Study Evaluating Desvenlafaxine Succinate Sustained Release In Outpatients With Major Depressive Disorder

• Sponsor: Wyeth is now a wholly owned subsidiary of Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00824291
• Collaborator: (none)
• Enrollment: 437
• Arms: 2
• Duration (Months): 9

Study Details

Study Description

Brief Summary

This is a multicenter study to assess the health and well-being in subjects who are outpatients with major depressive disorder that take desvenlafaxine succinate sustained release (DVS SR) or placebo for 12 weeks.

Condition or Disease	Intervention/Treatment	Phase
Depressive Disorder, Major	Drug: desvenlafaxine succinate sustained release; Genetic: Genotyping	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 437 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Double-Blind, Randomized, Placebo-Controlled Study To Evaluate Functional Outcome In Outpatients With Major Depressive Disorder Treated With Desvenlafaxine Succinare Sustained Release
• Study Start Date: Feb 1, 2009
• Actual Primary Completion Date: Oct 1, 2009
• Actual Study Completion Date: Nov 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: 1	Drug: desvenlafaxine succinate sustained release; 50 mg/day oral tablet for 12 weeks; Other Names: Pristiq
Experimental: 2	Genetic: Genotyping; CYP2D6 genotyping at randomization

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Hamilton Depression Scale (HAM-D) at Week 12 [At Baseline and Week 12.]

   HAM-D, clinician-rated interview, measures presence of depressive symptoms in 17 areas (symptoms such as depressed mood, guilt feelings, suicide, sleep disturbances, anxiety levels and weight loss). Total score ranges from 0 to 52; higher scores indicate more depression. Change from baseline: mean at observation minus mean at baseline.

Secondary Outcome Measures

1. Change From Baseline in Sheehan Disability Scale (SDS) Total Score at Week 12 [At Baseline and Week 12.]

   Participant rated scale was used to assess the effect of the participant's symptoms on their work/social/family life. Total scores range from 0 to 30 with higher values indicating greater disruption in the participant's work/social/family life. Individual item scores range from 0 to 10.

2. Clinical Global Impression Scale - Improvement (CGI- I) Score at Week 12 [At Baseline and Week 12.]

   CGI-I: 7-point clinician rated scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the scale. Higher score = more affected. Change = score at observation minus score at baseline.

3. Clinical Global Impressions Scale - Severity of Illness (CGI-S) at Week 12 [At Baseline and Week 12.]

   CGI-S: 7-point clinician rated scale to assess severity of participant's current illness state; range: 1 (normal - not ill at all) to 7 (among the most extremely ill patients). Higher score = more affected. Change: score at observation minus score at baseline.

4. Change From Baseline on Work and Activities Item of HAM-D17 at Week 12 [At Baseline and Week 12.]

   The Work and Activities Item of the HAM-D17 is item 7 of HAM-D17. Scoring range from 0 to 4.

5. Change From Baseline in Adjusted Mean on Montgomery-Asberg Depression Rating Scale (MADRS) at Week 12 [At Baseline and Week 12.]

   Measures the overall severity of depressive symptoms. The MADRS has a 10-item checklist. Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms).

6. Change From Baseline on Worry Anxiety Tension Scale (WATS) at Week 12 [At Baseline and Week 12.]

   WATS: a self-administered, 3-question rating scale assesses worry, anxiety, and tension. Each item was a visual analog scale on which the participant circles a number from 0 to 10. Higher scores indicated worse function. WATS total score was the sum of the 3 items. If 1 item was missing, the total score would be missing.

7. Change From Baseline on Stress and Social Support Scales at Week 12 [At Baseline and Week 12.]

   Stress and Social Support Scales: self-administered rating scale where item 1 is the stress vulnerability scale measuring how much the subject was set back by stressful events on an 11-point scale ranging from 0 (not at all) to 10 (extremely) and item 2 is an 11-point scale ranging from 0 to 100 percent of the amount of support the subject received from relatives and friends.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 19 Years to 74 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Outpatient men and women, between the ages of 18 to 75 years, fluent in both written and spoken English.

• Employed for 20 hours or more for a minimum of 1 month prior to baseline.

• Primary diagnosis of Major Depressive Disorder with symptoms for at least 30 days prior to baseline.

