Trial Outcomes & Findings for Efficacy and Safety Study of a Combination Product [Drug:BCI-024 (Buspirone) and Drug:BCI-049 (Melatonin)] to Treat Major Depressive Disorder (MDD) (NCT NCT00705003)

NCT ID: NCT00705003

Last Updated: 2014-06-18

Results Overview

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 1. Very much improved 2. Much improved 3. Minimally improved 4. No change 5. Minimally worse 6. Much worse 7. Very much worse

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

142 participants

Primary outcome timeframe

Week 6

Results posted on

2014-06-18

Participant Flow

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

Participant milestones

Participant milestones
Measure
BCI-024 and BCI-049 (Buspirone and Melatonin)
1 over-encapsulated tablet of buspirone 15 mg and 1 over-encapsulated tablet of melatonin 3 mg QD
BCI-024 (Buspirone)
1 over-encapsulated tablet of buspirone 15 mg QD
Placebo
Matching placebo QD
Enrolled
STARTED
71
37
34
Enrolled
COMPLETED
67
34
33
Enrolled
NOT COMPLETED
4
3
1
Treated
STARTED
67
34
33
Treated
COMPLETED
54
28
30
Treated
NOT COMPLETED
13
6
3

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
BCI-024 and BCI-049
n=67 Participants
Buspirone 15 mg and Melatonin 3 mg QD
BCI-024
n=34 Participants
Buspirone 15 mg QD
Placebo
n=33 Participants
Placebo QD
Total
n=134 Participants
Total of all reporting groups
Age, Categorical
<=18 years
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
Age, Categorical
Between 18 and 65 years
67 Participants
n=5 Participants
34 Participants
n=7 Participants
33 Participants
n=5 Participants
134 Participants
n=4 Participants
Age, Categorical
>=65 years
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
Age, Continuous
43.1 years
STANDARD_DEVIATION 12.06 • n=5 Participants
40.8 years
STANDARD_DEVIATION 12.55 • n=7 Participants
42.7 years
STANDARD_DEVIATION 11.62 • n=5 Participants
42.4 years
STANDARD_DEVIATION 12.03 • n=4 Participants
Sex: Female, Male
Female
43 Participants
n=5 Participants
20 Participants
n=7 Participants
24 Participants
n=5 Participants
87 Participants
n=4 Participants
Sex: Female, Male
Male
24 Participants
n=5 Participants
14 Participants
n=7 Participants
9 Participants
n=5 Participants
47 Participants
n=4 Participants
Region of Enrollment
United States
67 participants
n=5 Participants
34 participants
n=7 Participants
33 participants
n=5 Participants
134 participants
n=4 Participants

PRIMARY outcome

Timeframe: Week 6

Population: 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.

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 1. Very much improved 2. Much improved 3. Minimally improved 4. No change 5. Minimally worse 6. Much worse 7. Very much worse

Outcome measures

Outcome measures
Measure
BCI-024+BCI-049
n=67 Participants
Buspirone 15 mg and Melatonin 3 mg QD
BCI-024
n=34 Participants
Buspirone 15 mg QD
Placebo
n=33 Participants
Placebo QD
The Score on the Clinical Global Impression-Improvement (CGI-I) at Week 6
2.37 units on a scale
Standard Error 0.97
2.82 units on a scale
Standard Error 1.24
2.86 units on a scale
Standard Error 1.09

SECONDARY outcome

Timeframe: Baseline and Week 6

Population: 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.

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 1. Normal, not ill at all 2. Borderline mentally ill 3. Mildly ill 4. Moderately ill 5. Markedly ill 6. Severely ill 7. 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.

Outcome measures

Outcome measures
Measure
BCI-024+BCI-049
n=67 Participants
Buspirone 15 mg and Melatonin 3 mg QD
BCI-024
n=34 Participants
Buspirone 15 mg QD
Placebo
n=33 Participants
Placebo QD
The Change From Baseline in the CGI-S at Week 6
1.43 units on a scale
Standard Deviation 1.08
.93 units on a scale
Standard Deviation 1.07
0.97 units on a scale
Standard Deviation 1.16

SECONDARY outcome

Timeframe: Week 0 and Week 6

Population: 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.

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.

Outcome measures

Outcome measures
Measure
BCI-024+BCI-049
n=67 Participants
Buspirone 15 mg and Melatonin 3 mg QD
BCI-024
n=34 Participants
Buspirone 15 mg QD
Placebo
n=33 Participants
Placebo QD
The Change From Baseline in the IDS-C30 at Week 6
19.24 units on a scale
Standard Error 1.60
16.35 units on a scale
Standard Error 2.22
14.42 units on a scale
Standard Error 2.14

SECONDARY outcome

Timeframe: Baseline and Week 6

Population: 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.

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: 1. highest score from items 1-4 (Sleep Items) 2. item 5 score 3. highest score from items 6-9 (appetite/weight) 4. item 10 score 5. item 11 score 6. item 12 score 7. item 13 score 8. item 14 score 9. 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

Outcome measures

Outcome measures
Measure
BCI-024+BCI-049
n=67 Participants
Buspirone 15 mg and Melatonin 3 mg QD
BCI-024
n=34 Participants
Buspirone 15 mg QD
Placebo
n=33 Participants
Placebo QD
The Change From Baseline in the Quick Inventory of Depressive Symptomatology - 16 Item Self-Report (QIDS-SR16) at Week 6
8.57 units on a scale
Standard Error 0.66
6.65 units on a scale
Standard Error 0.92
7.31 units on a scale
Standard Error 0.89

SECONDARY outcome

Timeframe: Week 0 and Week 6

Population: 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.

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.

Outcome measures

Outcome measures
Measure
BCI-024+BCI-049
n=67 Participants
Buspirone 15 mg and Melatonin 3 mg QD
BCI-024
n=34 Participants
Buspirone 15 mg QD
Placebo
n=33 Participants
Placebo QD
The Change From Baseline on the HAM-A at Week 6
9.04 units on a scale
Standard Error 0.87
6.69 units on a scale
Standard Error 1.20
6.51 units on a scale
Standard Error 1.16

Adverse Events

BCI-024 and BCI-049

Serious events: 0 serious events
Other events: 16 other events
Deaths: 0 deaths

BCI-024

Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths

Placebo

Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
BCI-024 and BCI-049
n=67 participants at risk
Buspirone 15 mg and Melatonin 3 mg QD
BCI-024
n=34 participants at risk
Buspirone 15 mg QD
Placebo
n=33 participants at risk
Placebo QD
Gastrointestinal disorders
Diarrhea
9.0%
6/67 • Number of events 6
2.9%
1/34 • Number of events 1
6.1%
2/33 • Number of events 2
Gastrointestinal disorders
Constipation
1.5%
1/67 • Number of events 1
5.9%
2/34 • Number of events 2
0.00%
0/33
Nervous system disorders
Dizziness
6.0%
4/67 • Number of events 4
2.9%
1/34 • Number of events 1
0.00%
0/33
Nervous system disorders
Headache
7.5%
5/67 • Number of events 5
8.8%
3/34 • Number of events 3
6.1%
2/33 • Number of events 2

Additional Information

Maurizio Fava, MD

Massachusetts General Hospital

Phone: 617-724-2513

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place