Trial · NCT01467700

Efficacy and Safety of Ramelteon Sublingual in Adult Patients With Acute Depressive Episodes Associated With Bipolar I Disorder

NCT01467700, Phase 3, Terminated, Takeda; results first posted 2016-05-16

3 sourcestrials-2026-11-12-0.5.0

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ConductScience Library. Efficacy and Safety of Ramelteon Sublingual in Adult Patients With Acute Depressive Episodes Associated With Bipolar I Disorder. Trials, record NCT01467700. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT01467700

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Trial

As registered on ClinicalTrials.gov, in the graph's capture of the registry.

Title: Efficacy and Safety of Ramelteon Sublingual in Adult Patients With Acute Depressive Episodes Associated With Bipolar I Disorder
NCT number: NCT01467700
Status: Terminated
Phases: Phase 3
Enrollment: 490 participants, actual
Lead sponsor: Takeda
Conditions: Acute Depressive Episode
Interventions: Ramelteon SL, Placebo
First posted: 2011-11-09
Last updated: 2016-05-16
Results first posted: 2016-05-16

Source ClinicalTrials.gov

Registered outcomes9

Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.

List	Outcome	Time frame	Description
Primary	Change From Baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score at Week 6	Baseline and Week 6	The change between MADRS score at week 6 relative to Baseline. MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms (i.e., apparent sadness, reported sadness, inner tension, etc.) rated on a 7-point Likert scale from 0 (normal) to 6 (most abnormal) with a total score range from 0 to 60. Higher scores indicate greater severity of symptoms. A negative change from Baseline indicates improvement. A mixed measures repeated measures (MMRM) model was used for analysis with baseline\week, pooled center, week, treatment, baseline, and week\treatment as factors in the analysis.
Secondary	Change From Baseline in Quality of Life, Enjoyment and Satisfaction Questionnaire (Q-LES-Q-SF) Short Form Total Score at Week 6	Baseline and Week 6	Q-LES-Q -SF is a self-administered, 16-item questionnaire to assess the degree of enjoyment and satisfaction experienced by participants in various areas of daily functioning, such as social relationships, living/housing, physical health, medication, and global satisfaction. The questionnaire consists of 16 items rated by the participants on a 5-point scale. Of these, 14 items are summed to produce a total quality of life score with a maximum of 70 points. In addition, there are two global items that are scored individually. These items rate satisfaction with study medication and overall life satisfaction. The questionnaire is usually scored as a percent of total possible score, with higher scores indicating better health status. A positive change from Baseline indicates improvement. A MMRM model was used for analysis with baseline\week, pooled center, week, treatment, baseline, and week\treatment as factors in the analysis.
Secondary	Percentage of Participants With MADRS Response at Week 6, With Response Defined as a ≥ 50% Decrease in the MADRS Total Score From Baseline	Baseline and Week 6	MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms (i.e., apparent sadness, reported sadness, inner tension, etc.) rated on a 7-point Likert scale from 0 (normal) to 6 (most abnormal) with a total score range from 0 to 60. Higher scores indicate greater severity of symptoms.
Secondary	Change From Baseline in Young Mania Rating Scale (YMRS) Total Score at Week 6	Baseline and Week 6	The YMRS total score at week 6 relative to baseline. YMRS is a four item scale to assess manic symptoms, rated on a scale from 0 (symptom not present) to 8 (symptom extremely severe), with 7 items rated on a scale from 0 (symptom not present) to 4 (symptom extremely severe) with higher scores reflecting greater levels of mania. The YMRS total score is calculated as the sum of the 11 individual item scores and ranges from 0-60. Higher scores indicate greater severity of symptoms. A negative change from Baseline indicates improvement. A MMRM model was used for analyses with baseline\week, pooled center, week, treatment, baseline, and week\treatment as factors in the analysis.
