A Study of Duloxetine (LY248686) in Japanese Children and Adolescents With Depressive Disorder

• Sponsor: Shionogi (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03315793
• Collaborator: Eli Lilly and Company (Industry)
• Enrollment: 149
• Location: 1
• Arms: 2
• Actual Duration (Months): 23.1
• Patients Per Site Per Month: 6.4

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the efficacy of duloxetine hydrochloride versus placebo in the treatment of Japanese children and adolescents with depressive disorder.

Condition or Disease	Intervention/Treatment	Phase
Depressive Disorder	Drug: Duloxetine Hydrochloride; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 149 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Double-blind, Efficacy and Safety Study of Duloxetine Hydrochloride Versus Placebo in the Treatment of Japanese Children and Adolescents With Depressive Disorder
• Actual Study Start Date: Dec 4, 2017
• Actual Primary Completion Date: Nov 8, 2019
• Actual Study Completion Date: Nov 8, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Duloxetine Hydrochloride Duloxetine hydrochloride given orally.	Drug: Duloxetine Hydrochloride; Administered orally; Other Names: LY248686
Placebo Comparator: Placebo Placebo given orally.	Drug: Placebo; Administered orally

Outcome Measures

Primary Outcome Measures

1. Change From Baseline on the Children's Depression Rating Scale-Revised (CDRS-R) Total Score [Baseline, Week 6]

   Change from baseline on the Children's Depression Rating Scale-Revised (CDRS-R) total score. CDRS-R Total score measures the presence and severity of depression in children. The scale consists of 17 items scored on a 1-to-5- or 1-to-7-point scale. A rating of 1 indicates normal functioning and a higher number indicates a greater degree of depression. The total sum of scores range from 17 to 113. In general, scores below 20 indicate an absence of depression, scores of 20 to 30 indicate borderline depression, scores of 40 to 60 indicate moderate depression, and scores greater than 60 indicate severe depression. Least squares (LS) mean was calculated using a mixed-effects model repeated measures (MMRM) approach including treatment group, observation time-points, and interaction between treatment group and observation time-points as fixed effects, and baseline CDRS-R total score and age as covariates.

Secondary Outcome Measures

1. Percentage of Participants Whose Children's Depression Rating Scale-Revised (CDRS-R) Total Score Decreased by More Than 30% From Baseline [Baseline, Week 6]

   The Children's Depression Rating Scale-Revised (CDRS-R) Total score measures the presence and severity of depression in children. The scale consists of 17 items scored on a 1-to-5- or 1-to-7-point scale. A rating of 1 indicates normal functioning and higher numbers indicate a greater degree of depression. The total sum of scores range from 17 to 113. In general, scores below 20 indicate an absence of depression, scores of 20 to 30 indicate borderline depression, scores of 40 to 60 indicate moderate depression, and scores greater than 60 indicate severe depression.

2. Percentage of Participants Whose CDRS-R Total Score Decreased by More Than 50% From Baseline [Baseline, Week 6]

   The Children's Depression Rating Scale-Revised (CDRS-R) total score measures the presence and severity of depression in children. The scale consists of 17 items scored on a 1-to-5- or 1-to-7-point scale. A rating of 1 indicates normal functioning with higher numbers indicating a greater degree of depression . The total sum of scores range from 17 to 113. The total sum of scores range from 17 to 113. In general, scores below 20 indicate an absence of depression, scores of 20 to 30 indicate borderline depression, scores of 40 to 60 indicate moderate depression, and scores greater than 60 indicate severe depression.

3. Percentage of Participants With Total Children's Depression Rating Scale-Revised (CDRS-R) Score ≤ 28 [Baseline, Week 6]

   The Children's Depression Rating Scale-Revised (CDRS-R) total score measures the presence and severity of depression in children. The scale consists of 17 items scored on a 1-to-5- or 1-to-7-point scale. A rating of 1 indicates normal functioning and higher numbers indicate a greater degree of depression. The total sum of scores range from 17 to 113. In general, scores below 20 indicate an absence of depression, scores of 20 to 30 indicate borderline depression, scores of 40 to 60 indicate moderate depression, and scores greater than 60 indicate severe depression. Remission was defined for the CDRS-R total score below 28.

