A Study Of DVS SR In Treatment Of Children And Adolescent Outpatients With MDD

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01371734
• Collaborator: (none)
• Enrollment: 363
• Locations: 42
• Arms: 3
• Duration (Months): 49
• Patients Per Site: 8.6
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This is a double-blind study evaluating Desvenlafaxine Succinate Sustained-Release (DVS SR) versus placebo in the Treatment of Children and Adolescent Outpatients with Major Depressive Disorder (MDD).

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Disorder	Drug: Desvenlafaxine Succinate Sustained-Release; Drug: Desvenlafaxine Succinate Sustained-Release; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 363 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study To Evaluate The Efficacy, Safety And Tolerability Of Desvenlafaxine Succinate Sustained-release (Dvs Sr) In The Treatment Of Children And Adolescent Outpatients With Major Depressive Disorder
• Study Start Date: Aug 1, 2011
• Actual Primary Completion Date: Sep 1, 2015
• Actual Study Completion Date: Sep 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Experimental Arm 1 - high dose	Drug: Desvenlafaxine Succinate Sustained-Release; Subjects randomized to DVS SR treatment arm will receive 25, 35, or 50 mg/day based on subject weight at the Baseline visit.
Experimental: Experimental Arm 2 - low dose	Drug: Desvenlafaxine Succinate Sustained-Release; Subjects randomized to DVS SR treatment arm will receive 20, 25, or 35 mg/day based on subject weight at the Baseline visit.
Placebo Comparator: Placebo Arm	Drug: Placebo; Subjects randomized to the Placebo treatment arm will receive placebo tablets

Outcome Measures

Primary Outcome Measures

1. Change From Baseline to Week 8 in the Children's Depression Rating Scale, Revised (CDRS-R) Total Score (n=102, 104, 106) [Baseline and Week 8]

   Clinician-rated interview-based scale (with both child and parent or guardian) to assess 17 distinct symptom areas to derive an index of depression severity. Discrepancies between informants' responses were resolved by using most impaired rating given by valid informant. Rated on a 7-point scale; range from 1 (no impairment) to 7 (indicates greater impairment). Total score calculated as sum of the 17 items (range 1 to 119); higher score indicates greater impairment. Mean change from baseline was adjusted for the baseline total score, age group and gender.

Secondary Outcome Measures

1. Change From Baseline to Week 8 in the Clinical Global Impression of Severity (CGI-S) Score (n=102, 105, 106) [Baseline and Week 8]

   A 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. Mean change from baseline was adjusted for the baseline total score, age group and gender.

2. Percentage of Participants by Clinical Global Impression Improvement (CGI-I) Score at Weeks 1, 2, 3, 4, 6, and 8 [Weeks 1, 2, 3, 4, 6, and 8]

   A 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 equals (=) more affected.

3. Percentage of Participants With a CGI-I Response Defined as a Score of 'Very Much Improved' or 'Much Improved' [Weeks 1, 2, 3, 4, 6, and 8]

   A 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) or 2 (much improved) on the scale. Higher score = more affected.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 7 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age >=7 and <18 years of age

• Primary diagnosis of major depressive disorder (MDD)

• CDRS-R score >40

Exclusion Criteria:

