Depressive Disorder, Major
Conditions
Keywords
paediatric
Brief summary
Investigation of the efficacy and safety of a new potential treatment of Major depressive disorder (MDD) in paediatric participants (age 7 to 11 years).
Interventions
10 mg/day, encapsulated tablet, orally (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 5 mg/day. No dose increase will be allowed
20 mg/day, encapsulated tablet, orally (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 5 mg/day. No dose increase will be allowed
DRUGFluoxetine 20mg/day
20 mg/day, encapsulated tablet, orally (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 10 mg/day. No dose increase will be allowed
OTHERPlacebo
Encapsulated tablet, orally
Sponsors
Takeda
H. Lundbeck A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
7 Years to 11 Years
Healthy volunteers
No
Inclusion criteria
1. The participant has MDD, diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5™). 2. The participant has a CDRS-R total score ≥45 at the Screening Visit and the Baseline. 3. The participant has a CGI-S score ≥4 at the Screening Visit and the Baseline. 4. The participant is a boy or girl, aged ≥7 and \<12 years at Screening Visit 5. The participant has provided assent to participation and parent(s)/legal representative (s) signed the Informed Consent Form.
Exclusion criteria
1. The participant has participated in a clinical study \<30 days prior to the Screening Visit. 2. The participant has previously participated in a study with vortioxetine. Other protocol defined inclusion and
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Children Depression Rating Scale - Revised (CDRS-R) Total Score at Week 8 of Phase B | Baseline (Week 4 of Phase A), Week 8 of Phase B | The CDRS-R is a clinician-rated scale to measure the severity of depression in children and adolescents. The CDRS-R was rated by a clinician following interviews with the child and parent and consisted of 17 items out of which 3 items rated nonverbal observations (listless speech, hypoactivity, and depressed affect). Fourteen items were rated on a 7-point scale from 1 to 7, and 3 items (sleep disturbance, appetite disturbance, and listless speech) were scored on a 5-point scale from 1 to 5. A rating of 1 indicated normal functioning and a higher number indicated a greater degree of depression. The total score ranged from 17 (normal) to 113 (severe depression). Least square (LS) mean was estimated using a restricted maximum likelihood (REML)-based Mixed Model Repeated Measurements (MMRM) approach. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in CDRS-R Subscores (Mood, Somatic, Subjective, and Behaviour) at Weeks 2, 4, 6, and 8 of Phase B | Baseline (Week 4 of Phase A), Weeks 2, 4, 6, and 8 of Phase B | The CDRS-R was rated by a clinician following interviews with the child and parent and consisted of 17 items out of which 3 items rated nonverbal observations (listless speech, hypoactivity, and depressed affect). Fourteen items were rated on a 7-point scale from 1 to 7, and 3 items (sleep disturbance, appetite disturbance, and listless speech) were scored on a 5-point scale from 1 to 5. A rating of 1 indicated normal functioning and a higher number indicated a greater degree of depression. The total score ranged from 17 (normal) to 113 (severe depression). Four subscores were defined based on the CDRS-R: Mood: sum of items 8, 11, 14, 15; score range 4 to 28, Somatic: sum of items 4, 5, 6, 7, 16, 17; score range 6 to 36, Subjective: sum of items 9, 10, 12, 13; score range 4 to 28, and Behaviour: sum of items 1, 2, 3; score range 3 to 21. Higher scores indicated the most severe measure of depression. |
| Percentage of Participants With CDRS-R Response | Weeks 2, 4, 6, and 8 of Phase B | CDRS-R response was defined as a ≥50% decrease in CDRS-R total score, calculated as: (change from baseline \[Randomization\])/(baseline value - 17). The CDRS-R is a clinician-rated scale to measure the severity of depression in children and adolescents. The CDRS-R was rated by a clinician following interviews with the child and parent and consisted of 17 items out of which 3 items rated nonverbal observations (listless speech, hypoactivity, and depressed affect). Fourteen items were rated on a 7-point scale from 1 to 7, and 3 items (sleep disturbance, appetite disturbance, and listless speech) were scored on a 5-point scale from 1 to 5. A rating of 1 indicated normal functioning and a higher number indicated a greater degree of depression. The total score ranged from 17 (normal) to 113 (severe depression). |
| Percentage of Participants With CDRS-R Remission | Weeks 2, 4, 6, and 8 of Phase B | CDRS-R remission was defined as a CDRS-R total score ≤28. The CDRS-R is a clinician-rated scale to measure the severity of depression in children and adolescents. The CDRS-R was rated by a clinician following interviews with the child and parent and consisted of 17 items out of which 3 items rated nonverbal observations (listless speech, hypoactivity, and depressed affect). Fourteen items were rated on a 7-point scale from 1 to 7, and 3 items (sleep disturbance, appetite disturbance, and listless speech) were scored on a 5-point scale from 1 to 5. A rating of 1 indicated normal functioning and a higher number indicated a greater degree of depression. The total score ranged from 17 (normal) to 113 (severe depression). |
| Change From Baseline in General Behaviour Inventory (GBI) Depression Subscale Score, Using the 10-Item Depression Subscale Assessed by Parent (PGBI-10D) and Child (CGBI-10D) at Weeks 2, 4, 6, and 8 of Phase B | Baseline (Week 4 of Phase A), Weeks 2, 4, 6, and 8 of Phase B | The GBI 10-item depression scale was developed to screen for depressive symptoms in children and adolescents. Two versions of the GBI 10-item depression scale were used, the child rated version (CGBI) and the parent rated version (PGBI). The 10 depression items were rated on a 4-point scale from 0 (never or hardly ever) to 3 (very often or almost constantly). The total score ranged from 0 to 30, with higher scores indicating greater pathology. |
| Parent Global Assessment (PGA) Score | Weeks 2, 4, 6, and 8 of Phase B | The PGA is a parent-rated variation of the CGI-I to evaluate the severity of the child's symptoms. The PGA reflects assessments of symptoms using a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). |
| Change From Baseline in Clinical Global Impression - Severity of Illness (CGI-S) Score at Weeks 1, 2, 3, 4, 6, and 8 of Phase B | Baseline (Week 4 of Phase A), Weeks 1, 2, 3, 4, 6, and 8 of Phase B | The CGI-S provides the clinician's impression of the participant's current state of mental illness. The clinician uses his or her clinical experience of this participant population to rate the severity of the participant's current mental illness on a 7-point scale ranging from 1 (normal - not at all ill) to 7 (among the most extremely ill participants). |
| Clinical Global Impression - Global Improvement (CGI-I) Score | Weeks 1, 2, 3, 4, 6, and 8 of Phase B | The CGI-I provides the clinician's impression of the participant's improvement (or worsening). The clinician assesses the participant's condition relative to a baseline on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). |
| Percentage of Participants With CGI-S Remission | Weeks 1, 2, 3, 4, 6, and 8 of Phase B | CGI-S remission was defined as a CGI-S score of 1 or 2. The CGI-S provides the clinician's impression of the participant's current state of mental illness. The clinician uses his or her clinical experience of this participant population to rate the severity of the participant's current mental illness on a 7-point scale ranging from 1 (normal - not at all ill) to 7 (among the most extremely ill participants). |
| Change From Baseline in Children's Global Assessment Scale (CGAS) Score at Weeks 4 and 8 of Phase B | Baseline (Week 4 of Phase A), Weeks 4 and 8 of Phase B | The CGAS is a clinician-rated global scale to measure the lowest level of functioning for a child (4 to 16 years) during a specified time period. The CGAS contains behaviourally-oriented descriptors at each anchor point that depict behaviours and life situations applicable to a child. The score ranges from 1 (most functionally impaired child) to 100 (the healthiest). A score greater than 70 indicates normal function. |
| Change From Baseline in CDRS-R Total Score at Weeks 2, 4, and 6 of Phase B | Baseline (Week 4 of Phase A), Weeks 2, 4, and 6 of Phase B | The CDRS-R is a clinician-rated scale to measure the severity of depression in children and adolescents. The CDRS-R was rated by a clinician following interviews with the child and parent and consisted of 17 items out of which 3 items rated nonverbal observations (listless speech, hypoactivity, and depressed affect). Fourteen items were rated on a 7-point scale from 1 to 7, and 3 items (sleep disturbance, appetite disturbance, and listless speech) were scored on a 5-point scale from 1 to 5. A rating of 1 indicated normal functioning and a higher number indicated a greater degree of depression. The total score ranged from 17 (normal) to 113 (severe depression). |
| Change From Baseline in PedsQL VAS: Sad or Blue (Sadness) Score at Weeks 4 and 8 of Phase B | Baseline (Week 4 of Phase A), Weeks 4 and 8 of Phase B | The PedsQL™ VAS is designed to measure at-that-moment functioning in children and adolescents. The PedsQL VAS consists of 6 domains: anxiety, sadness, anger, worry, fatigue and pain using visual analogue scales. The functionality for each domain is measured on a 10 cm line with a happy face at one end and a sad face at the other (0-10 points). The participants are asked to mark on the line how they feel. A lower value represents a better outcome. |
| Change From Baseline in PedsQL VAS: Angry Score at Weeks 4 and 8 of Phase B | Baseline (Week 4 of Phase A), Weeks 4 and 8 of Phase B | The PedsQL™ VAS is designed to measure at-that-moment functioning in children and adolescents. The PedsQL VAS consists of 6 domains: anxiety, sadness, anger, worry, fatigue and pain using visual analogue scales. The functionality for each domain is measured on a 10 cm line with a happy face at one end and a sad face at the other (0-10 points). The participants are asked to mark on the line how they feel. A lower value represents a better outcome. |
| Change From Baseline in PedsQL VAS: Worry Score at Weeks 4 and 8 of Phase B | Baseline (Week 4 of Phase A), Weeks 4 and 8 of Phase B | The PedsQL™ VAS is designed to measure at-that-moment functioning in children and adolescents. The PedsQL VAS consists of 6 domains: anxiety, sadness, anger, worry, fatigue and pain using visual analogue scales. The functionality for each domain is measured on a 10 cm line with a happy face at one end and a sad face at the other (0-10 points). The participants are asked to mark on the line how they feel. A lower value represents a better outcome. |
| Change From Baseline in PedsQL VAS: Tired (Fatigue) Score at Weeks 4 and 8 of Phase B | Baseline (Week 4 of Phase A), Weeks 4 and 8 of Phase B | The PedsQL™ VAS is designed to measure at-that-moment functioning in children and adolescents. The PedsQL VAS consists of 6 domains: anxiety, sadness, anger, worry, fatigue and pain using visual analogue scales. The functionality for each domain is measured on a 10 cm line with a happy face at one end and a sad face at the other (0-10 points). The participants are asked to mark on the line how they feel. A lower value represents a better outcome. |
| Change From Baseline in PedsQL VAS: Pain or Hurt Score at Weeks 4 and 8 of Phase B | Baseline (Week 4 of Phase A), Weeks 4 and 8 of Phase B | The PedsQL™ VAS is designed to measure at-that-moment functioning in children and adolescents. The PedsQL VAS consists of 6 domains: anxiety, sadness, anger, worry, fatigue and pain using visual analogue scales. The functionality for each domain is measured on a 10 cm line with a happy face at one end and a sad face at the other (0-10 points). The participants are asked to mark on the line how they feel. A lower value represents a better outcome. |
| Change From Baseline in PedsQL VAS Total Average Score at Weeks 4 and 8 of Phase B | Baseline (Week 4 of Phase A), Weeks 4 and 8 of Phase B | The PedsQL™ VAS is designed to measure at-that-moment functioning in children and adolescents. The PedsQL™ VAS consists of 6 domains: anxiety, sadness, anger, worry, fatigue, and pain using visual analogue scales. The functionality for each domain is measured on a 10cm line with a happy face at one end and a sad face at the other (0-10 points). The participants are asked to mark on the line how they feel. The total score is the average of all 6 items. A lower value represents a better outcome. |
| Change From Baseline in PedsQL Emotional Distress Summary Average Score at Weeks 4 and 8 of Phase B | Baseline (Week 4 of Phase A), Weeks 4 and 8 of Phase B | The PedsQL™ VAS is designed to measure at-that-moment functioning in children and adolescents. The PedsQL VAS consists of 6 domains: anxiety, sadness, anger, worry, fatigue and pain using visual analogue scales. The functionality for each domain is measured on a 10 cm line with a happy face at one end and a sad face at the other (0-10 points). The participants are asked to mark on the line how they feel. The average emotional distress summary score is the mean of the anxiety, sadness, anger, and worry items. A lower value represents a better outcome. |
| Change From Baseline in Paediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q) Total Score (Items 1 to 14) at Weeks 4 and 8 of Phase B | Baseline (Week 4 of Phase A), Weeks 4 and 8 of Phase B | The PQ-LES-Q is a patient-rated scale designed to assess satisfaction with life. It is an adaptation of the Quality of Life Enjoyment and Satisfaction Questionnaire, which is used to measure quality of life in adults. The PQ-LES-Q consist of 15 items, item 1 to 14 assess the degree of satisfaction experienced by participants in various areas of daily functioning, and item 15 allows subjects to summarise their experience in a global rating. Each item is rated on a 5-point scale from 1 (very poor) to 5 (very good). The total score range of item 1 to 14 is 14 to 70, with higher scores indicating greater satisfaction. |
| Change From Baseline in PQ-LES-Q Overall Evaluation Score (Item 15) at Weeks 4 and 8 of Phase B | Baseline (Week 4 of Phase A), Weeks 4 and 8 of Phase B | The PQ-LES-Q is a patient-rated scale designed to assess satisfaction with life. It is an adaptation of the Quality of Life Enjoyment and Satisfaction Questionnaire, which is used to measure quality of life in adults. The PQ-LES-Q consist of 15 items, item 1 to 14 assess the degree of satisfaction experienced by participants in various areas of daily functioning, and item 15 allows subjects to summarize their experience in a global rating. Item 15 is rated on a 5-point scale from 1 (very poor) to 5 (very good). |
| Change From Baseline in Pediatric Quality of Life Inventory (PedsQL) Visual Analogue Scales (VAS): Afraid or Scared (Anxiety) Score at Weeks 4 and 8 of Phase B | Baseline (Week 4 of Phase A), Weeks 4 and 8 of Phase B | The PedsQL™ VAS is designed to measure at-that-moment functioning in children and adolescents. The PedsQL VAS consists of 6 domains: anxiety, sadness, anger, worry, fatigue and pain using visual analogue scales. The functionality for each domain is measured on a 10 cm line with a happy face at one end and a sad face at the other (0-10 points). The participants are asked to mark on the line how they feel. A lower value represents a better outcome. |
Countries
Bulgaria, Canada, Colombia, Estonia, France, Germany, Hungary, Israel, Italy, Latvia, Mexico, Poland, Russia, Serbia, South Africa, South Korea, Spain, Ukraine, United States
Participant flow
Recruitment details
This study included 2 periods: single-blind (SB) (treatment with standardized brief psychosocial intervention \[BPI\] and placebo) and double-blind (DB) (treatment with BPI and placebo, vortioxetine 10 milligrams \[mg\]/day, vortioxetine 20 mg/day, or fluoxetine 20 mg/day).
