Study Evaluating Desvenlafaxine Succinate Sustained-Release Tablets (DVS SR) In The Treatment Of Child and Adolescent Outpatients With Major Depressive Disorder

6-Month, Multicenter, Open-Label, Flexible-Dose Study To Evaluate Safety, Efficacy, And Tolerability Of Desvenlafaxine Succinate Sustained-Release Tablets In The Treatment Of Child And Adolescent Outpatients With Major Depressive Disorder

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00669110

Enrollment

Registered

2008-04-29

Start date

2008-05-31

Completion date

2010-05-31

Last updated

2021-08-19

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Depressive Disorder, Major Depressive Disorder

Keywords

MDD, Depression, Pediatrics, Major Depressive Disorder

Brief summary

The primary purpose of this study is to evaluate the long-term safety and tolerability of Desvenlafaxine Succinate Sustained-Release (DVS SR) in child and adolescent outpatients with major depressive disorder. A secondary aim is to evaluate the efficacy of DVS SR in the treatment of child and adolescent outpatients with major depressive disorder in an exploratory manner.

Interventions

DRUGDesvenlafaxine Succinate Sustained-Release Tablets (DVS SR)

* tablet * subjects randomly assigned to 10-200 mg/day by age group * 6 month treatment period(\ 182 days)

Study design

Allocation

RANDOMIZED

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

7 Years to 18 Years

Healthy volunteers

Inclusion criteria

* Outpatients who have completed 8-weeks of treatment in the preceding study, 3151A6-2000, and who, in the opinion of the investigator, would benefit from long-term treatment. * Study participants who are not surgically sterile or postmenopausal must agree and commit to the use of a reliable method of birth control for the duration of the study and for 15 days after the last dose of test article. Sexually active study participants must agree and commit to the use of condoms in addition to other contraceptive methods.

Exclusion criteria

* Clinically important abnormalities on baseline physical examination or any clinically significant abnormality on electrocardiogram (ECG), laboratory test results, or vital signs recorded before the final study day (day 56 visit) of the preceding study 3151A6-2000. * Unresolved clinically significant adverse events or serious adverse events in the preceding study 3151A6-2000. * Poor compliance with the preceding study 3151A6-2000, as assessed by the investigator and the medical monitor. * Other

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With Adverse Events AEs) and Serious Adverse Events (SAEs)	Baseline (Extension study) up to Extension study Week 29 Follow up visit	AEs are any untoward, undesired, or unplanned event in the form of signs, symptoms, disease, or laboratory or physiologic observations occurring in a person given study treatment. The event does not need to be causally related to the study treatment. SAEs are adverse events that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in persistent or significant disability or incapacity, result in cancer, or result in a congenital anomaly or birth defect.
Number of Participants for Columbia Suicide-Severity Rating Scale (C-SSRS) According to the Columbia Classification Algorithm of Suicide Assessment (C-CASA) Categories	Postbaseline (≥Day 1 in Core study NCT00619619) up to Week 26 (Extension study)	C-SSRS is a participant rated questionnaire to assess suicidal ideation, suicidal behavior, actual attempts (yes or no responses), and intensity of ideation (rated 1=low severity to 5=high severity). Yes/No responses are mapped to Columbia Classification Algorithm of Suicide Assessment (C-CASA) categories: Completed suicide, suicide attempt, preparatory acts toward imminent suicidal behavior, suicidal ideation, and self-injurious behavior, or no suicidal intent. A participant could have a yes or no response in more than one category.