• History of suicidal behavior or requires precaution against suicide

• Not in generally healthy medical condition

• History of psychosis or bipolar disorder

• Seizure disorder

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital of Alabama Laboratory	Birmingham	Alabama	United States	35233
2	The University of Alabama at Birmingham, Office of Psychiatric Research	Birmingham	Alabama	United States	35294
3	Center for Advanced Improvement	Tucson	Arizona	United States	85719
4	Sun Valley Research Center	Imperial	California	United States	92251
5	MCB Clinical Research Centers	Colorado Springs	Colorado	United States	80910
6	Bliss Basement Pharmacy - Hartford Hospital	Hartford	Connecticut	United States	06102
7	Institute of Living/Hartford Hospital	Hartford	Connecticut	United States	06106
8	Institute of Living	Hartford	Connecticut	United States	06106
9	SJS Clinical Research, Inc.	Destin	Florida	United States	32541
10	Sarkis Clinical Trials	Gainesville	Florida	United States	32607
11	Clinical Neuroscience Solutions	Jacksonville	Florida	United States	32256
12	Medical Research Group of Central Florida	Orange City	Florida	United States	32763
13	Millenia Psychiatry & Research, Inc.	Orlando	Florida	United States	32839
14	Janus Center for Psychiatric Research	West Palm Beach	Florida	United States	33407
15	Northwest Behavioral Research Center	Marietta	Georgia	United States	30060
16	Capstone Clinical Research	Libertyville	Illinois	United States	60048
17	AMR-Baber Research Inc.	Naperville	Illinois	United States	60563
18	Clinco	Terre Haute	Indiana	United States	47802
19	Louisiana State University Health Sciences Center-Psychopharmacology Research Clinic	Shreveport	Louisiana	United States	71103
20	Drug:University Health Shreveport Outpatient	Shreveport	Louisiana	United States	71130
21	Pharmasite Research Inc	Baltimore	Maryland	United States	21208
22	Millennium Psychiatric Associates, LLC	Creve Coeur	Missouri	United States	63141
23	Premier Psychiatric Research Institute, LLC	Lincoln	Nebraska	United States	68526
24	Erie County Medical Center / State University of New York at Buffalo affiliate	Buffalo	New York	United States	14215
25	The Zucker Hillside Hospital, North Shore-Long Island Jewish Health System	Glen Oaks	New York	United States	11004
26	Bioscience Research, LLC.	Mount Kisco	New York	United States	10549
27	Finger Lakes Clinical Research	Rochester	New York	United States	14618
28	Stony Brook University Medical Center, Child And Adolescent Psychiatry	Stony Brook	New York	United States	11794-8790
29	Neuro-Behavioral Clinical Research, Inc.	Canton	Ohio	United States	44718
30	Discovery and Wellness Center for Children/University Hospitals Case Medical Center	Cleveland	Ohio	United States	44106
31	Sooner Clinical Research	Oklahoma City	Oklahoma	United States	73112
32	Research Strategies of Memphis, LLC.	Memphis	Tennessee	United States	38119
33	FutureSearch Trials	Austin	Texas	United States	78731
34	Clinical Trials of Texas, Inc.	San Antonio	Texas	United States	78229
35	Alliance Research Group	Richmond	Virginia	United States	23230
36	Virginia Commonwealth University	Richmond	Virginia	United States	23298
37	Virginia Treatment Center	Richmond	Virginia	United States	23298
38	Carilion Medical Center	Roanoke	Virginia	United States	24014
39	Eastside Therapeutic Resource	Kirkland	Washington	United States	98033
40	Biomedica Research Group	Santiago	Region Metropolitana	Chile	7500710
41	Optima Salud	Santiago	Region Metropolitana	Chile	8320325
42	Hospital Universitario Dr. Jose Eleuterio Gonzalez, Departamento de Psiquiatria	Monterrey	Nuevo Leon	Mexico	064460

Sponsors and Collaborators

• 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.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT01371734
• Other Study ID Numbers: B2061032; 3151A6-3343; 2008-001875-32
• First Posted: Jun 13, 2011
• Last Update Posted: Mar 20, 2017
• Last Verified: Jan 1, 2017

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

Study Results

Participant Flow

Arm/Group Title	Placebo	DVS SR Low Dose	DVS SR High Dose
Arm/Group Description	Matched placebo tablets administered once daily for 8 weeks (treatment phase), followed by placebo tablets administered once daily for 1 week (taper phase) only for those participants not entering the extension study.	DVS SR tablets 10 or 20 mg (based on weight at the baseline visit) administered once daily for the first week of treatment (titration phase) then 20, 25 or 35 mg (based on weight at the baseline visit) administered once daily for the next 7 weeks of treatment, followed by 10 or 20 mg (based on weight at the baseline visit) administered once daily for 1 week (taper phase) only for those participants not entering the extension study.	DVS SR tablets 10 or 20 mg (based on weight at the baseline visit) administered once daily for the first week of treatment (titration phase) then 25, 35 or 50 mg (based on weight at the baseline visit) administered once daily for the next 7 weeks of treatment, followed by 10 or 20 mg (based on weight at the baseline visit) administered once daily for 1 week (taper phase) only for those participants not entering the extension study.
Period Title: Overall Study
STARTED	120	122	121
COMPLETED	97	103	104
NOT COMPLETED	23	19	17

