Brexpiprazole as Adjunctive Therapy With Major Depressive Disorder and an Inadequate Response to Previous Adjunctive Therapy

• Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02012218
• Collaborator: Otsuka Pharmaceutical Co., Ltd. (Industry)
• Enrollment: 61
• Locations: 24
• Arm: 1
• Duration (Months): 11
• Patients Per Site: 2.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The objectives of this exploratory trial are to evaluate the efficacy, safety, and subjects' subjective satisfaction when switching to adjunctive brexpiprazole in subjects with MDD who have responded inadequately to preceding adjunctive drug therapy.

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Disorder (MDD)	Drug: ADT; Drug: Brexpiprazole	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 61 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 3b, Multicenter, Open-label Exploratory Trial to Evaluate the Efficacy, Safety, and Subject Satisfaction With Brexpiprazole as Adjunctive Therapy in the Treatment of Adults With Major Depressive Disorder and an Inadequate Response to Previous Adjunctive Therapy
• Study Start Date: Nov 1, 2013
• Actual Primary Completion Date: Oct 1, 2014
• Actual Study Completion Date: Oct 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ADT and Brexpiprazole ADT and Brexpiprazole	Drug: ADT; Drug: Brexpiprazole

Outcome Measures

Primary Outcome Measures

1. Mean Change From Baseline to Week 6 in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score [Baseline and Week 6]

   The MADRS was used as the primary efficacy assessment of level of depression. The MADRS was administered using the Structured Interview Guide for the MADRS. Detailed instructions were provided.The MADRS consists of 10 items each, with 7 defined grades of severity (ie, 0 to 6, with 0 being the "best" rating and 6 being the "worst" rating). The MADRS total score is the sum of ratings for all 10 items; therefore, possible total scores range from 0 to 60. The MADRS total score least squares (LS) mean changes from baseline to Week 6 is mentioned below.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Clinical diagnosis of MDD

• In current major depressive episode of ≥ 8 weeks in duration and includes an inadequate response to at least 1 adjunctive treatment.

• Positive history of at least 1 additional failure to an adequate monotherapy antidepressant treatment.

• HAM-D17 total score≥ 18

• Currently receiving SSRI of SNRI with adjunctive treatment for at least 6 weeks before screening.

• Willing to discontinue use of all prohibited psychotropic medications

• Historical positive serological results for HIV, hepatitis B/C

• Able to provide written informed consent prior to the initiation of any protocol-required procedures

• Subjects who could potentially benefit from adjunctive treatment with Brexpiprazole

Exclusion Criteria:

• Sexually active women of childbearing potential

• Male subjects not practicing 2 different methods of birth control

• Females who are breastfeeding and/or who have a positive pregnancy test result

• Subjects who have received ECT for the current major depressive episode.

• Subjects who have had an inadequate response to ECT

• Current need for involuntary commitment or who have been hospitalized within 4 weeks of screening

• Current Axis I (DSM-IV-TR)

• Current Axis II (DSM-IV-TR)

• Subjects experiencing hallucinations, delusions, or any psychotic symptomatology in the current major depressive episode.

• Subjects receiving new onset psychotherapy.

• Subjects who answer "Yes" on the C-SSRS Suicidal Ideation Item 4, Item 5, or on any of the 5 C-SSRS Suicidal Behavior Items

• Subjects who have met DSM-IV-TR criteria for substance abuse or dependence within the past 180 days

• Hypothyroidism or hyperthyroidism

• Clinically significant neurological, hepatic, renal, metabolic, haematological, immunological, cardiovascular, pulmonary, or gastrointestinal disorders

• Currently treated with insulin for diabetes

• Uncontrolled hypertension or symptomatic hypotension, or orthostatic hypotension

• Known ischemic heart disease or history of myocardial infarction, congestive heart failure, angioplasty, stenting, or coronary artery bypass surgery

• Epilepsy or history of seizures

• Positive drug screen

• The following laboratory test and ECG results are exclusionary:

1. Platelets ≤ 75,000/mm3

2. Hemoglobin ≤ 9 g/dL

3. Neutrophils, absolute ≤ 1000/mm3

4. AST > 2 × ULN

5. ALT > 2 × ULN

6. CPK > 3 × ULN, unless discussed with and approved by the medical monitor

7. Creatinine ≥ 2 mg/dL

8. HbA1c ≥ 7.0%

9. Abnormal free T4 (Note: Free T4 is measured only if result for TSH is abnormal.)

10. QTcF ≥ 470 msec for females and ≥ 450 msec for males

• Treatment with an MAOI or EMSAM within 14 days of the Baseline visit.

