From Baseline in Investigator-administered HADS-A (Hospital Anxiety and Depression Scale - Anxiety Subscale) Score
The Investigator-administered Hospital Anxiety and Depression Scale (HADS) subscales comprises of 7 questions regarding Depression and 7 questions regarding Anxiety. Each question is rated on a scale from 0 - 3. The outcome of the HADS questionnaire is two total scores, the HADS-A (for anxiety) and the HADS-D (for depression). Both total scores are graded on a scale of 0 - 21 and can be categorized as Normal (0 - 7), Borderline Abnormal (8 - 10) and Abnormal (11 - 21). Higher scores indicate higher levels of anxiety and depression.
Time frame: Week 8
Population: The full analysis set (FAS) contained all patients in the randomized set who received at least 1 dose of study medication and had at least 1 post-dose efficacy assessment
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BTRX-246040 | Change From Baseline in Investigator-administered HADS-A (Hospital Anxiety and Depression Scale - Anxiety Subscale) Score | -2.6 Change in score on a scale from baseline | Standard Error 0.67 |
| Placebo | Change From Baseline in Investigator-administered HADS-A (Hospital Anxiety and Depression Scale - Anxiety Subscale) Score | -3.5 Change in score on a scale from baseline | Standard Error 0.7 |
p-value: 0.390695% CI: [-1.1, 2.8]MMRM
Secondary
Change From Baseline in Investigator-administered HADS-D (Hospital Anxiety and Depression Scale - Depression Subscale) Score
The Investigator-administered Hospital Anxiety and Depression Scale (HADS) subscales comprises of 7 questions regarding Depression and 7 questions regarding Anxiety. Each question is rated on a scale from 0 - 3. The outcome of the HADS questionnaire is two total scores, the HADS-A (for anxiety) and the HADS-D (for depression). Both total scores are graded on a scale of 0 - 21 and can be categorized as Normal (0 - 7), Borderline Abnormal (8 - 10) and Abnormal (11 - 21). Higher scores indicate higher levels of anxiety and depression.
Time frame: Week 8
Population: The full analysis set (FAS) contained all patients in the randomized set who received at least 1 dose of study medication and had at least 1 post-dose efficacy assessment
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BTRX-246040 | Change From Baseline in Investigator-administered HADS-D (Hospital Anxiety and Depression Scale - Depression Subscale) Score | -5.0 Change in score on a scale from baseline | Standard Error 0.76 |
| Placebo | Change From Baseline in Investigator-administered HADS-D (Hospital Anxiety and Depression Scale - Depression Subscale) Score | -5.9 Change in score on a scale from baseline | Standard Error 0.8 |
p-value: 0.418795% CI: [-1.3, 3.1]MMRM
Secondary
Change From Baseline in Investigator-administered MADRS-6 Total Score
The Investigator-administered MADRS-6 subscale focuses on the core symptoms of depression and assesses the following symptoms: apparent sadness, reported sadness, inner tension, lassitude, inability to feel, and pessimistic thoughts. Each item is scored from 0 (absence of symptom) to 6 (severe symptom); the overall score ranges from 0 to 36. The change from baseline in the Investigator-administered MADRS-6 subscale was analyzed using the same method as the MADRS efficacy endpoint, substituting the baseline MADRS-6 subscale as the covariate in place of the MADRS total score.
Time frame: Week 8
Population: The full analysis set (FAS) contained all patients in the randomized set who received at least 1 dose of study medication and had at least 1 post-dose efficacy assessment
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BTRX-246040 | Change From Baseline in Investigator-administered MADRS-6 Total Score | -10.7 Change in score on a scale from baseline | Standard Error 1.17 |
| Placebo | Change From Baseline in Investigator-administered MADRS-6 Total Score | -9.7 Change in score on a scale from baseline | Standard Error 1.21 |
Comparison: Analysis of Change from Baseline in Investigator-administered MADRS-6 Total Score at week 8p-value: 0.550395% CI: [-4.4, 2.3]MMRM
Secondary
Change From Baseline in Investigator-administered Snaith-Hamilton Pleasure Scale (SHAPS) Score
The Investigator-administered Snaith Hamilton Pleasure Scale (SHAPS) is a 14-item questionnaire. The SHAPS is scored two different ways. Under the original scoring method, each question has 4 responses, 2 of which imply agreement (Definitely Agree, Agree; each scored as 0) and 2 which imply disagreement (Disagree, Strongly Disagree; each scored as 1). Therefore, the SHAPS total score ranges 0 - 14. In this study, in addition to the traditional scoring method, an alternative scoring method will assign 1 - Strongly Agree, 2 - Agree, 3 - Disagree, and 4 - Strongly Disagree. Using this alternative scoring method, the total score ranges 14-56. In both scoring systems, higher scores indicate greater anhedonia.
Time frame: Week 8
Population: The full analysis set (FAS) contained all patients in the randomized set who received at least 1 dose of study medication and had at least 1 post-dose efficacy assessment
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BTRX-246040 | Change From Baseline in Investigator-administered Snaith-Hamilton Pleasure Scale (SHAPS) Score | -6.7 Change in score on a scale from baseline | Standard Error 1.24 |
| Placebo | Change From Baseline in Investigator-administered Snaith-Hamilton Pleasure Scale (SHAPS) Score | -7.9 Change in score on a scale from baseline | Standard Error 1.28 |
p-value: 0.517895% CI: [-2.4, 4.7]MMRM