Other

Measure	Time frame	Description
Change From Baseline (Bsl) in Hamilton Rating Scale for Depression 17-item (HAM-D17) Total Score	Baseline (Extension study), Extension study Outpatient Weeks 1, 2, 4, 6, 10, 14, 18, 22, 26, and >26 (up to Week 29)	HAM-D17 is a clinician-rated interview to measure presence of depressive symptoms in 17 areas (symptoms such as depressed mood, guilty feelings, suicide, sleep disturbances, anxiety levels, and weight loss). Total score ranges from 0 to 52; higher scores reflect higher severity of current illness states.
Percentage of Participants With a Categorical Clinical Global Impressions Scales - Severity (CGI-S) Score	Extension study Outpatient Weeks 1, 2, 4, 6, 10, 14, 18, 22, 26, and >26 (up to Week 29)	CGI-S: 7-point clinician rated scale to assess severity of participant's current illness state; range: 1=normal, not ill at all, 2=borderline mentally ill, 3=mildly ill, 4=moderately ill, 5=markedly ill, 6=severely ill, 7=among the most extremely ill patients. Higher scores reflect higher severity of current illness states.
Percentage of Participants With a Categorical Clinical Global Impressions Scales - Improvement (CGI-I) Score	Baseline (Core study NCT00619619), Extension study Outpatient Weeks 1, 2, 4, 6, 10, 14, 18, 22, 26, and >26 (up to Week 29)	CGI-I: 7-point clinician rated scale ranging from 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse, 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. Scores above 4 reflect worsening of illness state as compared to baseline.
Percentage of Participants With a Response of Much Improved or Very Much Improved Based on the Clinical Global Impressions Scales - Improvement (CGI-I) Score	Baseline (Core study NCT00619619), Extension study Outpatient Weeks 1, 2, 4, 6, 10, 14, 18, 22, 26, and >26 (up to Week 29)	CGI-I: 7-point clinician rated scale ranging from 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse, to 7=very much worse. Participant with response is defined as having a score of 1 (very much improved) or 2 (much improved).
Change From Baseline in Number of Participants for Tanner Assessment at Week 26: Females	Baseline (Extension study), Week 26 (Extension study)	Tanner Children and Adolescent Pubertal Staging questionnaire used to document the stage of development of secondary sexual characteristics. Female pubertal development staged by pubic hair development and breast size (test categories). Rated in 5 stages: stage 1 (no development) to 5 (adult-like development in quantity and size). Change categories: 0=no change in stage, 1=change of 1 stage, 2=change of 2 stages, 3=change of 3 stages, and 4=change of 4 stages. Participants may be represented in more than 1 test category.
Change From Baseline in Number of Participants for Tanner Assessment at Week 26: Males	Baseline (Extension study), Week 26 (Extension study)	Tanner Children and Adolescent Pubertal Staging questionnaire used to document the stage of development of secondary sexual characteristics. Male pubertal development staged by size of the genitalia and development of pubic hair (test categories). Rated in 5 stages: stage 1 (no development) to 5 (adult-like development in quantity and size). Change categories: 0=no change in stage, 1=change of 1 stage, 2=change of 2 stages, 3=change of 3 stages, and 4=change of 4 stages. Participants may be represented in more than 1 test category.
Change From Baseline (Bsl) in Children's Depression Rating Scale - Revised (CDRS-R) Total Score at Final On-therapy Visit	Baseline (Extension study), Extension study Outpatient Weeks 26 and >Week 26 (up to Week 29 or early termination)	CDRS-R total score: scale measures 17 depressive symptoms, of which 3 are rated 1 to 5 and 14 are rated 1 to 7 (1 = no symptom difficulties; 5 to 7 = severe clinically significant difficulties) for a total score range of 17 to 113. Lower total scores indicate lower intensity of symptoms.
Number of Participants With Vital Sign Results of Potential Clinical Importance (PCI): Weight	Baseline (Extension study) up to Week 26 (Extension study)	Vitals signs meeting the PCI criteria for weight categorized according to an increase of ≥7 percent or a decrease of ≥3.5 percent in body weight.
Number of Participants With Vital Sign Results of Potential Clinical Importance (PCI): Pulse Rate	Baseline (Extension study) up to Week 26 (Extension study)	PCI criteria for females: supine pulse rate (beats per minute \[bpm\]) ranges from \<68 or \>126 at age 6 to pulse \<63 or \>121 at age 11; pulse from \<63 or \>121 at age 12 to \<54 or \>110 at age 17; pulse from \<50 or \>104 at age 18. Criteria for males: pulse ranges from \<68 or \>126 at age 6 to pulse \<63 or \>121 at age 11; pulse from \<58 or \>116 at age 12 to \<50 or \>104 at age 17; pulse from \<45 or \>99 at age 18. Vitals signs meeting criteria for PCI categorized as Low or as postural change in pulse (increase in pulse ≥20 bpm for last supine to first standing pulse \[supine to standing\]).
Number of Participants With Electrocardiogram (ECG) Results of Potential Clinical Importance (PCI)	Baseline (Extension study) up to Week 26 (Extension study)	ECG results meeting the criteria for PCI categorized as PR interval ≥200 milliseconds (msec); QT interval ≥480msec; QRS interval ≥120 msec; corrected QT (QTc) ≥500 msec ); \>450 msec for males and \>470 msec for females or increase of ≥60 msec or ≥30 msec change from baseline QTcB=QT corrected using Bazett formula; QTcF=QT corrected using the Fridericia formula.
Number of Participants With Electrocardiogram (ECG) Results of Potential Clinical Importance (PCI): Heart Rate (Low)	Baseline (Extension study) up to Week 26 (Extension study)	PCI criteria for females: heart rate (bpm) ranges from \<68 and \>126 at age 6 to \<63 and \>121 at age 11; heart rate from \<63 and \>121 at age 12 to \<54 and \>110 at age 17; heart rate \<50 and \>104 at age 18. Criteria for males: heart rate ranges from \< 68 and \>126 at age 6 to \<63 and \>121 at age 11; heart rate \<58 and \>116 at age 12 up \<50 and \>104 at age 17; heart rate \<45 and \>99 at age 18. Heart rates meeting the criteria for PCI categorized as low (less than the lower limit specified for age).
Number of Participants With Laboratory Test Results of Potential Clinical Importance (PCI)	Baseline (Extension study) up to Week 26 (Extension study)	Laboratory test results meeting the criteria for PCI categorized as bicarbonate increase or decrease from baseline of ≥4 millimoles per liter (mmol/L); hematocrit \<0.32 or \>0.50 (females) or \<0.37 or \>0.55 (males) liters per liter (L/L); high density lipoprotein (HDL) cholesterol (fasting or nonfasting / unknown) decrease \>0.21 mmol/L and test value ≥1.16 mmol/L; triglycerides (fasting or nonfasting / unknown) ≥2.258 mmol/L or increase ≥1.13 mmol/L and test value ≥3.39 mmol/L; urine specific gravity \<1.001 or \>1.035; and positive urinalysis result for protein (albumin), hemoglobin, or ketones.
Number of Participants With Vital Sign Results of Potential Clinical Importance (PCI): Blood Pressure (BP)	Baseline (Extension study) up to Week 26 (Extension study)	PCI criteria for females: systolic BP \[SBP\] ranges from \>110 and diastolic BP \[DBP\] \>73 (\>110/73) at age 6 up to BP \>124/81 at age 11; BP from \>121/79 at age 12 up to BP \>132/86 at age 17. Criteria for males: BP ranges from \>112/73 at age 6 up to BP \>123/82 at age 10; BP from \>119/79 at age 11 up to BP \>140/89 at age 17. Vitals signs meeting the criteria for PCI categorized as BP elevation for 3 consecutive visits or as postural change in BP (decrease in SBP ≥20 millimeters of mercury \[mmHg\] or in DBP ≥15 mmHg for the last supine to first standing BP \[supine to standing\]).
Percentage of Participants With Remission (Total Score ≤28) Based on Children's Depression Rating Scale - Revised (CDRS-R)	Extension study Outpatient Weeks 1, 2, 4, 6, 10, 14, 18, 22, 26, and >26 (up to Week 29)	CDRS-R total score: scale measures 17 depressive symptoms, of which 3 are rated 1 to 5 and 14 are rated 1 to 7 (1 = no symptom difficulties; 5 to 7 = severe clinically significant difficulties) for a total score range of 17 to 113. Lower total scores indicate lower intensity of symptoms. Remission defined as a CDRS-R total score ≤28 (coded value of 1).

