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

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01372150
• Collaborator: (none)
• Enrollment: 340
• Locations: 43
• Arms: 3
• Actual Duration (Months): 40
• Patients Per Site: 7.9
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This is a Double-blind Study Evaluating Desvenlafaxine Succinate (DVS SR) Sustained Release vs 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: fluoxetine; Drug: placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 340 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, FLUOXETINE-REFERENCED, 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
• Actual Study Start Date: Nov 17, 2011
• Actual Primary Completion Date: Mar 20, 2015
• Actual Study Completion Date: Mar 20, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: DVS SR	Drug: desvenlafaxine succinate sustained release; Subjects randomized to DVS SR group receive 25, 35 or 50 mg/day based on subject weight at the Baseline visit. DVS SR provided as oral tablets.
Other: Fluoxetine Active control for assay sensitivity	Drug: fluoxetine; Subjects randomized to the fluoxetine group receive 20 mg/day. Fluoxetine provided as oral capsules
Experimental: Placebo	Drug: placebo; Subjects randomized to the placebo group receive corresponding placebo tablets and/capsules

Outcome Measures

Primary Outcome Measures

1. Change From Baseline to Week 8 in the Children's Depression Rating Scale, Revised (CDRS-R) Total Score [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. Adjusted mean presented.

Secondary Outcome Measures

1. Change From Baseline to Week 8 in the Clinical Global Impression of Severity (CGI-S) Score [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. Adjusted mean presented.

2. Percentage of Participants by Clinical Global Impression Improvement (CGI-I) Score at Weeks 1, 2, 3, 4, 6, and 8 [Baseline and 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 = 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), 2 (much improved), or 3 (minimally 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 behaviour, 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	Harmonex Neuroscience Research, Inc.	Dothan	Alabama	United States	36303
2	Dedicated Clinical Research	Goodyear	Arizona	United States	85395
3	University of Arizona Clinical and Translational Science Center (CATS)	Tucson	Arizona	United States	85724
4	University of Arizona College of Medicine Dept of Psychiatry	Tucson	Arizona	United States	85724
5	Arkansas Psychiatric Clinic Clinical Research Trials, P.A.	Little Rock	Arkansas	United States	72211
6	ATP Clinical Research, Inc. 1	Costa Mesa	California	United States	92626
7	Behavioral Research Specialists, LLC	Glendale	California	United States	91206
8	Synergy Clinical Research Center	National City	California	United States	91950
9	Neuropsychiatric Research Center of Orange County	Orange	California	United States	92868
10	Pacific Clinical Research Medical Group	Orange	California	United States	92868
11	Sharp Mesa Vista Hospital	San Diego	California	United States	92123
12	Elite Clinical Trials, Incorporated	Wildomar	California	United States	92595
13	Children's Hospital Colorado	Aurora	Colorado	United States	80045
14	Amedica Research Institute, Incorporated	Hialeah	Florida	United States	33013
15	Clinical Neuroscience Solutions, Inc.	Orlando	Florida	United States	32801
16	Kolin Research Group	Winter Park	Florida	United States	32789-3747
17	Winter Park Memorial Hospital	Winter Park	Florida	United States	32792
18	Atlanta Center for Medical Research	Atlanta	Georgia	United States	30331
19	Institute for Behavioral Medicine	Smyrna	Georgia	United States	30080
20	Psychiatric Associates	Overland Park	Kansas	United States	66211
21	Lake Charles Clinical Trials,	Lake Charles	Louisiana	United States	70629
22	Neuroscientific Insights	Rockville	Maryland	United States	20852
23	Precise Research Centers	Flowood	Mississippi	United States	39232
24	Midwest Research Group	Saint Charles	Missouri	United States	63304
25	St. Charles Psychiatric Associates - Midwest Research Group	Saint Charles	Missouri	United States	63304
26	Heartland Pharma Developments	North Platte	Nebraska	United States	69101
27	Creighton University	Omaha	Nebraska	United States	68131
28	Center for Psychiatry and Behavioral Medicine, Incorporated	Las Vegas	Nevada	United States	89128
29	Cincinnati Children's Hospital Medical Center (New)	Cincinnati	Ohio	United States	45229
30	Nina F. Wimpie, MD Pediatrics	Middleburg Heights	Ohio	United States	44130
31	North Star Medical Research, LLC	Middleburg Heights	Ohio	United States	44130
32	IPS Research Company	Oklahoma City	Oklahoma	United States	73103
33	Cutting Edge Research Group	Oklahoma City	Oklahoma	United States	73116
34	Paradigm Research Professionals, LLC	Oklahoma City	Oklahoma	United States	73118
35	Summit Research Network (Oregon), Incorporated	Portland	Oregon	United States	97210
36	Clinical Neuroscience Solutions, Inc	Memphis	Tennessee	United States	38119
37	Focus & Balance, LLC	San Antonio	Texas	United States	78229
38	Grayline Clinical Drug Trials	Wichita Falls	Texas	United States	76309
39	Northwest Clinical Research Center	Bellevue	Washington	United States	98007
40	Summit Research Network (Seattle) LLC	Seattle	Washington	United States	98104
41	Rogers Center For Research And Training	Milwaukee	Wisconsin	United States	53227
42	Hospital Aranda de la Parra S.A. de C.V.	Leon	Guanajuato	Mexico	37000
43	CIT - Neuropsique, S.C.	Monterrey	Nuevo LEON	Mexico	64610