Secondary	Clinical Global Impression Scale-Improvement (CGI-I) Score at Week 6	6 Weeks	The CGI-I assesses the clinician's impression of the participant's state of mental illness improvement and consists of one question for the investigator: "Compared to his condition at the start of the study, how much has this patient changed?" which is rated on a seven-point scale (1=very much improved; 2=much improved; 3=minimally improved; 4=no change relative to baseline; 5=minimally worse; 6= much worse; 7=very much worse). Higher scores indicate greater severity of illness. A MMRM model was used for analysis with baseline\week, pooled center, week, treatment, baseline, and week\treatment as factors in the analysis.
Secondary	Change From Baseline in Clinical Global Impression Scale-Severity (CGI-S) at Week 6	Baseline and Week 6	The CGI-S at week 6 relative to Baseline. The CGI-S assesses the clinician's impression of the participant's current state of mental illness and consists of one question for the investigator: "Considering your total clinical experience with this particular population, how mentally ill is the patient at this time?" which is rated on a seven-point scale (1=normal, not ill at all; 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill). Higher scores indicate greater severity of illness. A MMRM model was used for analysis with baseline\week, pooled center, week, treatment, baseline, and week\treatment as factors in the analysis.
Secondary	Percentage of Participants With MADRS Remission at Week 6, With Remission Defined as a MADRS Total Score ≤10	Week 6	MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms (i.e., apparent sadness, reported sadness, inner tension, etc.) rated on a 7-point Likert scale from 0 (normal) to 6 (most abnormal) with a total score range from 0 to 60. Higher scores indicate greater severity of symptoms.
Secondary	Change From Baseline in the Quick Inventory of Depressive Symptomatology - Self-Rated16 (QIDS-SR16) Total Score at Week 6	Baseline and Week 6	The 16 item QIDS-SR16 version is designed to assess the severity of depressive symptoms. The QIDS-SR16 assesses all the criterion symptom domains designated by the American Psychiatry Association Diagnostic and Statistical Manual of Mental Disorders - 4th edition, DSM-IV, to diagnose a major depressive episode. QIDS-SR16 assessment has been used to screen for depression and also to measure symptom severity. This scale is also used to distinguish response from remission, as well as to quantify between group treatments effects in open label and randomized controlled trials. The patient is asked to rate the severity and frequency of specific symptoms present over the last 7 days. The QIDS-SR16 total scores range from 0 to 27. Higher scores indicate greater severity of impairment. A negative change from Baseline indicates improvement. A MMRM model was used for analysis with baseline\week, pooled center, week, treatment, baseline, and week\treatment as factors in the analysis.
Secondary	Change From Baseline in Sheehan Disability Scale (SDS) Total Score at Week 6	Baseline and Week 6	The SDS comprises patient-rated items designed to measure the extent to which the subject's life is impaired by panic, anxiety, phobic, or depressive symptoms. The participant rates the extent to which his or her (1) work, (2) social life or leisure activities, and (3) home life or family responsibilities, are impaired by his or her symptoms on 10-point visual analogue scales from 0 (not at all) to 10 (extremely) with a total score range from 0 to 30. Higher scores indicate greater severity of impairment. There are verbal descriptors for the points on the scales as well as numerical scores that provide more precise levels of the verbal descriptors. In addition, the SDS addresses the number of days lost and the number of days under-productive due to the symptoms. A negative change from Baseline indicates improvement. A MMRM model was used for analysis with baseline\week, pooled center, week, treatment, baseline, and week\treatment as factors in the analysis.

Source ClinicalTrials.gov

Outcomes9

Each outcome the trial posted results for, in ClinicalTrials.gov's words.

