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

• Sponsor: Massachusetts General Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT00705003
• Collaborator: BrainCells Inc. (Industry)
• Enrollment: 142
• Locations: 9
• Arms: 3
• Duration (Months): 7
• Patients Per Site: 15.8
• Patients Per Site Per Month: 2.2

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Disorder	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	Phase 2

Detailed Description

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 142 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Double-Blind, Placebo-Controlled Study of a Combination Product (BCI-024 and BCI-049) in Patients With Major Depressive Disorder (MDD)
• Study Start Date: May 1, 2008
• Actual Primary Completion Date: Dec 1, 2008
• Actual Study Completion Date: Dec 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Active Drug Combination 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; 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; Other Names: Buspar is the brand name of buspirone.
Active Comparator: BCI-024 (Buspirone) BCI-024: over-encapsulated Buspirone 15 mg QD	Drug: BCI-024 (Buspirone); Drug BCI-024 (Buspirone) taken once a day at bedtime for 6 weeks.; Other Names: Buspar is the brand name of buspirone.
Placebo Comparator: Matching placebo Placebo: 1 capsule QD	Drug: Matching placebo; Placebo comparator once a day at bedtime for 6 weeks.

Outcome Measures

Primary Outcome Measures

1. The Score on the Clinical Global Impression-Improvement (CGI-I) at Week 6 [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

Secondary Outcome Measures

1. The Change From Baseline in the CGI-S at Week 6 [Baseline and 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.

2. The Change From Baseline in the IDS-C30 at Week 6 [Week 0 and 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.

3. The Change From Baseline in the Quick Inventory of Depressive Symptomatology - 16 Item Self-Report (QIDS-SR16) at Week 6 [Baseline and 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

4. The Change From Baseline on the HAM-A at Week 6 [Week 0 and 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Collaborative Neuroscience Network, Inc.	Garden Grove	California	United States	92845
2	Synergy Research Centers	San Diego	California	United States	91950
3	Atlanta Institute of Medicine & Research, Inc.	Altanta	Georgia	United States	30328
4	Capital Clinical Research Associates	Rockville	Maryland	United States	20852
5	NorthCoast Clinical Trials	Beachwood	Ohio	United States	44122
6	CRI Worldwide	Philadelphia	Pennsylvania	United States	19139
7	FutureSearch Clinical Trials, L.P.	Austin	Texas	United States	78756
8	FutureSearch Trials of Dallas, L.P.	Dallas	Texas	United States	75231
9	Claghorn-Lesem Research Clinic, Ltd.	Houston	Texas	United States	77008

Sponsors and Collaborators

• Massachusetts General Hospital
• BrainCells Inc.

Investigators

• Principal Investigator: Maurizio Fava, MD, Massachusetts General Hospital
• Principal Investigator: Andrew A Nierenberg, MD, Massachusetts General Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Maurizio Fava, MD, Fava, Maurizio MD., Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT00705003
• Other Study ID Numbers: CBM-IT-01
• First Posted: Jun 25, 2008
• Last Update Posted: Jun 18, 2014
• Last Verified: Jun 1, 2014

• Keywords provided by Maurizio Fava, MD, Fava, Maurizio MD., Massachusetts General Hospital: depression
• Additional relevant MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major; Melatonin; Buspirone

Study Results

Participant Flow

Recruitment Details	Patients were recruited at 9 study centers between April and December 2008

Arm/Group Title	BCI-024 and BCI-049 (Buspirone and Melatonin)	BCI-024 (Buspirone)	Placebo
Arm/Group Description	1 over-encapsulated tablet of buspirone 15 mg and 1 over-encapsulated tablet of melatonin 3 mg QD	1 over-encapsulated tablet of buspirone 15 mg QD	Matching placebo QD
Period Title: Enrolled
STARTED	71	37	34
COMPLETED	67	34	33
NOT COMPLETED	4	3	1
Period Title: Enrolled
STARTED	67	34	33
COMPLETED	54	28	30
NOT COMPLETED	13	6	3

Baseline Characteristics

Arm/Group Title	BCI-024 and BCI-049	BCI-024	Placebo	Total
Arm/Group Description	Buspirone 15 mg and Melatonin 3 mg QD	Buspirone 15 mg QD	Placebo QD	Total of all reporting groups
Overall Participants	67	34	33	134
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	67 100%	34 100%	33 100%	134 100%
>=65 years	0 0%	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	43.1 (12.06)	40.8 (12.55)	42.7 (11.62)	42.4 (12.03)
Sex: Female, Male (Count of Participants)
Female	43 64.2%	20 58.8%	24 72.7%	87 64.9%
Male	24 35.8%	14 41.2%	9 27.3%	47 35.1%
Region of Enrollment (participants) [Number]
United States	67 100%	34 100%	33 100%	134 100%

Outcome Measures

1. Primary Outcome

Title	The Score on the Clinical Global Impression-Improvement (CGI-I) at Week 6
Description	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
Time Frame	Week 6

Outcome Measure Data

Analysis Population Description

142 subjects were enrolled and randomized in the study. 8 of these subjects were randomized but never received study drug. Subjects included in the MITT analysis received at least 1 dose of study drug and provided at least 1 post-baseline CGI-I assessment. Subjects included in the analysis of safety received at least 1 dose of study drug.