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: NCT01372150
• Other Study ID Numbers: B2061014; 3151A6-3356; 2008-002063-13
• First Posted: Jun 13, 2011
• Last Update Posted: Jan 15, 2019
• Last Verified: Jan 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Pfizer: major depressive disorder; MDD; depression
• Additional relevant MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major; Fluoxetine; Desvenlafaxine Succinate

Study Results

Participant Flow

Arm/Group Title	Placebo	Fluoxetine	Desvenlafaxine Succinate Sustained Release (DVS SR)
Arm/Group Description	Placebo tablets and capsules administered once daily for 8 weeks (treatment phase), followed by placebo tablets and capsules administered once daily as appropriate for 1 week (taper/transition phase).	Fluoxetine capsules 10 (milligram) mg administered once daily for the first week of treatment (titration phase) then 20 mg administered once daily for the next 7 weeks of treatment, followed by placebo capsules administered once daily as appropriate for 1 week (taper/transition phase).	DVS SR capsules 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) (taper phase) or 25 mg (transition phase) administered once daily as appropriate for 1 week.
Period Title: Overall Study
STARTED	112	113	115
Treated	112	112	115
COMPLETED	99	99	99
NOT COMPLETED	13	14	16

Baseline Characteristics

Arm/Group Title	Placebo	Fluoxetine	DVS SR	Total
Arm/Group Description	Placebo tablets and capsules administered once daily for 8 weeks (treatment phase), followed by placebo tablets and capsules administered once daily as appropriate for 1 week (taper/transition phase).	Fluoxetine capsules 10 mg administered once daily for the first week of treatment (titration phase) then 20 mg administered once daily for the next 7 weeks of treatment, followed by placebo capsules administered once daily for 1 week as appropriate (taper/transition phase).	DVS SR capsules 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) (taper phase) or 25 mg (transition phase) administered once daily as appropriate for 1 week.	Total of all reporting groups
Overall Participants	112	112	115	339
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	12.6 (2.89)	12.6 (2.89)	12.9 (3.12)	12.7 (2.96)
Sex: Female, Male (Count of Participants)
Female	64 57.1%	57 50.9%	63 54.8%	184 54.3%
Male	48 42.9%	55 49.1%	52 45.2%	155 45.7%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline to Week 8 in the Children's Depression Rating Scale, Revised (CDRS-R) Total Score
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. Adjusted mean presented.
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.

