Depressive Disorder, Major
Conditions
Keywords
paediatric patients
Brief summary
Evaluating the efficacy of vortioxetine 10 mg/day and 20 mg/day versus placebo on depressive symptoms in adolescents (age ≥12 and ≤17 years) with a DSM-5™ (Diagnostic and Statistical Manual of Mental Disorders, 5th edition) diagnosis of Major depressive disorder (MDD).
Interventions
10 mg/day, encapsulated tablet (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 (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 20 mg/day
20 mg/day, encapsulated tablet (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
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
12 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* The patient is a male or female, aged ≥12 and ≤17 years at Screening (patients who turn 18 years during the study will be allowed to continue in the study). * The patient has Major depressive disorder (MDD), diagnosed according to DSM-5™. * The patient has a Children Depression Rating Scale - Revised (CDRS-R) total score ≥45 at the Screening Visit and at the Baseline. * The patient has a Clinical Global Impression - Severity of Illness (CGI-S) score ≥4 at the Screening Visit and at the Baseline * The patient has provided assent to participation and parent(s)/legal representative (s) signed the Informed Consent Form.
Exclusion criteria
* The patient has participated in a clinical study \<30 days prior to the Screening Visit. Other protocol defined inclusion and
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Children Depression Rating Scale - Revised (CDRS-R) Total Score After Treatment | From Randomization to Week 8 | The CDRS-R is a clinician-rated scale to measure the severity of depression of children and adolescents. The CDRS-R consists of 17 items: 14 items rate verbal observations, and three items rate nonverbal observations (tempo of language, hypoactivity, and nonverbal expression of depressed affect). Depression symptoms are rated on a 5-point scale from 1 to 5 for the verbal observations, and a 7-point scale from 1 to 7 for the nonverbal observations. The total score ranges from 17 (normal) to 113 (severe depression). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in CDRS-R Total Score During Treatment (at Week 4) | At week 4 | The CDRS-R is a clinician-rated scale to measure the severity of depression of children and adolescents. The CDRS-R consists of 17 items: 14 items rate verbal observations, and three items rate nonverbal observations (tempo of language, hypoactivity, and nonverbal expression of depressed affect). Depression symptoms are rated on a 5-point scale from 1 to 5 for the verbal observations, and a 7-point scale from 1 to 7 for the nonverbal observations. The total score ranges from 17 (normal) to 113 (severe depression). |
| Change in CDRS-R Total Score During Treatment (at Week 6) | At week 6 | The CDRS-R is a clinician-rated scale to measure the severity of depression of children and adolescents. The CDRS-R consists of 17 items: 14 items rate verbal observations, and three items rate nonverbal observations (tempo of language, hypoactivity, and nonverbal expression of depressed affect). Depression symptoms are rated on a 5-point scale from 1 to 5 for the verbal observations, and a 7-point scale from 1 to 7 for the nonverbal observations. The total score ranges from 17 (normal) to 113 (severe depression). |
| Change in CDRS-R Mood Score | From randomization to Week 8 | Change in Children Depression Rating Scale - Revised (CDRS-R) Mood. The CDRS-R has been widely used for the evaluation of children and adolescents with major depressive disorder (MDD). The CDRS-R total score is the sum of the responses to 17 items. Each item is graded on a 5- or 7-point scale. Mood is one of four subscores defined in the CDRS-R: sum of items 8, 11, 14, 15; score range 4 to 28. The highest possible score indicates the most severe measure of depression. |
| Change in CDRS-R Somatic Score | From Randomization to Week 8 | Change in Children Depression Rating Scale - Revised (CDRS-R): Somatic. The CDRS-R has been widely used for the evaluation of children and adolescents with major depressive disorder (MDD). The CDRS-R total score is the sum of the responses to 17 items. Each item is graded on a 5- or 7-point scale. Somatic is one of four subscores defined in the CDRS-R: sum of items 4, 5, 6, 7, 16, 17; score ranges from 6 to 36. The highest possible score indicates the most severe measure of depression. |