Countries

United States

Participant flow

Recruitment details

Eligible participants transitioned from preceding Core study NCT00619619 (3151A6-2000 \[B2061012\]) on Day 56 to this Extension study NCT00669110 (3151A6-2001 \[B2061013\]) to continue treatment on a flexible dose schedule. A total of 8 participants (Children n=2 and Adolescent n=6) discontinued during Taper/post-study or Follow-up phase of Core study.

Pre-assignment details

Baseline (Day-1) in the Extension study = Week 8 (Day 56) in the Core study. However, Baseline for the Clinical Global Impressions Scale - Improvement (CGI-I) = Inpatient Day 1 through 4 in the Core study and Baseline for the Columbia Suicide-Severity Rating Scale (C-SSRS) = Day-1 in the Core study.

Participants by arm

Arm	Count
DVS SR - Children Desvenlafaxine succinate sustained-release (DVS SR) formulation tablet(s) by mouth (PO) administered as flexible dosing adjusted by the investigator as clinically indicated. Total daily dose will be flexible between 10 milligrams (mg), 25 mg, 50 mg, and 100 mg for children 7 to 11 years of age at baseline in the preceding Core study NCT00619619.	20
DVS SR - Adolescents Desvenlafaxine succinate sustained-release (DVS SR) formulation tablet(s) by mouth (PO) administered as flexible dosing adjusted by the investigator as clinically indicated. Total daily dose will be flexible between 25 mg, 50 mg, 100 mg, and 200 mg for adolescents 12 to 17 years of age at baseline in the preceding Core study NCT00619619.	20
Total	40

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	4	3
Overall Study	Caregiver request	3	2
Overall Study	Lost to Follow-up	1	0
Overall Study	Physician Decision	0	1
Overall Study	Protocol Violation	0	5
Overall Study	Withdrawal by Subject	0	2