Pre-assignment details
Participants who demonstrated an incomplete improvement in depressive symptoms at the end of the SB period (Week 4) entered the DB period to receive BPI (2 sessions) and treatment as follows: Prior to the interim analysis, participants were randomized in a 1:1:1:1 ratio to placebo, vortioxetine 10 mg/day, vortioxetine 20 mg/day, or fluoxetine 20 mg/day. After interim analysis, participants were randomized in a 1:1:1 ratio to placebo, vortioxetine 10 mg/day, or vortioxetine 20 mg/day.
Participants by arm
| Arm | Count |
|---|---|
| Single-Blind: Placebo Participants received BPI (3 sessions) and placebo capsules orally once daily for 4 weeks. | 677 |
| Total | 677 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Double-Blind Phase (8 Weeks) | Adverse Event | 0 | 1 | 2 | 3 | 0 |
| Double-Blind Phase (8 Weeks) | Lack of Efficacy | 0 | 2 | 0 | 0 | 1 |
| Double-Blind Phase (8 Weeks) | Lost to Follow-up | 0 | 1 | 0 | 2 | 0 |
| Double-Blind Phase (8 Weeks) | Non-compliance with study drug | 0 | 1 | 3 | 6 | 1 |
| Double-Blind Phase (8 Weeks) | Other than specified | 0 | 5 | 7 | 5 | 2 |
| Double-Blind Phase (8 Weeks) | Protocol Violation | 0 | 1 | 0 | 0 | 0 |
| Double-Blind Phase (8 Weeks) | Withdrawal by Subject | 0 | 4 | 4 | 4 | 1 |
| Single-Blind Phase (4 Weeks) | Adverse Event | 2 | 0 | 0 | 0 | 0 |
| Single-Blind Phase (4 Weeks) | Enrolled but not treated | 6 | 0 | 0 | 0 | 0 |
| Single-Blind Phase (4 Weeks) | Failure to meet randomization criteria | 85 | 0 | 0 | 0 | 0 |
| Single-Blind Phase (4 Weeks) | Lack of Efficacy | 8 | 0 | 0 | 0 | 0 |
| Single-Blind Phase (4 Weeks) | Lost to Follow-up | 1 | 0 | 0 | 0 | 0 |
| Single-Blind Phase (4 Weeks) | Non-compliance with study drug | 3 | 0 | 0 | 0 | 0 |
| Single-Blind Phase (4 Weeks) | Other than specified | 20 | 0 | 0 | 0 | 0 |
| Single-Blind Phase (4 Weeks) | Protocol Violation | 3 | 0 | 0 | 0 | 0 |
| Single-Blind Phase (4 Weeks) | Withdrawal by Subject | 15 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Single-Blind: Placebo |
|---|---|
| Age, Continuous | 9.3 years STANDARD_DEVIATION 1.42 |
| Children Depression Rating Scale - Revised (CDRS-R) Total Score | 63.4 units on a scale STANDARD_DEVIATION 9.12 |
| Race/Ethnicity, Customized Race American Indian or Alaska Native | 1 Participants |
| Race/Ethnicity, Customized Race Asian | 2 Participants |
| Race/Ethnicity, Customized Race Black or African American | 112 Participants |
| Race/Ethnicity, Customized Race Not Reported | 12 Participants |
| Race/Ethnicity, Customized Race Other | 229 Participants |
| Race/Ethnicity, Customized Race White | 321 Participants |
| Sex: Female, Male Female | 312 Participants |
| Sex: Female, Male Male | 365 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 677 | 0 / 153 | 0 / 151 | 0 / 153 | 0 / 83 |
| other Total, other adverse events | 106 / 677 | 45 / 153 | 55 / 151 | 42 / 153 | 27 / 83 |
| serious Total, serious adverse events | 6 / 677 | 3 / 153 | 1 / 151 | 2 / 153 | 1 / 83 |
Outcome results
Primary
Change From Baseline in Children Depression Rating Scale - Revised (CDRS-R) Total Score at Week 8 of Phase B
The CDRS-R is a clinician-rated scale to measure the severity of depression in children and adolescents. The CDRS-R was rated by a clinician following interviews with the child and parent and consisted of 17 items out of which 3 items rated nonverbal observations (listless speech, hypoactivity, and depressed affect). Fourteen items were rated on a 7-point scale from 1 to 7, and 3 items (sleep disturbance, appetite disturbance, and listless speech) were scored on a 5-point scale from 1 to 5. A rating of 1 indicated normal functioning and a higher number indicated a greater degree of depression. The total score ranged from 17 (normal) to 113 (severe depression). Least square (LS) mean was estimated using a restricted maximum likelihood (REML)-based Mixed Model Repeated Measurements (MMRM) approach.
Time frame: Baseline (Week 4 of Phase A), Week 8 of Phase B
Population: Full analysis set (FAS) included all participants randomized to the double-blind, 8-week treatment period (Phase B) who took at least 1 dose of double-blind study drug and who had a valid baseline (Week 4 of Phase A) assessment and at least 1 valid post-baseline assessment of the CDRS-R total score. Overall number of participants analyzed = participants evaluated for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Double-Blind: Placebo | Change From Baseline in Children Depression Rating Scale - Revised (CDRS-R) Total Score at Week 8 of Phase B | -17.48 units on a scale | Standard Error 1.35 |
| Double-Blind: Vortioxetine 10 mg | Change From Baseline in Children Depression Rating Scale - Revised (CDRS-R) Total Score at Week 8 of Phase B | -19.20 units on a scale | Standard Error 1.37 |
| Double-Blind: Vortioxetine 20 mg | Change From Baseline in Children Depression Rating Scale - Revised (CDRS-R) Total Score at Week 8 of Phase B | -19.94 units on a scale | Standard Error 1.37 |
| Double-Blind: Fluoxetine 20 mg | Change From Baseline in Children Depression Rating Scale - Revised (CDRS-R) Total Score at Week 8 of Phase B | -20.78 units on a scale | Standard Error 1.6 |
| Vortioxetine Average (Avg. VOR) | Change From Baseline in Children Depression Rating Scale - Revised (CDRS-R) Total Score at Week 8 of Phase B | -19.57 units on a scale | Standard Error 1.16 |
Comparison: Analysis was performed using an REML-based MMRM approach with freely varying mean and covariance structure and with country, treatment (vortioxetine 10 mg/day, vortioxetine 20 mg/day, fluoxetine, and placebo), and Week as fixed factors and Baseline CDRS-R total score as a continuous covariate, the treatment-by-week interaction, and Baseline CDRS-R-by-Week interaction.p-value: 0.093795% CI: [-4.54, 0.36]Mixed Models Analysis
Comparison: Analysis was performed using an REML-based MMRM approach with freely varying mean and covariance structure and with country, treatment (vortioxetine 10 mg/day, vortioxetine 20 mg/day, fluoxetine, and placebo), and Week as fixed factors and Baseline CDRS-R total score as a continuous covariate, the treatment-by-week interaction, and Baseline CDRS-R-by-Week interaction.p-value: 0.233695% CI: [-4.56, 1.11]Mixed Models Analysis
Comparison: Analysis was performed using an REML-based MMRM approach with freely varying mean and covariance structure and with country, treatment (vortioxetine 10 mg/day, vortioxetine 20 mg/day, fluoxetine, and placebo), and Week as fixed factors and Baseline CDRS-R total score as a continuous covariate, the treatment-by-week interaction, and Baseline CDRS-R-by-Week interaction.p-value: 0.087995% CI: [-5.29, 0.37]Mixed Models Analysis
Comparison: Analysis was performed using an REML-based MMRM approach with freely varying mean and covariance structure and with country, treatment (vortioxetine 10 mg/day, vortioxetine 20 mg/day, fluoxetine, and placebo), and Week as fixed factors and Baseline CDRS-R total score as a continuous covariate, the treatment-by-week interaction, and Baseline CDRS-R-by-Week interaction.p-value: 0.053195% CI: [-6.65, 0.04]Mixed Models Analysis
Secondary
Change From Baseline in CDRS-R Subscores (Mood, Somatic, Subjective, and Behaviour) at Weeks 2, 4, 6, and 8 of Phase B
The CDRS-R was rated by a clinician following interviews with the child and parent and consisted of 17 items out of which 3 items rated nonverbal observations (listless speech, hypoactivity, and depressed affect). Fourteen items were rated on a 7-point scale from 1 to 7, and 3 items (sleep disturbance, appetite disturbance, and listless speech) were scored on a 5-point scale from 1 to 5. A rating of 1 indicated normal functioning and a higher number indicated a greater degree of depression. The total score ranged from 17 (normal) to 113 (severe depression). Four subscores were defined based on the CDRS-R: Mood: sum of items 8, 11, 14, 15; score range 4 to 28, Somatic: sum of items 4, 5, 6, 7, 16, 17; score range 6 to 36, Subjective: sum of items 9, 10, 12, 13; score range 4 to 28, and Behaviour: sum of items 1, 2, 3; score range 3 to 21. Higher scores indicated the most severe measure of depression.
Time frame: Baseline (Week 4 of Phase A), Weeks 2, 4, 6, and 8 of Phase B
Population: FAS included all participants randomized to the double-blind, 8-week treatment period (Phase B) who took at least 1 dose of double-blind study drug and who had a valid baseline (Week 4 of Phase A) assessment and at least 1 valid post-baseline assessment of the CDRS-R total score. Overall number of participants analyzed = participants evaluated for this outcome measure. Number analyzed = participants evaluable for specified categories.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind: Placebo | Change From Baseline in CDRS-R Subscores (Mood, Somatic, Subjective, and Behaviour) at Weeks 2, 4, 6, and 8 of Phase B | Somatic Score: Change at Week 2 | -2.81 units on a scale | Standard Error 0.44 |
| Double-Blind: Placebo | Change From Baseline in CDRS-R Subscores (Mood, Somatic, Subjective, and Behaviour) at Weeks 2, 4, 6, and 8 of Phase B | Mood Score: Change at Week 4 | -3.69 units on a scale | Standard Error 0.42 |
| Double-Blind: Placebo | Change From Baseline in CDRS-R Subscores (Mood, Somatic, Subjective, and Behaviour) at Weeks 2, 4, 6, and 8 of Phase B | Mood Score: Change at Week 6 | -4.67 units on a scale | Standard Error 0.43 |
| Double-Blind: Placebo | Change From Baseline in CDRS-R Subscores (Mood, Somatic, Subjective, and Behaviour) at Weeks 2, 4, 6, and 8 of Phase B | Mood Score: Change at Week 8 | -5.08 units on a scale | Standard Error 0.44 |
| Double-Blind: Placebo | Change From Baseline in CDRS-R Subscores (Mood, Somatic, Subjective, and Behaviour) at Weeks 2, 4, 6, and 8 of Phase B | Mood Score: Change at Week 2 | -2.82 units on a scale | Standard Error 0.4 |
| Double-Blind: Placebo | Change From Baseline in CDRS-R Subscores (Mood, Somatic, Subjective, and Behaviour) at Weeks 2, 4, 6, and 8 of Phase B | Somatic Score: Change at Week 4 | -4.08 units on a scale | Standard Error 0.47 |
| Double-Blind: Placebo | Change From Baseline in CDRS-R Subscores (Mood, Somatic, Subjective, and Behaviour) at Weeks 2, 4, 6, and 8 of Phase B | Somatic Score: Change at Week 6 | -4.86 units on a scale | Standard Error 0.48 |
| Double-Blind: Placebo | Change From Baseline in CDRS-R Subscores (Mood, Somatic, Subjective, and Behaviour) at Weeks 2, 4, 6, and 8 of Phase B | Somatic Score: Change at Week 8 | -5.38 units on a scale | Standard Error 0.49 |
| Double-Blind: Placebo | Change From Baseline in CDRS-R Subscores (Mood, Somatic, Subjective, and Behaviour) at Weeks 2, 4, 6, and 8 of Phase B | Subjective Score: Change at Week 2 | -1.44 units on a scale | Standard Error 0.22 |
| Double-Blind: Placebo | Change From Baseline in CDRS-R Subscores (Mood, Somatic, Subjective, and Behaviour) at Weeks 2, 4, 6, and 8 of Phase B | Subjective Score: Change at Week 4 | -2.04 units on a scale | Standard Error 0.23 |
| Double-Blind: Placebo | Change From Baseline in CDRS-R Subscores (Mood, Somatic, Subjective, and Behaviour) at Weeks 2, 4, 6, and 8 of Phase B | Subjective Score: Change at Week 6 | -2.43 units on a scale | Standard Error 0.24 |
| Double-Blind: Placebo | Change From Baseline in CDRS-R Subscores (Mood, Somatic, Subjective, and Behaviour) at Weeks 2, 4, 6, and 8 of Phase B | Subjective Score: Change at Week 8 | -2.56 units on a scale | Standard Error 0.24 |
| Double-Blind: Placebo | Change From Baseline in CDRS-R Subscores (Mood, Somatic, Subjective, and Behaviour) at Weeks 2, 4, 6, and 8 of Phase B | Behaviour Score: Change at Week 2 | -2.16 units on a scale | Standard Error 0.34 |
| Double-Blind: Placebo | Change From Baseline in CDRS-R Subscores (Mood, Somatic, Subjective, and Behaviour) at Weeks 2, 4, 6, and 8 of Phase B | Behaviour Score: Change at Week 4 | -3.39 units on a scale | Standard Error 0.38 |
| Double-Blind: Placebo | Change From Baseline in CDRS-R Subscores (Mood, Somatic, Subjective, and Behaviour) at Weeks 2, 4, 6, and 8 of Phase B | Behaviour Score: Change at Week 6 | -4.09 units on a scale | Standard Error 0.39 |
| Double-Blind: Placebo | Change From Baseline in CDRS-R Subscores (Mood, Somatic, Subjective, and Behaviour) at Weeks 2, 4, 6, and 8 of Phase B | Behaviour Score: Change at Week 8 | -4.47 units on a scale | Standard Error 0.4 |