| Change in CDRS-R Subjective Score | From Randomization to Week 8 | Change in Children Depression Rating Scale - Revised (CDRS-R): Subjective. The CDRS-R has been widely used for the evaluation of children and adolescents with major depressive disorder (MDD). The CDRS-R total score is the sum of the responses to 17 items. Each item is graded on a 5- or 7-point scale. Subjective is one of four subscores defined in the CDRS-R: sum of items 9, 10, 12, 13; score ranges from 4 to 28. The highest possible score indicates the most severe measure of depression. |
| Change in CDRS-R Behaviour Score | From Randomization to Week 8 | Change in Children Depression Rating Scale - Revised (CDRS-R): Behaviour. The CDRS-R has been widely used for the evaluation of children and adolescents with major depressive disorder (MDD). The CDRS-R total score is the sum of the responses to 17 items. Each item is graded on a 5- or 7-point scale. behaviour is one of four subscores defined in the CDRS-R:sum of items 1, 2, 3; score ranges from 3 to 21. The highest possible score indicates the most severe measure of depression. |
| CDRS-R Response | From Randomization to Week 8 | Children Depression Rating Scale - Response: defined as a \>= 50% decrease in CDRS-R total score, calculated as (change from baseline \[Randomization\])/(baseline value - 17). |
| CDRS-R Remission | From Randomization to Week 8 | Remission is defined as a CDRS-R total score \<= 28. |
| Change in General Behaviour Inventory (GBI) Depression Sub Scale Score Assessed by the Parents | From randomization to week 8 | Using the 10-item depression subscale, assessed by parent (PGBI-10D). Change from randomization to Week 8 in GBI Total Parent/Guardian Version Depression score. GBI is a self-report inventory with 73 items focused on mood-related behaviors including depressive, hypomanic, and biphasic symptoms. One 20-item subscale completed by parent/guardian. Symptoms rated on 4-point Likert scale from 0 (never/hardly ever) to 3 (often/almost constantly). Minimum score 0=better outcome, maximum score 60=worse outcome. |
| Change General Behaviour Inventory (GBI) Depression Subscale Score Assessed by the Child | From randomization to Week 8 | The GBI 10-item mania scale is a parent- and subject-rated scale designed to screen for manic symptoms in children and adolescents. The 10 items are rated on a scale from 0 (never or hardly ever) to 3 (very often or almost constantly). The total score ranges from 0 to 30 points, with high scores indicating greater pathology. |
| Parent Global Assessment-Global Improvement (PGA) Score | From Randomization to Week 8 | 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 change from Baseline symptoms using a 7 point scale ranging from 1 (very much improved) to 7 (very much worse). |
| Change in Symbol Digit Modalities Test (SDMT) | From Randomization to Week 8 | The Symbol Digit Modalities Test (SDMT) is a cognitive test designed to assess speed of performance requiring visual perception, spatial decision-making and psychomotor skills. The SDMT consists of 110 geometric symbols that the patient has to substitute with a corresponding digit in a 90-second period. Each correct digit is counted, and the total score ranges from 0 (less than normal functioning) to 110 (greater than normal functioning). |
| Change in Clinical Global Impression Severity of Illness (CGI-S) Score | From Randomization to Week 8 | The CGI-S provides the clinician's impression of the patient's current state of mental illness. The clinician uses his or her clinical experience of this patient population to rate the severity of the patient's current mental illness on a 7-point scale ranging from 1 (normal - not at all ill) to 7 (among the most extremely ill patients). |
| Change in CDRS-R Total Score During Treatment (at Week 2) | At week 2 | The CDRS-R is a clinician-rated scale to measure the severity of depression of children and adolescents. The CDRS-R consists of 17 items: 14 items rate verbal observations, and three items rate nonverbal observations (tempo of language, hypoactivity, and nonverbal expression of depressed affect). Depression symptoms are rated on a 5-point scale from 1 to 5 for the verbal observations, and a 7-point scale from 1 to 7 for the nonverbal observations. The total score ranges from 17 (normal) to 113 (severe depression).Children and parents answer separately. Rater judges and selects 'Best'. |