• Use of benzodiazepines and/or hypnotics within 7 days prior to the first dose of IMP

• Use of oral neuroleptics within 7 days prior or long-acting approved atypical antipsychotics ≤ 1 full cycle plus ½ cycle prior to the first dose of IMP

• Subjects who would be likely to require prohibited concomitant therapy during the trial.

• Subjects who previously participated in any prior brexpiprazole trial

• History of neuroleptic malignant syndrome or serotonin syndrome

• History of true allergic response to more than one class of medications

• Prisoners or subjects who are compulsorily detained for treatment of either a psychiatric or physical illness.

• Subjects who participated in a clinical trial within the last 180 days or who participated in more than 2 clinical trials within the past year.

• Any subject who, in the opinion of the investigator or medical monitor, should not participate.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Collaborative NeuroScience Network, Inc.	Garden Grove	California	United States	92845
2	Viking Clinical Research, Ltd.	Temecula	California	United States	92591
3	Clinical Neuroscience Solutions Pharmacology	Orlando	Florida	United States	32806
4	Carman Research	Smyrna	Georgia	United States	30080
5	Goldpoint Clinical Research	Indianapolis	Indiana	United States	46260
6	Alpine Clinic	Lafayette	Indiana	United States	47905
7	Pharmasite Research	Baltimore	Maryland	United States	21208
8	Boston Clinical Trials	Boston	Massachusetts	United States	02131
9	Coastal Research Associates, Inc.	Weymouth	Massachusetts	United States	02190
10	Rochester Center for Behavioral Medicine	Rochester Hills	Michigan	United States	48307
11	St. Louis Clinical Trials	St. Louis	Missouri	United States	63118
12	Center for Emotional Fitness	Cherry Hill	New Jersey	United States	08002
13	Behavioral Medical Research of Staten Island	Staten Island	New York	United States	10305
14	Richard H. Weisler, MD, PA	Raleigh	North Carolina	United States	27609
15	Midwest Clinical Research Center MCRC	Dayton	Ohio	United States	45417-3445
16	Cutting Edge Research Group	Oklahoma City	Oklahoma	United States	73116
17	Oregon Center for Clinical Investigations, Inc.	Portland	Oregon	United States	97210
18	Oregon Center for Clinical Investigations, Inc.	Salem	Oregon	United States	97301
19	Lehigh Center for Clinical Research	Allentown	Pennsylvania	United States	18104
20	Lincoln Research, LLC	Lincoln	Rhode Island	United States	02865
21	Research Strategies of Memphis, LLC	Memphis	Tennessee	United States	38119
22	Future Search Trials of Dallas, LP	Dallas	Texas	United States	75231
23	NeuropsychiatricAssociates	Woodstock	Vermont	United States	05091
24	Frontier Institute	Spokane	Washington	United States	99204

Sponsors and Collaborators

• Otsuka Pharmaceutical Development & Commercialization, Inc.
• Otsuka Pharmaceutical Co., Ltd.

Investigators

• Study Director: Junichi Hashimoto, PhD, Otsuka Pharmaceutical Co., Ltd Japan (OPCJ)

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc.
• ClinicalTrials.gov Identifier: NCT02012218
• Other Study ID Numbers: 331-13-001
• First Posted: Dec 16, 2013
• Last Update Posted: Dec 29, 2015
• Last Verified: Nov 1, 2015

• Keywords provided by Otsuka Pharmaceutical Development & Commercialization, Inc.: Major Depressive Disorder, Depression
• Additional relevant MeSH terms: Disease; Depressive Disorder; Depression; Depressive Disorder, Major; Brexpiprazole

Study Results

Participant Flow

Recruitment Details	This trial was conducted in 61 participants in 28 trial sites, all of which were located in the United States.
Pre-assignment Detail	The trial consisted of a continuous 6-week open-label treatment period including an initial 2-week titration period with a 30-day (+2 days) follow-up period.