| Double-Blind: Vortioxetine 10 mg | Change From Baseline in CDRS-R Subscores (Mood, Somatic, Subjective, and Behaviour) at Weeks 2, 4, 6, and 8 of Phase B | Somatic Score: Change at Week 4 | -4.30 units on a scale | Standard Error 0.48 |
| Double-Blind: Vortioxetine 10 mg | Change From Baseline in CDRS-R Subscores (Mood, Somatic, Subjective, and Behaviour) at Weeks 2, 4, 6, and 8 of Phase B | Subjective Score: Change at Week 2 | -1.46 units on a scale | Standard Error 0.22 |
| Double-Blind: Vortioxetine 10 mg | Change From Baseline in CDRS-R Subscores (Mood, Somatic, Subjective, and Behaviour) at Weeks 2, 4, 6, and 8 of Phase B | Behaviour Score: Change at Week 8 | -4.80 units on a scale | Standard Error 0.41 |
| Double-Blind: Vortioxetine 10 mg | Change From Baseline in CDRS-R Subscores (Mood, Somatic, Subjective, and Behaviour) at Weeks 2, 4, 6, and 8 of Phase B | Subjective Score: Change at Week 8 | -2.59 units on a scale | Standard Error 0.24 |
| Double-Blind: Vortioxetine 10 mg | Change From Baseline in CDRS-R Subscores (Mood, Somatic, Subjective, and Behaviour) at Weeks 2, 4, 6, and 8 of Phase B | Behaviour Score: Change at Week 6 | -4.31 units on a scale | Standard Error 0.39 |
| Double-Blind: Vortioxetine 10 mg | Change From Baseline in CDRS-R Subscores (Mood, Somatic, Subjective, and Behaviour) at Weeks 2, 4, 6, and 8 of Phase B | Subjective Score: Change at Week 4 | -2.12 units on a scale | Standard Error 0.23 |
| Double-Blind: Vortioxetine 10 mg | Change From Baseline in CDRS-R Subscores (Mood, Somatic, Subjective, and Behaviour) at Weeks 2, 4, 6, and 8 of Phase B | Mood Score: Change at Week 6 | -5.39 units on a scale | Standard Error 0.44 |
| Double-Blind: Vortioxetine 10 mg | Change From Baseline in CDRS-R Subscores (Mood, Somatic, Subjective, and Behaviour) at Weeks 2, 4, 6, and 8 of Phase B | Subjective Score: Change at Week 6 | -2.42 units on a scale | Standard Error 0.24 |
| Double-Blind: Vortioxetine 10 mg | Change From Baseline in CDRS-R Subscores (Mood, Somatic, Subjective, and Behaviour) at Weeks 2, 4, 6, and 8 of Phase B | Somatic Score: Change at Week 2 | -2.61 units on a scale | Standard Error 0.44 |
| Double-Blind: Vortioxetine 10 mg | Change From Baseline in CDRS-R Subscores (Mood, Somatic, Subjective, and Behaviour) at Weeks 2, 4, 6, and 8 of Phase B | Somatic Score: Change at Week 6 | -5.53 units on a scale | Standard Error 0.49 |
| Double-Blind: Vortioxetine 10 mg | Change From Baseline in CDRS-R Subscores (Mood, Somatic, Subjective, and Behaviour) at Weeks 2, 4, 6, and 8 of Phase B | Mood Score: Change at Week 8 | -5.64 units on a scale | Standard Error 0.44 |
| Double-Blind: Vortioxetine 10 mg | Change From Baseline in CDRS-R Subscores (Mood, Somatic, Subjective, and Behaviour) at Weeks 2, 4, 6, and 8 of Phase B | Mood Score: Change at Week 4 | -4.39 units on a scale | Standard Error 0.43 |
| Double-Blind: Vortioxetine 10 mg | Change From Baseline in CDRS-R Subscores (Mood, Somatic, Subjective, and Behaviour) at Weeks 2, 4, 6, and 8 of Phase B | Behaviour Score: Change at Week 2 | -2.40 units on a scale | Standard Error 0.34 |
| Double-Blind: Vortioxetine 10 mg | Change From Baseline in CDRS-R Subscores (Mood, Somatic, Subjective, and Behaviour) at Weeks 2, 4, 6, and 8 of Phase B | Somatic Score: Change at Week 8 | -6.15 units on a scale | Standard Error 0.5 |
| Double-Blind: Vortioxetine 10 mg | Change From Baseline in CDRS-R Subscores (Mood, Somatic, Subjective, and Behaviour) at Weeks 2, 4, 6, and 8 of Phase B | Behaviour Score: Change at Week 4 | -3.77 units on a scale | Standard Error 0.39 |
| Double-Blind: Vortioxetine 10 mg | Change From Baseline in CDRS-R Subscores (Mood, Somatic, Subjective, and Behaviour) at Weeks 2, 4, 6, and 8 of Phase B | Mood Score: Change at Week 2 | -3.10 units on a scale | Standard Error 0.4 |
| Double-Blind: Vortioxetine 20 mg | Change From Baseline in CDRS-R Subscores (Mood, Somatic, Subjective, and Behaviour) at Weeks 2, 4, 6, and 8 of Phase B | Somatic Score: Change at Week 4 | -4.70 units on a scale | Standard Error 0.48 |
| Double-Blind: Vortioxetine 20 mg | Change From Baseline in CDRS-R Subscores (Mood, Somatic, Subjective, and Behaviour) at Weeks 2, 4, 6, and 8 of Phase B | Somatic Score: Change at Week 2 | -2.88 units on a scale | Standard Error 0.44 |
| Double-Blind: Vortioxetine 20 mg | Change From Baseline in CDRS-R Subscores (Mood, Somatic, Subjective, and Behaviour) at Weeks 2, 4, 6, and 8 of Phase B | Behaviour Score: Change at Week 4 | -4.00 units on a scale | Standard Error 0.39 |
| Double-Blind: Vortioxetine 20 mg | Change From Baseline in CDRS-R Subscores (Mood, Somatic, Subjective, and Behaviour) at Weeks 2, 4, 6, and 8 of Phase B | Somatic Score: Change at Week 6 | -5.33 units on a scale | Standard Error 0.49 |
| Double-Blind: Vortioxetine 20 mg | Change From Baseline in CDRS-R Subscores (Mood, Somatic, Subjective, and Behaviour) at Weeks 2, 4, 6, and 8 of Phase B | Somatic Score: Change at Week 8 | -6.08 units on a scale | Standard Error 0.5 |
| Double-Blind: Vortioxetine 20 mg | Change From Baseline in CDRS-R Subscores (Mood, Somatic, Subjective, and Behaviour) at Weeks 2, 4, 6, and 8 of Phase B | Behaviour Score: Change at Week 8 | -5.09 units on a scale | Standard Error 0.41 |
| Double-Blind: Vortioxetine 20 mg | Change From Baseline in CDRS-R Subscores (Mood, Somatic, Subjective, and Behaviour) at Weeks 2, 4, 6, and 8 of Phase B | Subjective Score: Change at Week 2 | -1.43 units on a scale | Standard Error 0.22 |
| Double-Blind: Vortioxetine 20 mg | Change From Baseline in CDRS-R Subscores (Mood, Somatic, Subjective, and Behaviour) at Weeks 2, 4, 6, and 8 of Phase B | Subjective Score: Change at Week 4 | -2.20 units on a scale | Standard Error 0.23 |
| Double-Blind: Vortioxetine 20 mg | Change From Baseline in CDRS-R Subscores (Mood, Somatic, Subjective, and Behaviour) at Weeks 2, 4, 6, and 8 of Phase B | Behaviour Score: Change at Week 6 | -4.83 units on a scale | Standard Error 0.4 |
| Double-Blind: Vortioxetine 20 mg | Change From Baseline in CDRS-R Subscores (Mood, Somatic, Subjective, and Behaviour) at Weeks 2, 4, 6, and 8 of Phase B | Subjective Score: Change at Week 6 | -2.65 units on a scale | Standard Error 0.24 |
| Double-Blind: Vortioxetine 20 mg | Change From Baseline in CDRS-R Subscores (Mood, Somatic, Subjective, and Behaviour) at Weeks 2, 4, 6, and 8 of Phase B | Subjective Score: Change at Week 8 | -2.84 units on a scale | Standard Error 0.24 |
| Double-Blind: Vortioxetine 20 mg | Change From Baseline in CDRS-R Subscores (Mood, Somatic, Subjective, and Behaviour) at Weeks 2, 4, 6, and 8 of Phase B | Mood Score: Change at Week 2 | -3.47 units on a scale | Standard Error 0.4 |
| Double-Blind: Vortioxetine 20 mg | Change From Baseline in CDRS-R Subscores (Mood, Somatic, Subjective, and Behaviour) at Weeks 2, 4, 6, and 8 of Phase B | Mood Score: Change at Week 4 | -4.77 units on a scale | Standard Error 0.43 |
| Double-Blind: Vortioxetine 20 mg | Change From Baseline in CDRS-R Subscores (Mood, Somatic, Subjective, and Behaviour) at Weeks 2, 4, 6, and 8 of Phase B | Behaviour Score: Change at Week 2 | -2.56 units on a scale | Standard Error 0.35 |
| Double-Blind: Vortioxetine 20 mg | Change From Baseline in CDRS-R Subscores (Mood, Somatic, Subjective, and Behaviour) at Weeks 2, 4, 6, and 8 of Phase B | Mood Score: Change at Week 6 | -5.52 units on a scale | Standard Error 0.44 |
| Double-Blind: Vortioxetine 20 mg | Change From Baseline in CDRS-R Subscores (Mood, Somatic, Subjective, and Behaviour) at Weeks 2, 4, 6, and 8 of Phase B | Mood Score: Change at Week 8 | -5.95 units on a scale | Standard Error 0.45 |
| Double-Blind: Fluoxetine 20 mg | Change From Baseline in CDRS-R Subscores (Mood, Somatic, Subjective, and Behaviour) at Weeks 2, 4, 6, and 8 of Phase B | Behaviour Score: Change at Week 8 | -5.83 units on a scale | Standard Error 0.48 |
| Double-Blind: Fluoxetine 20 mg | Change From Baseline in CDRS-R Subscores (Mood, Somatic, Subjective, and Behaviour) at Weeks 2, 4, 6, and 8 of Phase B | Somatic Score: Change at Week 8 | -6.44 units on a scale | Standard Error 0.57 |
| Double-Blind: Fluoxetine 20 mg | Change From Baseline in CDRS-R Subscores (Mood, Somatic, Subjective, and Behaviour) at Weeks 2, 4, 6, and 8 of Phase B | Mood Score: Change at Week 6 | -4.97 units on a scale | Standard Error 0.51 |
| Double-Blind: Fluoxetine 20 mg | Change From Baseline in CDRS-R Subscores (Mood, Somatic, Subjective, and Behaviour) at Weeks 2, 4, 6, and 8 of Phase B | Mood Score: Change at Week 2 | -3.02 units on a scale | Standard Error 0.45 |
| Double-Blind: Fluoxetine 20 mg | Change From Baseline in CDRS-R Subscores (Mood, Somatic, Subjective, and Behaviour) at Weeks 2, 4, 6, and 8 of Phase B | Behaviour Score: Change at Week 4 | -3.80 units on a scale | Standard Error 0.45 |
| Double-Blind: Fluoxetine 20 mg | Change From Baseline in CDRS-R Subscores (Mood, Somatic, Subjective, and Behaviour) at Weeks 2, 4, 6, and 8 of Phase B | Somatic Score: Change at Week 6 | -5.57 units on a scale | Standard Error 0.57 |
| Double-Blind: Fluoxetine 20 mg | Change From Baseline in CDRS-R Subscores (Mood, Somatic, Subjective, and Behaviour) at Weeks 2, 4, 6, and 8 of Phase B | Behaviour Score: Change at Week 2 | -2.61 units on a scale | Standard Error 0.39 |
| Double-Blind: Fluoxetine 20 mg | Change From Baseline in CDRS-R Subscores (Mood, Somatic, Subjective, and Behaviour) at Weeks 2, 4, 6, and 8 of Phase B | Mood Score: Change at Week 4 | -3.73 units on a scale | Standard Error 0.49 |
| Double-Blind: Fluoxetine 20 mg | Change From Baseline in CDRS-R Subscores (Mood, Somatic, Subjective, and Behaviour) at Weeks 2, 4, 6, and 8 of Phase B | Somatic Score: Change at Week 2 | -3.02 units on a scale | Standard Error 0.5 |
| Double-Blind: Fluoxetine 20 mg | Change From Baseline in CDRS-R Subscores (Mood, Somatic, Subjective, and Behaviour) at Weeks 2, 4, 6, and 8 of Phase B | Subjective Score: Change at Week 4 | -2.17 units on a scale | Standard Error 0.27 |
| Double-Blind: Fluoxetine 20 mg | Change From Baseline in CDRS-R Subscores (Mood, Somatic, Subjective, and Behaviour) at Weeks 2, 4, 6, and 8 of Phase B | Somatic Score: Change at Week 4 | -4.26 units on a scale | Standard Error 0.56 |
| Double-Blind: Fluoxetine 20 mg | Change From Baseline in CDRS-R Subscores (Mood, Somatic, Subjective, and Behaviour) at Weeks 2, 4, 6, and 8 of Phase B | Subjective Score: Change at Week 6 | -2.38 units on a scale | Standard Error 0.28 |
| Double-Blind: Fluoxetine 20 mg | Change From Baseline in CDRS-R Subscores (Mood, Somatic, Subjective, and Behaviour) at Weeks 2, 4, 6, and 8 of Phase B | Behaviour Score: Change at Week 6 | -4.80 units on a scale | Standard Error 0.46 |
| Double-Blind: Fluoxetine 20 mg | Change From Baseline in CDRS-R Subscores (Mood, Somatic, Subjective, and Behaviour) at Weeks 2, 4, 6, and 8 of Phase B | Subjective Score: Change at Week 2 | -1.56 units on a scale | Standard Error 0.25 |
| Double-Blind: Fluoxetine 20 mg | Change From Baseline in CDRS-R Subscores (Mood, Somatic, Subjective, and Behaviour) at Weeks 2, 4, 6, and 8 of Phase B | Mood Score: Change at Week 8 | -5.84 units on a scale | Standard Error 0.51 |
| Double-Blind: Fluoxetine 20 mg | Change From Baseline in CDRS-R Subscores (Mood, Somatic, Subjective, and Behaviour) at Weeks 2, 4, 6, and 8 of Phase B | Subjective Score: Change at Week 8 | -2.65 units on a scale | Standard Error 0.28 |
Secondary
Change From Baseline in CDRS-R Total Score at Weeks 2, 4, and 6 of Phase B
The CDRS-R is a clinician-rated scale to measure the severity of depression in children and adolescents. The CDRS-R was rated by a clinician following interviews with the child and parent and consisted of 17 items out of which 3 items rated nonverbal observations (listless speech, hypoactivity, and depressed affect). Fourteen items were rated on a 7-point scale from 1 to 7, and 3 items (sleep disturbance, appetite disturbance, and listless speech) were scored on a 5-point scale from 1 to 5. A rating of 1 indicated normal functioning and a higher number indicated a greater degree of depression. The total score ranged from 17 (normal) to 113 (severe depression).