Baseline characteristics

Characteristic	DVS SR - Children	DVS SR - Adolescents	Total
Age, Continuous	9.65 years STANDARD_DEVIATION 1.31	13.55 years STANDARD_DEVIATION 1.64	11.60 years STANDARD_DEVIATION 2.46
Number of participants for Tanner Assessment: Females Breasts Stage 1	4 participants	0 participants	4 participants
Number of participants for Tanner Assessment: Females Breasts Stage 2	4 participants	1 participants	5 participants
Number of participants for Tanner Assessment: Females Breasts Stage 3	1 participants	0 participants	1 participants
Number of participants for Tanner Assessment: Females Breasts Stage 4	0 participants	1 participants	1 participants
Number of participants for Tanner Assessment: Females Breasts Stage 5	0 participants	7 participants	7 participants
Number of participants for Tanner Assessment: Females Pubic hair Stage 1	6 participants	0 participants	6 participants
Number of participants for Tanner Assessment: Females Pubic hair Stage 2	3 participants	2 participants	5 participants
Number of participants for Tanner Assessment: Females Pubic hair Stage 3	0 participants	0 participants	0 participants
Number of participants for Tanner Assessment: Females Pubic hair Stage 4	0 participants	2 participants	2 participants
Number of participants for Tanner Assessment: Females Pubic hair Stage 5	0 participants	5 participants	5 participants
Number of participants for Tanner Assessment: Males Penis Stage 1	5 participants	0 participants	5 participants
Number of participants for Tanner Assessment: Males Penis Stage 2	3 participants	2 participants	5 participants
Number of participants for Tanner Assessment: Males Penis Stage 3	1 participants	2 participants	3 participants
Number of participants for Tanner Assessment: Males Penis Stage 4	0 participants	3 participants	3 participants
Number of participants for Tanner Assessment: Males Penis Stage 5	0 participants	3 participants	3 participants
Number of participants for Tanner Assessment: Males Pubic hair Stage 1	6 participants	0 participants	6 participants
Number of participants for Tanner Assessment: Males Pubic hair Stage 2	2 participants	1 participants	3 participants
Number of participants for Tanner Assessment: Males Pubic hair Stage 3	1 participants	3 participants	4 participants
Number of participants for Tanner Assessment: Males Pubic hair Stage 4	0 participants	4 participants	4 participants
Number of participants for Tanner Assessment: Males Pubic hair Stage 5	0 participants	2 participants	2 participants
Number of participants for Tanner Assessment: Males Testes Stage 1	5 participants	0 participants	5 participants
Number of participants for Tanner Assessment: Males Testes Stage 2	2 participants	1 participants	3 participants
Number of participants for Tanner Assessment: Males Testes Stage 3	2 participants	3 participants	5 participants
Number of participants for Tanner Assessment: Males Testes Stage 4	0 participants	3 participants	3 participants
Number of participants for Tanner Assessment: Males Testes Stage 5	0 participants	3 participants	3 participants
Sex: Female, Male Female	11 Participants	9 Participants	20 Participants
Sex: Female, Male Male	9 Participants	11 Participants	20 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	13 / 20	15 / 20
serious Total, serious adverse events	1 / 20	0 / 20

Outcome results

Primary

Number of Participants for Columbia Suicide-Severity Rating Scale (C-SSRS) According to the Columbia Classification Algorithm of Suicide Assessment (C-CASA) Categories

C-SSRS is a participant rated questionnaire to assess suicidal ideation, suicidal behavior, actual attempts (yes or no responses), and intensity of ideation (rated 1=low severity to 5=high severity). Yes/No responses are mapped to Columbia Classification Algorithm of Suicide Assessment (C-CASA) categories: Completed suicide, suicide attempt, preparatory acts toward imminent suicidal behavior, suicidal ideation, and self-injurious behavior, or no suicidal intent. A participant could have a yes or no response in more than one category.

Time frame: Postbaseline (≥Day 1 in Core study NCT00619619) up to Week 26 (Extension study)

Population: Safety population (Baseline=Core study) includes all treatment assigned participants with at least 1 dose of study treatment during Core study NCT00619619 and Extension study NCT00669110.