Arm/Group Title	Placebo	Fluoxetine	DVS SR
Arm/Group Description	Placebo tablets and capsules administered once daily for 8 weeks (treatment phase), followed by placebo tablets and capsules administered once daily as appropriate for 1 week (taper/transition phase).	Fluoxetine capsules 10 mg administered once daily for the first week of treatment (titration phase) then 20 mg administered once daily for the next 7 weeks of treatment, followed by placebo capsules administered once daily for 1 week as appropriate (taper/transition phase).	DVS SR capsules 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) (taper phase) or 25 mg (transition phase) administered once daily as appropriate for 1 week.
Measure Participants	99	101	99
Mean (Standard Error) [Score on a Scale]	-23.07 (1.18)	-24.79 (1.17)	-22.61 (1.17)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Fluoxetine
	Comments	Fluoxetine versus Placebo
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.226
	Comments
	Method	Mixed-effects model for repeated measure
	Comments	Mixed-effects model for repeated measures (MMRM)
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.71
	Confidence Interval	(2-Sided) 95%; -1.06 to 4.48
	Parameter Dispersion	Type: Value:
	Estimation Comments	Adjusted mean difference = placebo - fluoxetine

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, DVS SR
	Comments	DVS SR versus Placebo
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.739
	Comments
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.47
	Confidence Interval	(2-Sided) 95%; -3.23 to 2.30
	Parameter Dispersion	Type: Value:
	Estimation Comments	Adjusted mean difference = Placebo - DVS SR

2. Secondary Outcome

Title	Change From Baseline to Week 8 in the Clinical Global Impression of Severity (CGI-S) Score
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. Adjusted mean presented.
Time Frame	Baseline and Week 8

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo	Fluoxetine	DVS SR
Arm/Group Description	Placebo tablets and capsules administered once daily for 8 weeks (treatment phase), followed by placebo tablets and capsules administered once daily as appropriate for 1 week (taper/transition phase).	Fluoxetine capsules 10 mg administered once daily for the first week of treatment (titration phase) then 20 mg administered once daily for the next 7 weeks of treatment, followed by placebo capsules administered once daily for 1 week as appropriate (taper/transition phase).	DVS SR capsules 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) (taper phase) or 25 mg (transition phase) administered once daily as appropriate for 1 week.
Measure Participants	99	101	99
Mean (Standard Error) [Score on a Scale]	-1.71 (0.12)	-1.88 (0.12)	-1.70 (0.11)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Fluoxetine
	Comments	Fluoxetine versus Placebo
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.224
	Comments
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.18
	Confidence Interval	(2-Sided) 95%; -0.11 to 0.46
	Parameter Dispersion	Type: Value:
	Estimation Comments	Adjusted mean difference = Placebo - Fluoxetine

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, DVS SR
	Comments	DVS SR versus Placebo
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.944
	Comments
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.01
	Confidence Interval	(2-Sided) 95%; -0.29 to 0.27
	Parameter Dispersion	Type: Value:
	Estimation Comments	Adjusted mean difference = Placebo - DVS SR

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 = more affected.
Time Frame	Baseline and Weeks 1, 2, 3, 4, 6, and 8