Time frame: Baseline (Week 4 of Phase A), Weeks 2, 4, and 6 of Phase B
Population: FAS included all participants randomized to the double-blind, 8-week treatment period (Phase B) who took at least 1 dose of double-blind study drug and who had a valid baseline (Week 4 of Phase A) assessment and at least 1 valid post-baseline assessment of the CDRS-R total score. Overall number of participants analyzed = participants evaluated for this outcome measure. Number analyzed = participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind: Placebo | Change From Baseline in CDRS-R Total Score at Weeks 2, 4, and 6 of Phase B | Change at Week 2 | -9.20 units on a scale | Standard Error 1.17 |
| Double-Blind: Placebo | Change From Baseline in CDRS-R Total Score at Weeks 2, 4, and 6 of Phase B | Change at Week 6 | -16.00 units on a scale | Standard Error 1.32 |
| Double-Blind: Placebo | Change From Baseline in CDRS-R Total Score at Weeks 2, 4, and 6 of Phase B | Change at Week 4 | -13.15 units on a scale | Standard Error 1.28 |
| Double-Blind: Vortioxetine 10 mg | Change From Baseline in CDRS-R Total Score at Weeks 2, 4, and 6 of Phase B | Change at Week 2 | -9.54 units on a scale | Standard Error 1.18 |
| Double-Blind: Vortioxetine 10 mg | Change From Baseline in CDRS-R Total Score at Weeks 2, 4, and 6 of Phase B | Change at Week 6 | -17.64 units on a scale | Standard Error 1.34 |
| Double-Blind: Vortioxetine 10 mg | Change From Baseline in CDRS-R Total Score at Weeks 2, 4, and 6 of Phase B | Change at Week 4 | -14.56 units on a scale | Standard Error 1.3 |
| Double-Blind: Vortioxetine 20 mg | Change From Baseline in CDRS-R Total Score at Weeks 2, 4, and 6 of Phase B | Change at Week 4 | -15.62 units on a scale | Standard Error 1.3 |
| Double-Blind: Vortioxetine 20 mg | Change From Baseline in CDRS-R Total Score at Weeks 2, 4, and 6 of Phase B | Change at Week 2 | -10.30 units on a scale | Standard Error 1.19 |
| Double-Blind: Vortioxetine 20 mg | Change From Baseline in CDRS-R Total Score at Weeks 2, 4, and 6 of Phase B | Change at Week 6 | -18.28 units on a scale | Standard Error 1.34 |
| Double-Blind: Fluoxetine 20 mg | Change From Baseline in CDRS-R Total Score at Weeks 2, 4, and 6 of Phase B | Change at Week 2 | -10.17 units on a scale | Standard Error 1.32 |
| Double-Blind: Fluoxetine 20 mg | Change From Baseline in CDRS-R Total Score at Weeks 2, 4, and 6 of Phase B | Change at Week 6 | -17.75 units on a scale | Standard Error 1.56 |
| Double-Blind: Fluoxetine 20 mg | Change From Baseline in CDRS-R Total Score at Weeks 2, 4, and 6 of Phase B | Change at Week 4 | -13.97 units on a scale | Standard Error 1.5 |
Secondary
Change From Baseline in Children's Global Assessment Scale (CGAS) Score at Weeks 4 and 8 of Phase B
The CGAS is a clinician-rated global scale to measure the lowest level of functioning for a child (4 to 16 years) during a specified time period. The CGAS contains behaviourally-oriented descriptors at each anchor point that depict behaviours and life situations applicable to a child. The score ranges from 1 (most functionally impaired child) to 100 (the healthiest). A score greater than 70 indicates normal function.
Time frame: Baseline (Week 4 of Phase A), Weeks 4 and 8 of Phase B
Population: FAS included all participants randomized to the double-blind, 8-week treatment period (Phase B) who took at least 1 dose of double-blind study drug and who had a valid baseline (Week 4 of Phase A) assessment and at least 1 valid post-baseline assessment of the CDRS-R total score. Overall number of participants analyzed = participants evaluated for this outcome measure. Number analyzed = participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind: Placebo | Change From Baseline in Children's Global Assessment Scale (CGAS) Score at Weeks 4 and 8 of Phase B | Change at Week 4 | 8.93 units on a scale | Standard Error 1.23 |
| Double-Blind: Placebo | Change From Baseline in Children's Global Assessment Scale (CGAS) Score at Weeks 4 and 8 of Phase B | Change at Week 8 | 12.71 units on a scale | Standard Error 1.31 |
| Double-Blind: Vortioxetine 10 mg | Change From Baseline in Children's Global Assessment Scale (CGAS) Score at Weeks 4 and 8 of Phase B | Change at Week 8 | 12.98 units on a scale | Standard Error 1.33 |
| Double-Blind: Vortioxetine 10 mg | Change From Baseline in Children's Global Assessment Scale (CGAS) Score at Weeks 4 and 8 of Phase B | Change at Week 4 | 9.84 units on a scale | Standard Error 1.25 |
| Double-Blind: Vortioxetine 20 mg | Change From Baseline in Children's Global Assessment Scale (CGAS) Score at Weeks 4 and 8 of Phase B | Change at Week 4 | 8.73 units on a scale | Standard Error 1.26 |
| Double-Blind: Vortioxetine 20 mg | Change From Baseline in Children's Global Assessment Scale (CGAS) Score at Weeks 4 and 8 of Phase B | Change at Week 8 | 13.22 units on a scale | Standard Error 1.34 |
| Double-Blind: Fluoxetine 20 mg | Change From Baseline in Children's Global Assessment Scale (CGAS) Score at Weeks 4 and 8 of Phase B | Change at Week 4 | 10.54 units on a scale | Standard Error 1.39 |
| Double-Blind: Fluoxetine 20 mg | Change From Baseline in Children's Global Assessment Scale (CGAS) Score at Weeks 4 and 8 of Phase B | Change at Week 8 | 16.35 units on a scale | Standard Error 1.51 |
Secondary
Change From Baseline in Clinical Global Impression - Severity of Illness (CGI-S) Score at Weeks 1, 2, 3, 4, 6, and 8 of Phase B
The CGI-S provides the clinician's impression of the participant's current state of mental illness. The clinician uses his or her clinical experience of this participant population to rate the severity of the participant's current mental illness on a 7-point scale ranging from 1 (normal - not at all ill) to 7 (among the most extremely ill participants).
Time frame: Baseline (Week 4 of Phase A), Weeks 1, 2, 3, 4, 6, and 8 of Phase B
Population: FAS included all participants randomized to the double-blind, 8-week treatment period (Phase B) who took at least 1 dose of double-blind study drug and who had a valid baseline (Week 4 of Phase A) assessment and at least 1 valid post-baseline assessment of the CDRS-R total score. Overall number of participants analyzed = participants evaluated for this outcome measure. Number analyzed = participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind: Placebo | Change From Baseline in Clinical Global Impression - Severity of Illness (CGI-S) Score at Weeks 1, 2, 3, 4, 6, and 8 of Phase B | Change at Week 1 | -0.25 units on a scale | Standard Error 0.07 |
| Double-Blind: Placebo | Change From Baseline in Clinical Global Impression - Severity of Illness (CGI-S) Score at Weeks 1, 2, 3, 4, 6, and 8 of Phase B | Change at Week 2 | -0.50 units on a scale | Standard Error 0.08 |
| Double-Blind: Placebo | Change From Baseline in Clinical Global Impression - Severity of Illness (CGI-S) Score at Weeks 1, 2, 3, 4, 6, and 8 of Phase B | Change at Week 3 | -0.67 units on a scale | Standard Error 0.08 |
| Double-Blind: Placebo | Change From Baseline in Clinical Global Impression - Severity of Illness (CGI-S) Score at Weeks 1, 2, 3, 4, 6, and 8 of Phase B | Change at Week 4 | -0.95 units on a scale | Standard Error 0.09 |
| Double-Blind: Placebo | Change From Baseline in Clinical Global Impression - Severity of Illness (CGI-S) Score at Weeks 1, 2, 3, 4, 6, and 8 of Phase B | Change at Week 6 | -1.13 units on a scale | Standard Error 0.1 |
| Double-Blind: Placebo | Change From Baseline in Clinical Global Impression - Severity of Illness (CGI-S) Score at Weeks 1, 2, 3, 4, 6, and 8 of Phase B | Change at Week 8 | -1.31 units on a scale | Standard Error 0.1 |
| Double-Blind: Vortioxetine 10 mg | Change From Baseline in Clinical Global Impression - Severity of Illness (CGI-S) Score at Weeks 1, 2, 3, 4, 6, and 8 of Phase B | Change at Week 8 | -1.40 units on a scale | Standard Error 0.11 |
| Double-Blind: Vortioxetine 10 mg | Change From Baseline in Clinical Global Impression - Severity of Illness (CGI-S) Score at Weeks 1, 2, 3, 4, 6, and 8 of Phase B | Change at Week 4 | -1.00 units on a scale | Standard Error 0.09 |
| Double-Blind: Vortioxetine 10 mg | Change From Baseline in Clinical Global Impression - Severity of Illness (CGI-S) Score at Weeks 1, 2, 3, 4, 6, and 8 of Phase B | Change at Week 1 | -0.27 units on a scale | Standard Error 0.07 |
| Double-Blind: Vortioxetine 10 mg | Change From Baseline in Clinical Global Impression - Severity of Illness (CGI-S) Score at Weeks 1, 2, 3, 4, 6, and 8 of Phase B | Change at Week 3 | -0.62 units on a scale | Standard Error 0.08 |
| Double-Blind: Vortioxetine 10 mg | Change From Baseline in Clinical Global Impression - Severity of Illness (CGI-S) Score at Weeks 1, 2, 3, 4, 6, and 8 of Phase B | Change at Week 2 | -0.60 units on a scale | Standard Error 0.08 |
| Double-Blind: Vortioxetine 10 mg | Change From Baseline in Clinical Global Impression - Severity of Illness (CGI-S) Score at Weeks 1, 2, 3, 4, 6, and 8 of Phase B | Change at Week 6 | -1.22 units on a scale | Standard Error 0.1 |
| Double-Blind: Vortioxetine 20 mg | Change From Baseline in Clinical Global Impression - Severity of Illness (CGI-S) Score at Weeks 1, 2, 3, 4, 6, and 8 of Phase B | Change at Week 2 | -0.65 units on a scale | Standard Error 0.08 |
| Double-Blind: Vortioxetine 20 mg | Change From Baseline in Clinical Global Impression - Severity of Illness (CGI-S) Score at Weeks 1, 2, 3, 4, 6, and 8 of Phase B | Change at Week 3 | -0.79 units on a scale | Standard Error 0.08 |
| Double-Blind: Vortioxetine 20 mg | Change From Baseline in Clinical Global Impression - Severity of Illness (CGI-S) Score at Weeks 1, 2, 3, 4, 6, and 8 of Phase B | Change at Week 4 | -1.06 units on a scale | Standard Error 0.09 |
| Double-Blind: Vortioxetine 20 mg | Change From Baseline in Clinical Global Impression - Severity of Illness (CGI-S) Score at Weeks 1, 2, 3, 4, 6, and 8 of Phase B | Change at Week 8 | -1.44 units on a scale | Standard Error 0.11 |
| Double-Blind: Vortioxetine 20 mg | Change From Baseline in Clinical Global Impression - Severity of Illness (CGI-S) Score at Weeks 1, 2, 3, 4, 6, and 8 of Phase B | Change at Week 6 | -1.27 units on a scale | Standard Error 0.1 |
| Double-Blind: Vortioxetine 20 mg | Change From Baseline in Clinical Global Impression - Severity of Illness (CGI-S) Score at Weeks 1, 2, 3, 4, 6, and 8 of Phase B | Change at Week 1 | -0.28 units on a scale | Standard Error 0.07 |
| Double-Blind: Fluoxetine 20 mg | Change From Baseline in Clinical Global Impression - Severity of Illness (CGI-S) Score at Weeks 1, 2, 3, 4, 6, and 8 of Phase B | Change at Week 6 | -1.23 units on a scale | Standard Error 0.12 |
| Double-Blind: Fluoxetine 20 mg | Change From Baseline in Clinical Global Impression - Severity of Illness (CGI-S) Score at Weeks 1, 2, 3, 4, 6, and 8 of Phase B | Change at Week 8 | -1.57 units on a scale | Standard Error 0.13 |
| Double-Blind: Fluoxetine 20 mg | Change From Baseline in Clinical Global Impression - Severity of Illness (CGI-S) Score at Weeks 1, 2, 3, 4, 6, and 8 of Phase B | Change at Week 2 | -0.63 units on a scale | Standard Error 0.1 |
| Double-Blind: Fluoxetine 20 mg | Change From Baseline in Clinical Global Impression - Severity of Illness (CGI-S) Score at Weeks 1, 2, 3, 4, 6, and 8 of Phase B | Change at Week 4 | -1.01 units on a scale | Standard Error 0.12 |
| Double-Blind: Fluoxetine 20 mg | Change From Baseline in Clinical Global Impression - Severity of Illness (CGI-S) Score at Weeks 1, 2, 3, 4, 6, and 8 of Phase B | Change at Week 1 | -0.22 units on a scale | Standard Error 0.08 |
| Double-Blind: Fluoxetine 20 mg | Change From Baseline in Clinical Global Impression - Severity of Illness (CGI-S) Score at Weeks 1, 2, 3, 4, 6, and 8 of Phase B | Change at Week 3 | -0.77 units on a scale | Standard Error 0.1 |
Secondary
Change From Baseline in General Behaviour Inventory (GBI) Depression Subscale Score, Using the 10-Item Depression Subscale Assessed by Parent (PGBI-10D) and Child (CGBI-10D) at Weeks 2, 4, 6, and 8 of Phase B
The GBI 10-item depression scale was developed to screen for depressive symptoms in children and adolescents. Two versions of the GBI 10-item depression scale were used, the child rated version (CGBI) and the parent rated version (PGBI). The 10 depression items were rated on a 4-point scale from 0 (never or hardly ever) to 3 (very often or almost constantly). The total score ranged from 0 to 30, with higher scores indicating greater pathology.