Arm/Group Title	Group 1A	Group 1B	Group 2	Group 3	Group 4
Arm/Group Description	Participants who had received a prescribed number of tablets of aripiprazole (baseline/primary antidepressant therapy [ADT]) and adjunctive therapy were switched to ADT plus one tablet of brexpiprazole as adjunctive therapy daily throughout the 6-week treatment period.	Participants who had received a prescribed number of tablets of quetiapine IR (immediate release) or XR (extended release) (baseline/primary ADT) and adjunctive therapy were switched to ADT plus one tablet of brexpiprazole as adjunctive therapy daily throughout the 6-week treatment period.	Participants who had received a prescribed number of tablets of any Selective Serotonin Reuptake Inhibitors (SSRI), any Serotonin-norepinephrine Reuptake Inhibitors (SNRI), any tricyclic antidepressant, or Oleptro (trazodone hydrochloride) IR or XR (baseline/primary ADT) and adjunctive therapy were switched to ADT plus one tablet of brexpiprazole as adjunctive therapy daily throughout the 6-week treatment period.	Participants who had received a prescribed number of tablets of bupropion (baseline/primary ADT) and adjunctive therapy were switched to ADT plus one tablet of brexpiprazole as adjunctive therapy daily throughout the 6-week treatment period.	Participants who had received a prescribed number of tablets of stimulants such as modafinil, methylphenidate, or psychostimulant (baseline/primary ADT) and adjunctive therapy were switched to ADT plus one tablet of brexpiprazole as adjunctive therapy daily throughout the 6-week treatment period.
Period Title: Overall Study
STARTED	12	11	13	19	6
COMPLETED	8	10	11	17	5
NOT COMPLETED	4	1	2	2	1

Baseline Characteristics

Arm/Group Title	Group 1A	Group 1B	Group 2	Group 3	Group 4	Total
Arm/Group Description	Participants who had received a prescribed number of tablets of aripiprazole (baseline/primary antidepressant therapy [ADT]) and adjunctive therapy were switched to ADT plus one tablet of brexpiprazole as adjunctive therapy daily throughout the 6-week treatment period.	Participants who had received a prescribed number of tablets of quetiapine IR (immediate release) or XR (extended release) (baseline/primary ADT) and adjunctive therapy were switched to ADT plus one tablet of brexpiprazole as adjunctive therapy daily throughout the 6-week treatment period.	Participants who had received a prescribed number of tablets of any Selective Serotonin Reuptake Inhibitors (SSRI), any Serotonin-norepinephrine Reuptake Inhibitors (SNRI), any tricyclic antidepressant, or Oleptro (trazodone hydrochloride) IR or XR (baseline/primary ADT) and adjunctive therapy were switched to ADT plus one tablet of brexpiprazole as adjunctive therapy daily throughout the 6-week treatment period.	Participants who had received a prescribed number of tablets of bupropion (baseline/primary ADT) and adjunctive therapy were switched to ADT plus one tablet of brexpiprazole as adjunctive therapy daily throughout the 6-week treatment period.	Participants who had received a prescribed number of tablets of stimulants such as modafinil, methylphenidate, or psychostimulant (baseline/primary ADT) and adjunctive therapy were switched to ADT plus one tablet of brexpiprazole as adjunctive therapy daily throughout the 6-week treatment period.	Total of all reporting groups
Overall Participants	12	11	13	19	6	61
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	50.2 (8.13)	41.8 (13.57)	48.5 (12.20)	44.1 (13.64)	41.7 (13.59)	45.6 (12.44)
Sex: Female, Male (Count of Participants)
Female	7 58.3%	7 63.6%	11 84.6%	15 78.9%	3 50%	43 70.5%
Male	5 41.7%	4 36.4%	2 15.4%	4 21.1%	3 50%	18 29.5%

Outcome Measures

1. Primary Outcome

Title	Mean Change From Baseline to Week 6 in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
Description	The MADRS was used as the primary efficacy assessment of level of depression. The MADRS was administered using the Structured Interview Guide for the MADRS. Detailed instructions were provided.The MADRS consists of 10 items each, with 7 defined grades of severity (ie, 0 to 6, with 0 being the "best" rating and 6 being the "worst" rating). The MADRS total score is the sum of ratings for all 10 items; therefore, possible total scores range from 0 to 60. The MADRS total score least squares (LS) mean changes from baseline to Week 6 is mentioned below.
Time Frame	Baseline and Week 6

Outcome Measure Data

Analysis Population Description

All participants who took at least one dose of brexpiprazole and who had a valid baseline assessment and at least one valid post-baseline efficacy assessment.