Arm	Measure	Group	Value (NUMBER)
DVS SR - Children	Number of Participants for Columbia Suicide-Severity Rating Scale (C-SSRS) According to the Columbia Classification Algorithm of Suicide Assessment (C-CASA) Categories	Completed suicide: No	20 participants
DVS SR - Children	Number of Participants for Columbia Suicide-Severity Rating Scale (C-SSRS) According to the Columbia Classification Algorithm of Suicide Assessment (C-CASA) Categories	Suicide attempt: No	20 participants
DVS SR - Children	Number of Participants for Columbia Suicide-Severity Rating Scale (C-SSRS) According to the Columbia Classification Algorithm of Suicide Assessment (C-CASA) Categories	Preparatory acts - imminent suicidal behavior: No	20 participants
DVS SR - Children	Number of Participants for Columbia Suicide-Severity Rating Scale (C-SSRS) According to the Columbia Classification Algorithm of Suicide Assessment (C-CASA) Categories	Suicidal ideation: Yes	0 participants
DVS SR - Children	Number of Participants for Columbia Suicide-Severity Rating Scale (C-SSRS) According to the Columbia Classification Algorithm of Suicide Assessment (C-CASA) Categories	Suicidal ideation: No	20 participants
DVS SR - Children	Number of Participants for Columbia Suicide-Severity Rating Scale (C-SSRS) According to the Columbia Classification Algorithm of Suicide Assessment (C-CASA) Categories	Any suicidal behavior and/or ideation: Yes	0 participants
DVS SR - Children	Number of Participants for Columbia Suicide-Severity Rating Scale (C-SSRS) According to the Columbia Classification Algorithm of Suicide Assessment (C-CASA) Categories	Any suicidal behavior and/or ideation: No	20 participants
DVS SR - Children	Number of Participants for Columbia Suicide-Severity Rating Scale (C-SSRS) According to the Columbia Classification Algorithm of Suicide Assessment (C-CASA) Categories	Self-injurious behavior, no suicidal intent: No	20 participants
DVS SR - Adolescents	Number of Participants for Columbia Suicide-Severity Rating Scale (C-SSRS) According to the Columbia Classification Algorithm of Suicide Assessment (C-CASA) Categories	Self-injurious behavior, no suicidal intent: No	20 participants
DVS SR - Adolescents	Number of Participants for Columbia Suicide-Severity Rating Scale (C-SSRS) According to the Columbia Classification Algorithm of Suicide Assessment (C-CASA) Categories	Completed suicide: No	20 participants
DVS SR - Adolescents	Number of Participants for Columbia Suicide-Severity Rating Scale (C-SSRS) According to the Columbia Classification Algorithm of Suicide Assessment (C-CASA) Categories	Suicidal ideation: No	17 participants
DVS SR - Adolescents	Number of Participants for Columbia Suicide-Severity Rating Scale (C-SSRS) According to the Columbia Classification Algorithm of Suicide Assessment (C-CASA) Categories	Suicide attempt: No	20 participants
DVS SR - Adolescents	Number of Participants for Columbia Suicide-Severity Rating Scale (C-SSRS) According to the Columbia Classification Algorithm of Suicide Assessment (C-CASA) Categories	Any suicidal behavior and/or ideation: No	17 participants
DVS SR - Adolescents	Number of Participants for Columbia Suicide-Severity Rating Scale (C-SSRS) According to the Columbia Classification Algorithm of Suicide Assessment (C-CASA) Categories	Preparatory acts - imminent suicidal behavior: No	20 participants
DVS SR - Adolescents	Number of Participants for Columbia Suicide-Severity Rating Scale (C-SSRS) According to the Columbia Classification Algorithm of Suicide Assessment (C-CASA) Categories	Any suicidal behavior and/or ideation: Yes	3 participants
DVS SR - Adolescents	Number of Participants for Columbia Suicide-Severity Rating Scale (C-SSRS) According to the Columbia Classification Algorithm of Suicide Assessment (C-CASA) Categories	Suicidal ideation: Yes	3 participants

Primary

Number of Participants With Adverse Events AEs) and Serious Adverse Events (SAEs)

AEs are any untoward, undesired, or unplanned event in the form of signs, symptoms, disease, or laboratory or physiologic observations occurring in a person given study treatment. The event does not need to be causally related to the study treatment. SAEs are adverse events that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in persistent or significant disability or incapacity, result in cancer, or result in a congenital anomaly or birth defect.

Time frame: Baseline (Extension study) up to Extension study Week 29 Follow up visit

Population: Safety population (Baseline=Extension study) includes all treatment assigned participants with at least 1 dose of study treatment during Extension study NCT00669110.

Arm	Measure	Group	Value (NUMBER)
DVS SR - Children	Number of Participants With Adverse Events AEs) and Serious Adverse Events (SAEs)	Adverse events	13 participants
DVS SR - Children	Number of Participants With Adverse Events AEs) and Serious Adverse Events (SAEs)	Serious adverse events	1 participants
DVS SR - Adolescents	Number of Participants With Adverse Events AEs) and Serious Adverse Events (SAEs)	Adverse events	15 participants
DVS SR - Adolescents	Number of Participants With Adverse Events AEs) and Serious Adverse Events (SAEs)	Serious adverse events	0 participants

Other Pre-specified

Change From Baseline (Bsl) in Children's Depression Rating Scale - Revised (CDRS-R) Total Score at Final On-therapy Visit

CDRS-R total score: scale measures 17 depressive symptoms, of which 3 are rated 1 to 5 and 14 are rated 1 to 7 (1 = no symptom difficulties; 5 to 7 = severe clinically significant difficulties) for a total score range of 17 to 113. Lower total scores indicate lower intensity of symptoms.

Time frame: Baseline (Extension study), Extension study Outpatient Weeks 26 and >Week 26 (up to Week 29 or early termination)

Population: Intent to Treat population (ITT): all treatment assigned participants with a baseline primary efficacy evaluation, at least 1 dose of study treatment, and at least 1 primary efficacy evaluation after first dose in Extension study NCT00669110. Last observation carried forward (LOCF).