Time frame: Baseline (Week 4 of Phase A), Weeks 2, 4, 6, and 8 of Phase B
Population: FAS included all participants randomized to the double-blind, 8-week treatment period (Phase B) who took at least 1 dose of double-blind study drug and who had a valid baseline (Week 4 of Phase A) assessment and at least 1 valid post-baseline assessment of the CDRS-R total score. Overall number of participants analyzed = participants evaluated for this outcome measure. Number analyzed = participants evaluable for specified categories.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind: Placebo | Change From Baseline in General Behaviour Inventory (GBI) Depression Subscale Score, Using the 10-Item Depression Subscale Assessed by Parent (PGBI-10D) and Child (CGBI-10D) at Weeks 2, 4, 6, and 8 of Phase B | PGBI: Change at Week 2 | -3.33 units on a scale | Standard Error 0.55 |
| Double-Blind: Placebo | Change From Baseline in General Behaviour Inventory (GBI) Depression Subscale Score, Using the 10-Item Depression Subscale Assessed by Parent (PGBI-10D) and Child (CGBI-10D) at Weeks 2, 4, 6, and 8 of Phase B | PGBI: Change at Week 4 | -4.11 units on a scale | Standard Error 0.58 |
| Double-Blind: Placebo | Change From Baseline in General Behaviour Inventory (GBI) Depression Subscale Score, Using the 10-Item Depression Subscale Assessed by Parent (PGBI-10D) and Child (CGBI-10D) at Weeks 2, 4, 6, and 8 of Phase B | PGBI: Change at Week 6 | -5.32 units on a scale | Standard Error 0.58 |
| Double-Blind: Placebo | Change From Baseline in General Behaviour Inventory (GBI) Depression Subscale Score, Using the 10-Item Depression Subscale Assessed by Parent (PGBI-10D) and Child (CGBI-10D) at Weeks 2, 4, 6, and 8 of Phase B | PGBI: Change at Week 8 | -5.81 units on a scale | Standard Error 0.61 |
| Double-Blind: Placebo | Change From Baseline in General Behaviour Inventory (GBI) Depression Subscale Score, Using the 10-Item Depression Subscale Assessed by Parent (PGBI-10D) and Child (CGBI-10D) at Weeks 2, 4, 6, and 8 of Phase B | CGBI: Change at Week 2 | -2.66 units on a scale | Standard Error 0.61 |
| Double-Blind: Placebo | Change From Baseline in General Behaviour Inventory (GBI) Depression Subscale Score, Using the 10-Item Depression Subscale Assessed by Parent (PGBI-10D) and Child (CGBI-10D) at Weeks 2, 4, 6, and 8 of Phase B | CGBI: Change at Week 4 | -3.65 units on a scale | Standard Error 0.65 |
| Double-Blind: Placebo | Change From Baseline in General Behaviour Inventory (GBI) Depression Subscale Score, Using the 10-Item Depression Subscale Assessed by Parent (PGBI-10D) and Child (CGBI-10D) at Weeks 2, 4, 6, and 8 of Phase B | CGBI: Change at Week 6 | -4.62 units on a scale | Standard Error 0.63 |
| Double-Blind: Placebo | Change From Baseline in General Behaviour Inventory (GBI) Depression Subscale Score, Using the 10-Item Depression Subscale Assessed by Parent (PGBI-10D) and Child (CGBI-10D) at Weeks 2, 4, 6, and 8 of Phase B | CGBI: Change at Week 8 | -5.26 units on a scale | Standard Error 0.65 |
| Double-Blind: Vortioxetine 10 mg | Change From Baseline in General Behaviour Inventory (GBI) Depression Subscale Score, Using the 10-Item Depression Subscale Assessed by Parent (PGBI-10D) and Child (CGBI-10D) at Weeks 2, 4, 6, and 8 of Phase B | CGBI: Change at Week 4 | -4.15 units on a scale | Standard Error 0.65 |
| Double-Blind: Vortioxetine 10 mg | Change From Baseline in General Behaviour Inventory (GBI) Depression Subscale Score, Using the 10-Item Depression Subscale Assessed by Parent (PGBI-10D) and Child (CGBI-10D) at Weeks 2, 4, 6, and 8 of Phase B | CGBI: Change at Week 2 | -3.32 units on a scale | Standard Error 0.61 |
| Double-Blind: Vortioxetine 10 mg | Change From Baseline in General Behaviour Inventory (GBI) Depression Subscale Score, Using the 10-Item Depression Subscale Assessed by Parent (PGBI-10D) and Child (CGBI-10D) at Weeks 2, 4, 6, and 8 of Phase B | PGBI: Change at Week 4 | -4.72 units on a scale | Standard Error 0.59 |
| Double-Blind: Vortioxetine 10 mg | Change From Baseline in General Behaviour Inventory (GBI) Depression Subscale Score, Using the 10-Item Depression Subscale Assessed by Parent (PGBI-10D) and Child (CGBI-10D) at Weeks 2, 4, 6, and 8 of Phase B | CGBI: Change at Week 8 | -6.12 units on a scale | Standard Error 0.66 |
| Double-Blind: Vortioxetine 10 mg | Change From Baseline in General Behaviour Inventory (GBI) Depression Subscale Score, Using the 10-Item Depression Subscale Assessed by Parent (PGBI-10D) and Child (CGBI-10D) at Weeks 2, 4, 6, and 8 of Phase B | CGBI: Change at Week 6 | -5.43 units on a scale | Standard Error 0.64 |
| Double-Blind: Vortioxetine 10 mg | Change From Baseline in General Behaviour Inventory (GBI) Depression Subscale Score, Using the 10-Item Depression Subscale Assessed by Parent (PGBI-10D) and Child (CGBI-10D) at Weeks 2, 4, 6, and 8 of Phase B | PGBI: Change at Week 8 | -6.51 units on a scale | Standard Error 0.62 |
| Double-Blind: Vortioxetine 10 mg | Change From Baseline in General Behaviour Inventory (GBI) Depression Subscale Score, Using the 10-Item Depression Subscale Assessed by Parent (PGBI-10D) and Child (CGBI-10D) at Weeks 2, 4, 6, and 8 of Phase B | PGBI: Change at Week 6 | -5.58 units on a scale | Standard Error 0.59 |
| Double-Blind: Vortioxetine 10 mg | Change From Baseline in General Behaviour Inventory (GBI) Depression Subscale Score, Using the 10-Item Depression Subscale Assessed by Parent (PGBI-10D) and Child (CGBI-10D) at Weeks 2, 4, 6, and 8 of Phase B | PGBI: Change at Week 2 | -3.38 units on a scale | Standard Error 0.55 |
| Double-Blind: Vortioxetine 20 mg | Change From Baseline in General Behaviour Inventory (GBI) Depression Subscale Score, Using the 10-Item Depression Subscale Assessed by Parent (PGBI-10D) and Child (CGBI-10D) at Weeks 2, 4, 6, and 8 of Phase B | CGBI: Change at Week 6 | -5.17 units on a scale | Standard Error 0.63 |
| Double-Blind: Vortioxetine 20 mg | Change From Baseline in General Behaviour Inventory (GBI) Depression Subscale Score, Using the 10-Item Depression Subscale Assessed by Parent (PGBI-10D) and Child (CGBI-10D) at Weeks 2, 4, 6, and 8 of Phase B | PGBI: Change at Week 6 | -5.82 units on a scale | Standard Error 0.59 |
| Double-Blind: Vortioxetine 20 mg | Change From Baseline in General Behaviour Inventory (GBI) Depression Subscale Score, Using the 10-Item Depression Subscale Assessed by Parent (PGBI-10D) and Child (CGBI-10D) at Weeks 2, 4, 6, and 8 of Phase B | PGBI: Change at Week 8 | -6.46 units on a scale | Standard Error 0.62 |
| Double-Blind: Vortioxetine 20 mg | Change From Baseline in General Behaviour Inventory (GBI) Depression Subscale Score, Using the 10-Item Depression Subscale Assessed by Parent (PGBI-10D) and Child (CGBI-10D) at Weeks 2, 4, 6, and 8 of Phase B | CGBI: Change at Week 2 | -3.27 units on a scale | Standard Error 0.61 |
| Double-Blind: Vortioxetine 20 mg | Change From Baseline in General Behaviour Inventory (GBI) Depression Subscale Score, Using the 10-Item Depression Subscale Assessed by Parent (PGBI-10D) and Child (CGBI-10D) at Weeks 2, 4, 6, and 8 of Phase B | CGBI: Change at Week 4 | -4.16 units on a scale | Standard Error 0.65 |
| Double-Blind: Vortioxetine 20 mg | Change From Baseline in General Behaviour Inventory (GBI) Depression Subscale Score, Using the 10-Item Depression Subscale Assessed by Parent (PGBI-10D) and Child (CGBI-10D) at Weeks 2, 4, 6, and 8 of Phase B | CGBI: Change at Week 8 | -5.48 units on a scale | Standard Error 0.65 |
| Double-Blind: Vortioxetine 20 mg | Change From Baseline in General Behaviour Inventory (GBI) Depression Subscale Score, Using the 10-Item Depression Subscale Assessed by Parent (PGBI-10D) and Child (CGBI-10D) at Weeks 2, 4, 6, and 8 of Phase B | PGBI: Change at Week 2 | -3.78 units on a scale | Standard Error 0.56 |
| Double-Blind: Vortioxetine 20 mg | Change From Baseline in General Behaviour Inventory (GBI) Depression Subscale Score, Using the 10-Item Depression Subscale Assessed by Parent (PGBI-10D) and Child (CGBI-10D) at Weeks 2, 4, 6, and 8 of Phase B | PGBI: Change at Week 4 | -5.33 units on a scale | Standard Error 0.59 |
| Double-Blind: Fluoxetine 20 mg | Change From Baseline in General Behaviour Inventory (GBI) Depression Subscale Score, Using the 10-Item Depression Subscale Assessed by Parent (PGBI-10D) and Child (CGBI-10D) at Weeks 2, 4, 6, and 8 of Phase B | PGBI: Change at Week 6 | -6.05 units on a scale | Standard Error 0.68 |
| Double-Blind: Fluoxetine 20 mg | Change From Baseline in General Behaviour Inventory (GBI) Depression Subscale Score, Using the 10-Item Depression Subscale Assessed by Parent (PGBI-10D) and Child (CGBI-10D) at Weeks 2, 4, 6, and 8 of Phase B | PGBI: Change at Week 8 | -6.56 units on a scale | Standard Error 0.72 |
| Double-Blind: Fluoxetine 20 mg | Change From Baseline in General Behaviour Inventory (GBI) Depression Subscale Score, Using the 10-Item Depression Subscale Assessed by Parent (PGBI-10D) and Child (CGBI-10D) at Weeks 2, 4, 6, and 8 of Phase B | PGBI: Change at Week 4 | -4.45 units on a scale | Standard Error 0.68 |
| Double-Blind: Fluoxetine 20 mg | Change From Baseline in General Behaviour Inventory (GBI) Depression Subscale Score, Using the 10-Item Depression Subscale Assessed by Parent (PGBI-10D) and Child (CGBI-10D) at Weeks 2, 4, 6, and 8 of Phase B | PGBI: Change at Week 2 | -3.78 units on a scale | Standard Error 0.63 |
| Double-Blind: Fluoxetine 20 mg | Change From Baseline in General Behaviour Inventory (GBI) Depression Subscale Score, Using the 10-Item Depression Subscale Assessed by Parent (PGBI-10D) and Child (CGBI-10D) at Weeks 2, 4, 6, and 8 of Phase B | CGBI: Change at Week 2 | -2.94 units on a scale | Standard Error 0.7 |
| Double-Blind: Fluoxetine 20 mg | Change From Baseline in General Behaviour Inventory (GBI) Depression Subscale Score, Using the 10-Item Depression Subscale Assessed by Parent (PGBI-10D) and Child (CGBI-10D) at Weeks 2, 4, 6, and 8 of Phase B | CGBI: Change at Week 8 | -5.46 units on a scale | Standard Error 0.76 |
| Double-Blind: Fluoxetine 20 mg | Change From Baseline in General Behaviour Inventory (GBI) Depression Subscale Score, Using the 10-Item Depression Subscale Assessed by Parent (PGBI-10D) and Child (CGBI-10D) at Weeks 2, 4, 6, and 8 of Phase B | CGBI: Change at Week 6 | -5.14 units on a scale | Standard Error 0.73 |
| Double-Blind: Fluoxetine 20 mg | Change From Baseline in General Behaviour Inventory (GBI) Depression Subscale Score, Using the 10-Item Depression Subscale Assessed by Parent (PGBI-10D) and Child (CGBI-10D) at Weeks 2, 4, 6, and 8 of Phase B | CGBI: Change at Week 4 | -3.16 units on a scale | Standard Error 0.76 |
Secondary
Change From Baseline in Paediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q) Total Score (Items 1 to 14) at Weeks 4 and 8 of Phase B
The PQ-LES-Q is a patient-rated scale designed to assess satisfaction with life. It is an adaptation of the Quality of Life Enjoyment and Satisfaction Questionnaire, which is used to measure quality of life in adults. The PQ-LES-Q consist of 15 items, item 1 to 14 assess the degree of satisfaction experienced by participants in various areas of daily functioning, and item 15 allows subjects to summarise their experience in a global rating. Each item is rated on a 5-point scale from 1 (very poor) to 5 (very good). The total score range of item 1 to 14 is 14 to 70, with higher scores indicating greater satisfaction.
Time frame: Baseline (Week 4 of Phase A), Weeks 4 and 8 of Phase B
Population: FAS included all participants randomized to the double-blind, 8-week treatment period (Phase B) who took at least 1 dose of double-blind study drug and who had a valid baseline (Week 4 of Phase A) assessment and at least 1 valid post-baseline assessment of the CDRS-R total score. Overall number of participants analyzed = participants evaluated for this outcome measure. Number analyzed = participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind: Placebo | Change From Baseline in Paediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q) Total Score (Items 1 to 14) at Weeks 4 and 8 of Phase B | Change at Week 4 | 3.94 units on a scale | Standard Error 0.95 |
| Double-Blind: Placebo | Change From Baseline in Paediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q) Total Score (Items 1 to 14) at Weeks 4 and 8 of Phase B | Change at Week 8 | 6.22 units on a scale | Standard Error 0.98 |
| Double-Blind: Vortioxetine 10 mg | Change From Baseline in Paediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q) Total Score (Items 1 to 14) at Weeks 4 and 8 of Phase B | Change at Week 8 | 7.08 units on a scale | Standard Error 0.99 |
| Double-Blind: Vortioxetine 10 mg | Change From Baseline in Paediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q) Total Score (Items 1 to 14) at Weeks 4 and 8 of Phase B | Change at Week 4 | 4.90 units on a scale | Standard Error 0.96 |
| Double-Blind: Vortioxetine 20 mg | Change From Baseline in Paediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q) Total Score (Items 1 to 14) at Weeks 4 and 8 of Phase B | Change at Week 4 | 4.90 units on a scale | Standard Error 0.97 |
| Double-Blind: Vortioxetine 20 mg | Change From Baseline in Paediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q) Total Score (Items 1 to 14) at Weeks 4 and 8 of Phase B | Change at Week 8 | 7.14 units on a scale | Standard Error 1 |
| Double-Blind: Fluoxetine 20 mg | Change From Baseline in Paediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q) Total Score (Items 1 to 14) at Weeks 4 and 8 of Phase B | Change at Week 4 | 4.36 units on a scale | Standard Error 1.09 |
| Double-Blind: Fluoxetine 20 mg | Change From Baseline in Paediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q) Total Score (Items 1 to 14) at Weeks 4 and 8 of Phase B | Change at Week 8 | 6.79 units on a scale | Standard Error 1.12 |
Secondary
Change From Baseline in Pediatric Quality of Life Inventory (PedsQL) Visual Analogue Scales (VAS): Afraid or Scared (Anxiety) Score at Weeks 4 and 8 of Phase B
The PedsQL™ VAS is designed to measure at-that-moment functioning in children and adolescents. The PedsQL VAS consists of 6 domains: anxiety, sadness, anger, worry, fatigue and pain using visual analogue scales. The functionality for each domain is measured on a 10 cm line with a happy face at one end and a sad face at the other (0-10 points). The participants are asked to mark on the line how they feel. A lower value represents a better outcome.