Baseline Characteristics

Arm/Group Title	Placebo	DVS SR Low Dose	DVS SR High Dose	Total
Arm/Group Description	Matched placebo tablets administered once daily for 8 weeks (treatment phase), followed by placebo tablets administered once daily for 1 week (taper phase) only for those participants not entering the extension study.	DVS SR tablets 10 or 20 mg (based on weight at the baseline visit) administered once daily for the first week of treatment (titration phase) then 20, 25 or 35 mg (based on weight at the baseline visit) administered once daily for the next 7 weeks of treatment, followed by 10 or 20 mg (based on weight at the baseline visit) administered once daily for 1 week (taper phase) only for those participants not entering the extension study.	DVS SR tablets 10 or 20 mg (based on weight at the baseline visit) administered once daily for the first week of treatment (titration phase) then 25, 35 or 50 mg (based on weight at the baseline visit) administered once daily for the next 7 weeks of treatment, followed by 10 or 20 mg (based on weight at the baseline visit) administered once daily for 1 week (taper phase) only for those participants not entering the extension study.	Total of all reporting groups
Overall Participants	120	122	121	363
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	13.2 (2.68)	13.1 (2.80)	12.9 (3.01)	13.0 (2.83)
Sex: Female, Male (Count of Participants)
Female	60 50%	69 56.6%	76 62.8%	205 56.5%
Male	60 50%	53 43.4%	45 37.2%	158 43.5%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline to Week 8 in the Children's Depression Rating Scale, Revised (CDRS-R) Total Score (n=102, 104, 106)
Description	Clinician-rated interview-based scale (with both child and parent or guardian) to assess 17 distinct symptom areas to derive an index of depression severity. Discrepancies between informants' responses were resolved by using most impaired rating given by valid informant. Rated on a 7-point scale; range from 1 (no impairment) to 7 (indicates greater impairment). Total score calculated as sum of the 17 items (range 1 to 119); higher score indicates greater impairment. Mean change from baseline was adjusted for the baseline total score, age group and gender.
Time Frame	Baseline and Week 8

Outcome Measure Data

Analysis Population Description

Intention-To-Treat (ITT) Population - included all randomized participants who received at least 1 dose of study drug, had a baseline primary efficacy assessment, and had at least one post-baseline primary efficacy assessment. n is the number of participants with evaluable data.

Arm/Group Title	Placebo	DVS SR Low Dose	DVS SR High Dose
Arm/Group Description	Matched placebo tablets administered once daily for 8 weeks (treatment phase), followed by placebo tablets administered once daily for 1 week (taper phase) only for those participants not entering the extension study.	DVS SR tablets 10 or 20 mg (based on weight at the baseline visit) administered once daily for the first week of treatment (titration phase) then 20, 25 or 35 mg (based on weight at the baseline visit) administered once daily for the next 7 weeks of treatment, followed by 10 or 20 mg (based on weight at the baseline visit) administered once daily for 1 week (taper phase) only for those participants not entering the extension study.	DVS SR tablets 10 or 20 mg (based on weight at the baseline visit) administered once daily for the first week of treatment (titration phase) then 25, 35 or 50 mg (based on weight at the baseline visit) administered once daily for the next 7 weeks of treatment, followed by 10 or 20 mg (based on weight at the baseline visit) administered once daily for 1 week (taper phase) only for those participants not entering the extension study.
Measure Participants	119	120	121
Least Squares Mean (Standard Error) [Score on a scale]	-22.85 (1.13)	-23.70 (1.12)	-24.37 (1.12)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, DVS SR Low Dose
	Comments	Adjusted mean difference = Placebo - DVS SR Low Dose
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.587
	Comments
	Method	Mixed-effects model for repeated measure
	Comments	Hochberg procedure was used to control for multiplicity
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.85
	Confidence Interval	(2-Sided) 95%; -2.23 to 3.94
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, DVS SR High Dose
	Comments	Adjusted mean difference = Placebo - DVS SR High Dose
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.333
	Comments
	Method	Mixed-effects model for repeated measure
	Comments	Hochberg procedure was used to control for multiplicity
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.52
	Confidence Interval	(2-Sided) 95%; -1.56 to 4.61
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline to Week 8 in the Clinical Global Impression of Severity (CGI-S) Score (n=102, 105, 106)
Description	A 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. Mean change from baseline was adjusted for the baseline total score, age group and gender.
Time Frame	Baseline and Week 8