| CGI-S Remission | From Randomization to Week 8 | Remission defined as CGI-S score of 1 or 2. |
| Change in Children's Global Assessment Scale (CGAS) Score | From Randomization to Week 8 | The Children's Global Assessment Score (CGAS) is a rating scale which measures psychological, social and school functioning for children. 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 items range in value from 1 (most functionally impaired child) to 100 (the healthiest). A total score above 70 indicates normal function. |
| Change in Pediatric Quality of Life Inventory (PedsQL) Visual Analogue Scales (VAS): Afraid or Scared (Anxiety) Score | From Randomization to Week 8 | 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 patients are asked to mark on the line how they feel. A lower value represents a better outcome. |
| Change in PedsQL VAS: Sad or Blue (Sadness) Score | From Randomization to Week 8 | 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 patients are asked to mark on the line how they feel. A lower value represents a better outcome. |
| Change in PedsQL VAS: Angry Score | From Randomization to Week 8 | 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 patients are asked to mark on the line how they feel. A lower value represents a better outcome. |
| Change in PedsQL VAS: Worry Score | From Randomization to Week 8 | 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 patients are asked to mark on the line how they feel. A lower value represents a better outcome. |
| Change in PedsQL VAS: Tired (Fatigue) Score | From Randomization to week 8 | 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 patients are asked to mark on the line how they feel. A lower value represents a better outcome. |
| Change in PedsQL VAS: Pain or Hurt Score | From Randomization to Week 8 | 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 patients are asked to mark on the line how they feel. A lower value represents a better outcome. |
| Change in PedsQL VAS Total Average Score | From Randomization to week 8 | 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 patients 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 in PedsQL Emotional Distress Summary Average Score | From Randomization to week 8 | 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 patients 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 in Paediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q) Total Scores | From Randomization to Week 8 | PQ-LES-Q total score (items 1 to 14). 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 (Q-LES-Q), which is used to measure quality of life in adults. The PQ LES Q consist of 15 items, item 1-14 assess the degree of satisfaction experienced by subjects in various areas of daily functioning (and item 15 allows subjects to summarize 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 1-14 (this outcome measurement) is 14 to 70, with higher scores indicating greater satisfaction. |
| Change in PQ-LES-Q Overall Score | From Randomization to Week 8 | PQ-LES-Q overall evaluation score (item 15). 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 (Q-LES-Q), which is used to measure quality of life in adults. The PQ-LES-Q consist of 15 items, item 1-14 assess the degree of satisfaction experienced by subjects in various areas of daily functioning and item 15 allows subjects to summarize their experience in a global rating (this outcome measurement). Item 15 is rated on a 5-point scale from 1 (very poor) to 5 (very good). |
| Clinical Global Impression - Global Improvement (CGI-I) Score | From Randomization to Week 8 | The CGI-I provides the clinician's impression of the patient's improvement (or worsening). The clinician assesses the patient's condition relative to a baseline on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). In all cases, the assessment should be made independent of whether the rater believes the improvement is drug-related or not. |
Countries
Bulgaria, Canada, Colombia, Estonia, France, Germany, Hungary, Italy, Latvia, Mexico, Poland, Russia, Serbia, South Africa, South Korea, Spain, Ukraine, United Kingdom, United States
Participant flow
Pre-assignment details
Patients who did not fulfil the randomization criteria for the Double-blind treatment (DBT) Period, were withdrawn from the study after the Single-blind treatment (SBT) period. Patients who fulfilled the randomization criteria for the DBT Period, continued into the DBT Period.