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo	Fluoxetine	DVS SR
Arm/Group Description	Placebo tablets and capsules administered once daily for 8 weeks (treatment phase), followed by placebo tablets and capsules administered once daily as appropriate for 1 week (taper/transition phase).	Fluoxetine capsules 10 mg administered once daily for the first week of treatment (titration phase) then 20 mg administered once daily for the next 7 weeks of treatment, followed by placebo capsules administered once daily for 1 week as appropriate (taper/transition phase).	DVS SR capsules 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) (taper phase) or 25 mg (transition phase) administered once daily as appropriate for 1 week.
Measure Participants	105	105	111
Week 1, Very Much Improved (n=102, 101, 111)	1.0 0.9%	3.0 2.7%	2.7 2.3%
Week 1, Much Improved (n=102, 101, 111)	7.8 7%	11.9 10.6%	6.3 5.5%
Week 1, Minimally Improved (n=102, 101, 111)	46.1 41.2%	35.6 31.8%	43.2 37.6%
Week 1, No Change (n=102, 101, 111)	43.1 38.5%	47.5 42.4%	45.9 39.9%
Week 1, Minimally Worse (n=102, 101, 111)	2.0 1.8%	2.0 1.8%	1.8 1.6%
Week 1, Much Worse (n=102, 101, 111)	0 0%	0 0%	0 0%
Week 1, Very Much Worse (n=102, 101, 111)	0 0%	0 0%	0 0%
Week 2, Very Much Improved (n=103, 105, 110)	3.9 3.5%	6.7 6%	3.6 3.1%
Week 2, Much Improved (n=103, 105, 110)	25.2 22.5%	26.7 23.8%	31.8 27.7%
Week 2, Minimally Improved (n=103, 105, 110)	38.8 34.6%	42.9 38.3%	44.5 38.7%
Week 2, No Change (n=103, 105, 110)	30.1 26.9%	22.9 20.4%	19.1 16.6%
Week 2, Minimally Worse (n=103, 105, 110)	1.9 1.7%	1.0 0.9%	0.9 0.8%
Week 2, Much Worse (n=103, 105, 110)	0 0%	0 0%	0 0%
Week 2, Very Much Worse (n=103, 105, 110)	0 0%	0 0%	0 0%
Week 3, Very Much Improved (n=105, 102, 107)	13.3 11.9%	14.7 13.1%	7.5 6.5%
Week 3, Much Improved (n=105, 102, 107)	29.5 26.3%	36.3 32.4%	42.1 36.6%
Week 3, Minimally Improved (n=105, 102, 107)	41.0 36.6%	36.3 32.4%	38.3 33.3%
Week 3, No Change (n=105, 102, 107)	15.2 13.6%	11.8 10.5%	11.2 9.7%
Week 3, Minimally Worse (n=105, 102, 107)	1.0 0.9%	1.0 0.9%	0.9 0.8%
Week 3, Much Worse (n=105, 102, 107)	0 0%	0 0%	0 0%
Week 3, Very Much Worse (n=105, 102, 107)	0 0%	0 0%	0 0%
Week 4, Very Much Improved (n=101, 101, 100)	15.8 14.1%	13.9 12.4%	20.0 17.4%
Week 4, Much Improved (n=101, 101, 100)	38.6 34.5%	47.5 42.4%	44.0 38.3%
Week 4, Minimally Improved (n=101, 101, 100)	29.7 26.5%	27.7 24.7%	25.0 21.7%
Week 4, No Change (n=101, 101, 100)	13.9 12.4%	9.9 8.8%	10.0 8.7%
Week 4, Minimally Worse (n=101, 101, 100)	2.0 1.8%	1.0 0.9%	1.0 0.9%
Week 4, Much Worse (n=101, 101, 100)	0 0%	0 0%	0 0%
Week 4, Very Much Worse (n=101, 101, 100)	0 0%	0 0%	0 0%
Week 6, Very Much Improved (n=100, 100, 102)	18.0 16.1%	26.0 23.2%	23.5 20.4%
Week 6, Much Improved (n=100, 100, 102)	41.0 36.6%	45.0 40.2%	45.1 39.2%
Week 6, Minimally Improved (n=100, 100, 102)	34.0 30.4%	24.0 21.4%	20.6 17.9%
Week 6, No Change (n=100, 100, 102)	6.0 5.4%	5.0 4.5%	9.8 8.5%
Week 6, Minimally Worse (n=100, 100, 102)	0 0%	0 0%	1.0 0.9%
Week 6, Much Worse (n=100, 100, 102)	1.0 0.9%	0 0%	0 0%
Week 6, Very Much Worse (n=100, 100, 102)	0 0%	0 0%	0 0%
Week 8, Very Much Improved (n=99, 101, 99)	27.3 24.4%	30.7 27.4%	23.2 20.2%
Week 8, Much Improved (n=99, 101, 99)	35.4 31.6%	47.5 42.4%	45.5 39.6%
Week 8, Minimally Improved (n=99, 101, 99)	32.3 28.8%	16.8 15%	21.2 18.4%
Week 8, No Change (n=99, 101, 99)	4.0 3.6%	4.0 3.6%	9.1 7.9%
Week 8, Minimally Worse (n=99, 101, 99)	1.0 0.9%	1.0 0.9%	1.0 0.9%
Week 8, Much Worse (n=99, 101, 99)	0 0%	0 0%	0 0%
Week 8, Very Much Worse (n=99, 101, 99)	0 0%	0 0%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Fluoxetine