Arm/Group Title	Group 1A	Group 1B	Group 2	Group 3	Group 4
Arm/Group Description	Participants who had received a prescribed number of tablets of aripiprazole (baseline/primary antidepressant therapy [ADT]) and adjunctive therapy were switched to ADT plus one tablet of brexpiprazole as adjunctive therapy daily throughout the 6-week treatment period.	Participants who had received a prescribed number of tablets of quetiapine IR (immediate release) or XR (extended release) (baseline/primary ADT) and adjunctive therapy were switched to ADT plus one tablet of brexpiprazole as adjunctive therapy daily throughout the 6-week treatment period.	Participants who had received a prescribed number of tablets of any Selective Serotonin Reuptake Inhibitors (SSRI), any Serotonin-norepinephrine Reuptake Inhibitors (SNRI), any tricyclic antidepressant, or Oleptro (trazodone hydrochloride) IR or XR (baseline/primary ADT) and adjunctive therapy were switched to ADT plus one tablet of brexpiprazole as adjunctive therapy daily throughout the 6-week treatment period.	Participants who had received a prescribed number of tablets of bupropion (baseline/primary ADT) and adjunctive therapy were switched to ADT plus one tablet of brexpiprazole as adjunctive therapy daily throughout the 6-week treatment period.	Participants who had received a prescribed number of tablets of stimulants such as modafinil, methylphenidate, or psychostimulant (baseline/primary ADT) and adjunctive therapy were switched to ADT plus one tablet of brexpiprazole as adjunctive therapy daily throughout the 6-week treatment period.
Measure Participants	12	10	12	19	6
Least Squares Mean (Standard Error) [Units on a scale]	-12.8 (2.26)	-18.4 (2.10)	-19.5 (1.99)	-19.2 (1.59)	-16.8 (2.97)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1A, Group 1B, Group 2, Group 3, Group 4
	Comments	The null hypothesis of zero in mean change from baseline in MADRS total score at Week 6 was tested for each treatment group at significance level of 0.05 (2-sided).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values were calculated according to testing a null hypothesis of zero mean change.
	Method	Mixed Models Analysis
	Comments	This analysis was conducted using a mixed model repeated measures analysis on observed case data.