Exclusion Criteria:

• Treatment with desvenlafaxine succinate sustained release at any time in the past and/or venlafaxine (Effexor or Effexor XR) 1 year prior to baseline.

• Treatment-resistant defined as any of the following failed treatments in the past 3 years: 3 or more previous adequate trials of >=2 classes of antidepressant medication, electroconvulsive therapy, or psychotherapy (2 adequate trials).

• Current (within 12 months prior to the screening visit) psychoactive substance abuse or dependence (including alcohol), manic episode, posttraumatic stress disorder, obsessive-compulsive disorder, or a lifetime diagnosis of bipolar or psychotic disorder.

• Clinically important abnormalities on physical examination, electrocardiogram (ECG), or laboratory evaluations.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Wyeth is now a wholly owned subsidiary of Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00824291
• Other Study ID Numbers: 3151A1-4415; B2061006
• First Posted: Jan 16, 2009
• Last Update Posted: Mar 10, 2011
• Last Verified: Mar 1, 2011

• Keywords provided by , ,: Major Depressive Disorder
• Additional relevant MeSH terms: Disease; Depressive Disorder; Depression; Depressive Disorder, Major; Desvenlafaxine Succinate

Study Results

Participant Flow

Recruitment Details	A total of 752 potential participants were screened for this study. 437 participants were randomized to treatment groups while 315 participants were not randomized (288: did not meet the study criteria; 27 were not randomized for other reasons). Of the 437 randomized participants, 10 participants did not receive the study treatment.

Arm/Group Title	DVS SR 50 mg	Placebo
Arm/Group Description	Participants were administered an oral dose of Desvenlafaxine Succinate Sustained Release (DVS SR) 50 mg tablet once daily with or without food.	Participants were administered an oral dose of placebo once daily with or without food.
Period Title: Overall Study
STARTED	285	142
COMPLETED	231	107
NOT COMPLETED	54	35

Baseline Characteristics

Arm/Group Title	DVS SR 50 mg	Placebo	Total
Arm/Group Description	Participants were administered an oral dose of Desvenlafaxine Succinate Sustained Release (DVS SR) 50 mg tablet once daily with or without food.	Participants were administered an oral dose of placebo once daily with or without food.	Total of all reporting groups
Overall Participants	285	142	427
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	43.16 (11.72)	41.57 (12.64)	42.63 (12.04)
Sex: Female, Male (Count of Participants)
Female	188 66%	93 65.5%	281 65.8%
Male	97 34%	49 34.5%	146 34.2%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Hamilton Depression Scale (HAM-D) at Week 12
Description	HAM-D, clinician-rated interview, measures presence of depressive symptoms in 17 areas (symptoms such as depressed mood, guilt feelings, suicide, sleep disturbances, anxiety levels and weight loss). Total score ranges from 0 to 52; higher scores indicate more depression. Change from baseline: mean at observation minus mean at baseline.
Time Frame	At Baseline and Week 12.

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) analysis set, Last Observation Carried Forward (LOCF)

Arm/Group Title	DVS SR 50 mg	Placebo
Arm/Group Description	Participants were administered an oral dose of Desvenlafaxine Succinate Sustained Release (DVS SR) 50 mg tablet once daily with or without food.	Participants were administered an oral dose of placebo once daily with or without food.
Measure Participants	285	142
Mean (Standard Error) [Scores on a scale]	-12.61 (0.45)	-10.50 (0.60)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DVS SR 50 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	2.12
	Confidence Interval	(2-Sided) 95%; 0.78 to 3.46
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline in Sheehan Disability Scale (SDS) Total Score at Week 12
Description	Participant rated scale was used to assess the effect of the participant's symptoms on their work/social/family life. Total scores range from 0 to 30 with higher values indicating greater disruption in the participant's work/social/family life. Individual item scores range from 0 to 10.
Time Frame	At Baseline and Week 12.