4. Change From Baseline on Clinical Global Impression-Severity (CGI-S) [Baseline, Week 6]

   CGI-S measures severity of illness at the time of assessment compared with start of treatment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). Presented here are the LS mean change from baseline on CGI-S calculated using a mixed-effects model repeated measures (MMRM) approach including treatment group, observation time-points, and interaction between treatment group and observation time-points as fixed effects, and baseline CGI-S and age as covariates.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 9 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Participants diagnosed with Major Depressive Disorder or persistent depressive disorder and completely meet the criteria of major depressive episode as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) with the Mini International Neuropsychiatric Interview for Children and Adolescents (MINI-KID) ver.7.0.2.

• Participants whose incipient age of depression was ≥7 years old.

• Total score of CDRS-R is ≥40 and CGI-S score is ≥4 at both screening and baseline.

Exclusion Criteria:

• Have remarkable response to psycho-education (defined as >30% decrease in the total score of CDRS-R between screening and baseline).

• Have a current or previous diagnosis (DSM-5) of the following as judged by the investigator:

• Neurodevelopmental disorders

• Schizophrenia spectrum and other psychotic disorders

• Bipolar and related disorders

• Trauma and stressor-related disorders

• Disruptive · Impulse Control · and Conduct disorders

• Have a current diagnosis (DSM-5) of the following as judged by the investigator:

• Obsessive-compulsive and related disorders

• Anorexia nervosa, Bulimia nervosa, Binge-eating disorder

• Sleep-wake disorders

• Neurocognitive disorders

• Disruptive mood dysregulation disorder

• Have personality disorders, in the judgement of the investigator.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Shionogi	Osaka		Japan	541-0045

Sponsors and Collaborators

• Shionogi
• Eli Lilly and Company

Investigators

• Study Director: Shionogi Clinical Trial Administrator Clinical Support Help Line, Shionogi

Study Documents (Full-Text)

• Study Protocol - Aug 8, 2018
• Statistical Analysis Plan - Jan 17, 2020

More Information

Publications

None provided.

• Responsible Party: Shionogi
• ClinicalTrials.gov Identifier: NCT03315793
• Other Study ID Numbers: 14937; F1J-JE-B058; 1701A3631
• First Posted: Oct 20, 2017
• Last Update Posted: Jan 5, 2021
• Last Verified: Dec 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Additional relevant MeSH terms: Depressive Disorder; Depression; Duloxetine Hydrochloride

Study Results

Participant Flow

Arm/Group Title	Duloxetine	Placebo
Arm/Group Description	20 mg Duloxetine was administered every day for 1 week. Then 40 mg Duloxetine was administered for 1 week. Then flexible doses of 40 mg or 60 mg Duloxetine were administered for 4 weeks. Lower doses of Duloxetine were administered for 1 week during tapering off period.	Placebo was administered every day for 7 weeks.
Period Title: Overall Study
STARTED	75	74
Received at Least 1 Dose of Study Drug	75	74
COMPLETED	70	71
NOT COMPLETED	5	3

