Efficacy and Safety Study of a Combination Product [Drug:BCI-024 (Buspirone) and Drug:BCI-049 (Melatonin)] to Treat Major Depressive Disorder (MDD)

Study Overview
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Brief Summary
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The primary objective of this study are to evaluate the synergistic effect of a combination product, consisting of drug BCI-024 (buspirone) and drug BCI-049 (melatonin), in reducing symptoms of depression in patients with Major Depressive Disorder. The safety and tolerability of the combination product will also be evaluated as measured by adverse events and vital signs.

Detailed Description
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Approximately 120 adult outpatients meeting the study's inclusion and exclusion criteria will be randomized in the study.

Official Title
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A Double-Blind, Placebo-Controlled Study of a Combination Product (BCI-024 and BCI-049) in Patients With Major Depressive Disorder (MDD)

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Drug: BCI-024: over-encapsulated Buspirone tablet 15 mg QD and BCI-049: over-encapsulated Melatonin tablet 3 mg QD
* Drug: BCI-024 (Buspirone)
* Drug: Matching placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects will be male and female subjects between the ages of 18 to 65 meeting the Diagnostic and Statistical Manual of Mental Disorders-IV-Text Revision (DSM-IV-TR) criteria for Major Depressive Disorder with a Quick Inventory of Depressive Symptomatology-16 Item Self Report (QIDS-SR16) score of >14 at the Screening and Baseline Visits. Female subjects must be on a stable and medically reliable form of birth control, must agree to continue use of this birth control during the study, and must have negative urine pregnancy tests at the Screening Visit. Exclusion Criteria: Subjects with any other psychiatric Axis-I disorder as a principal diagnosis within 6 months of screening or subjects with a history of obsessive compulsive disorder, psychotic disorder, bipolar disorder, or mental retardation at any time are not eligible for the study. Subjects who pose a suicidal risk or who have a history of eating disorder or substance dependence within 6 months of screening, or a history of substance abuse within 3 months of screening are also ineligible. Subjects with clinically significant abnormalities on any Screening or Baseline assessments, including laboratory tests, are excluded. Subjects with a known intolerance to either buspirone or melatonin are excluded, as are subjects with clinically significant medical or psychiatric conditions that might be detrimental to the subject should they participate in the study. Subjects who have used selective serotonin reuptake inhibitors (SSRIs) within 2 weeks of Screening (within 4 weeks for fluoxetine) are excluded as are subjects requiring concomitant use of antipsychotic and anxiolytic medications and any drugs with known psychotropic properties. Concomitant medications that are not excluded by the protocol and that are taken chronically must be at a stable dosage for at least 4 weeks prior to screening.