Outcome Measure Data

Analysis Population Description

ITT, LOCF

Arm/Group Title	DVS SR 50 mg	Placebo
Arm/Group Description	Participants were administered an oral dose of Desvenlafaxine Succinate Sustained Release (DVS SR) 50 mg tablet once daily with or without food.	Participants were administered an oral dose of placebo once daily with or without food.
Measure Participants	285	142
Mean (Standard Error) [Scores on a scale]	-9.41 (0.48)	-8.08 (0.63)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DVS SR 50 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.067
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.33
	Confidence Interval	(2-Sided) 95%; -0.09 to 2.76
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Clinical Global Impression Scale - Improvement (CGI- I) Score at Week 12
Description	CGI-I: 7-point clinician rated scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the scale. Higher score = more affected. Change = score at observation minus score at baseline.
Time Frame	At Baseline and Week 12.

Outcome Measure Data

Analysis Population Description

ITT, LOCF

Arm/Group Title	DVS SR 50 mg	Placebo
Arm/Group Description	Participants were administered an oral dose of Desvenlafaxine Succinate Sustained Release (DVS SR) 50 mg tablet once daily with or without food.	Participants were administered an oral dose of placebo once daily with or without food.
Measure Participants	285	142
1 (Very Much Improved)	103 (0.07)	31 (0.10)
2 (Much Improved)	84	44
3 (Minimally Improved)	53	31
4 (No Change)	34	30
5 (Minimally Worse)	10	5
6 (Much Worse)	0	1
7 (Very Much Worse)	1	0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DVS SR 50 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

4. Secondary Outcome

Title	Clinical Global Impressions Scale - Severity of Illness (CGI-S) at Week 12
Description	CGI-S: 7-point clinician rated scale to assess severity of participant's current illness state; range: 1 (normal - not ill at all) to 7 (among the most extremely ill patients). Higher score = more affected. Change: score at observation minus score at baseline.
Time Frame	At Baseline and Week 12.

Outcome Measure Data

Analysis Population Description

ITT, LOCF

Arm/Group Title	DVS SR 50 mg	Placebo
Arm/Group Description	Participants were administered an oral dose of Desvenlafaxine Succinate Sustained Release (DVS SR) 50 mg tablet once daily with or without food.	Participants were administered an oral dose of placebo once daily with or without food.
Measure Participants	285	142
1 (Very Much Improved)	69 (0.08)	23 (0.11)
2 (Much Improved)	68	30
3 (Minimally Improved)	77	31
4 (No Change)	56	43
5 (Minimally Worse)	14	15
6 (Much Worse)	1	0
7 (Very Much Worse)	0	0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DVS SR 50 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

5. Secondary Outcome

Title	Change From Baseline on Work and Activities Item of HAM-D17 at Week 12
Description	The Work and Activities Item of the HAM-D17 is item 7 of HAM-D17. Scoring range from 0 to 4.
Time Frame	At Baseline and Week 12.

Outcome Measure Data

Analysis Population Description

ITT, LOCF

Arm/Group Title	DVS SR 50 mg	Placebo
Arm/Group Description	Participants were administered an oral dose of Desvenlafaxine Succinate Sustained Release (DVS SR) 50 mg tablet once daily with or without food.	Participants were administered an oral dose of placebo once daily with or without food.
Measure Participants	285	142
Mean (Standard Error) [Scores on a scale]	-1.68 (0.07)	-1.45 (0.10)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DVS SR 50 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.040
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.23
	Confidence Interval	(2-Sided) 95%; 0.01 to 0.44
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Change From Baseline in Adjusted Mean on Montgomery-Asberg Depression Rating Scale (MADRS) at Week 12
Description	Measures the overall severity of depressive symptoms. The MADRS has a 10-item checklist. Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms).
Time Frame	At Baseline and Week 12.

Outcome Measure Data

Analysis Population Description

ITT, LOCF

Arm/Group Title	DVS SR 50 mg	Placebo
Arm/Group Description	Participants were administered an oral dose of Desvenlafaxine Succinate Sustained Release (DVS SR) 50 mg tablet once daily with or without food.	Participants were administered an oral dose of placebo once daily with or without food.
Measure Participants	265	125
Mean (Standard Error) [Scores on a scale]	-18.44 (0.69)	-16.18 (0.94)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DVS SR 50 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.035
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	2.26
	Confidence Interval	(2-Sided) 95%; 0.16 to 4.37
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Change From Baseline on Worry Anxiety Tension Scale (WATS) at Week 12
Description	WATS: a self-administered, 3-question rating scale assesses worry, anxiety, and tension. Each item was a visual analog scale on which the participant circles a number from 0 to 10. Higher scores indicated worse function. WATS total score was the sum of the 3 items. If 1 item was missing, the total score would be missing.
Time Frame	At Baseline and Week 12.