Baseline Characteristics

Arm/Group Title	Duloxetine	Placebo	Total
Arm/Group Description	20 mg Duloxetine was administered for 1 week. Then 40 mg Duloxetine was administered for 1 week. Then flexible doses of 40 mg or 60 mg Duloxetine were administered for 4 weeks. Lower doses Duloxetine were administered for 1 week during tapering off period.	Placebo was administered every day for 7 weeks.	Total of all reporting groups
Overall Participants	74	74	148
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	14 (1.9)	14.6 (2.0)	14.5 (1.9)
Sex: Female, Male (Count of Participants)
Female	46 62.2%	47 63.5%	93 62.8%
Male	28 37.8%	27 36.5%	55 37.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	74 100%	74 100%	148 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
Japan	74 100%	74 100%	148 100%
Children's Depression Rating Scale-Revised (CDRS-R) Total Score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	65.7 (10.5)	63.3 (12.4)	64.5 (11.5)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline on the Children's Depression Rating Scale-Revised (CDRS-R) Total Score
Description	Change from baseline on the Children's Depression Rating Scale-Revised (CDRS-R) total score. CDRS-R Total score measures the presence and severity of depression in children. The scale consists of 17 items scored on a 1-to-5- or 1-to-7-point scale. A rating of 1 indicates normal functioning and a higher number indicates a greater degree of depression. The total sum of scores range from 17 to 113. In general, scores below 20 indicate an absence of depression, scores of 20 to 30 indicate borderline depression, scores of 40 to 60 indicate moderate depression, and scores greater than 60 indicate severe depression. Least squares (LS) mean was calculated using a mixed-effects model repeated measures (MMRM) approach including treatment group, observation time-points, and interaction between treatment group and observation time-points as fixed effects, and baseline CDRS-R total score and age as covariates.
Time Frame	Baseline, Week 6

Outcome Measure Data

Analysis Population Description

All randomized participants who received 1 dose of study drug and had 1 post-baseline CDRS-S score. One participant in the duloxetine group had no post-dose CDRS-R Total Score and was not included in the analysis.

Arm/Group Title	Duloxetine	Placebo
Arm/Group Description	20 mg Duloxetine was administered every day for 1 week. Then 40 mg Duloxetine was administered for 1 week. Then flexible doses of 40 mg or 60 mg Duloxetine were administered for 4 weeks. Lower doses of Duloxetine were administered for 1 week during tapering off period.	Placebo was administered every day for 7 weeks.
Measure Participants	74	74
Least Squares Mean (Standard Error) [units on a scale]	-21.03 (2.04)	-22.42 (2.05)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Duloxetine, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5587
	Comments
	Method	mixed-effects model repeated measures
	Comments
Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	1.39
	Confidence Interval	(2-Sided) 98%; -3.30 to 6.08
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percentage of Participants Whose Children's Depression Rating Scale-Revised (CDRS-R) Total Score Decreased by More Than 30% From Baseline
Description	The Children's Depression Rating Scale-Revised (CDRS-R) Total score measures the presence and severity of depression in children. The scale consists of 17 items scored on a 1-to-5- or 1-to-7-point scale. A rating of 1 indicates normal functioning and higher numbers indicate a greater degree of depression. The total sum of scores range from 17 to 113. In general, scores below 20 indicate an absence of depression, scores of 20 to 30 indicate borderline depression, scores of 40 to 60 indicate moderate depression, and scores greater than 60 indicate severe depression.
Time Frame	Baseline, Week 6

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug and had at least 1 post-dose CDRS-R Total Score. One participant in the duloxetine group had no post-dose CDRS-R Total Score and was not included in the analysis. The last observation carried forward (LOCF) method was used.

Arm/Group Title	Duloxetine	Placebo
Arm/Group Description	20 mg Duloxetine was administered for 1 week. Then 40 mg Duloxetine was administered for 1 week. Then flexible doses of 40 mg or 60 mg Duloxetine were administered for 4 weeks. Lower doses Duloxetine were administered for 1 week during tapering off period.	Placebo was administered every day for 7 weeks.
Measure Participants	74	74
Number [percentage of participants]	48.6 65.7%	43.2 58.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Duloxetine, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5111
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by age
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	5.4
	Confidence Interval	(2-Sided) 95%; -10.7 to 21.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Percentage of Participants Whose CDRS-R Total Score Decreased by More Than 50% From Baseline
Description	The Children's Depression Rating Scale-Revised (CDRS-R) total score measures the presence and severity of depression in children. The scale consists of 17 items scored on a 1-to-5- or 1-to-7-point scale. A rating of 1 indicates normal functioning with higher numbers indicating a greater degree of depression . The total sum of scores range from 17 to 113. The total sum of scores range from 17 to 113. In general, scores below 20 indicate an absence of depression, scores of 20 to 30 indicate borderline depression, scores of 40 to 60 indicate moderate depression, and scores greater than 60 indicate severe depression.
Time Frame	Baseline, Week 6

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug and had at least 1 post-dose CDRS-R Total Score. One participant in the duloxetine group had no post-dose CDRS-R Total Score and was not included in the analysis. The last observation carried forward (LOCF) method was used.

