Trial Outcomes & Findings for Ramelteon for the Treatment of Insomnia and Mood Stability in Patients With Euthymic Bipolar Disorder (NCT NCT00552760)
NCT ID: NCT00552760
Last Updated: 2014-04-14
Results Overview
Self-rated scale to measure quality of sleep via questions regarding sleep latency, duration, efficiency, disturbances, use of sleep medication, and daytime dysfunction. Scores range from 0-21, higher scores represent more significant sleep disturbance.
COMPLETED
PHASE4
90 participants
Monthly for 6 months
2014-04-14
Participant Flow
Recruitment began in October 2007 and was completed by August 2009. Participants, who at the time were receiving outpatient psychiatric services through Lehigh Valley Hospital, were recruited via referral through the department of psychiatry, and also through print advertisement. Participants received a $20 travel stipend for each appointment.
90 participants signed the informed consent document, 7 were screen failures, and 83 were randomized to receive either Ramelteon or placebo. During the study, both groups were maintained on their usual medications for bipolar disorder and were not allowed to have any meds changed, as this would signify a manic or depressed event.
Participant milestones
| Measure |
Ramelteon
one 8 mg tablet at bedtime for up to 6 months
|
Placebo
one tablet at bedtime for up to 6 months
|
|---|---|---|
|
Overall Study
STARTED
|
42
|
41
|
|
Overall Study
COMPLETED
|
16
|
8
|
|
Overall Study
NOT COMPLETED
|
26
|
33
|
Reasons for withdrawal
| Measure |
Ramelteon
one 8 mg tablet at bedtime for up to 6 months
|
Placebo
one tablet at bedtime for up to 6 months
|
|---|---|---|
|
Overall Study
Adverse Event
|
3
|
5
|
|
Overall Study
Relapsed- Depressed Event
|
10
|
16
|
|
Overall Study
Relapse- Manic Event
|
3
|
3
|
|
Overall Study
Relapsed- Mixed Event
|
3
|
5
|
|
Overall Study
Protocol Violation
|
0
|
1
|
|
Overall Study
Lost to Follow-up
|
1
|
1
|
|
Overall Study
Non-compliance
|
1
|
1
|
|
Overall Study
Medical Condition
|
1
|
1
|
|
Overall Study
Withdrawal by Subject
|
3
|
0
|
|
Overall Study
Medication Change
|
1
|
0
|
Baseline Characteristics
Ramelteon for the Treatment of Insomnia and Mood Stability in Patients With Euthymic Bipolar Disorder
Baseline characteristics by cohort
| Measure |
Ramelteon
n=42 Participants
one 8 mg tablet at bedtime for up to 6 months
|
Placebo
n=41 Participants
one tablet at bedtime for up to 6 months
|
Total
n=83 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
|
|
Age, Categorical
Between 18 and 65 years
|
42 Participants
n=5 Participants
|
41 Participants
n=7 Participants
|
83 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
46.6 years
STANDARD_DEVIATION 11.0 • n=5 Participants
|
45.2 years
STANDARD_DEVIATION 10.8 • n=7 Participants
|
45.9 years
STANDARD_DEVIATION 10.9 • n=5 Participants
|
|
Sex: Female, Male
Female
|
26 Participants
n=5 Participants
|
26 Participants
n=7 Participants
|
52 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
16 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
31 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
42 participants
n=5 Participants
|
41 participants
n=7 Participants
|
83 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Monthly for 6 monthsPopulation: Intent to Treat Analysis; excludes 7 screen failures.
Self-rated scale to measure quality of sleep via questions regarding sleep latency, duration, efficiency, disturbances, use of sleep medication, and daytime dysfunction. Scores range from 0-21, higher scores represent more significant sleep disturbance.
Outcome measures
| Measure |
Ramelteon
n=42 Participants
one 8 mg tablet at bedtime for up to 6 months
|
Placebo
n=41 Participants
one tablet at bedtime for up to 6 months
|
|---|---|---|
|
Pittsburgh Sleep Quality Index (PSQI) Global Score
Baseline
|
10.17 units on scale
Standard Error 0.53
|
10.88 units on scale
Standard Error 0.53
|
|
Pittsburgh Sleep Quality Index (PSQI) Global Score
Month 1
|
8.16 units on scale
Standard Error 0.56
|
9.28 units on scale
Standard Error 0.57
|
|
Pittsburgh Sleep Quality Index (PSQI) Global Score
Month 2
|
7.93 units on scale
Standard Error 0.63
|
9.71 units on scale
Standard Error 0.64
|
|
Pittsburgh Sleep Quality Index (PSQI) Global Score
Month 3
|
7.89 units on scale
Standard Error 0.68
|
10.38 units on scale
Standard Error 0.78
|
|
Pittsburgh Sleep Quality Index (PSQI) Global Score
Month 4
|
7.21 units on scale
Standard Error 0.62
|
9.03 units on scale
Standard Error 0.75
|
|
Pittsburgh Sleep Quality Index (PSQI) Global Score
Month 5
|
6.62 units on scale
Standard Error 0.59
|
8.66 units on scale
Standard Error 0.77
|
|
Pittsburgh Sleep Quality Index (PSQI) Global Score
Month 6
|
6.90 units on scale
Standard Error 0.72
|
8.76 units on scale
Standard Error 0.98
|
SECONDARY outcome
Timeframe: Monthly for 6 monthsPopulation: Intent to Treat Analysis; excludes 7 screen failures
10-item, standardized, well-validated scale used to measure severity of depressive symptoms; sensitive to treatment effects in depressed outpatients. Scores range from 0-60, higher scores represent more severe depressive symptoms.