Outcome Measure Data

Analysis Population Description

ITT, LOCF

Arm/Group Title	DVS SR 50 mg	Placebo
Arm/Group Description	Participants were administered an oral dose of Desvenlafaxine Succinate Sustained Release (DVS SR) 50 mg tablet once daily with or without food.	Participants were administered an oral dose of placebo once daily with or without food.
Measure Participants	285	142
Mean (Standard Error) [Scores on a scale]	-13.39 (0.79)	-10.95 (1.04)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DVS SR 50 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.041
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	2.44
	Confidence Interval	(2-Sided) 95%; 0.10 to 4.78
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Change From Baseline on Stress and Social Support Scales at Week 12
Description	Stress and Social Support Scales: self-administered rating scale where item 1 is the stress vulnerability scale measuring how much the subject was set back by stressful events on an 11-point scale ranging from 0 (not at all) to 10 (extremely) and item 2 is an 11-point scale ranging from 0 to 100 percent of the amount of support the subject received from relatives and friends.
Time Frame	At Baseline and Week 12.

Outcome Measure Data

Analysis Population Description

ITT, LOCF

Arm/Group Title	DVS SR 50 mg	Placebo
Arm/Group Description	Participants were administered an oral dose of Desvenlafaxine Succinate Sustained Release (DVS SR) 50 mg tablet once daily with or without food.	Participants were administered an oral dose of placebo once daily with or without food.
Measure Participants	285	142
Mean (Standard Error) [Scores on a scale]	-2.53 (0.18)	-2.14 (0.23)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DVS SR 50 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.145
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.39
	Confidence Interval	(2-Sided) 95%; -0.13 to 0.91
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Arm/Group Title	DVS SR 50 mg		Placebo
Arm/Group Description	Participants were administered an oral dose of Desvenlafaxine Succinate Sustained Release (DVS SR) 50 mg tablet once daily with or without food.		Participants were administered an oral dose of placebo once daily with or without food.
All Cause Mortality
	DVS SR 50 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	DVS SR 50 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/285 (0.7%)		2/142 (1.4%)
Injury, poisoning and procedural complications
Road traffic accident	0/285 (0%)		1/142 (0.7%)
Nervous system disorders
Amnesia	1/285 (0.4%)		0/142 (0%)
Cerebrovascular disorder	0/285 (0%)		1/142 (0.7%)
Psychiatric disorders
Major depression	1/285 (0.4%)		0/142 (0%)
Respiratory, thoracic and mediastinal disorders
Asthma	0/285 (0%)		1/142 (0.7%)
Bronchitis	0/285 (0%)		1/142 (0.7%)
Other (Not Including Serious) Adverse Events