Arm/Group Title	Duloxetine	Placebo
Arm/Group Description	20 mg Duloxetine was administered for 1 week. Then 40 mg Duloxetine was administered for 1 week. Then flexible doses of 40 mg or 60 mg Duloxetine were administered for 4 weeks. Lower doses Duloxetine were administered for 1 week during tapering off period.	Placebo was administered every day for 7 weeks.
Measure Participants	74	74
Number [percentage of participants]	21.6 29.2%	21.6 29.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Duloxetine, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1.0000
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by age
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -13.5 to 13.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Percentage of Participants With Total Children's Depression Rating Scale-Revised (CDRS-R) Score ≤ 28
Description	The Children's Depression Rating Scale-Revised (CDRS-R) total score measures the presence and severity of depression in children. The scale consists of 17 items scored on a 1-to-5- or 1-to-7-point scale. A rating of 1 indicates normal functioning and higher numbers indicate a greater degree of depression. The total sum of scores range from 17 to 113. In general, scores below 20 indicate an absence of depression, scores of 20 to 30 indicate borderline depression, scores of 40 to 60 indicate moderate depression, and scores greater than 60 indicate severe depression. Remission was defined for the CDRS-R total score below 28.
Time Frame	Baseline, Week 6

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had at least 1 post-dose CDRS-R Total Score. One participant in the duloxetine group had no post-dose CDRS-R Total Score and was not included in the analysis. The last observation carried forward (LOCF) method was used.

Arm/Group Title	Duloxetine	Placebo
Arm/Group Description	20 mg Duloxetine was administered for 1 week. Then 40 mg Duloxetine was administered for 1 week. Then flexible doses of 40 mg or 60 mg Duloxetine were administered for 4 weeks. Lower doses of Duloxetine were administered for 1 week during tapering off period.	Placebo was administered every day for 7 weeks.
Measure Participants	74	74
Number [percentage of participants]	9.5 12.8%	13.5 18.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Duloxetine, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4423
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by age
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-4.1
	Confidence Interval	(2-Sided) 95%; -14.4 to 6.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Change From Baseline on Clinical Global Impression-Severity (CGI-S)
Description	CGI-S measures severity of illness at the time of assessment compared with start of treatment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). Presented here are the LS mean change from baseline on CGI-S calculated using a mixed-effects model repeated measures (MMRM) approach including treatment group, observation time-points, and interaction between treatment group and observation time-points as fixed effects, and baseline CGI-S and age as covariates.
Time Frame	Baseline, Week 6

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had at least 1 post-dose CDRS-R Total score. One duloxetine participant had no post-dose CDRS-R Total Score and was not included in the analysis.