Outcome measures
| Measure |
Ramelteon
n=42 Participants
one 8 mg tablet at bedtime for up to 6 months
|
Placebo
n=41 Participants
one tablet at bedtime for up to 6 months
|
|---|---|---|
|
Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
Baseline
|
7.79 units on scale
Standard Error 0.42
|
8.27 units on scale
Standard Error 0.43
|
|
Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
Month 1
|
8.34 units on scale
Standard Error 0.67
|
8.90 units on scale
Standard Error 0.68
|
|
Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
Month 2
|
7.23 units on scale
Standard Error 0.84
|
11.13 units on scale
Standard Error 0.85
|
|
Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
Month 3
|
9.17 units on scale
Standard Error 1.00
|
11.85 units on scale
Standard Error 1.24
|
|
Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
Month 4
|
8.45 units on scale
Standard Error 1.05
|
13.03 units on scale
Standard Error 1.39
|
|
Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
Month 5
|
8.56 units on scale
Standard Error 1.24
|
11.59 units on scale
Standard Error 1.73
|
|
Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
Month 6
|
10.40 units on scale
Standard Error 1.48
|
10.46 units on scale
Standard Error 2.18
|
SECONDARY outcome
Timeframe: Monthly for 6 monthsPopulation: Intent to Treat Analysis; excludes 7 screen failures
11-item standardized, well-validated scale used to measure manic symptoms; sensitive to treatment effects in manic patients. Scores range from 0-60, higher scores represent more severe manic symptoms.
Outcome measures
| Measure |
Ramelteon
n=42 Participants
one 8 mg tablet at bedtime for up to 6 months
|
Placebo
n=41 Participants
one tablet at bedtime for up to 6 months
|
|---|---|---|
|
Young Mania Rating Scale (YMRS) Total Score
Month 6
|
6.51 units on scale
Standard Error 1.00
|
6.72 units on scale
Standard Error 1.35
|
|
Young Mania Rating Scale (YMRS) Total Score
Baseline
|
7.02 units on scale
Standard Error 0.43
|
6.59 units on scale
Standard Error 0.44
|
|
Young Mania Rating Scale (YMRS) Total Score
Month 1
|
5.89 units on scale
Standard Error 0.51
|
6.46 units on scale
Standard Error 0.52
|
|
Young Mania Rating Scale (YMRS) Total Score
Month 2
|
5.91 units on scale
Standard Error 0.80
|
7.75 units on scale
Standard Error 0.82
|
|
Young Mania Rating Scale (YMRS) Total Score
Month 3
|
6.60 units on scale
Standard Error 0.84
|
8.09 units on scale
Standard Error 1.00
|
|
Young Mania Rating Scale (YMRS) Total Score
Month 4
|
5.93 units on scale
Standard Error 0.70
|
4.95 units on scale
Standard Error 0.93
|
|
Young Mania Rating Scale (YMRS) Total Score
Month 5
|
5.18 units on scale
Standard Error 0.65
|
5.71 units on scale
Standard Error 0.88
|
SECONDARY outcome
Timeframe: Monthly for 6 monthsPopulation: Intent to Treat Analysis; excludes 7 screen failures
3-part (mania, depression, overall bipolar illness), physician-administered scale used to assess global illness severity; used to measure change. Each part is rated from 1-7, higher scores represent more severe mental illness. Only overall bipolar rating was used.
