BTRX-246040 Administered Once Daily to Patients With Major Depressive Disorder

Study Overview
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Brief Summary
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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.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Efficacy And Safety Study Of BTRX-246040 Administered Once Daily In Patients With Major Depressive Disorder With Or Without Anhedonia

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Drug: BTRX-246040 oral capsule(s)
* Drug: Placebo oral capsule(s)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BTRX-246040<br>40 mg administered orally as 1 capsule QD for 1 week, followed by 80 mg as 2 capsules QD for 7 weeks. | Drug: BTRX-246040 oral capsule(s)<br>* BTRX-246040 administered once daily to patients with MDD for 8 weeks<br>|
| Placebo Comparator: Placebo<br>administered orally as 1 capsule QD for 1 week, followed by 2 capsules QD for 7 weeks. | Drug: Placebo oral capsule(s)<br>* administered once daily to patients with MDD for 8 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Week 8 | 
| 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. | Week 8 | 
| 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. | Week 8 | 
| 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. | Week 8 | 
| 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. | Week 8 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Major Depressive Disorder, Anhedonia, antidepressant, Nociceptin, NOPR