Outcome Measure Data

Analysis Population Description

ITT Population n is the number of participants with evaluable data.

Arm/Group Title	Placebo	DVS SR Low Dose	DVS SR High Dose
Arm/Group Description	Matched placebo tablets administered once daily for 8 weeks (treatment phase), followed by placebo tablets administered once daily for 1 week (taper phase) only for those participants not entering the extension study.	DVS SR tablets 10 or 20 mg (based on weight at the baseline visit) administered once daily for the first week of treatment (titration phase) then 20, 25 or 35 mg (based on weight at the baseline visit) administered once daily for the next 7 weeks of treatment, followed by 10 or 20 mg (based on weight at the baseline visit) administered once daily for 1 week (taper phase) only for those participants not entering the extension study.	DVS SR tablets 10 or 20 mg (based on weight at the baseline visit) administered once daily for the first week of treatment (titration phase) then 25, 35 or 50 mg (based on weight at the baseline visit) administered once daily for the next 7 weeks of treatment, followed by 10 or 20 mg (based on weight at the baseline visit) administered once daily for 1 week (taper phase) only for those participants not entering the extension study.
Measure Participants	119	120	121
Least Squares Mean (Standard Error) [Score on a scale]	-1.49 (0.11)	-1.51 (0.11)	-1.65 (0.11)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, DVS SR Low Dose
	Comments	Adjusted mean difference = Placebo - DVS SR Low Dose
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.923
	Comments
	Method	Mixed-effects model for repeated measure
	Comments	Hochberg procedure was used to control for multiplicity
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.015
	Confidence Interval	(2-Sided) 95%; -0.29 to 0.32
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, DVS SR High Dose
	Comments	Adjusted mean difference = Placebo - DVS SR High Dose
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.302
	Comments
	Method	Mixed-effects model for repeated measure
	Comments	Hochberg procedure was used to control for multiplicity
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.161
	Confidence Interval	(2-Sided) 95%; -0.14 to 0.47
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Percentage of Participants by Clinical Global Impression Improvement (CGI-I) Score at Weeks 1, 2, 3, 4, 6, and 8
Description	A 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 equals (=) more affected.
Time Frame	Weeks 1, 2, 3, 4, 6, and 8