	Comments	Fluoxetine versus Placebo - Week 1
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.924
	Comments	P-value obtained from the Cochran-Mantel-Haenszel test for the alternative hypothesis of "Row Mean Scores Differences".
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, DVS SR
	Comments	DVS SR versus Placebo - Week 1
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.698
	Comments	P-value obtained from the Cochran-Mantel-Haenszel test for the alternative hypothesis of "Row Mean Scores Differences".
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Fluoxetine
	Comments	Fluoxetine versus Placebo - Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.214
	Comments	P-value obtained from the Cochran-Mantel-Haenszel test for the alternative hypothesis of "Row Mean Scores Differences".
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, DVS SR
	Comments	DVS SR versus Placebo - Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.113
	Comments	P-value obtained from the Cochran-Mantel-Haenszel test for the alternative hypothesis of "Row Mean Scores Differences".
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Fluoxetine
	Comments	Fluoxetine versus Placebo - Week 3
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.314
	Comments	P-value obtained from the Cochran-Mantel-Haenszel test for the alternative hypothesis of "Row Mean Scores Differences".
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, DVS SR
	Comments	DVS SR versus Placebo - Week 3
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.659
	Comments	P-value obtained from the Cochran-Mantel-Haenszel test for the alternative hypothesis of "Row Mean Scores Differences".
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, Fluoxetine
	Comments	Fluoxetine versus Placebo - Week 4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.577
	Comments	P-value obtained from the Cochran-Mantel-Haenszel test for the alternative hypothesis of "Row Mean Scores Differences".
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, DVS SR
	Comments	DVS SR versus Placebo - Week 4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.187
	Comments	P-value obtained from the Cochran-Mantel-Haenszel test for the alternative hypothesis of "Row Mean Scores Differences".
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, Fluoxetine
	Comments	Fluoxetine versus Placebo - Week 6
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.051
	Comments	P-value obtained from the Cochran-Mantel-Haenszel test for the alternative hypothesis of "Row Mean Scores Differences".
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo, DVS SR
	Comments	DVS SR versus Placebo - Week 6
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.266
	Comments	P-value obtained from the Cochran-Mantel-Haenszel test for the alternative hypothesis of "Row Mean Scores Differences".
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Placebo, Fluoxetine
	Comments	Fluoxetine versus Placebo - Week 8
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.095
	Comments	P-value obtained from the Cochran-Mantel-Haenszel test for the alternative hypothesis of "Row Mean Scores Differences".
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Placebo, DVS SR
	Comments	DVS SR versus Placebo - Week 8
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.852
	Comments	P-value obtained from the Cochran-Mantel-Haenszel test for the alternative hypothesis of "Row Mean Scores Differences".
	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), 2 (much improved), or 3 (minimally 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