Type	Outcome	Time frame	Population	Units	Measured as
PRIMARY	Change From Baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score at Week 6	Baseline and Week 6	Participants from full analysis set (FAS), all randomized participants who, received at least 1 dose of study drug, and had at least 1 valid post-baseline value for assessment of primary efficacy, with data available for analyses.	score on a scale	LEAST_SQUARES_MEAN
SECONDARY	Change From Baseline in Quality of Life, Enjoyment and Satisfaction Questionnaire (Q-LES-Q-SF) Short Form Total Score at Week 6	Baseline and Week 6	Participants from FAS, all randomized participants who, received at least 1 dose of study drug, and had at least 1 valid post-baseline value for assessment of primary efficacy, with data available for analyses.	percent of maximum score on a scale	LEAST_SQUARES_MEAN
SECONDARY	Percentage of Participants With MADRS Response at Week 6, With Response Defined as a ≥ 50% Decrease in the MADRS Total Score From Baseline	Baseline and Week 6	Participants from FAS, all randomized participants who, received at least 1 dose of study drug, and had at least 1 valid post-baseline value for assessment of primary efficacy, with data available for analyses.	percentage of participants	NUMBER
SECONDARY	Change From Baseline in Young Mania Rating Scale (YMRS) Total Score at Week 6	Baseline and Week 6	Participants from FAS, all randomized participants who, received at least 1 dose of study drug, and had at least 1 valid post-baseline value for assessment of primary efficacy, with data available for analyses.	score on a scale	LEAST_SQUARES_MEAN
SECONDARY	Clinical Global Impression Scale-Improvement (CGI-I) Score at Week 6	6 Weeks	Participants from FAS, all randomized participants who, received at least 1 dose of study drug, and had at least 1 valid post-baseline value for assessment of primary efficacy, with data available for analyses.	score on a scale	LEAST_SQUARES_MEAN
SECONDARY	Change From Baseline in Clinical Global Impression Scale-Severity (CGI-S) at Week 6	Baseline and Week 6	Participants from FAS, all randomized participants who, received at least 1 dose of study drug, and had at least 1 valid post-baseline value for assessment of primary efficacy, with data available for analyses.	score on a scale	LEAST_SQUARES_MEAN
SECONDARY	Percentage of Participants With MADRS Remission at Week 6, With Remission Defined as a MADRS Total Score ≤10	Week 6	Participants from FAS, all randomized participants who, received at least 1 dose of study drug, and had at least 1 valid post-baseline value for assessment of primary efficacy, with data available for analyses.	percentage of participants	NUMBER
SECONDARY	Change From Baseline in the Quick Inventory of Depressive Symptomatology - Self-Rated16 (QIDS-SR16) Total Score at Week 6	Baseline and Week 6	Participants from FAS, all randomized participants who, received at least 1 dose of study drug, and had at least 1 valid post-baseline value for assessment of primary efficacy, with data available for analyses.	score on a scale	LEAST_SQUARES_MEAN
SECONDARY	Change From Baseline in Sheehan Disability Scale (SDS) Total Score at Week 6	Baseline and Week 6	Participants from FAS, all randomized participants who, received at least 1 dose of study drug, and had at least 1 valid post-baseline value for assessment of primary efficacy, with data available for analyses.	score on a scale	LEAST_SQUARES_MEAN

Source ClinicalTrials.gov

Results by group36

Each measurement the trial posted, group by group, in the words and numbers it posted.

Outcome	Group	Value	Spread	Units
Change From Baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score at Week 6	Placebo	-14.5	Standard Error 0.94	score on a scale
Change From Baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score at Week 6	Ramelteon SL 0.1 mg	-14.4	Standard Error 0.89	score on a scale
Change From Baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score at Week 6	Ramelteon SL 0.4 mg	-11.8	Standard Error 0.91	score on a scale
Change From Baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score at Week 6	Ramelteon SL 0.8 mg	-14.8	Standard Error 0.91	score on a scale
Change From Baseline in Quality of Life, Enjoyment and Satisfaction Questionnaire (Q-LES-Q-SF) Short Form Total Score at Week 6	Placebo	8.4	Standard Error 1.67	percent of maximum score on a scale
Change From Baseline in Quality of Life, Enjoyment and Satisfaction Questionnaire (Q-LES-Q-SF) Short Form Total Score at Week 6	Ramelteon SL 0.1 mg	13.1	Standard Error 1.56	percent of maximum score on a scale
Change From Baseline in Quality of Life, Enjoyment and Satisfaction Questionnaire (Q-LES-Q-SF) Short Form Total Score at Week 6	Ramelteon SL 0.4 mg	9.2	Standard Error 1.61	percent of maximum score on a scale
Change From Baseline in Quality of Life, Enjoyment and Satisfaction Questionnaire (Q-LES-Q-SF) Short Form Total Score at Week 6	Ramelteon SL 0.8 mg	14.8	Standard Error 1.57	percent of maximum score on a scale
Percentage of Participants With MADRS Response at Week 6, With Response Defined as a ≥ 50% Decrease in the MADRS Total Score From Baseline	Placebo	45.2		percentage of participants
Percentage of Participants With MADRS Response at Week 6, With Response Defined as a ≥ 50% Decrease in the MADRS Total Score From Baseline	Ramelteon SL 0.1 mg	50.5		percentage of participants