	DVS SR 50 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	213/285 (74.7%)		90/142 (63.4%)
Blood and lymphatic system disorders
Anemia	1/285 (0.4%)		1/142 (0.7%)
Leukopenia	1/285 (0.4%)		0/142 (0%)
Cardiac disorders
Palpitations	5/285 (1.8%)		1/142 (0.7%)
Sinus bradycardia	1/285 (0.4%)		0/142 (0%)
Tachycardia	1/285 (0.4%)		1/142 (0.7%)
Ear and labyrinth disorders
Ear congestion	0/285 (0%)		1/142 (0.7%)
Tinnitus	3/285 (1.1%)		1/142 (0.7%)
Vertigo	1/285 (0.4%)		0/142 (0%)
Endocrine disorders
Hypothyroidism	1/285 (0.4%)		0/142 (0%)
Eye disorders
Blepharospasm	1/285 (0.4%)		0/142 (0%)
Contact lens intolerance	1/285 (0.4%)		0/142 (0%)
Eyelid ptosis	1/285 (0.4%)		0/142 (0%)
Mydriasis	1/285 (0.4%)		0/142 (0%)
Photopsia	0/285 (0%)		1/142 (0.7%)
Vision blurred	1/285 (0.4%)		2/142 (1.4%)
Visual impairment	1/285 (0.4%)		0/142 (0%)
Gastrointestinal disorders
Abdominal discomfort	2/285 (0.7%)		1/142 (0.7%)
Abdominal pain	0/285 (0%)		1/142 (0.7%)
Abdominal pain upper	4/285 (1.4%)		1/142 (0.7%)
Constipation	18/285 (6.3%)		11/142 (7.7%)
Diarrhea	18/285 (6.3%)		10/142 (7%)
Dry mouth	48/285 (16.8%)		9/142 (6.3%)
Dyspepsia	4/285 (1.4%)		2/142 (1.4%)
Eructation	2/285 (0.7%)		1/142 (0.7%)
Flatulence	3/285 (1.1%)		6/142 (4.2%)
Food poisoning	1/285 (0.4%)		1/142 (0.7%)
Gastrooesophageal reflux disease	1/285 (0.4%)		0/142 (0%)
Nausea	56/285 (19.6%)		8/142 (5.6%)
Toothache	1/285 (0.4%)		1/142 (0.7%)
Vomiting	6/285 (2.1%)		4/142 (2.8%)
General disorders
Asthenia	3/285 (1.1%)		1/142 (0.7%)
Facial pain	1/285 (0.4%)		0/142 (0%)
Fatigue	16/285 (5.6%)		5/142 (3.5%)
Feeling abnormal	0/285 (0%)		1/142 (0.7%)
Feeling drunk	0/285 (0%)		1/142 (0.7%)
Feeling jittery	5/285 (1.8%)		0/142 (0%)
Influenza like illness	1/285 (0.4%)		1/142 (0.7%)
Irritability	3/285 (1.1%)		4/142 (2.8%)
Non-cardiac chest pain	0/285 (0%)		1/142 (0.7%)
Edema peripheral	2/285 (0.7%)		1/142 (0.7%)
Pyrexia	2/285 (0.7%)		0/142 (0%)
Thirst	1/285 (0.4%)		0/142 (0%)
Vaginal infection	1/285 (0.4%)		0/142 (0%)
Immune system disorders
Seasonal allergy	1/285 (0.4%)		1/142 (0.7%)
Infections and infestations
Bronchitis	2/285 (0.7%)		2/142 (1.4%)
Cystitis	1/285 (0.4%)		1/142 (0.7%)
Ear infection	2/285 (0.7%)		0/142 (0%)
Fungal infection	1/285 (0.4%)		0/142 (0%)
Gastroenteritis	1/285 (0.4%)		1/142 (0.7%)
Gastroenteritis viral	2/285 (0.7%)		0/142 (0%)
Giardiasis	1/285 (0.4%)		0/142 (0%)
Herpes simplex	1/285 (0.4%)		0/142 (0%)
Influenza	3/285 (1.1%)		2/142 (1.4%)
Nasopharyngitis	5/285 (1.8%)		3/142 (2.1%)
Otitis media	1/285 (0.4%)		0/142 (0%)
Pharyngitis	1/285 (0.4%)		1/142 (0.7%)
Pharyngitis bacterial	1/285 (0.4%)		0/142 (0%)
Pneumonia	1/285 (0.4%)		0/142 (0%)
Pneumonia primary atypical	1/285 (0.4%)		0/142 (0%)
Tooth abscess	1/285 (0.4%)		1/142 (0.7%)
Tooth infection	0/285 (0%)		1/142 (0.7%)
Upper respiratory tract infection	7/285 (2.5%)		2/142 (1.4%)
Urinary tract infection	2/285 (0.7%)		2/142 (1.4%)
Vulvovaginal candidiasis	1/285 (0.4%)		0/142 (0%)