Arm/Group Title	BCI-024+BCI-049	BCI-024	Placebo
Arm/Group Description	Buspirone 15 mg and Melatonin 3 mg QD	Buspirone 15 mg QD	Placebo QD
Measure Participants	67	34	33
Mean (Standard Error) [units on a scale]	2.37 (0.97)	2.82 (1.24)	2.86 (1.09)

2. Secondary Outcome

Title	The Change From Baseline in the CGI-S at Week 6
Description	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.
Time Frame	Baseline and Week 6

Outcome Measure Data

Analysis Population Description

Efficacy analysis were completed for the MITT Population: Subjects included in the MITT analysis received at least 1 dose of study drug and provided at least 1 post-baseline CGI-I assessment. Subjects included in the analysis of safety received at least 1 dose of study drug.

Arm/Group Title	BCI-024 and BCI-049	BCI-024	Placebo
Arm/Group Description	Buspirone 15 mg and Melatonin 3 mg QD	Buspirone 15 mg QD	Placebo QD
Measure Participants	67	34	33
Mean (Standard Deviation) [units on a scale]	1.43 (1.08)	.93 (1.07)	0.97 (1.16)

3. Secondary Outcome

Title	The Change From Baseline in the IDS-C30 at Week 6
Description	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.
Time Frame	Week 0 and Week 6

Outcome Measure Data

Analysis Population Description

Efficacy analysis were completed for the MITT Population: Subjects included in the MITT analysis received at least 1 dose of study drug and provided at least 1 post-baseline CGI-I assessment. Subjects included in the analysis of safety received at least 1 dose of study drug.

Arm/Group Title	BCI-024 and BCI-049	BCI-024	Placebo
Arm/Group Description	Buspirone 15 mg and Melatonin 3 mg QD	Buspirone 15 mg QD	Placebo QD
Measure Participants	67	34	33
Mean (Standard Error) [units on a scale]	19.24 (1.60)	16.35 (2.22)	14.42 (2.14)

4. Secondary Outcome

Title	The Change From Baseline in the Quick Inventory of Depressive Symptomatology - 16 Item Self-Report (QIDS-SR16) at Week 6
Description	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
Time Frame	Baseline and Week 6

Outcome Measure Data

Analysis Population Description

Efficacy analysis were completed for the MITT Population: Subjects included in the MITT analysis received at least 1 dose of study drug and provided at least 1 post-baseline CGI-I assessment. Subjects included in the analysis of safety received at least 1 dose of study drug.

Arm/Group Title	BCI-024 and BCI-049	BCI-024	Placebo
Arm/Group Description	Buspirone 15 mg and Melatonin 3 mg QD	Buspirone 15 mg QD	Placebo QD
Measure Participants	67	34	33
Mean (Standard Error) [units on a scale]	8.57 (0.66)	6.65 (0.92)	7.31 (0.89)

5. Secondary Outcome

Title	The Change From Baseline on the HAM-A at Week 6
Description	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.
Time Frame	Week 0 and Week 6

Outcome Measure Data

Analysis Population Description

Efficacy analysis were completed for the MITT Population: Subjects included in the MITT analysis received at least 1 dose of study drug and provided at least 1 post-baseline CGI-I assessment. Subjects included in the analysis of safety received at least 1 dose of study drug.

Arm/Group Title	BCI-024 and BCI-049	BCI-024	Placebo
Arm/Group Description	Buspirone 15 mg and Melatonin 3 mg QD	Buspirone 15 mg QD	Placebo QD
Measure Participants	67	34	33
Mean (Standard Error) [units on a scale]	9.04 (0.87)	6.69 (1.20)	6.51 (1.16)

Adverse Events

Arm/Group Title	BCI-024 and BCI-049		BCI-024		Placebo
Arm/Group Description	Buspirone 15 mg and Melatonin 3 mg QD		Buspirone 15 mg QD		Placebo QD
All Cause Mortality
	BCI-024 and BCI-049		BCI-024		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	BCI-024 and BCI-049		BCI-024		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/67 (0%)		0/34 (0%)		0/33 (0%)
Other (Not Including Serious) Adverse Events
	BCI-024 and BCI-049		BCI-024		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/67 (23.9%)		7/34 (20.6%)		4/33 (12.1%)
Gastrointestinal disorders
Diarrhea	6/67 (9%)	6	1/34 (2.9%)	1	2/33 (6.1%)	2
Constipation	1/67 (1.5%)	1	2/34 (5.9%)	2	0/33 (0%)	0
Nervous system disorders
Dizziness	4/67 (6%)	4	1/34 (2.9%)	1	0/33 (0%)	0
Headache	5/67 (7.5%)	5	3/34 (8.8%)	3	2/33 (6.1%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.