1 to 10 of 36Source ClinicalTrials.gov

See all 36 results by group

Participant flow16

How many started, completed or left each group, period by period.

Period	Milestone	Group	Participants
Overall Study	STARTED	Placebo	115
Overall Study	STARTED	Ramelteon SL 0.1 mg	128
Overall Study	STARTED	Ramelteon SL 0.4 mg	124
Overall Study	STARTED	Ramelteon SL 0.8 mg	123
Overall Study	Safety Set - Received Treatment	Placebo	115
Overall Study	Safety Set - Received Treatment	Ramelteon SL 0.1 mg	127
Overall Study	Safety Set - Received Treatment	Ramelteon SL 0.4 mg	124
Overall Study	Safety Set - Received Treatment	Ramelteon SL 0.8 mg	123
Overall Study	COMPLETED	Placebo	86
Overall Study	COMPLETED	Ramelteon SL 0.1 mg	100

1 to 10 of 16Source ClinicalTrials.gov

See all 16 participant flow

Adverse events48

Each adverse event the trial posted, group by group: the participants affected out of those at risk.

Type	Event	Organ system	Group	Affected	At risk
other	Dry mouth	Gastrointestinal disorders	Placebo	1	115
other	Dry mouth	Gastrointestinal disorders	Ramelteon SL 0.1 mg	2	127
other	Dry mouth	Gastrointestinal disorders	Ramelteon SL 0.4 mg	8	124
other	Dry mouth	Gastrointestinal disorders	Ramelteon SL 0.8 mg	5	123
other	Nasopharyngitis	Infections and infestations	Placebo	2	115
other	Nasopharyngitis	Infections and infestations	Ramelteon SL 0.1 mg	7	127
other	Nasopharyngitis	Infections and infestations	Ramelteon SL 0.4 mg	2	124
other	Nasopharyngitis	Infections and infestations	Ramelteon SL 0.8 mg	6	123
other	Headache	Nervous system disorders	Placebo	8	115
other	Headache	Nervous system disorders	Ramelteon SL 0.1 mg	3	127

1 to 10 of 48Source ClinicalTrials.gov

See all 48 adverse events

Adverse event totals12

The totals the trial posted for each group.

Total	Group	Affected	At risk
Total, all-cause mortality	Placebo
Total, all-cause mortality	Ramelteon SL 0.1 mg
Total, all-cause mortality	Ramelteon SL 0.4 mg
Total, all-cause mortality	Ramelteon SL 0.8 mg
Total, other adverse events	Placebo	10	115
Total, other adverse events	Ramelteon SL 0.1 mg	17	127
Total, other adverse events	Ramelteon SL 0.4 mg	19	124
Total, other adverse events	Ramelteon SL 0.8 mg	19	123
Total, serious adverse events	Placebo	4	115
Total, serious adverse events	Ramelteon SL 0.1 mg	5	127

1 to 10 of 12Source ClinicalTrials.gov

See all 12 adverse event totals

Papers0

The papers the trial lists on ClinicalTrials.gov.

None in this release.

Grants0

The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.

None in this release.

Trial comparisons0

Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.

None in this release.

Tests0

The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.

None in this release.

Data dates

The day each source was copied for this release.

ClinicalTrials.gov: 2026-11-12; ClinicalTrials.gov
Results, from AACT: 2026-03-23; AACT
NIH grant links: 2026-11-13; NIH RePORTER

Sources 3

ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
ClinicalTrials.govNo license stated
NIH RePORTER's clinical studies and project filesPublic domain

Each source's terms

ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
ClinicalTrials.govnone stated
NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)

ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.

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