Adverse Events

Time Frame	Adverse events were reported from the signing of the informed consent until the end of trial with a safety follow-up of 30 (+2 ) days.
Arm/Group Title	Group 1A		Group 1B		Group 2		Group 3		Group 4
Arm/Group Description	Participants who had received a prescribed number of tablets of aripiprazole (baseline/primary antidepressant therapy [ADT]) and adjunctive therapy were switched to ADT plus one tablet of brexpiprazole as adjunctive therapy daily throughout the 6-week treatment period.		Participants who had received a prescribed number of tablets of quetiapine IR (immediate release) or XR (extended release) (baseline/primary ADT) and adjunctive therapy were switched to ADT plus one tablet of brexpiprazole as adjunctive therapy daily throughout the 6-week treatment period.		Participants who had received a prescribed number of tablets of any Selective Serotonin Reuptake Inhibitors (SSRI), any Serotonin-norepinephrine Reuptake Inhibitors (SNRI), any tricyclic antidepressant, or Oleptro (trazodone hydrochloride) IR or XR (baseline/primary ADT) and adjunctive therapy were switched to ADT plus one tablet of brexpiprazole as adjunctive therapy daily throughout the 6-week treatment period.		Participants who had received a prescribed number of tablets of bupropion (baseline/primary ADT) and adjunctive therapy were switched to ADT plus one tablet of brexpiprazole as adjunctive therapy daily throughout the 6-week treatment period.		Participants who had received a prescribed number of tablets of stimulants such as modafinil, methylphenidate, or psychostimulant (baseline/primary ADT) and adjunctive therapy were switched to ADT plus one tablet of brexpiprazole as adjunctive therapy daily throughout the 6-week treatment period.
All Cause Mortality
	Group 1A		Group 1B		Group 2		Group 3		Group 4
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Group 1A		Group 1B		Group 2		Group 3		Group 4
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		1/11 (9.1%)		0/13 (0%)		0/19 (0%)		0/6 (0%)
Musculoskeletal and connective tissue disorders
Rhabdomyolysis	0/12 (0%)		1/11 (9.1%)		0/13 (0%)		0/19 (0%)		0/6 (0%)
Other (Not Including Serious) Adverse Events
	Group 1A		Group 1B		Group 2		Group 3		Group 4
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/12 (58.3%)		8/11 (72.7%)		6/13 (46.2%)		15/19 (78.9%)		5/6 (83.3%)
Cardiac disorders
Atrioventricular block first degree	0/12 (0%)		0/11 (0%)		0/13 (0%)		0/19 (0%)		1/6 (16.7%)
Eye disorders
Vision blurred	1/12 (8.3%)		0/11 (0%)		0/13 (0%)		1/19 (5.3%)		0/6 (0%)
Gastrointestinal disorders
Dry mouth	2/12 (16.7%)		0/11 (0%)		1/13 (7.7%)		2/19 (10.5%)		0/6 (0%)
Diarrhoea	0/12 (0%)		0/11 (0%)		1/13 (7.7%)		3/19 (15.8%)		0/6 (0%)
Abdominal distension	0/12 (0%)		0/11 (0%)		0/13 (0%)		0/19 (0%)		1/6 (16.7%)
Constipation	0/12 (0%)		0/11 (0%)		0/13 (0%)		1/19 (5.3%)		0/6 (0%)
Nausea	0/12 (0%)		0/11 (0%)		1/13 (7.7%)		0/19 (0%)		0/6 (0%)
Oesophagitis	0/12 (0%)		0/11 (0%)		0/13 (0%)		1/19 (5.3%)		0/6 (0%)
General disorders
Fatigue	1/12 (8.3%)		0/11 (0%)		2/13 (15.4%)		3/19 (15.8%)		3/6 (50%)
Infections and infestations
Upper respiratory tract infection	1/12 (8.3%)		1/11 (9.1%)		0/13 (0%)		1/19 (5.3%)		0/6 (0%)
Nasopharyngitis	0/12 (0%)		0/11 (0%)		0/13 (0%)		0/19 (0%)		1/6 (16.7%)
Sinusitis	0/12 (0%)		1/11 (9.1%)		0/13 (0%)		0/19 (0%)		0/6 (0%)
Viral infection	0/12 (0%)		1/11 (9.1%)		0/13 (0%)		0/19 (0%)		0/6 (0%)
Injury, poisoning and procedural complications
Fall	0/12 (0%)		1/11 (9.1%)		0/13 (0%)		0/19 (0%)		0/6 (0%)