Arm	Measure	Group	Value (MEAN)	Dispersion
DVS SR - Children	Change From Baseline (Bsl) in Children's Depression Rating Scale - Revised (CDRS-R) Total Score at Final On-therapy Visit	Baseline mean	32.40 scores on a scale	Standard Deviation 7.61
DVS SR - Children	Change From Baseline (Bsl) in Children's Depression Rating Scale - Revised (CDRS-R) Total Score at Final On-therapy Visit	Change from Bsl Outpatient Week 26	-1.85 scores on a scale	Standard Deviation 5.51
DVS SR - Children	Change From Baseline (Bsl) in Children's Depression Rating Scale - Revised (CDRS-R) Total Score at Final On-therapy Visit	Change from Bsl Outpatient Week >26	-1.85 scores on a scale	Standard Deviation 5.51
DVS SR - Adolescents	Change From Baseline (Bsl) in Children's Depression Rating Scale - Revised (CDRS-R) Total Score at Final On-therapy Visit	Baseline mean	33.70 scores on a scale	Standard Deviation 6.34
DVS SR - Adolescents	Change From Baseline (Bsl) in Children's Depression Rating Scale - Revised (CDRS-R) Total Score at Final On-therapy Visit	Change from Bsl Outpatient Week 26	-1.95 scores on a scale	Standard Deviation 6.85
DVS SR - Adolescents	Change From Baseline (Bsl) in Children's Depression Rating Scale - Revised (CDRS-R) Total Score at Final On-therapy Visit	Change from Bsl Outpatient Week >26	-1.70 scores on a scale	Standard Deviation 6.67

Other Pre-specified

Change From Baseline (Bsl) in Hamilton Rating Scale for Depression 17-item (HAM-D17) Total Score

HAM-D17 is a clinician-rated interview to measure presence of depressive symptoms in 17 areas (symptoms such as depressed mood, guilty feelings, suicide, sleep disturbances, anxiety levels, and weight loss). Total score ranges from 0 to 52; higher scores reflect higher severity of current illness states.

Time frame: Baseline (Extension study), Extension study Outpatient Weeks 1, 2, 4, 6, 10, 14, 18, 22, 26, and >26 (up to Week 29)

Population: ITT population; LOCF.