Participants by arm
| Arm | Count |
|---|---|
| Single-blind Treatment (SBT), Placebo Single-blind treatment, Placebo (encapsulated, orally) and Brief Psychosocial Intervention (BPI) for 4 weeks | 168 |
| DBT, Vortioxetine 10 mg Eligible patients from SBT period (patients with incomplete improvement), will be randomly assigned (1:1:1:1) double-blind treatment in DBT Period, 8 weeks.
Vortioxetine 10 mg/day, encapsulated tablets, orally. | 147 |
| DBT, Vortioxetine 20 mg Eligible patients from SBT period (patients with incomplete improvement), will be randomly assigned (1:1:1:1) double-blind treatment in DBT Period, 8 weeks.
Vortioxetine 20 mg/day, encapsulated tablets, orally. | 162 |
| DBT, Fluoxetine 20 mg Eligible patients from SBT period (patients with incomplete improvement), will be randomly assigned (1:1:1:1) double-blind treatment in DBT Period, 8 weeks.
Fluoxetine 20 mg/day, encapsulated tablets, orally. | 153 |
| DBT, Placebo Eligible patients from SBT period (patients with incomplete improvement), will be randomly assigned (1:1:1:1) double-blind treatment in DBT Period, 8 weeks.
Placebo, encapsulated tablets, orally. | 154 |
| Total | 784 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Phase A (Single-blind Treatment Period) | Adverse Event | 2 | 0 | 0 | 0 | 0 |
| Phase A (Single-blind Treatment Period) | Do not fulfill rand criteria for DBT | 103 | 0 | 0 | 0 | 0 |
| Phase A (Single-blind Treatment Period) | Enrolled not treated | 7 | 0 | 0 | 0 | 0 |
| Phase A (Single-blind Treatment Period) | Lack of Efficacy | 7 | 0 | 0 | 0 | 0 |
| Phase A (Single-blind Treatment Period) | Lost to Follow-up | 7 | 0 | 0 | 0 | 0 |
| Phase A (Single-blind Treatment Period) | Non-compliance with study drug | 12 | 0 | 0 | 0 | 0 |
| Phase A (Single-blind Treatment Period) | Not sepcified | 14 | 0 | 0 | 0 | 0 |
| Phase A (Single-blind Treatment Period) | Protocol Violation | 4 | 0 | 0 | 0 | 0 |
| Phase A (Single-blind Treatment Period) | Withdrawal by Subject | 12 | 0 | 0 | 0 | 0 |
| Phase B (Double-blind Treatment Period) | Adverse Event | 0 | 4 | 8 | 5 | 2 |
| Phase B (Double-blind Treatment Period) | enrolled not treated | 0 | 0 | 1 | 0 | 0 |
| Phase B (Double-blind Treatment Period) | Lack of Efficacy | 0 | 3 | 0 | 1 | 2 |
| Phase B (Double-blind Treatment Period) | Lost to Follow-up | 0 | 4 | 2 | 0 | 2 |
| Phase B (Double-blind Treatment Period) | Non-compliance with study drug | 0 | 1 | 4 | 1 | 0 |
| Phase B (Double-blind Treatment Period) | Other | 0 | 6 | 5 | 6 | 7 |
| Phase B (Double-blind Treatment Period) | Protocol Violation | 0 | 1 | 0 | 0 | 2 |
| Phase B (Double-blind Treatment Period) | Withdrawal by Subject | 0 | 2 | 2 | 2 | 1 |
Baseline characteristics
| Characteristic | Single-blind Treatment (SBT), Placebo | DBT, Vortioxetine 10 mg | DBT, Vortioxetine 20 mg | DBT, Fluoxetine 20 mg | DBT, Placebo | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 14.7 years STANDARD_DEVIATION 1.61 | 14.8 years STANDARD_DEVIATION 1.66 | 14.5 years STANDARD_DEVIATION 1.63 | 14.8 years STANDARD_DEVIATION 1.6 | 14.6 years STANDARD_DEVIATION 1.6 | 14.67 years STANDARD_DEVIATION 1.62 |
| CDRS-R total score at Enrolment | 61.24 units on a scale STANDARD_DEVIATION 10 | 64.82 units on a scale STANDARD_DEVIATION 9.38 | 65.29 units on a scale STANDARD_DEVIATION 9.73 | 64.06 units on a scale STANDARD_DEVIATION 8.65 | 64.02 units on a scale STANDARD_DEVIATION 8.96 | 63.85 units on a scale STANDARD_DEVIATION 9.46 |