Arm/Group Title	Placebo	Fluoxetine	DVS SR
Arm/Group Description	Placebo tablets and capsules administered once daily for 8 weeks (treatment phase), followed by placebo tablets and capsules administered once daily as appropriate for 1 week (taper/transition phase).	Fluoxetine capsules 10 mg administered once daily for the first week of treatment (titration phase) then 20 mg administered once daily for the next 7 weeks of treatment, followed by placebo capsules administered once daily for 1 week as appropriate (taper/transition phase).	DVS SR capsules 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) (taper phase) or 25 mg (transition phase) administered once daily as appropriate for 1 week.
Measure Participants	105	105	111
Week 1 (n=102, 101, 111)	8.82 7.9%	14.85 13.3%	9.01 7.8%
Week 2 (n=103, 105, 110)	29.13 26%	33.33 29.8%	35.45 30.8%
Week 3 (n=105, 102, 107)	42.86 38.3%	50.98 45.5%	49.53 43.1%
Week 4 (n=101, 101, 100)	54.46 48.6%	61.39 54.8%	64.00 55.7%
Week 6 (n=100, 100, 102)	59.00 52.7%	71.00 63.4%	68.63 59.7%
Week 8 (n=99, 101, 99)	62.63 55.9%	78.22 69.8%	68.69 59.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Fluoxetine
	Comments	Fluoxetine versus Placebo - Week 1
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.186
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.550
	Confidence Interval	(2-Sided) 95%; 0.226 to 1.335
	Parameter Dispersion	Type: Value:
	Estimation Comments	Logistic Regression using Response (Y/N) at each time point (excluding Week 9) as a response variable and treatment, age group and country as factors.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, DVS SR
	Comments	DVS SR versus Placebo - Week 1
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.984
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.990
	Confidence Interval	(2-Sided) 95%; 0.382 to 2.567
	Parameter Dispersion	Type: Value:
	Estimation Comments	Logistic Regression using Response (Y/N) at each time point (excluding Week 9) as a response variable and treatment, age group and country as factors.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Fluoxetine
	Comments	Fluoxetine versus Placebo - Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.462
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.795
	Confidence Interval	(2-Sided) 95%; 0.431 to 1.465
	Parameter Dispersion	Type: Value:
	Estimation Comments	Logistic Regression using Response (Y/N) at each time point (excluding Week 9) as a response variable and treatment, age group and country as factors.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, DVS SR
	Comments	DVS SR versus Placebo - Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.297
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.726
	Confidence Interval	(2-Sided) 95%; 0.399 to 1.324
	Parameter Dispersion	Type: Value:
	Estimation Comments	Logistic Regression using Response (Y/N) at each time point (excluding Week 9) as a response variable and treatment, age group and country as factors.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Fluoxetine
	Comments	Fluoxetine versus Placebo - Week 3
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.194
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.688
	Confidence Interval	(2-Sided) 95%; 0.391 to 1.210
	Parameter Dispersion	Type: Value:
	Estimation Comments	Logistic Regression using Response (Y/N) at each time point (excluding Week 9) as a response variable and treatment, age group and country as factors.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, DVS SR
	Comments	DVS SR versus Placebo - Week 3
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.272
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.732
	Confidence Interval	(2-Sided) 95%; 0.419 to 1.277
	Parameter Dispersion	Type: Value:
	Estimation Comments	Logistic Regression using Response (Y/N) at each time point (excluding Week 9) as a response variable and treatment, age group and country as factors.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, Fluoxetine
	Comments	Flouxetine versus Placebo - Week 4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.313
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.748
	Confidence Interval	(2-Sided) 95%; 0.426 to 1.314
	Parameter Dispersion	Type: Value:
	Estimation Comments	Logistic Regression using Response (Y/N) at each time point (excluding Week 9) as a response variable and treatment, age group and country as factors.