Time frame: Baseline (Week 4 of Phase A), Weeks 4 and 8 of Phase B
Population: FAS included all participants randomized to the double-blind, 8-week treatment period (Phase B) who took at least 1 dose of double-blind study drug and who had a valid baseline (Week 4 of Phase A) assessment and at least 1 valid post-baseline assessment of the CDRS-R total score. Overall number of participants analyzed = participants evaluated for this outcome measure. Number analyzed = participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind: Placebo | Change From Baseline in Pediatric Quality of Life Inventory (PedsQL) Visual Analogue Scales (VAS): Afraid or Scared (Anxiety) Score at Weeks 4 and 8 of Phase B | Change at Week 4 | -0.48 units on a scale | Standard Error 0.27 |
| Double-Blind: Placebo | Change From Baseline in Pediatric Quality of Life Inventory (PedsQL) Visual Analogue Scales (VAS): Afraid or Scared (Anxiety) Score at Weeks 4 and 8 of Phase B | Change at Week 8 | -0.73 units on a scale | Standard Error 0.26 |
| Double-Blind: Vortioxetine 10 mg | Change From Baseline in Pediatric Quality of Life Inventory (PedsQL) Visual Analogue Scales (VAS): Afraid or Scared (Anxiety) Score at Weeks 4 and 8 of Phase B | Change at Week 8 | -1.07 units on a scale | Standard Error 0.27 |
| Double-Blind: Vortioxetine 10 mg | Change From Baseline in Pediatric Quality of Life Inventory (PedsQL) Visual Analogue Scales (VAS): Afraid or Scared (Anxiety) Score at Weeks 4 and 8 of Phase B | Change at Week 4 | -0.51 units on a scale | Standard Error 0.27 |
| Double-Blind: Vortioxetine 20 mg | Change From Baseline in Pediatric Quality of Life Inventory (PedsQL) Visual Analogue Scales (VAS): Afraid or Scared (Anxiety) Score at Weeks 4 and 8 of Phase B | Change at Week 4 | -0.48 units on a scale | Standard Error 0.27 |
| Double-Blind: Vortioxetine 20 mg | Change From Baseline in Pediatric Quality of Life Inventory (PedsQL) Visual Analogue Scales (VAS): Afraid or Scared (Anxiety) Score at Weeks 4 and 8 of Phase B | Change at Week 8 | -1.01 units on a scale | Standard Error 0.27 |
| Double-Blind: Fluoxetine 20 mg | Change From Baseline in Pediatric Quality of Life Inventory (PedsQL) Visual Analogue Scales (VAS): Afraid or Scared (Anxiety) Score at Weeks 4 and 8 of Phase B | Change at Week 4 | -0.41 units on a scale | Standard Error 0.31 |
| Double-Blind: Fluoxetine 20 mg | Change From Baseline in Pediatric Quality of Life Inventory (PedsQL) Visual Analogue Scales (VAS): Afraid or Scared (Anxiety) Score at Weeks 4 and 8 of Phase B | Change at Week 8 | -1.08 units on a scale | Standard Error 0.29 |
Secondary
Change From Baseline in PedsQL Emotional Distress Summary Average Score at Weeks 4 and 8 of Phase B
The PedsQL™ VAS is designed to measure at-that-moment functioning in children and adolescents. The PedsQL VAS consists of 6 domains: anxiety, sadness, anger, worry, fatigue and pain using visual analogue scales. The functionality for each domain is measured on a 10 cm line with a happy face at one end and a sad face at the other (0-10 points). The participants are asked to mark on the line how they feel. The average emotional distress summary score is the mean of the anxiety, sadness, anger, and worry items. A lower value represents a better outcome.
Time frame: Baseline (Week 4 of Phase A), Weeks 4 and 8 of Phase B
Population: FAS included all participants randomized to the double-blind, 8-week treatment period (Phase B) who took at least 1 dose of double-blind study drug and who had a valid baseline (Week 4 of Phase A) assessment and at least 1 valid post-baseline assessment of the CDRS-R total score. Overall number of participants analyzed = participants evaluated for this outcome measure. Number analyzed = participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind: Placebo | Change From Baseline in PedsQL Emotional Distress Summary Average Score at Weeks 4 and 8 of Phase B | Change at Week 4 | -0.84 units on a scale | Standard Error 0.21 |
| Double-Blind: Placebo | Change From Baseline in PedsQL Emotional Distress Summary Average Score at Weeks 4 and 8 of Phase B | Change at Week 8 | -1.22 units on a scale | Standard Error 0.22 |
| Double-Blind: Vortioxetine 10 mg | Change From Baseline in PedsQL Emotional Distress Summary Average Score at Weeks 4 and 8 of Phase B | Change at Week 8 | -1.80 units on a scale | Standard Error 0.22 |
| Double-Blind: Vortioxetine 10 mg | Change From Baseline in PedsQL Emotional Distress Summary Average Score at Weeks 4 and 8 of Phase B | Change at Week 4 | -1.28 units on a scale | Standard Error 0.21 |
| Double-Blind: Vortioxetine 20 mg | Change From Baseline in PedsQL Emotional Distress Summary Average Score at Weeks 4 and 8 of Phase B | Change at Week 4 | -1.22 units on a scale | Standard Error 0.22 |
| Double-Blind: Vortioxetine 20 mg | Change From Baseline in PedsQL Emotional Distress Summary Average Score at Weeks 4 and 8 of Phase B | Change at Week 8 | -1.51 units on a scale | Standard Error 0.22 |
| Double-Blind: Fluoxetine 20 mg | Change From Baseline in PedsQL Emotional Distress Summary Average Score at Weeks 4 and 8 of Phase B | Change at Week 4 | -1.13 units on a scale | Standard Error 0.24 |
| Double-Blind: Fluoxetine 20 mg | Change From Baseline in PedsQL Emotional Distress Summary Average Score at Weeks 4 and 8 of Phase B | Change at Week 8 | -1.66 units on a scale | Standard Error 0.25 |
Secondary
Change From Baseline in PedsQL VAS: Angry Score at Weeks 4 and 8 of Phase B
The PedsQL™ VAS is designed to measure at-that-moment functioning in children and adolescents. The PedsQL VAS consists of 6 domains: anxiety, sadness, anger, worry, fatigue and pain using visual analogue scales. The functionality for each domain is measured on a 10 cm line with a happy face at one end and a sad face at the other (0-10 points). The participants are asked to mark on the line how they feel. A lower value represents a better outcome.
Time frame: Baseline (Week 4 of Phase A), Weeks 4 and 8 of Phase B
Population: FAS included all participants randomized to the double-blind, 8-week treatment period (Phase B) who took at least 1 dose of double-blind study drug and who had a valid baseline (Week 4 of Phase A) assessment and at least 1 valid post-baseline assessment of the CDRS-R total score. Overall number of participants analyzed = participants evaluated for this outcome measure. Number analyzed = participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind: Placebo | Change From Baseline in PedsQL VAS: Angry Score at Weeks 4 and 8 of Phase B | Change at Week 4 | -0.98 units on a scale | Standard Error 0.3 |
| Double-Blind: Placebo | Change From Baseline in PedsQL VAS: Angry Score at Weeks 4 and 8 of Phase B | Change at Week 8 | -1.24 units on a scale | Standard Error 0.31 |
| Double-Blind: Vortioxetine 10 mg | Change From Baseline in PedsQL VAS: Angry Score at Weeks 4 and 8 of Phase B | Change at Week 8 | -1.98 units on a scale | Standard Error 0.32 |
| Double-Blind: Vortioxetine 10 mg | Change From Baseline in PedsQL VAS: Angry Score at Weeks 4 and 8 of Phase B | Change at Week 4 | -1.36 units on a scale | Standard Error 0.31 |
| Double-Blind: Vortioxetine 20 mg | Change From Baseline in PedsQL VAS: Angry Score at Weeks 4 and 8 of Phase B | Change at Week 4 | -1.33 units on a scale | Standard Error 0.31 |
| Double-Blind: Vortioxetine 20 mg | Change From Baseline in PedsQL VAS: Angry Score at Weeks 4 and 8 of Phase B | Change at Week 8 | -1.36 units on a scale | Standard Error 0.32 |
| Double-Blind: Fluoxetine 20 mg | Change From Baseline in PedsQL VAS: Angry Score at Weeks 4 and 8 of Phase B | Change at Week 4 | -1.22 units on a scale | Standard Error 0.35 |
| Double-Blind: Fluoxetine 20 mg | Change From Baseline in PedsQL VAS: Angry Score at Weeks 4 and 8 of Phase B | Change at Week 8 | -1.67 units on a scale | Standard Error 0.36 |
Secondary
Change From Baseline in PedsQL VAS: Pain or Hurt Score at Weeks 4 and 8 of Phase B
The PedsQL™ VAS is designed to measure at-that-moment functioning in children and adolescents. The PedsQL VAS consists of 6 domains: anxiety, sadness, anger, worry, fatigue and pain using visual analogue scales. The functionality for each domain is measured on a 10 cm line with a happy face at one end and a sad face at the other (0-10 points). The participants are asked to mark on the line how they feel. A lower value represents a better outcome.
Time frame: Baseline (Week 4 of Phase A), Weeks 4 and 8 of Phase B
Population: FAS included all participants randomized to the double-blind, 8-week treatment period (Phase B) who took at least 1 dose of double-blind study drug and who had a valid baseline (Week 4 of Phase A) assessment and at least 1 valid post-baseline assessment of the CDRS-R total score. Overall number of participants analyzed = participants evaluated for this outcome measure. Number analyzed = participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind: Placebo | Change From Baseline in PedsQL VAS: Pain or Hurt Score at Weeks 4 and 8 of Phase B | Change at Week 4 | -0.22 units on a scale | Standard Error 0.28 |
| Double-Blind: Placebo | Change From Baseline in PedsQL VAS: Pain or Hurt Score at Weeks 4 and 8 of Phase B | Change at Week 8 | -0.70 units on a scale | Standard Error 0.28 |
| Double-Blind: Vortioxetine 10 mg | Change From Baseline in PedsQL VAS: Pain or Hurt Score at Weeks 4 and 8 of Phase B | Change at Week 8 | -0.79 units on a scale | Standard Error 0.28 |
| Double-Blind: Vortioxetine 10 mg | Change From Baseline in PedsQL VAS: Pain or Hurt Score at Weeks 4 and 8 of Phase B | Change at Week 4 | -0.81 units on a scale | Standard Error 0.28 |
| Double-Blind: Vortioxetine 20 mg | Change From Baseline in PedsQL VAS: Pain or Hurt Score at Weeks 4 and 8 of Phase B | Change at Week 4 | -0.45 units on a scale | Standard Error 0.28 |
| Double-Blind: Vortioxetine 20 mg | Change From Baseline in PedsQL VAS: Pain or Hurt Score at Weeks 4 and 8 of Phase B | Change at Week 8 | -1.02 units on a scale | Standard Error 0.28 |
| Double-Blind: Fluoxetine 20 mg | Change From Baseline in PedsQL VAS: Pain or Hurt Score at Weeks 4 and 8 of Phase B | Change at Week 4 | -0.50 units on a scale | Standard Error 0.32 |
| Double-Blind: Fluoxetine 20 mg | Change From Baseline in PedsQL VAS: Pain or Hurt Score at Weeks 4 and 8 of Phase B | Change at Week 8 | -0.69 units on a scale | Standard Error 0.32 |
Secondary
Change From Baseline in PedsQL VAS: Sad or Blue (Sadness) Score at Weeks 4 and 8 of Phase B
The PedsQL™ VAS is designed to measure at-that-moment functioning in children and adolescents. The PedsQL VAS consists of 6 domains: anxiety, sadness, anger, worry, fatigue and pain using visual analogue scales. The functionality for each domain is measured on a 10 cm line with a happy face at one end and a sad face at the other (0-10 points). The participants are asked to mark on the line how they feel. A lower value represents a better outcome.
Time frame: Baseline (Week 4 of Phase A), Weeks 4 and 8 of Phase B
Population: FAS included all participants randomized to the double-blind, 8-week treatment period (Phase B) who took at least 1 dose of double-blind study drug and who had a valid baseline (Week 4 of Phase A) assessment and at least 1 valid post-baseline assessment of the CDRS-R total score. Overall number of participants analyzed = participants evaluated for this outcome measure. Number analyzed = participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind: Placebo | Change From Baseline in PedsQL VAS: Sad or Blue (Sadness) Score at Weeks 4 and 8 of Phase B | Change at Week 4 | -1.20 units on a scale | Standard Error 0.31 |
| Double-Blind: Placebo | Change From Baseline in PedsQL VAS: Sad or Blue (Sadness) Score at Weeks 4 and 8 of Phase B | Change at Week 8 | -1.72 units on a scale | Standard Error 0.32 |
| Double-Blind: Vortioxetine 10 mg | Change From Baseline in PedsQL VAS: Sad or Blue (Sadness) Score at Weeks 4 and 8 of Phase B | Change at Week 8 | -2.23 units on a scale | Standard Error 0.32 |
| Double-Blind: Vortioxetine 10 mg | Change From Baseline in PedsQL VAS: Sad or Blue (Sadness) Score at Weeks 4 and 8 of Phase B | Change at Week 4 | -1.65 units on a scale | Standard Error 0.31 |
| Double-Blind: Vortioxetine 20 mg | Change From Baseline in PedsQL VAS: Sad or Blue (Sadness) Score at Weeks 4 and 8 of Phase B | Change at Week 4 | -1.78 units on a scale | Standard Error 0.31 |
| Double-Blind: Vortioxetine 20 mg | Change From Baseline in PedsQL VAS: Sad or Blue (Sadness) Score at Weeks 4 and 8 of Phase B | Change at Week 8 | -2.05 units on a scale | Standard Error 0.32 |
| Double-Blind: Fluoxetine 20 mg | Change From Baseline in PedsQL VAS: Sad or Blue (Sadness) Score at Weeks 4 and 8 of Phase B | Change at Week 4 | -1.42 units on a scale | Standard Error 0.35 |
| Double-Blind: Fluoxetine 20 mg | Change From Baseline in PedsQL VAS: Sad or Blue (Sadness) Score at Weeks 4 and 8 of Phase B | Change at Week 8 | -2.31 units on a scale | Standard Error 0.36 |
Secondary
Change From Baseline in PedsQL VAS: Tired (Fatigue) Score at Weeks 4 and 8 of Phase B
The PedsQL™ VAS is designed to measure at-that-moment functioning in children and adolescents. The PedsQL VAS consists of 6 domains: anxiety, sadness, anger, worry, fatigue and pain using visual analogue scales. The functionality for each domain is measured on a 10 cm line with a happy face at one end and a sad face at the other (0-10 points). The participants are asked to mark on the line how they feel. A lower value represents a better outcome.