| CGI-S at Enrolment | 4.82 units on a scale STANDARD_DEVIATION 0.68 | 4.99 units on a scale STANDARD_DEVIATION 0.77 | 5.00 units on a scale STANDARD_DEVIATION 0.71 | 4.97 units on a scale STANDARD_DEVIATION 0.68 | 4.92 units on a scale STANDARD_DEVIATION 0.69 | 4.94 units on a scale STANDARD_DEVIATION 0.71 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 0 Participants | 4 Participants | 2 Participants | 4 Participants | 13 Participants |
| Race (NIH/OMB) Black or African American | 37 Participants | 19 Participants | 19 Participants | 20 Participants | 22 Participants | 117 Participants |
| Race (NIH/OMB) More than one race | 15 Participants | 17 Participants | 25 Participants | 17 Participants | 21 Participants | 95 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 3 Participants | 4 Participants | 2 Participants | 1 Participants | 14 Participants |
| Race (NIH/OMB) White | 108 Participants | 108 Participants | 110 Participants | 112 Participants | 106 Participants | 544 Participants |
| Sex: Female, Male Female | 111 Participants | 93 Participants | 97 Participants | 103 Participants | 105 Participants | 509 Participants |
| Sex: Female, Male Male | 57 Participants | 54 Participants | 65 Participants | 50 Participants | 49 Participants | 275 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 / 777 | 0 / 147 | 0 / 161 | 0 / 153 | 0 / 154 |
| other Total, other adverse events | 128 / 777 | 47 / 147 | 57 / 161 | 40 / 153 | 30 / 154 |
| serious Total, serious adverse events | 13 / 777 | 4 / 147 | 7 / 161 | 3 / 153 | 1 / 154 |
Outcome results
Primary
Change in Children Depression Rating Scale - Revised (CDRS-R) Total Score After Treatment
The CDRS-R is a clinician-rated scale to measure the severity of depression of children and adolescents. The CDRS-R consists of 17 items: 14 items rate verbal observations, and three items rate nonverbal observations (tempo of language, hypoactivity, and nonverbal expression of depressed affect). Depression symptoms are rated on a 5-point scale from 1 to 5 for the verbal observations, and a 7-point scale from 1 to 7 for the nonverbal observations. The total score ranges from 17 (normal) to 113 (severe depression).
Time frame: From Randomization to Week 8
Population: Double-blind treatment period
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Vortioxetine 10 mg/Day | Change in Children Depression Rating Scale - Revised (CDRS-R) Total Score After Treatment | -17.09 units on a scale | Standard Error 1.27 |
| Vortioxetine 20 mg/Day | Change in Children Depression Rating Scale - Revised (CDRS-R) Total Score After Treatment | -18.94 units on a scale | Standard Error 1.22 |
| Fluoxetine 20 mg/Day, | Change in Children Depression Rating Scale - Revised (CDRS-R) Total Score After Treatment | -21.95 units on a scale | Standard Error 1.23 |
| Placebo | Change in Children Depression Rating Scale - Revised (CDRS-R) Total Score After Treatment | -18.22 units on a scale | Standard Error 1.22 |
| Vortioxetine Average (Avg. VOR) | Change in Children Depression Rating Scale - Revised (CDRS-R) Total Score After Treatment | -18.01 units on a scale | Standard Error 0.98 |
p-value: 0.470295% CI: [-1.94, 4.2]Mixed Model Repeated Analysis
p-value: 0.637395% CI: [-3.71, 2.27]Mixed Model Repeated Analysis
p-value: 0.015295% CI: [-6.74, -0.72]Mixed Model Repeated Analysis
p-value: 0.877895% CI: [-2.41, 2.82]Mixed Model Repeated Analysis
Secondary
CDRS-R Remission
Remission is defined as a CDRS-R total score \<= 28.