Outcome measures
| Measure |
Ramelteon
n=42 Participants
one 8 mg tablet at bedtime for up to 6 months
|
Placebo
n=41 Participants
one tablet at bedtime for up to 6 months
|
|---|---|---|
|
Clinical Global Impressions Bipolar Version(CGI-BP) Severity of Illness Overall Score
Month 1
|
2.29 units on scale
Standard Error 0.15
|
2.25 units on scale
Standard Error 0.15
|
|
Clinical Global Impressions Bipolar Version(CGI-BP) Severity of Illness Overall Score
Month 2
|
2.24 units on scale
Standard Error 0.18
|
2.90 units on scale
Standard Error 0.19
|
|
Clinical Global Impressions Bipolar Version(CGI-BP) Severity of Illness Overall Score
Month 3
|
2.53 units on scale
Standard Error 0.22
|
2.93 units on scale
Standard Error 0.27
|
|
Clinical Global Impressions Bipolar Version(CGI-BP) Severity of Illness Overall Score
Month 4
|
2.36 units on scale
Standard Error 0.21
|
2.98 units on scale
Standard Error 0.29
|
|
Clinical Global Impressions Bipolar Version(CGI-BP) Severity of Illness Overall Score
Month 5
|
2.46 units on scale
Standard Error 0.23
|
2.99 units on scale
Standard Error 0.34
|
|
Clinical Global Impressions Bipolar Version(CGI-BP) Severity of Illness Overall Score
Month 6
|
2.54 units on scale
Standard Error 0.23
|
2.41 units on scale
Standard Error 0.34
|
|
Clinical Global Impressions Bipolar Version(CGI-BP) Severity of Illness Overall Score
Baseline
|
2.14 units on scale
Standard Error 0.13
|
2.15 units on scale
Standard Error 0.13
|
SECONDARY outcome
Timeframe: Monthly for 6 monthsPopulation: Intent to Treat Analysis; excludes 7 screen failures.
Survival analysis techniques, including Kaplan Meier curves, were used to evaluate group differences in time to relapse. Relapse was defined as a medication initiation or change for manic/depressed/mixed symptoms, a hospitalization for manic/depressed/mixed symptoms, MADRS score \>= 16, YMRS score \> 14, and suicide risk or imminent risk of suicide. Time to relapse was measured discretely in terms of the number of assessment visits until discontinued from the study.
Outcome measures
| Measure |
Ramelteon
n=42 Participants
one 8 mg tablet at bedtime for up to 6 months
|
Placebo
n=41 Participants
one tablet at bedtime for up to 6 months
|
|---|---|---|
|
Cumulative Proportion of Participants in Each Arm Surviving Without Relapse
Baseline
|
1.00 Cumulative proportion of participants
|
1.00 Cumulative proportion of participants
|
|
Cumulative Proportion of Participants in Each Arm Surviving Without Relapse
Month 1
|
0.929 Cumulative proportion of participants
|
0.951 Cumulative proportion of participants
|
|
Cumulative Proportion of Participants in Each Arm Surviving Without Relapse
Month 2
|
0.849 Cumulative proportion of participants
|
0.588 Cumulative proportion of participants
|
|
Cumulative Proportion of Participants in Each Arm Surviving Without Relapse
Month 3
|
0.716 Cumulative proportion of participants
|
0.448 Cumulative proportion of participants
|
|
Cumulative Proportion of Participants in Each Arm Surviving Without Relapse
Month 4
|
0.661 Cumulative proportion of participants
|
0.384 Cumulative proportion of participants
|
|
Cumulative Proportion of Participants in Each Arm Surviving Without Relapse
Month 5
|
0.632 Cumulative proportion of participants
|
0.320 Cumulative proportion of participants
|
|
Cumulative Proportion of Participants in Each Arm Surviving Without Relapse
Month 6
|
0.566 Cumulative proportion of participants
|
0.320 Cumulative proportion of participants
|
Adverse Events
Ramelteon
Placebo
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Ramelteon
n=42 participants at risk
one 8 mg tablet at bedtime for up to 6 months
|
Placebo
n=41 participants at risk
one tablet at bedtime for up to 6 months
|
|---|---|---|
|
Psychiatric disorders
Anxiety
|
2.4%
1/42 • Number of events 1
|
4.9%
2/41 • Number of events 2
|
|
Gastrointestinal disorders
Diarrhea NOS
|
2.4%
1/42 • Number of events 1
|
0.00%
0/41
|
|
General disorders
Dizziness
|
2.4%
1/42 • Number of events 1
|
0.00%
0/41
|
|
General disorders
Dry mouth
|
0.00%
0/42
|
2.4%
1/41 • Number of events 1
|
|
General disorders
Fatigue
|
2.4%
1/42 • Number of events 1
|
9.8%
4/41 • Number of events 4
|
|
General disorders
Forgetfulness
|
0.00%
0/42
|
2.4%
1/41 • Number of events 1
|
|
General disorders
Headache NOS
|
2.4%
1/42 • Number of events 1
|
2.4%
1/41 • Number of events 1
|
|
General disorders
Insomnia exacerbated
|
2.4%
1/42 • Number of events 1
|
0.00%
0/41
|
|
General disorders
Restless legs
|
0.00%
0/42
|
2.4%
1/41 • Number of events 1
|
|
General disorders
Somnolence
|
7.1%
3/42 • Number of events 3
|
2.4%
1/41 • Number of events 1
|
|
General disorders
Vivid dreams
|
7.1%
3/42 • Number of events 3
|
2.4%
1/41 • Number of events 1
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place