Outcome Measure Data

Analysis Population Description

ITT Population n is the number of participants with non-missing values

Arm/Group Title	Placebo	DVS SR Low Dose	DVS SR High Dose
Arm/Group Description	Matched placebo tablets administered once daily for 8 weeks (treatment phase), followed by placebo tablets administered once daily for 1 week (taper phase) only for those participants not entering the extension study.	DVS SR tablets 10 or 20 mg (based on weight at the baseline visit) administered once daily for the first week of treatment (titration phase) then 20, 25 or 35 mg (based on weight at the baseline visit) administered once daily for the next 7 weeks of treatment, followed by 10 or 20 mg (based on weight at the baseline visit) administered once daily for 1 week (taper phase) only for those participants not entering the extension study.	DVS SR tablets 10 or 20 mg (based on weight at the baseline visit) administered once daily for the first week of treatment (titration phase) then 25, 35 or 50 mg (based on weight at the baseline visit) administered once daily for the next 7 weeks of treatment, followed by 10 or 20 mg (based on weight at the baseline visit) administered once daily for 1 week (taper phase) only for those participants not entering the extension study.
Measure Participants	119	120	121
Week 1, Very Much Improved (n=113, 112,115)	2.7 2.3%	0.9 0.7%	2.6 2.1%
Week 1, Much Improved (n=113, 112, 115)	6.2 5.2%	9.8 8%	12.2 10.1%
Week 1, Minimally Improved (n=113, 112, 115)	38.9 32.4%	37.5 30.7%	33.9 28%
Week 1, No Change (n=113, 112, 115)	49.6 41.3%	51.8 42.5%	46.1 38.1%
Week 1, Minimally Worse (n=113, 112, 115)	2.7 2.3%	0 0%	5.2 4.3%
Week 1, Much Worse (n=113, 112, 115)	0 0%	0 0%	0 0%
Week 1, Very Much Worse (n=113, 112, 115)	0 0%	0 0%	0 0%
Week 2, Very Much Improved (n=114, 115, 109)	4.4 3.7%	6.1 5%	10.1 8.3%
Week 2, Much Improved (n=114, 115, 109)	26.3 21.9%	26.1 21.4%	23.9 19.8%
Week 2, Minimally Improved (n=114, 115, 109)	36.8 30.7%	38.3 31.4%	35.8 29.6%
Week 2, No Change (n=114, 115, 109)	31.6 26.3%	25.2 20.7%	29.4 24.3%
Week 2, Minimally Worse (n=114, 115, 109)	0 0%	4.3 3.5%	0 0%
Week 2, Much Worse (n=114, 115, 109)	0.9 0.8%	0 0%	0.9 0.7%
Week 2, Very Much Worse (n=114, 115, 109)	0 0%	0 0%	0 0%
Week 3, Very Much Improved (n=108, 110, 110)	10.2 8.5%	10.9 8.9%	18.2 15%
Week 3, Much Improved (n=108, 110, 110)	20.4 17%	26.4 21.6%	24.5 20.2%
Week 3, Minimally Improved (n=108, 110, 110)	47.2 39.3%	44.5 36.5%	35.5 29.3%
Week 3, No Change (n=108, 110, 110)	20.4 17%	15.5 12.7%	21.8 18%
Week 3, Minimally Worse (n=108, 110, 110)	1.9 1.6%	1.8 1.5%	0 0%
Week 3, Much Worse (n=108, 110, 110)	0 0%	0 0%	0 0%
Week 3, Very Much Worse (n=108, 110, 110)	0 0%	0.9 0.7%	0 0%
Week 4, Very Much Improved (n=104,108,113)	14.4 12%	17.6 14.4%	15.0 12.4%
Week 4, Much Improved (n=104,108,113)	30.8 25.7%	36.1 29.6%	31.0 25.6%
Week 4, Minimally Improved (n=104,108,113)	35.6 29.7%	30.6 25.1%	35.4 29.3%
Week 4, No Change (n=104,108,113)	19.2 16%	14.8 12.1%	17.7 14.6%
Week 4, Minimally Worse (n=104,108,113)	0 0%	0.9 0.7%	0.9 0.7%
Week 4, Much Worse (n=104,108,113)	0 0%	0 0%	0 0%
Week 4, Very Much Worse (n=104,108,113)	0 0%	0 0%	0 0%
Week 6, Very Much Improved (n=106,104,104)	19.8 16.5%	20.2 16.6%	26.9 22.2%
Week 6, Much Improved (n=106,104,104)	29.2 24.3%	36.5 29.9%	24.0 19.8%
Week 6, Minimally Improved (n=106,104,104)	31.1 25.9%	24.0 19.7%	31.7 26.2%
Week 6, No Change (n=106,104,104)	16.0 13.3%	14.4 11.8%	14.4 11.9%
Week 6, Minimally Worse (n=106,104,104)	2.8 2.3%	2.9 2.4%	1.9 1.6%
Week 6, Much Worse (n=106,104,104)	0 0%	1.9 1.6%	1.0 0.8%
Week 6, Very Much Worse (n=106,104,104)	0.9 0.8%	0 0%	0 0%
Week 8, Very Much Improved (n=102,105,106)	21.6 18%	19.0 15.6%	25.5 21.1%
Week 8, Much Improved (n=102,105,106)	34.3 28.6%	37.1 30.4%	36.8 30.4%
Week 8, Minimally Improved (n=102,105,106)	28.4 23.7%	24.8 20.3%	21.7 17.9%
Week 8, No Change (n=102,105,106)	15.7 13.1%	18.1 14.8%	15.1 12.5%
Week 8, Minimally Worse (n=102,105,106)	0 0%	1.0 0.8%	0.9 0.7%
Week 8, Much Worse (n=102,105,106)	0 0%	0 0%	0 0%
Week 8, Very Much Worse (n=102,105,106)	0 0%	0 0%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, DVS SR Low Dose
	Comments	Week 1
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.729
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, DVS SR High Dose
	Comments	Week 1
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.756
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, DVS SR Low Dose
	Comments	Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.765
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, DVS SR High Dose
	Comments	Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.475
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, DVS SR Low Dose
	Comments	Week 3
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.310
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, DVS SR High Dose
	Comments	Week 3
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.105
	Comments
	Method	Chi-squared, Corrected
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, DVS SR Low Dose
	Comments	Week 4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.254
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, DVS SR High Dose
	Comments	Week 4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.887
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, DVS SR Low Dose
	Comments	Week 6
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.475
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo, DVS SR High Dose
	Comments	Week 6
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.407
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Placebo, DVS SR Low Dose
	Comments	Week 8
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.696
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Placebo, DVS SR High Dose
	Comments	Week 8
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.462
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