Time frame: From Randomization to Week 8
Population: Double-blind treatment period. There where overall numbers of participants analyzed are not consistent with numbers provided in the participant flow can be due to particpant flow module total number of patients also includes patients that were enrolled but not treated and other reasons of discontinuation from the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Vortioxetine 10 mg/Day | CDRS-R Remission | 21 Participants |
| Vortioxetine 20 mg/Day | CDRS-R Remission | 24 Participants |
| Fluoxetine 20 mg/Day, | CDRS-R Remission | 32 Participants |
| Placebo | CDRS-R Remission | 20 Participants |
Secondary
CDRS-R Response
Children Depression Rating Scale - Response: defined as a \>= 50% decrease in CDRS-R total score, calculated as (change from baseline \[Randomization\])/(baseline value - 17).
Time frame: From Randomization to Week 8
Population: Double-blind treatment period. There where overall numbers of participants analyzed are not consistent with numbers provided in the participant flow can be due to particpant flow module total number of patients also includes patients that were enrolled but not treated and other reasons of discontinuation from the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Vortioxetine 10 mg/Day | CDRS-R Response | 53 Participants |
| Vortioxetine 20 mg/Day | CDRS-R Response | 60 Participants |
| Fluoxetine 20 mg/Day, | CDRS-R Response | 68 Participants |
| Placebo | CDRS-R Response | 49 Participants |
Secondary
CGI-S Remission
Remission defined as CGI-S score of 1 or 2.
Time frame: From Randomization to Week 8
Population: Double-blind treatment period. There where overall numbers of participants analyzed are not consistent with numbers provided in the participant flow can be due to particpant flow module total number of patients also includes patients that were enrolled but not treated and other reasons of discontinuation from the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Vortioxetine 10 mg/Day | CGI-S Remission | 26 Participants |
| Vortioxetine 20 mg/Day | CGI-S Remission | 33 Participants |
| Fluoxetine 20 mg/Day, | CGI-S Remission | 36 Participants |
| Placebo | CGI-S Remission | 24 Participants |
Secondary
Change General Behaviour Inventory (GBI) Depression Subscale Score Assessed by the Child
The GBI 10-item mania scale is a parent- and subject-rated scale designed to screen for manic symptoms in children and adolescents. The 10 items are rated on a scale from 0 (never or hardly ever) to 3 (very often or almost constantly). The total score ranges from 0 to 30 points, with high scores indicating greater pathology.
Time frame: From randomization to Week 8
Population: Double-blind treatment period. There where overall numbers of participants analyzed are not consistent with numbers provided in the participant flow can be due to particpant flow module total number of patients also includes patients that were enrolled but not treated and other reasons of discontinuation from the study.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Vortioxetine 10 mg/Day | Change General Behaviour Inventory (GBI) Depression Subscale Score Assessed by the Child | -5.48 units on a scale | Standard Error 0.61 |
| Vortioxetine 20 mg/Day | Change General Behaviour Inventory (GBI) Depression Subscale Score Assessed by the Child | -5.55 units on a scale | Standard Error 0.59 |
| Fluoxetine 20 mg/Day, | Change General Behaviour Inventory (GBI) Depression Subscale Score Assessed by the Child | -6.30 units on a scale | Standard Error 0.59 |
| Placebo | Change General Behaviour Inventory (GBI) Depression Subscale Score Assessed by the Child | -6.03 units on a scale | Standard Error 0.58 |
Secondary
Change in CDRS-R Behaviour Score
Change in Children Depression Rating Scale - Revised (CDRS-R): Behaviour. The CDRS-R has been widely used for the evaluation of children and adolescents with major depressive disorder (MDD). The CDRS-R total score is the sum of the responses to 17 items. Each item is graded on a 5- or 7-point scale. behaviour is one of four subscores defined in the CDRS-R:sum of items 1, 2, 3; score ranges from 3 to 21. The highest possible score indicates the most severe measure of depression.