Arm	Measure	Group	Value (MEAN)	Dispersion
DVS SR - Children	Change From Baseline (Bsl) in Hamilton Rating Scale for Depression 17-item (HAM-D17) Total Score	Baseline mean	5.15 scores on a scale	Standard Deviation 3.01
DVS SR - Children	Change From Baseline (Bsl) in Hamilton Rating Scale for Depression 17-item (HAM-D17) Total Score	Change from Bsl Outpatient Week 10	-1.30 scores on a scale	Standard Deviation 3.06
DVS SR - Children	Change From Baseline (Bsl) in Hamilton Rating Scale for Depression 17-item (HAM-D17) Total Score	Change from Bsl Outpatient Week 2	-0.50 scores on a scale	Standard Deviation 2.8
DVS SR - Children	Change From Baseline (Bsl) in Hamilton Rating Scale for Depression 17-item (HAM-D17) Total Score	Change from Bsl Outpatient Week 14	-0.45 scores on a scale	Standard Deviation 2.58
DVS SR - Children	Change From Baseline (Bsl) in Hamilton Rating Scale for Depression 17-item (HAM-D17) Total Score	Change from Bsl Outpatient Week 26	-1.65 scores on a scale	Standard Deviation 2.94
DVS SR - Children	Change From Baseline (Bsl) in Hamilton Rating Scale for Depression 17-item (HAM-D17) Total Score	Change from Bsl Outpatient Week 18	-1.65 scores on a scale	Standard Deviation 2.48
DVS SR - Children	Change From Baseline (Bsl) in Hamilton Rating Scale for Depression 17-item (HAM-D17) Total Score	Change from Bsl Outpatient Week 4	-0.40 scores on a scale	Standard Deviation 2.28
DVS SR - Children	Change From Baseline (Bsl) in Hamilton Rating Scale for Depression 17-item (HAM-D17) Total Score	Change from Bsl Outpatient Week 22	-1.05 scores on a scale	Standard Deviation 2.26
DVS SR - Children	Change From Baseline (Bsl) in Hamilton Rating Scale for Depression 17-item (HAM-D17) Total Score	Change from Bsl Outpatient Week 1	0.53 scores on a scale	Standard Deviation 2.72
DVS SR - Children	Change From Baseline (Bsl) in Hamilton Rating Scale for Depression 17-item (HAM-D17) Total Score	Change from Bsl Outpatient Week >26	-1.65 scores on a scale	Standard Deviation 2.94
DVS SR - Children	Change From Baseline (Bsl) in Hamilton Rating Scale for Depression 17-item (HAM-D17) Total Score	Change from Bsl Outpatient Week 6	-0.45 scores on a scale	Standard Deviation 2.31
DVS SR - Adolescents	Change From Baseline (Bsl) in Hamilton Rating Scale for Depression 17-item (HAM-D17) Total Score	Change from Bsl Outpatient Week >26	-2.10 scores on a scale	Standard Deviation 3.37
DVS SR - Adolescents	Change From Baseline (Bsl) in Hamilton Rating Scale for Depression 17-item (HAM-D17) Total Score	Baseline mean	7.45 scores on a scale	Standard Deviation 4.1
DVS SR - Adolescents	Change From Baseline (Bsl) in Hamilton Rating Scale for Depression 17-item (HAM-D17) Total Score	Change from Bsl Outpatient Week 1	1.79 scores on a scale	Standard Deviation 2.97
DVS SR - Adolescents	Change From Baseline (Bsl) in Hamilton Rating Scale for Depression 17-item (HAM-D17) Total Score	Change from Bsl Outpatient Week 2	0.70 scores on a scale	Standard Deviation 3.01
DVS SR - Adolescents	Change From Baseline (Bsl) in Hamilton Rating Scale for Depression 17-item (HAM-D17) Total Score	Change from Bsl Outpatient Week 4	-0.95 scores on a scale	Standard Deviation 2.24
DVS SR - Adolescents	Change From Baseline (Bsl) in Hamilton Rating Scale for Depression 17-item (HAM-D17) Total Score	Change from Bsl Outpatient Week 6	-0.70 scores on a scale	Standard Deviation 2.68
DVS SR - Adolescents	Change From Baseline (Bsl) in Hamilton Rating Scale for Depression 17-item (HAM-D17) Total Score	Change from Bsl Outpatient Week 10	-1.40 scores on a scale	Standard Deviation 2.66
DVS SR - Adolescents	Change From Baseline (Bsl) in Hamilton Rating Scale for Depression 17-item (HAM-D17) Total Score	Change from Bsl Outpatient Week 14	-1.65 scores on a scale	Standard Deviation 3.08
DVS SR - Adolescents	Change From Baseline (Bsl) in Hamilton Rating Scale for Depression 17-item (HAM-D17) Total Score	Change from Bsl Outpatient Week 18	-2.45 scores on a scale	Standard Deviation 3.1
DVS SR - Adolescents	Change From Baseline (Bsl) in Hamilton Rating Scale for Depression 17-item (HAM-D17) Total Score	Change from Bsl Outpatient Week 26	-2.35 scores on a scale	Standard Deviation 3.39
DVS SR - Adolescents	Change From Baseline (Bsl) in Hamilton Rating Scale for Depression 17-item (HAM-D17) Total Score	Change from Bsl Outpatient Week 22	-2.15 scores on a scale	Standard Deviation 3.22

Other Pre-specified

Change From Baseline in Number of Participants for Tanner Assessment at Week 26: Females

Tanner Children and Adolescent Pubertal Staging questionnaire used to document the stage of development of secondary sexual characteristics. Female pubertal development staged by pubic hair development and breast size (test categories). Rated in 5 stages: stage 1 (no development) to 5 (adult-like development in quantity and size). Change categories: 0=no change in stage, 1=change of 1 stage, 2=change of 2 stages, 3=change of 3 stages, and 4=change of 4 stages. Participants may be represented in more than 1 test category.

Time frame: Baseline (Extension study), Week 26 (Extension study)

Population: Safety population (Baseline=Extension study); N=number of participants with evaluable data at observation. No participants had a change of 3 stages or change of 4 stages reported, therefore only changes for 0 stages through 2 stages are reported.

Arm	Measure	Group	Value (NUMBER)
DVS SR - Children	Change From Baseline in Number of Participants for Tanner Assessment at Week 26: Females	Breasts: 0=no stage change	5 participants
DVS SR - Children	Change From Baseline in Number of Participants for Tanner Assessment at Week 26: Females	Breasts: 1=change of 1 stage	1 participants
DVS SR - Children	Change From Baseline in Number of Participants for Tanner Assessment at Week 26: Females	Breasts: 2=change of 2 stages	1 participants
DVS SR - Children	Change From Baseline in Number of Participants for Tanner Assessment at Week 26: Females	Pubic hair: 0=no stage change	6 participants
DVS SR - Children	Change From Baseline in Number of Participants for Tanner Assessment at Week 26: Females	Pubic hair: 1=change of 1 stage	1 participants
DVS SR - Children	Change From Baseline in Number of Participants for Tanner Assessment at Week 26: Females	Pubic hair: 2=change of 2 stages	0 participants
DVS SR - Adolescents	Change From Baseline in Number of Participants for Tanner Assessment at Week 26: Females	Pubic hair: 1=change of 1 stage	0 participants
DVS SR - Adolescents	Change From Baseline in Number of Participants for Tanner Assessment at Week 26: Females	Breasts: 0=no stage change	1 participants
DVS SR - Adolescents	Change From Baseline in Number of Participants for Tanner Assessment at Week 26: Females	Pubic hair: 0=no stage change	2 participants
DVS SR - Adolescents	Change From Baseline in Number of Participants for Tanner Assessment at Week 26: Females	Breasts: 1=change of 1 stage	1 participants
DVS SR - Adolescents	Change From Baseline in Number of Participants for Tanner Assessment at Week 26: Females	Pubic hair: 2=change of 2 stages	1 participants
DVS SR - Adolescents	Change From Baseline in Number of Participants for Tanner Assessment at Week 26: Females	Breasts: 2=change of 2 stages	1 participants