4. Secondary Outcome

Title	Percentage of Participants With a CGI-I Response Defined as a Score of 'Very Much Improved' or 'Much Improved'
Description	A 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) or 2 (much improved) on the scale. Higher score = more affected.
Time Frame	Weeks 1, 2, 3, 4, 6, and 8

Outcome Measure Data

Analysis Population Description

ITT Population n is the number of participants with non-missing values

Arm/Group Title	Placebo	DVS SR Low Dose	DVS SR High Dose
Arm/Group Description	Matched placebo tablets administered once daily for 8 weeks (treatment phase), followed by placebo tablets administered once daily for 1 week (taper phase) only for those participants not entering the extension study.	DVS SR tablets 10 or 20 mg (based on weight at the baseline visit) administered once daily for the first week of treatment (titration phase) then 20, 25 or 35 mg (based on weight at the baseline visit) administered once daily for the next 7 weeks of treatment, followed by 10 or 20 mg (based on weight at the baseline visit) administered once daily for 1 week (taper phase) only for those participants not entering the extension study.	DVS SR tablets 10 or 20 mg (based on weight at the baseline visit) administered once daily for the first week of treatment (titration phase) then 25, 35 or 50 mg (based on weight at the baseline visit) administered once daily for the next 7 weeks of treatment, followed by 10 or 20 mg (based on weight at the baseline visit) administered once daily for 1 week (taper phase) only for those participants not entering the extension study.
Measure Participants	119	120	121
Week 1 (n=113, 112, 115)	8.85 7.4%	10.71 8.8%	14.78 12.2%
Week 2 (n=114, 115, 109)	30.70 25.6%	32.17 26.4%	33.94 28%
Week 3 (n=108, 110, 110)	30.56 25.5%	37.27 30.5%	42.73 35.3%
Week 4 (n=104, 108, 113)	45.19 37.7%	53.70 44%	46.02 38%
Week 6 (n=106, 104, 104)	49.06 40.9%	56.73 46.5%	50.96 42.1%
Week 8 (n=102, 105, 106)	55.88 46.6%	56.19 46.1%	62.26 51.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, DVS SR Low Dose
	Comments	Week 1
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.633
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.806
	Confidence Interval	(2-Sided) 95%; 0.333 to 1.951
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, DVS SR High Dose
	Comments	Week 1
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.172
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.561
	Confidence Interval	(2-Sided) 95%; 0.245 to 1.285
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, DVS SR Low Dose
	Comments	Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.826
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.939
	Confidence Interval	(2-Sided) 95%; 0.536 to 1.644
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, DVS SR High Dose
	Comments	Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.599
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.860
	Confidence Interval	(2-Sided) 95%; 0.489 to 1.511
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, DVS SR Low Dose
	Comments	Week 3
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.248
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.713
	Confidence Interval	(2-Sided) 95%; 0.402 to 1.265
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, DVS SR High Dose
	Comments	Week 3
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.048
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.564
	Confidence Interval	(2-Sided) 95%; 0.320 to 0.995
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, DVS SR Low Dose
	Comments	Week 4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.210
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.708
	Confidence Interval	(2-Sided) 95%; 0.412 to 1.216
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, DVS SR High Dose
	Comments	Week 4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.893
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.964
	Confidence Interval	(2-Sided) 95%; 0.564 to 1.646
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, DVS SR Low Dose