Arm/Group Title	Duloxetine	Placebo
Arm/Group Description	20 mg Duloxetine was administered for 1 week. Then 40 mg Duloxetine was administered for 1 week. Then flexible doses of 40 mg or 60 mg Duloxetine were administered for 4 weeks. Lower doses of Duloxetine were administered for 1 week during tapering off period.	Placebo was administered every day for 7 weeks.
Measure Participants	74	74
Least Squares Mean (Standard Error) [units on a scale]	-1.24 (0.14)	-1.38 (0.14)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Duloxetine, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3836
	Comments
	Method	mixed-effects model repeated measures
	Comments
Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	0.14
	Confidence Interval	(2-Sided) 95%; -0.18 to 0.46
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Baseline to 7 Weeks
Adverse Event Reporting Description	All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants At Risk adjusted accordingly.
Arm/Group Title	Duloxetine		Placebo
Arm/Group Description	20 mg Duloxetine was administered for 1 week. Then 40 mg Duloxetine was administered for 1 week. Then flexible doses of 40 mg or 60 mg Duloxetine were administered for 4 weeks. Lower doses of Duloxetine were administered for 1 week during tapering off period.		Placebo was administered every day for 7 weeks.
All Cause Mortality
	Duloxetine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/75 (0%)		0/74 (0%)
Serious Adverse Events
	Duloxetine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/75 (0%)		0/74 (0%)
Other (Not Including Serious) Adverse Events
	Duloxetine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	59/75 (78.7%)		46/74 (62.2%)
Blood and lymphatic system disorders
Anaemia	1/75 (1.3%)	1	1/74 (1.4%)	1
Cardiac disorders
Palpitations	2/75 (2.7%)	2	0/74 (0%)	0
Sinus arrhythmia	0/75 (0%)	0	1/74 (1.4%)	1
Tachycardia	2/75 (2.7%)	2	0/74 (0%)	0
Ear and labyrinth disorders
Tinnitus	1/75 (1.3%)	1	0/74 (0%)	0
Vertigo	0/75 (0%)	0	1/74 (1.4%)	1
Eye disorders
Conjunctivitis allergic	1/75 (1.3%)	1	0/74 (0%)	0
Gastrointestinal disorders
Abdominal discomfort	1/75 (1.3%)	1	0/74 (0%)	0
Abdominal pain upper	1/75 (1.3%)	1	1/74 (1.4%)	1
Constipation	5/75 (6.7%)	5	0/74 (0%)	0
Dental caries	0/75 (0%)	0	1/74 (1.4%)	1
Diarrhoea	7/75 (9.3%)	7	2/74 (2.7%)	2
Lip dry	1/75 (1.3%)	1	0/74 (0%)	0
Nausea	19/75 (25.3%)	20	9/74 (12.2%)	10
Vomiting	3/75 (4%)	3	4/74 (5.4%)	4
General disorders
Asthenia	1/75 (1.3%)	1	0/74 (0%)	0
Fatigue	1/75 (1.3%)	1	0/74 (0%)	0
Feeling abnormal	1/75 (1.3%)	1	0/74 (0%)	0
Feeling hot	1/75 (1.3%)	1	0/74 (0%)	0
Malaise	5/75 (6.7%)	5	0/74 (0%)	0
Pain	0/75 (0%)	0	1/74 (1.4%)	1
Pyrexia	2/75 (2.7%)	2	1/74 (1.4%)	1
Thirst	2/75 (2.7%)	2	0/74 (0%)	0
Vaccination site swelling	0/75 (0%)	0	1/74 (1.4%)	1
Withdrawal syndrome	1/75 (1.3%)	1	0/74 (0%)	0
Infections and infestations