Time frame: Baseline (Week 4 of Phase A), Weeks 4 and 8 of Phase B
Population: FAS included all participants randomized to the double-blind, 8-week treatment period (Phase B) who took at least 1 dose of double-blind study drug and who had a valid baseline (Week 4 of Phase A) assessment and at least 1 valid post-baseline assessment of the CDRS-R total score. Overall number of participants analyzed = participants evaluated for this outcome measure. Number analyzed = participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind: Placebo | Change From Baseline in PedsQL VAS: Tired (Fatigue) Score at Weeks 4 and 8 of Phase B | Change at Week 4 | -1.22 units on a scale | Standard Error 0.34 |
| Double-Blind: Placebo | Change From Baseline in PedsQL VAS: Tired (Fatigue) Score at Weeks 4 and 8 of Phase B | Change at Week 8 | -1.39 units on a scale | Standard Error 0.36 |
| Double-Blind: Vortioxetine 10 mg | Change From Baseline in PedsQL VAS: Tired (Fatigue) Score at Weeks 4 and 8 of Phase B | Change at Week 8 | -1.32 units on a scale | Standard Error 0.37 |
| Double-Blind: Vortioxetine 10 mg | Change From Baseline in PedsQL VAS: Tired (Fatigue) Score at Weeks 4 and 8 of Phase B | Change at Week 4 | -1.19 units on a scale | Standard Error 0.35 |
| Double-Blind: Vortioxetine 20 mg | Change From Baseline in PedsQL VAS: Tired (Fatigue) Score at Weeks 4 and 8 of Phase B | Change at Week 4 | -1.63 units on a scale | Standard Error 0.35 |
| Double-Blind: Vortioxetine 20 mg | Change From Baseline in PedsQL VAS: Tired (Fatigue) Score at Weeks 4 and 8 of Phase B | Change at Week 8 | -1.74 units on a scale | Standard Error 0.37 |
| Double-Blind: Fluoxetine 20 mg | Change From Baseline in PedsQL VAS: Tired (Fatigue) Score at Weeks 4 and 8 of Phase B | Change at Week 4 | -0.94 units on a scale | Standard Error 0.39 |
| Double-Blind: Fluoxetine 20 mg | Change From Baseline in PedsQL VAS: Tired (Fatigue) Score at Weeks 4 and 8 of Phase B | Change at Week 8 | -1.73 units on a scale | Standard Error 0.41 |
Secondary
Change From Baseline in PedsQL VAS Total Average Score at Weeks 4 and 8 of Phase B
The PedsQL™ VAS is designed to measure at-that-moment functioning in children and adolescents. The PedsQL™ VAS consists of 6 domains: anxiety, sadness, anger, worry, fatigue, and pain using visual analogue scales. The functionality for each domain is measured on a 10cm line with a happy face at one end and a sad face at the other (0-10 points). The participants are asked to mark on the line how they feel. The total score is the average of all 6 items. A lower value represents a better outcome.
Time frame: Baseline (Week 4 of Phase A), Weeks 4 and 8 of Phase B
Population: FAS included all participants randomized to the double-blind, 8-week treatment period (Phase B) who took at least 1 dose of double-blind study drug and who had a valid baseline (Week 4 of Phase A) assessment and at least 1 valid post-baseline assessment of the CDRS-R total score. Overall number of participants analyzed = participants evaluated for this outcome measure. Number analyzed = participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind: Placebo | Change From Baseline in PedsQL VAS Total Average Score at Weeks 4 and 8 of Phase B | Change at Week 4 | -0.81 units on a scale | Standard Error 0.19 |
| Double-Blind: Placebo | Change From Baseline in PedsQL VAS Total Average Score at Weeks 4 and 8 of Phase B | Change at Week 8 | -1.17 units on a scale | Standard Error 0.2 |
| Double-Blind: Vortioxetine 10 mg | Change From Baseline in PedsQL VAS Total Average Score at Weeks 4 and 8 of Phase B | Change at Week 8 | -1.55 units on a scale | Standard Error 0.2 |
| Double-Blind: Vortioxetine 10 mg | Change From Baseline in PedsQL VAS Total Average Score at Weeks 4 and 8 of Phase B | Change at Week 4 | -1.19 units on a scale | Standard Error 0.19 |
| Double-Blind: Vortioxetine 20 mg | Change From Baseline in PedsQL VAS Total Average Score at Weeks 4 and 8 of Phase B | Change at Week 4 | -1.17 units on a scale | Standard Error 0.2 |
| Double-Blind: Vortioxetine 20 mg | Change From Baseline in PedsQL VAS Total Average Score at Weeks 4 and 8 of Phase B | Change at Week 8 | -1.47 units on a scale | Standard Error 0.2 |
| Double-Blind: Fluoxetine 20 mg | Change From Baseline in PedsQL VAS Total Average Score at Weeks 4 and 8 of Phase B | Change at Week 4 | -1.01 units on a scale | Standard Error 0.22 |
| Double-Blind: Fluoxetine 20 mg | Change From Baseline in PedsQL VAS Total Average Score at Weeks 4 and 8 of Phase B | Change at Week 8 | -1.54 units on a scale | Standard Error 0.23 |
Secondary
Change From Baseline in PedsQL VAS: Worry Score at Weeks 4 and 8 of Phase B
The PedsQL™ VAS is designed to measure at-that-moment functioning in children and adolescents. The PedsQL VAS consists of 6 domains: anxiety, sadness, anger, worry, fatigue and pain using visual analogue scales. The functionality for each domain is measured on a 10 cm line with a happy face at one end and a sad face at the other (0-10 points). The participants are asked to mark on the line how they feel. A lower value represents a better outcome.
Time frame: Baseline (Week 4 of Phase A), Weeks 4 and 8 of Phase B
Population: FAS included all participants randomized to the double-blind, 8-week treatment period (Phase B) who took at least 1 dose of double-blind study drug and who had a valid baseline (Week 4 of Phase A) assessment and at least 1 valid post-baseline assessment of the CDRS-R total score. Overall number of participants analyzed = participants evaluated for this outcome measure. Number analyzed = participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind: Placebo | Change From Baseline in PedsQL VAS: Worry Score at Weeks 4 and 8 of Phase B | Change at Week 4 | -0.63 units on a scale | Standard Error 0.31 |
| Double-Blind: Placebo | Change From Baseline in PedsQL VAS: Worry Score at Weeks 4 and 8 of Phase B | Change at Week 8 | -1.08 units on a scale | Standard Error 0.32 |
| Double-Blind: Vortioxetine 10 mg | Change From Baseline in PedsQL VAS: Worry Score at Weeks 4 and 8 of Phase B | Change at Week 8 | -1.82 units on a scale | Standard Error 0.33 |
| Double-Blind: Vortioxetine 10 mg | Change From Baseline in PedsQL VAS: Worry Score at Weeks 4 and 8 of Phase B | Change at Week 4 | -1.48 units on a scale | Standard Error 0.32 |
| Double-Blind: Vortioxetine 20 mg | Change From Baseline in PedsQL VAS: Worry Score at Weeks 4 and 8 of Phase B | Change at Week 4 | -1.21 units on a scale | Standard Error 0.32 |
| Double-Blind: Vortioxetine 20 mg | Change From Baseline in PedsQL VAS: Worry Score at Weeks 4 and 8 of Phase B | Change at Week 8 | -1.45 units on a scale | Standard Error 0.33 |
| Double-Blind: Fluoxetine 20 mg | Change From Baseline in PedsQL VAS: Worry Score at Weeks 4 and 8 of Phase B | Change at Week 4 | -1.27 units on a scale | Standard Error 0.36 |
| Double-Blind: Fluoxetine 20 mg | Change From Baseline in PedsQL VAS: Worry Score at Weeks 4 and 8 of Phase B | Change at Week 8 | -1.41 units on a scale | Standard Error 0.36 |
Secondary
Change From Baseline in PQ-LES-Q Overall Evaluation Score (Item 15) at Weeks 4 and 8 of Phase B
The PQ-LES-Q is a patient-rated scale designed to assess satisfaction with life. It is an adaptation of the Quality of Life Enjoyment and Satisfaction Questionnaire, which is used to measure quality of life in adults. The PQ-LES-Q consist of 15 items, item 1 to 14 assess the degree of satisfaction experienced by participants in various areas of daily functioning, and item 15 allows subjects to summarize their experience in a global rating. Item 15 is rated on a 5-point scale from 1 (very poor) to 5 (very good).
Time frame: Baseline (Week 4 of Phase A), Weeks 4 and 8 of Phase B
Population: FAS included all participants randomized to the double-blind, 8-week treatment period (Phase B) who took at least 1 dose of double-blind study drug and who had a valid baseline (Week 4 of Phase A) assessment and at least 1 valid post-baseline assessment of the CDRS-R total score. Overall number of participants analyzed = participants evaluated for this outcome measure. Number analyzed = participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind: Placebo | Change From Baseline in PQ-LES-Q Overall Evaluation Score (Item 15) at Weeks 4 and 8 of Phase B | Change at Week 4 | 0.28 units on a scale | Standard Error 0.09 |
| Double-Blind: Placebo | Change From Baseline in PQ-LES-Q Overall Evaluation Score (Item 15) at Weeks 4 and 8 of Phase B | Change at Week 8 | 0.41 units on a scale | Standard Error 0.09 |
| Double-Blind: Vortioxetine 10 mg | Change From Baseline in PQ-LES-Q Overall Evaluation Score (Item 15) at Weeks 4 and 8 of Phase B | Change at Week 8 | 0.49 units on a scale | Standard Error 0.09 |
| Double-Blind: Vortioxetine 10 mg | Change From Baseline in PQ-LES-Q Overall Evaluation Score (Item 15) at Weeks 4 and 8 of Phase B | Change at Week 4 | 0.37 units on a scale | Standard Error 0.09 |
| Double-Blind: Vortioxetine 20 mg | Change From Baseline in PQ-LES-Q Overall Evaluation Score (Item 15) at Weeks 4 and 8 of Phase B | Change at Week 4 | 0.43 units on a scale | Standard Error 0.09 |
| Double-Blind: Vortioxetine 20 mg | Change From Baseline in PQ-LES-Q Overall Evaluation Score (Item 15) at Weeks 4 and 8 of Phase B | Change at Week 8 | 0.52 units on a scale | Standard Error 0.09 |
| Double-Blind: Fluoxetine 20 mg | Change From Baseline in PQ-LES-Q Overall Evaluation Score (Item 15) at Weeks 4 and 8 of Phase B | Change at Week 4 | 0.24 units on a scale | Standard Error 0.11 |
| Double-Blind: Fluoxetine 20 mg | Change From Baseline in PQ-LES-Q Overall Evaluation Score (Item 15) at Weeks 4 and 8 of Phase B | Change at Week 8 | 0.45 units on a scale | Standard Error 0.11 |
Secondary
Clinical Global Impression - Global Improvement (CGI-I) Score
The CGI-I provides the clinician's impression of the participant's improvement (or worsening). The clinician assesses the participant's condition relative to a baseline on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse).
Time frame: Weeks 1, 2, 3, 4, 6, and 8 of Phase B
Population: FAS included all participants randomized to the double-blind, 8-week treatment period (Phase B) who took at least 1 dose of double-blind study drug and who had a valid baseline (Week 4 of Phase A) assessment and at least 1 valid post-baseline assessment of the CDRS-R total score. Overall number of participants analyzed = participants evaluated for this outcome measure. Number analyzed = participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind: Placebo | Clinical Global Impression - Global Improvement (CGI-I) Score | Week 1 | 3.66 units on a scale | Standard Error 0.07 |
| Double-Blind: Placebo | Clinical Global Impression - Global Improvement (CGI-I) Score | Week 2 | 3.32 units on a scale | Standard Error 0.08 |
| Double-Blind: Placebo | Clinical Global Impression - Global Improvement (CGI-I) Score | Week 3 | 3.20 units on a scale | Standard Error 0.08 |
| Double-Blind: Placebo | Clinical Global Impression - Global Improvement (CGI-I) Score | Week 4 | 2.93 units on a scale | Standard Error 0.09 |
| Double-Blind: Placebo | Clinical Global Impression - Global Improvement (CGI-I) Score | Week 6 | 2.70 units on a scale | Standard Error 0.09 |
| Double-Blind: Placebo | Clinical Global Impression - Global Improvement (CGI-I) Score | Week 8 | 2.69 units on a scale | Standard Error 0.1 |
| Double-Blind: Vortioxetine 10 mg | Clinical Global Impression - Global Improvement (CGI-I) Score | Week 8 | 2.58 units on a scale | Standard Error 0.08 |
| Double-Blind: Vortioxetine 10 mg | Clinical Global Impression - Global Improvement (CGI-I) Score | Week 4 | 2.93 units on a scale | Standard Error 0.09 |
| Double-Blind: Vortioxetine 10 mg | Clinical Global Impression - Global Improvement (CGI-I) Score | Week 1 | 3.63 units on a scale | Standard Error 0.07 |
| Double-Blind: Vortioxetine 10 mg | Clinical Global Impression - Global Improvement (CGI-I) Score | Week 3 | 3.20 units on a scale | Standard Error 0.08 |
| Double-Blind: Vortioxetine 10 mg | Clinical Global Impression - Global Improvement (CGI-I) Score | Week 2 | 3.30 units on a scale | Standard Error 0.08 |
| Double-Blind: Vortioxetine 10 mg | Clinical Global Impression - Global Improvement (CGI-I) Score | Week 6 | 2.64 units on a scale | Standard Error 0.1 |
| Double-Blind: Vortioxetine 20 mg | Clinical Global Impression - Global Improvement (CGI-I) Score | Week 2 | 3.19 units on a scale | Standard Error 0.08 |
| Double-Blind: Vortioxetine 20 mg | Clinical Global Impression - Global Improvement (CGI-I) Score | Week 3 | 3.14 units on a scale | Standard Error 0.08 |
| Double-Blind: Vortioxetine 20 mg | Clinical Global Impression - Global Improvement (CGI-I) Score | Week 4 | 2.82 units on a scale | Standard Error 0.09 |
| Double-Blind: Vortioxetine 20 mg | Clinical Global Impression - Global Improvement (CGI-I) Score | Week 8 | 2.60 units on a scale | Standard Error 0.1 |
| Double-Blind: Vortioxetine 20 mg | Clinical Global Impression - Global Improvement (CGI-I) Score | Week 6 | 2.65 units on a scale | Standard Error 0.1 |
| Double-Blind: Vortioxetine 20 mg | Clinical Global Impression - Global Improvement (CGI-I) Score | Week 1 | 3.60 units on a scale | Standard Error 0.07 |
| Double-Blind: Fluoxetine 20 mg | Clinical Global Impression - Global Improvement (CGI-I) Score | Week 6 | 2.78 units on a scale | Standard Error 0.12 |
| Double-Blind: Fluoxetine 20 mg | Clinical Global Impression - Global Improvement (CGI-I) Score | Week 8 | 2.57 units on a scale | Standard Error 0.12 |
| Double-Blind: Fluoxetine 20 mg | Clinical Global Impression - Global Improvement (CGI-I) Score | Week 2 | 3.26 units on a scale | Standard Error 0.1 |
| Double-Blind: Fluoxetine 20 mg | Clinical Global Impression - Global Improvement (CGI-I) Score | Week 4 | 2.97 units on a scale | Standard Error 0.11 |
| Double-Blind: Fluoxetine 20 mg | Clinical Global Impression - Global Improvement (CGI-I) Score | Week 1 | 3.72 units on a scale | Standard Error 0.08 |
| Double-Blind: Fluoxetine 20 mg | Clinical Global Impression - Global Improvement (CGI-I) Score | Week 3 | 3.23 units on a scale | Standard Error 0.1 |
Secondary
Parent Global Assessment (PGA) Score
The PGA is a parent-rated variation of the CGI-I to evaluate the severity of the child's symptoms. The PGA reflects assessments of symptoms using a 7-point scale ranging from 1 (very much improved) to 7 (very much worse).