Sinusitis	1/285 (0.4%)		0/142 (0%)
Injury, poisoning and procedural complications
Accidental overdose	7/285 (2.5%)		4/142 (2.8%)
Burns second degree	1/285 (0.4%)		0/142 (0%)
Contusion	2/285 (0.7%)		0/142 (0%)
Fall	1/285 (0.4%)		0/142 (0%)
Foot fracture	2/285 (0.7%)		0/142 (0%)
Heat exhaustion	1/285 (0.4%)		0/142 (0%)
Injury	1/285 (0.4%)		0/142 (0%)
Joint dislocation	1/285 (0.4%)		0/142 (0%)
Joint sprain	0/285 (0%)		1/142 (0.7%)
Limb injury	1/285 (0.4%)		0/142 (0%)
Muscle injury	1/285 (0.4%)		0/142 (0%)
Procedural pain	0/285 (0%)		2/142 (1.4%)
Road traffic accident	1/285 (0.4%)		1/142 (0.7%)
Sunburn	0/285 (0%)		1/142 (0.7%)
Thermal burn	1/285 (0.4%)		0/142 (0%)
Investigations
Blood cholesterol increased	0/285 (0%)		1/142 (0.7%)
Blood pressure increased	2/285 (0.7%)		2/142 (1.4%)
Blood pressure systolic increased	1/285 (0.4%)		0/142 (0%)
Blood triglycerides increased	1/285 (0.4%)		1/142 (0.7%)
Electrocardiogram QT prolonged	0/285 (0%)		1/142 (0.7%)
Gamma-glutamyltransferase increased	1/285 (0.4%)		1/142 (0.7%)
Heart rate increased	1/285 (0.4%)		1/142 (0.7%)
Low density lipoprotein increased	0/285 (0%)		1/142 (0.7%)
Thyroxine free decreased	1/285 (0.4%)		0/142 (0%)
Transaminases increased	1/285 (0.4%)		0/142 (0%)
Weight decreased	2/285 (0.7%)		2/142 (1.4%)
Weight increased	4/285 (1.4%)		4/142 (2.8%)
White blood cell count increased	1/285 (0.4%)		0/142 (0%)
Tri-iodothyronine decreased	1/285 (0.4%)		0/142 (0%)
Metabolism and nutrition disorders
Decreased appetite	10/285 (3.5%)		2/142 (1.4%)
Gout	1/285 (0.4%)		0/142 (0%)
Hyperglycemia	1/285 (0.4%)		0/142 (0%)
Hyperlipidemia	0/285 (0%)		1/142 (0.7%)
Hypoglycemia	1/285 (0.4%)		0/142 (0%)
Increased appetite	3/285 (1.1%)		2/142 (1.4%)
Arthralgia	2/285 (0.7%)		2/142 (1.4%)
Back pain	10/285 (3.5%)		2/142 (1.4%)
Bursitis	1/285 (0.4%)		0/142 (0%)
Flank pain	1/285 (0.4%)		1/142 (0.7%)
Joint stiffness	1/285 (0.4%)		1/142 (0.7%)
Joint swelling	2/285 (0.7%)		2/142 (1.4%)
Muscle spasms	4/285 (1.4%)		1/142 (0.7%)
Musculoskeletal and connective tissue disorders
Muscle tightness	1/285 (0.4%)		0/142 (0%)
Muscle twitching	1/285 (0.4%)		0/142 (0%)
Musculoskeletal chest pain	2/285 (0.7%)		1/142 (0.7%)
Musculoskeletal pain	0/285 (0%)		2/142 (1.4%)
Myalgia	2/285 (0.7%)		0/142 (0%)
Neck pain	2/285 (0.7%)		1/142 (0.7%)
Pain in extremity	1/285 (0.4%)		1/142 (0.7%)
Sensation of heaviness	1/285 (0.4%)		0/142 (0%)
Nervous system disorders
Aphasia	1/285 (0.4%)		0/142 (0%)
Burning sensation	1/285 (0.4%)		0/142 (0%)
Crying	0/285 (0%)		1/142 (0.7%)
Disturbance in attention	3/285 (1.1%)		0/142 (0%)
Dizziness	28/285 (9.8%)		6/142 (4.2%)
Dizziness postural	0/285 (0%)		2/142 (1.4%)
Dysgeusia	1/285 (0.4%)		0/142 (0%)
Fine motor delay	1/285 (0.4%)		0/142 (0%)
Headache	43/285 (15.1%)		21/142 (14.8%)
Hypersomnia	0/285 (0%)		1/142 (0.7%)
Hypoaesthesia	1/285 (0.4%)		0/142 (0%)
Lethargy	2/285 (0.7%)		0/142 (0%)
Migraine	4/285 (1.4%)		2/142 (1.4%)