Head injury	0/12 (0%)		1/11 (9.1%)		0/13 (0%)		0/19 (0%)		0/6 (0%)
Ligament sprain	0/12 (0%)		0/11 (0%)		0/13 (0%)		1/19 (5.3%)		0/6 (0%)
Investigations
Weight increased	0/12 (0%)		1/11 (9.1%)		0/13 (0%)		1/19 (5.3%)		0/6 (0%)
Weight decreased	0/12 (0%)		0/11 (0%)		1/13 (7.7%)		0/19 (0%)		0/6 (0%)
Metabolism and nutrition disorders
Increased appetite	1/12 (8.3%)		1/11 (9.1%)		1/13 (7.7%)		2/19 (10.5%)		0/6 (0%)
Dyslipidaemia	0/12 (0%)		0/11 (0%)		0/13 (0%)		1/19 (5.3%)		0/6 (0%)
Food craving	0/12 (0%)		0/11 (0%)		1/13 (7.7%)		0/19 (0%)		0/6 (0%)
Musculoskeletal and connective tissue disorders
Back pain	1/12 (8.3%)		0/11 (0%)		0/13 (0%)		0/19 (0%)		0/6 (0%)
Muscle rigidity	0/12 (0%)		0/11 (0%)		0/13 (0%)		1/19 (5.3%)		0/6 (0%)
Musculoskeletal chest pain	1/12 (8.3%)		0/11 (0%)		0/13 (0%)		0/19 (0%)		0/6 (0%)
Tendonitis	0/12 (0%)		1/11 (9.1%)		0/13 (0%)		0/19 (0%)		0/6 (0%)
Nervous system disorders
Akathisia	2/12 (16.7%)		0/11 (0%)		0/13 (0%)		3/19 (15.8%)		0/6 (0%)
Headache	1/12 (8.3%)		1/11 (9.1%)		1/13 (7.7%)		1/19 (5.3%)		1/6 (16.7%)
Somnolence	0/12 (0%)		0/11 (0%)		1/13 (7.7%)		2/19 (10.5%)		1/6 (16.7%)
Disturbance in attention	0/12 (0%)		0/11 (0%)		2/13 (15.4%)		0/19 (0%)		0/6 (0%)
Poor quality sleep	0/12 (0%)		1/11 (9.1%)		0/13 (0%)		1/19 (5.3%)		0/6 (0%)
Sedation	0/12 (0%)		0/11 (0%)		1/13 (7.7%)		0/19 (0%)		1/6 (16.7%)
Tension headache	0/12 (0%)		0/11 (0%)		0/13 (0%)		2/19 (10.5%)		0/6 (0%)
Aphasia	0/12 (0%)		0/11 (0%)		0/13 (0%)		1/19 (5.3%)		0/6 (0%)
Cognitive disorder	0/12 (0%)		0/11 (0%)		0/13 (0%)		1/19 (5.3%)		0/6 (0%)
Dizziness	0/12 (0%)		0/11 (0%)		0/13 (0%)		1/19 (5.3%)		0/6 (0%)
Extrapyramidal disorder	1/12 (8.3%)		0/11 (0%)		0/13 (0%)		0/19 (0%)		0/6 (0%)
Glabellar reflex abnormal	0/12 (0%)		0/11 (0%)		1/13 (7.7%)		0/19 (0%)		0/6 (0%)
Lethargy	0/12 (0%)		0/11 (0%)		0/13 (0%)		1/19 (5.3%)		0/6 (0%)
Paraesthesia	0/12 (0%)		0/11 (0%)		0/13 (0%)		1/19 (5.3%)		0/6 (0%)
Memory impairment	0/12 (0%)		0/11 (0%)		0/13 (0%)		0/19 (0%)		1/6 (16.7%)
Psychiatric disorders
Restlessness	0/12 (0%)		1/11 (9.1%)		2/13 (15.4%)		2/19 (10.5%)		0/6 (0%)
Insomnia	0/12 (0%)		1/11 (9.1%)		2/13 (15.4%)		1/19 (5.3%)		0/6 (0%)
Anxiety	1/12 (8.3%)		1/11 (9.1%)		0/13 (0%)		0/19 (0%)		0/6 (0%)
Initial insomnia	0/12 (0%)		1/11 (9.1%)		0/13 (0%)		0/19 (0%)		1/6 (16.7%)
Agitation	0/12 (0%)		0/11 (0%)		0/13 (0%)		1/19 (5.3%)		0/6 (0%)
Depressive symptom	0/12 (0%)		0/11 (0%)		1/13 (7.7%)		0/19 (0%)		0/6 (0%)
Disinhibition	0/12 (0%)		0/11 (0%)		0/13 (0%)		1/19 (5.3%)		0/6 (0%)
Distractibility	0/12 (0%)		0/11 (0%)		0/13 (0%)		1/19 (5.3%)		0/6 (0%)
Middle insomnia	0/12 (0%)		0/11 (0%)		0/13 (0%)		1/19 (5.3%)		0/6 (0%)
Renal and urinary disorders
Urinary retention	0/12 (0%)		0/11 (0%)		0/13 (0%)		1/19 (5.3%)		0/6 (0%)
Reproductive system and breast disorders
Menstrual disorder	0/12 (0%)		0/11 (0%)		0/13 (0%)		1/19 (5.3%)		0/6 (0%)
Respiratory, thoracic and mediastinal disorders
Epistaxis	0/12 (0%)		0/11 (0%)		0/13 (0%)		1/19 (5.3%)		0/6 (0%)
Increased upper airway secretion	0/12 (0%)		0/11 (0%)		0/13 (0%)		1/19 (5.3%)		0/6 (0%)
Nasal congestion	1/12 (8.3%)		0/11 (0%)		0/13 (0%)		0/19 (0%)		0/6 (0%)
Yawning	0/12 (0%)		0/11 (0%)		0/13 (0%)		1/19 (5.3%)		0/6 (0%)
Skin and subcutaneous tissue disorders
Acne	0/12 (0%)		0/11 (0%)		0/13 (0%)		1/19 (5.3%)		0/6 (0%)
Dermatitis contact	0/12 (0%)		1/11 (9.1%)		0/13 (0%)		0/19 (0%)		0/6 (0%)
Intertrigo	0/12 (0%)		0/11 (0%)		1/13 (7.7%)		0/19 (0%)		0/6 (0%)

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.