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: Active Drug Combination<br>BCI-024: over-encapsulated Buspirone tablet 15 mg at bedtime(QD) and BCI-049: over-encapsulated Melatonin tablet 3 mg QD | Drug: BCI-024: over-encapsulated Buspirone tablet 15 mg QD and BCI-049: over-encapsulated Melatonin tablet 3 mg QD<br>* BCI-024: over-encapsulated Buspirone tablet 15 mg QD and Drug BCI-049: over-encapsulated Melatonin tablet 3 mg QD taken in combination for 6 weeks<br>* Other names: Buspar is the brand name of buspirone.;|
| Active Comparator: BCI-024 (Buspirone)<br>BCI-024: over-encapsulated Buspirone 15 mg QD | Drug: BCI-024 (Buspirone)<br>* Drug BCI-024 (Buspirone) taken once a day at bedtime for 6 weeks.<br>* Other names: Buspar is the brand name of buspirone.;|
| Placebo Comparator: Matching placebo<br>Placebo: 1 capsule QD | Drug: Matching placebo<br>* Placebo comparator once a day at bedtime for 6 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Score on the Clinical Global Impression-Improvement (CGI-I) at Week 6 | Clinical Global Impression (CGI) is a standardized, clinician-rated assessment designed to allow the clinician to rate severity of illness, change over time, and pharmacologic treatment effects with consideration of the patient's clinical condition and the severity of side effects experienced (Guy 1976). Specifically, it consists of two global subscales: Global Improvement (CGI-I) Severity of Illness (CGI-S) The CGI-I was administered at Weeks 2, 4 and 6. The CGI-I evaluation was performed with instruction to Rate the patient's total improvement whether or not, in your judgment, it is due entirely to drug treatment. The Investigator was asked Compared to the patient's condition at the Baseline visit, please assign a rating to how much the patient changed. Responses for the CGI-I evaluation included the following categories: 0: Not Assessed Very much improved Much improved Minimally improved No change Minimally worse Much worse Very much worse | Week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Change From Baseline in the CGI-S at Week 6 | Clinical Global Impression (CGI) is a standardized, clinician-rated assessment designed to allow the clinician to rate severity of illness, change over time, and pharmacologic treatment effects with consideration of the patient's clinical condition and the severity of side effects experienced (Guy 1976). The CGI-S is a sub-scale of the Clinical Global Impression. The Investigator was asked: Considering your total clinical experience with patients with this particular population, please assign a rating to how mentally ill the subject is at this time. Possible responses include the following: 0: Not Assessed Normal, not ill at all Borderline mentally ill Mildly ill Moderately ill Markedly ill Severely ill Among the most extremely ill patients. The change from baseline CGI-S score was calculated as the baseline CGI-S score minus the post-baseline CGI-S score, such that a positive change indicated an improvement from baseline. | Baseline and Week 6 | 
| The Change From Baseline in the IDS-C30 at Week 6 | The Inventory of Depressive Symptomatology is a 30-item scale that assesses criteria including mood, concentration, self criticism, suicidal ideation, interest, energy/fatigue, sleep, decrease/increase in appetite or weight, psychomotor agitation or retardation, diurnal mood variation, capacity for pleasure, sexual interest, bodily aches and pains, panic or phobic symptoms, digestive problems, interpersonal rejection sensitivity, and leaden paralysis. Items are scored on a 4 point scale with 0 reflecting no symptoms and 3 reflecting symptoms of maximum severity. The total score is calculated by summing the scores from 28 of the 30 items. Only one of items 11 or 12, and only one of items 13 or 14 are scored. The minimum score is 0 and the maximum score is 84. A score of 84 indicates maximum severity of depressive symptoms. Change from baseline is calculated as the baseline score minus the post-baseline score. A positive change indicates improvement. | Week 0 and Week 6 | 
| The Change From Baseline in the Quick Inventory of Depressive Symptomatology - 16 Item Self-Report (QIDS-SR16) at Week 6 | The QIDS-SR16 is a 16 question, patient rated scale that assesses the 9 Diagnostic & Statistical Manual of Mental Disorders-IV-Text Revision criterion diagnostic symptom domains including sad mood, concentration, self criticism, suicidal ideation, interest, energy/fatigue, sleep disturbance, decrease or increase in appetite or weight, & psychomotor agitation or retardation. Each item is measured on a scale of 0 to 3. To find total score, you enter: highest score from items 1-4 (Sleep Items) item 5 score highest score from items 6-9 (appetite/weight) item 10 score item 11 score item 12 score item 13 score item 14 score highest score from items 15-16 (psychomotor) These 9 scores are summed to find total score. Total minimum score is 0 units on a scale & total maximum score is 27 units, where higher scores indicate more severe depression. Change from baseline is calculated as baseline score minus Week 6 score. A positive change indicates improvement | Baseline and Week 6 | 
| The Change From Baseline on the HAM-A at Week 6 | The 14-item HAM-A scale rates the patient's level of anxiety based on feelings of anxiousness, tension, and depression; any phobias, sleep disturbance, or difficulty in concentrating; the presence of genitourinary, cardiovascular, respiratory, autonomic or somatic symptoms; and the interviewer's assessment of the patient's appearance and behavior during the interview. Each item is to be scored on a 5 point scale with 0 reflecting no symptoms and 4 reflecting symptoms of maximum symptom severity (Hamilton 1960). The items are summed to find the total score. The total minimum score is 0 units on a scale and the total maximum score is 56 units on a scale, where higher scores indicate more severe anxiety. Change from baseline is calculated as baseline score minus Week 6 score. A positive change indicates improvement. | Week 0 and Week 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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depression