Paresthesia	5/285 (1.8%)		1/142 (0.7%)
Presyncope	1/285 (0.4%)		0/142 (0%)
Sedation	4/285 (1.4%)		0/142 (0%)
Sinus headache	2/285 (0.7%)		0/142 (0%)
Somnolence	18/285 (6.3%)		3/142 (2.1%)
Syncope	1/285 (0.4%)		1/142 (0.7%)
Tension headache	1/285 (0.4%)		0/142 (0%)
Tremor	5/285 (1.8%)		0/142 (0%)
Psychiatric disorders
Abnormal dreams	2/285 (0.7%)		3/142 (2.1%)
Anorgasmia	1/285 (0.4%)		0/142 (0%)
Anxiety	4/285 (1.4%)		1/142 (0.7%)
Bereavement reaction	1/285 (0.4%)		0/142 (0%)
Bruxism	2/285 (0.7%)		0/142 (0%)
Depression	2/285 (0.7%)		0/142 (0%)
Euphoric mood	1/285 (0.4%)		0/142 (0%)
Initial insomnia	2/285 (0.7%)		0/142 (0%)
Insomnia	13/285 (4.6%)		5/142 (3.5%)
Libido decreased	5/285 (1.8%)		0/142 (0%)
Libido increased	1/285 (0.4%)		0/142 (0%)
Major depression	0/285 (0%)		1/142 (0.7%)
Middle insomnia	2/285 (0.7%)		0/142 (0%)
Nervousness	1/285 (0.4%)		1/142 (0.7%)
Panic attack	1/285 (0.4%)		0/142 (0%)
Restlessness	0/285 (0%)		1/142 (0.7%)
Sleep disorder	1/285 (0.4%)		0/142 (0%)
Violence-related symptom	0/285 (0%)		1/142 (0.7%)
Pollakiuria	2/285 (0.7%)		1/142 (0.7%)
Renal and urinary disorders
Nephrolithiasis	0/285 (0%)		1/142 (0.7%)
Reproductive system and breast disorders
Breast discharge	0/285 (0%)		1/142 (0.7%)
Breast tenderness	1/285 (0.4%)		0/142 (0%)
Dysmenorrhea	0/285 (0%)		1/142 (0.7%)
Ejaculation delayed	2/285 (0.7%)		0/142 (0%)
Erectile dysfunction	4/285 (1.4%)		1/142 (0.7%)
Menorrhagia	0/285 (0%)		1/142 (0.7%)
Menstruation irregular	2/285 (0.7%)		1/142 (0.7%)
Metrorrhagia	1/285 (0.4%)		0/142 (0%)
Sexual dysfunction	1/285 (0.4%)		0/142 (0%)
Vaginal discharge	1/285 (0.4%)		0/142 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	1/285 (0.4%)		3/142 (2.1%)
Dry throat	1/285 (0.4%)		0/142 (0%)
Dysphonia	1/285 (0.4%)		0/142 (0%)
Dyspnea	0/285 (0%)		1/142 (0.7%)
Epistaxis	0/285 (0%)		1/142 (0.7%)
Nasal congestion	1/285 (0.4%)		0/142 (0%)
Oropharyngeal pain	1/285 (0.4%)		0/142 (0%)
Sinus congestion	3/285 (1.1%)		0/142 (0%)
Upper respiratory tract congestion	0/285 (0%)		1/142 (0.7%)
Yawning	5/285 (1.8%)		0/142 (0%)
Skin and subcutaneous tissue disorders
Alopecia	0/285 (0%)		1/142 (0.7%)
Dermatitis contact	3/285 (1.1%)		0/142 (0%)
Ecchymosis	0/285 (0%)		1/142 (0.7%)
Erythema	0/285 (0%)		1/142 (0.7%)
Hyperhidrosis	4/285 (1.4%)		0/142 (0%)
Night sweats	2/285 (0.7%)		1/142 (0.7%)
Pruritus	2/285 (0.7%)		0/142 (0%)
Rash	3/285 (1.1%)		1/142 (0.7%)
Vascular disorders
Hot flush	4/285 (1.4%)		2/142 (1.4%)
Hypertension	9/285 (3.2%)		0/142 (0%)
Hypotension	0/285 (0%)		1/142 (0.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The PIs agreed to allow the sponsor 60 days to review and require changes to presentations or publications but only to protect confidential information and intellectual property, and for the sponsor to file a patent application, as applicable. The PIs also agreed for data to be presented first as a joint, multi-center publication.