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, DVS SR
	Comments	DVS SR versus Placebo - Week 4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.157
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.663
	Confidence Interval	(2-Sided) 95%; 0.376 to 1.171
	Parameter Dispersion	Type: Value:
	Estimation Comments	Logistic Regression using Response (Y/N) at each time point (excluding Week 9) as a response variable and treatment, age group and country as factors.

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, Fluoxetine
	Comments	Flouxetine versus Placebo - Week 6
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.072
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.579
	Confidence Interval	(2-Sided) 95%; 0.319 to 1.050
	Parameter Dispersion	Type: Value:
	Estimation Comments	Logistic Regression using Response (Y/N) at each time point (excluding Week 9) as a response variable and treatment, age group and country as factors.

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo, DVS SR
	Comments	DVS SR versus Placebo - Week 6
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.135
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.640
	Confidence Interval	(2-Sided) 95%; 0.356 to 1.149
	Parameter Dispersion	Type: Value:
	Estimation Comments	Logistic Regression using Response (Y/N) at each time point (excluding Week 9) as a response variable and treatment, age group and country as factors.

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Placebo, Fluoxetine
	Comments	Flouxetine versus Placebo - Week 8
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.017
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.465
	Confidence Interval	(2-Sided) 95%; 0.249 to 0.871
	Parameter Dispersion	Type: Value:
	Estimation Comments	Logistic Regression using Response (Y/N) at each time point (excluding Week 9) as a response variable and treatment, age group and country as factors.

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Placebo, DVS SR
	Comments	DVS SR versus Placebo - Week 8
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.343
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.751
	Confidence Interval	(2-Sided) 95%; 0.415 to 1.357
	Parameter Dispersion	Type: Value:
	Estimation Comments	Logistic Regression using Response (Y/N) at each time point (excluding Week 9) as a response variable and treatment, age group and country as factors.

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 9 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		Fluoxetine		DVS SR
Arm/Group Description	Placebo tablets and capsules administered once daily for 8 weeks (treatment phase), followed by placebo tablets and capsules administered once daily as appropriate for 1 week (taper/transition phase).		Fluoxetine capsules 10 mg administered once daily for the first week of treatment (titration phase) then 20 mg administered once daily for the next 7 weeks of treatment, followed by placebo capsules administered once daily for 1 week as appropriate (taper/transition phase).		DVS SR capsules 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) (taper phase) or 25 mg (transition phase) administered once daily as appropriate for 1 week.
All Cause Mortality
	Placebo		Fluoxetine		DVS SR
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Fluoxetine		DVS SR
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/112 (0%)		2/112 (1.8%)		2/115 (1.7%)
Psychiatric disorders
Disinhibition	0/112 (0%)		0/112 (0%)		1/115 (0.9%)
Suicidal ideation	0/112 (0%)		1/112 (0.9%)		1/115 (0.9%)
Suicide attempt	0/112 (0%)		1/112 (0.9%)		0/115 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Fluoxetine		DVS SR
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	44/112 (39.3%)		39/112 (34.8%)		47/115 (40.9%)
Gastrointestinal disorders
Abdominal pain upper	7/112 (6.3%)		9/112 (8%)		15/115 (13%)
Nausea	10/112 (8.9%)		13/112 (11.6%)		8/115 (7%)
Vomiting	4/112 (3.6%)		7/112 (6.3%)		5/115 (4.3%)
General disorders
Fatigue	2/112 (1.8%)		6/112 (5.4%)		2/115 (1.7%)
Infections and infestations
Influenza	0/112 (0%)		2/112 (1.8%)		6/115 (5.2%)
Nasopharyngitis	8/112 (7.1%)		7/112 (6.3%)		6/115 (5.2%)
Upper respiratory tract infection	6/112 (5.4%)		4/112 (3.6%)		6/115 (5.2%)
Nervous system disorders
Dizziness	6/112 (5.4%)		3/112 (2.7%)		7/115 (6.1%)
Headache	21/112 (18.8%)		16/112 (14.3%)		19/115 (16.5%)

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.