Bronchitis	0/75 (0%)	0	1/74 (1.4%)	1
Cystitis	0/75 (0%)	0	1/74 (1.4%)	1
Hand-foot-and-mouth disease	0/75 (0%)	0	1/74 (1.4%)	1
Hordeolum	0/75 (0%)	0	1/74 (1.4%)	1
Laryngitis	1/75 (1.3%)	1	0/74 (0%)	0
Nasopharyngitis	10/75 (13.3%)	10	12/74 (16.2%)	12
Otitis externa	1/75 (1.3%)	1	2/74 (2.7%)	2
Rhinitis	0/75 (0%)	0	1/74 (1.4%)	1
Injury, poisoning and procedural complications
Chillblains	0/75 (0%)	0	1/74 (1.4%)	1
Ligament sprain	1/75 (1.3%)	1	0/74 (0%)	0
Wound	1/75 (1.3%)	1	0/74 (0%)	0
Investigations
Alanine aminotransferase increased	1/75 (1.3%)	1	1/74 (1.4%)	1
Aspartate aminotransferase increased	1/75 (1.3%)	1	0/74 (0%)	0
Blood bilirubin increased	2/75 (2.7%)	2	1/74 (1.4%)	1
Blood creatine phosphokinase increased	0/75 (0%)	0	1/74 (1.4%)	1
Blood pressure decreased	1/75 (1.3%)	1	0/74 (0%)	0
Blood pressure increased	2/75 (2.7%)	2	1/74 (1.4%)	1
Blood triglycerides increased	1/75 (1.3%)	1	0/74 (0%)	0
Heart rate increased	1/75 (1.3%)	1	0/74 (0%)	0
Metabolism and nutrition disorders
Decreased appetite	13/75 (17.3%)	13	0/74 (0%)	0
Musculoskeletal and connective tissue disorders
Myalgia	0/75 (0%)	0	1/74 (1.4%)	1
Pain in extremity	1/75 (1.3%)	1	0/74 (0%)	0
Nervous system disorders
Akathisia	1/75 (1.3%)	1	1/74 (1.4%)	1
Dizziness	3/75 (4%)	3	1/74 (1.4%)	1
Dizziness postural	1/75 (1.3%)	1	0/74 (0%)	0
Head discomfort	1/75 (1.3%)	1	0/74 (0%)	0
Headache	6/75 (8%)	6	8/74 (10.8%)	9
Paraesthesia	1/75 (1.3%)	1	1/74 (1.4%)	1
Presyncope	0/75 (0%)	0	1/74 (1.4%)	1
Somnolence	17/75 (22.7%)	17	8/74 (10.8%)	8
Syncope	1/75 (1.3%)	1	0/74 (0%)	0
Psychiatric disorders
Aggression	1/75 (1.3%)	1	0/74 (0%)	0
Agitation	0/75 (0%)	0	1/74 (1.4%)	1
Euphoric mood	1/75 (1.3%)	1	0/74 (0%)	0
Initial insomnia	1/75 (1.3%)	1	0/74 (0%)	0
Insomnia	2/75 (2.7%)	2	0/74 (0%)	0
Intentional self-injury	3/75 (4%)	5	1/74 (1.4%)	1
Irritability	1/75 (1.3%)	1	2/74 (2.7%)	2
Nightmare	1/75 (1.3%)	1	0/74 (0%)	0
Sleep disorder	0/75 (0%)	0	1/74 (1.4%)	1
Suicidal ideation	2/75 (2.7%)	2	1/74 (1.4%)	1
Suicide attempt	1/75 (1.3%)	1	1/74 (1.4%)	1
Renal and urinary disorders
Urinary retention	1/75 (1.3%)	1	0/74 (0%)	0
Reproductive system and breast disorders
Erectile dysfunction	1/29 (3.4%)	1	0/27 (0%)	0
Menstruation irregular	0/46 (0%)	0	1/47 (2.1%)	1
Respiratory, thoracic and mediastinal disorders
Epistaxis	1/75 (1.3%)	1	1/74 (1.4%)	1
Oropharyngeal discomfort	1/75 (1.3%)	1	0/74 (0%)	0
Rhinitis allergic	0/75 (0%)	0	1/74 (1.4%)	1
Rhinorrhoea	0/75 (0%)	0	2/74 (2.7%)	2
Yawning	1/75 (1.3%)	1	0/74 (0%)	0
Skin and subcutaneous tissue disorders
Dermatitis atopic	0/75 (0%)	0	1/74 (1.4%)	1
Dermatitis contact	0/75 (0%)	0	1/74 (1.4%)	1
Eczema	1/75 (1.3%)	1	1/74 (1.4%)	1
Pruritus	1/75 (1.3%)	1	1/74 (1.4%)	1
Urticaria thermal	1/75 (1.3%)	1	0/74 (0%)	0
Vascular disorders
Hot flush	1/75 (1.3%)	1	0/74 (0%)	0
Orthostatic hypotension	2/75 (2.7%)	2	0/74 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.