Other Pre-specified

Change From Baseline in Number of Participants for Tanner Assessment at Week 26: Males

Tanner Children and Adolescent Pubertal Staging questionnaire used to document the stage of development of secondary sexual characteristics. Male pubertal development staged by size of the genitalia and development of pubic hair (test categories). Rated in 5 stages: stage 1 (no development) to 5 (adult-like development in quantity and size). Change categories: 0=no change in stage, 1=change of 1 stage, 2=change of 2 stages, 3=change of 3 stages, and 4=change of 4 stages. Participants may be represented in more than 1 test category.

Time frame: Baseline (Extension study), Week 26 (Extension study)

Arm	Measure	Group	Value (NUMBER)
DVS SR - Children	Change From Baseline in Number of Participants for Tanner Assessment at Week 26: Males	Penis: 1=change of 1 stage	1 participants
DVS SR - Children	Change From Baseline in Number of Participants for Tanner Assessment at Week 26: Males	Pubic hair: 2=change of 2 stages	0 participants
DVS SR - Children	Change From Baseline in Number of Participants for Tanner Assessment at Week 26: Males	Pubic hair: 0=no stage change	2 participants
DVS SR - Children	Change From Baseline in Number of Participants for Tanner Assessment at Week 26: Males	Testes: 0=no stage change	3 participants
DVS SR - Children	Change From Baseline in Number of Participants for Tanner Assessment at Week 26: Males	Penis: 2=change of 2 stages	0 participants
DVS SR - Children	Change From Baseline in Number of Participants for Tanner Assessment at Week 26: Males	Testes: 1=change of 1 stage	2 participants
DVS SR - Children	Change From Baseline in Number of Participants for Tanner Assessment at Week 26: Males	Pubic hair: 1=change of 1 stage	3 participants
DVS SR - Children	Change From Baseline in Number of Participants for Tanner Assessment at Week 26: Males	Testes: 2=change of 2 stages	0 participants
DVS SR - Children	Change From Baseline in Number of Participants for Tanner Assessment at Week 26: Males	Penis: 0=no stage change	4 participants
DVS SR - Adolescents	Change From Baseline in Number of Participants for Tanner Assessment at Week 26: Males	Testes: 2=change of 2 stages	1 participants
DVS SR - Adolescents	Change From Baseline in Number of Participants for Tanner Assessment at Week 26: Males	Penis: 0=no stage change	3 participants
DVS SR - Adolescents	Change From Baseline in Number of Participants for Tanner Assessment at Week 26: Males	Penis: 1=change of 1 stage	0 participants
DVS SR - Adolescents	Change From Baseline in Number of Participants for Tanner Assessment at Week 26: Males	Penis: 2=change of 2 stages	1 participants
DVS SR - Adolescents	Change From Baseline in Number of Participants for Tanner Assessment at Week 26: Males	Pubic hair: 0=no stage change	2 participants
DVS SR - Adolescents	Change From Baseline in Number of Participants for Tanner Assessment at Week 26: Males	Pubic hair: 1=change of 1 stage	1 participants
DVS SR - Adolescents	Change From Baseline in Number of Participants for Tanner Assessment at Week 26: Males	Pubic hair: 2=change of 2 stages	1 participants
DVS SR - Adolescents	Change From Baseline in Number of Participants for Tanner Assessment at Week 26: Males	Testes: 0=no stage change	3 participants
DVS SR - Adolescents	Change From Baseline in Number of Participants for Tanner Assessment at Week 26: Males	Testes: 1=change of 1 stage	0 participants

Other Pre-specified

Number of Participants With Electrocardiogram (ECG) Results of Potential Clinical Importance (PCI)

ECG results meeting the criteria for PCI categorized as PR interval ≥200 milliseconds (msec); QT interval ≥480msec; QRS interval ≥120 msec; corrected QT (QTc) ≥500 msec ); \>450 msec for males and \>470 msec for females or increase of ≥60 msec or ≥30 msec change from baseline QTcB=QT corrected using Bazett formula; QTcF=QT corrected using the Fridericia formula.