	Comments	Week 6
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.228
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.714
	Confidence Interval	(2-Sided) 95%; 0.413 to 1.235
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo, DVS SR High Dose
	Comments	Week 6
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.751
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.916
	Confidence Interval	(2-Sided) 95%; 0.531 to 1.579
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Placebo, DVS SR Low Dose
	Comments	Week 8
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.925
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.974
	Confidence Interval	(2-Sided) 95%; 0.561 to 1.689
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Placebo, DVS SR High Dose
	Comments	Week 8
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.342
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.764
	Confidence Interval	(2-Sided) 95%; 0.438 to 1.331
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Adverse events (AEs) were recorded from informed consent and assent through the first follow up visit (Week 11) for non-serious AEs; the second follow up visit (Week 13) for serious AEs (SAEs); or at Week 8 for participants entering the extension study.
Adverse Event Reporting Description	The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another participant, or 1 participant may have experienced both a serious and non-serious event during the study.
Arm/Group Title	Placebo		DVS SR Low Dose		DVS SR High Dose
Arm/Group Description	Matched placebo tablets administered once daily for 8 weeks (treatment phase), followed by placebo tablets administered once daily for 1 week (taper phase) only for those participants not entering the extension study.		DVS SR tablets 10 or 20 mg (based on weight at the baseline visit) administered once daily for the first week of treatment (titration phase) then 20, 25 or 35 mg (based on weight at the baseline visit) administered once daily for the next 7 weeks of treatment, followed by 10 or 20 mg (based on weight at the baseline visit) administered once daily for 1 week (taper phase) only for those participants not entering the extension study.		DVS SR tablets 10 or 20 mg (based on weight at the baseline visit) administered once daily for the first week of treatment (titration phase) then 25, 35 or 50 mg (based on weight at the baseline visit) administered once daily for the next 7 weeks of treatment, followed by 10 or 20 mg (based on weight at the baseline visit) administered once daily for 1 week (taper phase) only for those participants not entering the extension study.
All Cause Mortality
	Placebo		DVS SR Low Dose		DVS SR High Dose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		DVS SR Low Dose		DVS SR High Dose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/120 (1.7%)		2/122 (1.6%)		1/121 (0.8%)
Infections and infestations
Abscess	0/120 (0%)		0/122 (0%)		1/121 (0.8%)
Appendicitis	0/120 (0%)		0/122 (0%)		1/121 (0.8%)
Psychiatric disorders
Aggression	0/120 (0%)		1/122 (0.8%)		0/121 (0%)
Suicide attempt	1/120 (0.8%)		1/122 (0.8%)		0/121 (0%)
Skin and subcutaneous tissue disorders
Dermatomyositis	1/120 (0.8%)		0/122 (0%)		0/121 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		DVS SR Low Dose		DVS SR High Dose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	34/120 (28.3%)		46/122 (37.7%)		53/121 (43.8%)
Gastrointestinal disorders
Abdominal pain upper	9/120 (7.5%)		7/122 (5.7%)		11/121 (9.1%)
Nausea	7/120 (5.8%)		12/122 (9.8%)		14/121 (11.6%)
Vomiting	4/120 (3.3%)		1/122 (0.8%)		9/121 (7.4%)
General disorders
Fatigue	2/120 (1.7%)		4/122 (3.3%)		9/121 (7.4%)
Infections and infestations
Nasopharyngitis	2/120 (1.7%)		8/122 (6.6%)		7/121 (5.8%)
Nervous system disorders
Headache	15/120 (12.5%)		22/122 (18%)		25/121 (20.7%)
Psychiatric disorders
Insomnia	1/120 (0.8%)		7/122 (5.7%)		4/121 (3.3%)

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 less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.