Time frame: Weeks 2, 4, 6, and 8 of Phase B
Population: FAS included all participants randomized to the double-blind, 8-week treatment period (Phase B) who took at least 1 dose of double-blind study drug and who had a valid baseline (Week 4 of Phase A) assessment and at least 1 valid post-baseline assessment of the CDRS-R total score. Overall number of participants analyzed = participants evaluated for this outcome measure. Number analyzed = participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind: Placebo | Parent Global Assessment (PGA) Score | Week 2 | 3.31 units on a scale | Standard Error 0.09 |
| Double-Blind: Placebo | Parent Global Assessment (PGA) Score | Week 4 | 2.97 units on a scale | Standard Error 0.1 |
| Double-Blind: Placebo | Parent Global Assessment (PGA) Score | Week 6 | 2.73 units on a scale | Standard Error 0.1 |
| Double-Blind: Placebo | Parent Global Assessment (PGA) Score | Week 8 | 2.68 units on a scale | Standard Error 0.11 |
| Double-Blind: Vortioxetine 10 mg | Parent Global Assessment (PGA) Score | Week 4 | 2.90 units on a scale | Standard Error 0.1 |
| Double-Blind: Vortioxetine 10 mg | Parent Global Assessment (PGA) Score | Week 6 | 2.73 units on a scale | Standard Error 0.1 |
| Double-Blind: Vortioxetine 10 mg | Parent Global Assessment (PGA) Score | Week 8 | 2.62 units on a scale | Standard Error 0.11 |
| Double-Blind: Vortioxetine 10 mg | Parent Global Assessment (PGA) Score | Week 2 | 3.25 units on a scale | Standard Error 0.09 |
| Double-Blind: Vortioxetine 20 mg | Parent Global Assessment (PGA) Score | Week 6 | 2.68 units on a scale | Standard Error 0.1 |
| Double-Blind: Vortioxetine 20 mg | Parent Global Assessment (PGA) Score | Week 4 | 2.84 units on a scale | Standard Error 0.1 |
| Double-Blind: Vortioxetine 20 mg | Parent Global Assessment (PGA) Score | Week 8 | 2.61 units on a scale | Standard Error 0.11 |
| Double-Blind: Vortioxetine 20 mg | Parent Global Assessment (PGA) Score | Week 2 | 3.18 units on a scale | Standard Error 0.09 |
| Double-Blind: Fluoxetine 20 mg | Parent Global Assessment (PGA) Score | Week 8 | 2.59 units on a scale | Standard Error 0.13 |
| Double-Blind: Fluoxetine 20 mg | Parent Global Assessment (PGA) Score | Week 4 | 2.90 units on a scale | Standard Error 0.12 |
| Double-Blind: Fluoxetine 20 mg | Parent Global Assessment (PGA) Score | Week 2 | 3.13 units on a scale | Standard Error 0.11 |
| Double-Blind: Fluoxetine 20 mg | Parent Global Assessment (PGA) Score | Week 6 | 2.80 units on a scale | Standard Error 0.12 |
Secondary
Percentage of Participants With CDRS-R Remission
CDRS-R remission was defined as a CDRS-R total score ≤28. The CDRS-R is a clinician-rated scale to measure the severity of depression in children and adolescents. The CDRS-R was rated by a clinician following interviews with the child and parent and consisted of 17 items out of which 3 items rated nonverbal observations (listless speech, hypoactivity, and depressed affect). Fourteen items were rated on a 7-point scale from 1 to 7, and 3 items (sleep disturbance, appetite disturbance, and listless speech) were scored on a 5-point scale from 1 to 5. A rating of 1 indicated normal functioning and a higher number indicated a greater degree of depression. The total score ranged from 17 (normal) to 113 (severe depression).
Time frame: Weeks 2, 4, 6, and 8 of Phase B
Population: FAS included all participants randomized to the double-blind, 8-week treatment period (Phase B) who took at least 1 dose of double-blind study drug and who had a valid baseline (Week 4 of Phase A) assessment and at least 1 valid post-baseline assessment of the CDRS-R total score. Overall number of participants analyzed = participants evaluated for this outcome measure. Number analyzed = participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Double-Blind: Placebo | Percentage of Participants With CDRS-R Remission | Week 2 | 2.0 percentage of participants |
| Double-Blind: Placebo | Percentage of Participants With CDRS-R Remission | Week 4 | 9.0 percentage of participants |
| Double-Blind: Placebo | Percentage of Participants With CDRS-R Remission | Week 6 | 14.7 percentage of participants |
| Double-Blind: Placebo | Percentage of Participants With CDRS-R Remission | Week 8 | 14.7 percentage of participants |
| Double-Blind: Vortioxetine 10 mg | Percentage of Participants With CDRS-R Remission | Week 4 | 9.5 percentage of participants |
| Double-Blind: Vortioxetine 10 mg | Percentage of Participants With CDRS-R Remission | Week 6 | 15.4 percentage of participants |
| Double-Blind: Vortioxetine 10 mg | Percentage of Participants With CDRS-R Remission | Week 8 | 16.7 percentage of participants |
| Double-Blind: Vortioxetine 10 mg | Percentage of Participants With CDRS-R Remission | Week 2 | 5.4 percentage of participants |
| Double-Blind: Vortioxetine 20 mg | Percentage of Participants With CDRS-R Remission | Week 6 | 15.3 percentage of participants |
| Double-Blind: Vortioxetine 20 mg | Percentage of Participants With CDRS-R Remission | Week 4 | 10.1 percentage of participants |
| Double-Blind: Vortioxetine 20 mg | Percentage of Participants With CDRS-R Remission | Week 8 | 20.1 percentage of participants |
| Double-Blind: Vortioxetine 20 mg | Percentage of Participants With CDRS-R Remission | Week 2 | 2.7 percentage of participants |
| Double-Blind: Fluoxetine 20 mg | Percentage of Participants With CDRS-R Remission | Week 8 | 26.9 percentage of participants |
| Double-Blind: Fluoxetine 20 mg | Percentage of Participants With CDRS-R Remission | Week 4 | 9.0 percentage of participants |
| Double-Blind: Fluoxetine 20 mg | Percentage of Participants With CDRS-R Remission | Week 2 | 3.8 percentage of participants |
| Double-Blind: Fluoxetine 20 mg | Percentage of Participants With CDRS-R Remission | Week 6 | 14.1 percentage of participants |
Secondary
Percentage of Participants With CDRS-R Response
CDRS-R response was defined as a ≥50% decrease in CDRS-R total score, calculated as: (change from baseline \[Randomization\])/(baseline value - 17). The CDRS-R is a clinician-rated scale to measure the severity of depression in children and adolescents. The CDRS-R was rated by a clinician following interviews with the child and parent and consisted of 17 items out of which 3 items rated nonverbal observations (listless speech, hypoactivity, and depressed affect). Fourteen items were rated on a 7-point scale from 1 to 7, and 3 items (sleep disturbance, appetite disturbance, and listless speech) were scored on a 5-point scale from 1 to 5. A rating of 1 indicated normal functioning and a higher number indicated a greater degree of depression. The total score ranged from 17 (normal) to 113 (severe depression).
Time frame: Weeks 2, 4, 6, and 8 of Phase B
Population: FAS included all participants randomized to the double-blind, 8-week treatment period (Phase B) who took at least 1 dose of double-blind study drug and who had a valid baseline (Week 4 of Phase A) assessment and at least 1 valid post-baseline assessment of the CDRS-R total score. Overall number of participants analyzed = participants evaluated for this outcome measure. Number analyzed = participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Double-Blind: Placebo | Percentage of Participants With CDRS-R Response | Week 2 | 7.8 percentage of participants |
| Double-Blind: Placebo | Percentage of Participants With CDRS-R Response | Week 4 | 20.7 percentage of participants |
| Double-Blind: Placebo | Percentage of Participants With CDRS-R Response | Week 6 | 30.8 percentage of participants |
| Double-Blind: Placebo | Percentage of Participants With CDRS-R Response | Week 8 | 29.4 percentage of participants |
| Double-Blind: Vortioxetine 10 mg | Percentage of Participants With CDRS-R Response | Week 4 | 23.4 percentage of participants |
| Double-Blind: Vortioxetine 10 mg | Percentage of Participants With CDRS-R Response | Week 6 | 31.6 percentage of participants |
| Double-Blind: Vortioxetine 10 mg | Percentage of Participants With CDRS-R Response | Week 8 | 36.4 percentage of participants |
| Double-Blind: Vortioxetine 10 mg | Percentage of Participants With CDRS-R Response | Week 2 | 10.2 percentage of participants |
| Double-Blind: Vortioxetine 20 mg | Percentage of Participants With CDRS-R Response | Week 6 | 37.2 percentage of participants |
| Double-Blind: Vortioxetine 20 mg | Percentage of Participants With CDRS-R Response | Week 4 | 26.6 percentage of participants |
| Double-Blind: Vortioxetine 20 mg | Percentage of Participants With CDRS-R Response | Week 8 | 41.0 percentage of participants |
| Double-Blind: Vortioxetine 20 mg | Percentage of Participants With CDRS-R Response | Week 2 | 11.6 percentage of participants |
| Double-Blind: Fluoxetine 20 mg | Percentage of Participants With CDRS-R Response | Week 8 | 47.4 percentage of participants |
| Double-Blind: Fluoxetine 20 mg | Percentage of Participants With CDRS-R Response | Week 4 | 26.9 percentage of participants |
| Double-Blind: Fluoxetine 20 mg | Percentage of Participants With CDRS-R Response | Week 2 | 16.3 percentage of participants |
| Double-Blind: Fluoxetine 20 mg | Percentage of Participants With CDRS-R Response | Week 6 | 33.3 percentage of participants |
Secondary
Percentage of Participants With CGI-S Remission
CGI-S remission was defined as a CGI-S score of 1 or 2. The CGI-S provides the clinician's impression of the participant's current state of mental illness. The clinician uses his or her clinical experience of this participant population to rate the severity of the participant's current mental illness on a 7-point scale ranging from 1 (normal - not at all ill) to 7 (among the most extremely ill participants).
Time frame: Weeks 1, 2, 3, 4, 6, and 8 of Phase B
Population: FAS included all participants randomized to the double-blind, 8-week treatment period (Phase B) who took at least 1 dose of double-blind study drug and who had a valid baseline (Week 4 of Phase A) assessment and at least 1 valid post-baseline assessment of the CDRS-R total score. Number analyzed = participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Double-Blind: Placebo | Percentage of Participants With CGI-S Remission | Week 2 | 0.7 percentage of participants |
| Double-Blind: Placebo | Percentage of Participants With CGI-S Remission | Week 8 | 22.9 percentage of participants |
| Double-Blind: Placebo | Percentage of Participants With CGI-S Remission | Week 1 | 0 percentage of participants |
| Double-Blind: Placebo | Percentage of Participants With CGI-S Remission | Week 6 | 14.4 percentage of participants |
| Double-Blind: Placebo | Percentage of Participants With CGI-S Remission | Week 4 | 8.5 percentage of participants |
| Double-Blind: Placebo | Percentage of Participants With CGI-S Remission | Week 3 | 3.3 percentage of participants |
| Double-Blind: Vortioxetine 10 mg | Percentage of Participants With CGI-S Remission | Week 6 | 16.2 percentage of participants |
| Double-Blind: Vortioxetine 10 mg | Percentage of Participants With CGI-S Remission | Week 8 | 22.3 percentage of participants |
| Double-Blind: Vortioxetine 10 mg | Percentage of Participants With CGI-S Remission | Week 2 | 3.4 percentage of participants |
| Double-Blind: Vortioxetine 10 mg | Percentage of Participants With CGI-S Remission | Week 3 | 4.1 percentage of participants |
| Double-Blind: Vortioxetine 10 mg | Percentage of Participants With CGI-S Remission | Week 4 | 8.1 percentage of participants |
| Double-Blind: Vortioxetine 10 mg | Percentage of Participants With CGI-S Remission | Week 1 | 0.7 percentage of participants |
| Double-Blind: Vortioxetine 20 mg | Percentage of Participants With CGI-S Remission | Week 8 | 20.9 percentage of participants |
| Double-Blind: Vortioxetine 20 mg | Percentage of Participants With CGI-S Remission | Week 1 | 0 percentage of participants |
| Double-Blind: Vortioxetine 20 mg | Percentage of Participants With CGI-S Remission | Week 4 | 12.8 percentage of participants |
| Double-Blind: Vortioxetine 20 mg | Percentage of Participants With CGI-S Remission | Week 2 | 1.4 percentage of participants |
| Double-Blind: Vortioxetine 20 mg | Percentage of Participants With CGI-S Remission | Week 3 | 4.7 percentage of participants |
| Double-Blind: Vortioxetine 20 mg | Percentage of Participants With CGI-S Remission | Week 6 | 16.2 percentage of participants |
| Double-Blind: Fluoxetine 20 mg | Percentage of Participants With CGI-S Remission | Week 8 | 29.6 percentage of participants |
| Double-Blind: Fluoxetine 20 mg | Percentage of Participants With CGI-S Remission | Week 1 | 0 percentage of participants |
| Double-Blind: Fluoxetine 20 mg | Percentage of Participants With CGI-S Remission | Week 2 | 3.7 percentage of participants |
| Double-Blind: Fluoxetine 20 mg | Percentage of Participants With CGI-S Remission | Week 4 | 12.3 percentage of participants |
| Double-Blind: Fluoxetine 20 mg | Percentage of Participants With CGI-S Remission | Week 6 | 14.8 percentage of participants |
| Double-Blind: Fluoxetine 20 mg | Percentage of Participants With CGI-S Remission | Week 3 | 7.4 percentage of participants |