Time frame: From Randomization to Week 8
Population: Double-blind treatment period. There where overall numbers of participants analyzed are not consistent with numbers provided in the participant flow can be due to particpant flow module total number of patients also includes patients that were enrolled but not treated and other reasons of discontinuation from the study.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Vortioxetine 10 mg/Day | Change in CDRS-R Behaviour Score | -4.32 units on a scale | Standard Error 0.38 |
| Vortioxetine 20 mg/Day | Change in CDRS-R Behaviour Score | -4.90 units on a scale | Standard Error 0.36 |
| Fluoxetine 20 mg/Day, | Change in CDRS-R Behaviour Score | -5.52 units on a scale | Standard Error 0.37 |
| Placebo | Change in CDRS-R Behaviour Score | -4.73 units on a scale | Standard Error 0.36 |
Secondary
Change in CDRS-R Mood Score
Change in Children Depression Rating Scale - Revised (CDRS-R) Mood. The CDRS-R has been widely used for the evaluation of children and adolescents with major depressive disorder (MDD). The CDRS-R total score is the sum of the responses to 17 items. Each item is graded on a 5- or 7-point scale. Mood is one of four subscores defined in the CDRS-R: sum of items 8, 11, 14, 15; score range 4 to 28. The highest possible score indicates the most severe measure of depression.
Time frame: From randomization to Week 8
Population: Double-blind treatment period. There where overall numbers of participants analyzed are not consistent with numbers provided in the participant flow can be due to particpant flow module total number of patients also includes patients that were enrolled but not treated and other reasons of discontinuation from the study.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Vortioxetine 10 mg/Day | Change in CDRS-R Mood Score | -5.05 units on a scale | Standard Error 0.4 |
| Vortioxetine 20 mg/Day | Change in CDRS-R Mood Score | -5.47 units on a scale | Standard Error 0.38 |
| Fluoxetine 20 mg/Day, | Change in CDRS-R Mood Score | -6.53 units on a scale | Standard Error 0.38 |
| Placebo | Change in CDRS-R Mood Score | -5.32 units on a scale | Standard Error 0.38 |
Secondary
Change in CDRS-R Somatic Score
Change in Children Depression Rating Scale - Revised (CDRS-R): Somatic. The CDRS-R has been widely used for the evaluation of children and adolescents with major depressive disorder (MDD). The CDRS-R total score is the sum of the responses to 17 items. Each item is graded on a 5- or 7-point scale. Somatic is one of four subscores defined in the CDRS-R: sum of items 4, 5, 6, 7, 16, 17; score ranges from 6 to 36. The highest possible score indicates the most severe measure of depression.
Time frame: From Randomization to Week 8
Population: Double-blind treatment period. There where overall numbers of participants analyzed are not consistent with numbers provided in the participant flow can be due to particpant flow module total number of patients also includes patients that were enrolled but not treated and other reasons of discontinuation from the study.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Vortioxetine 10 mg/Day | Change in CDRS-R Somatic Score | -5.63 units on a scale | Standard Error 0.46 |
| Vortioxetine 20 mg/Day | Change in CDRS-R Somatic Score | -6.03 units on a scale | Standard Error 0.44 |
| Fluoxetine 20 mg/Day, | Change in CDRS-R Somatic Score | -6.79 units on a scale | Standard Error 0.45 |
| Placebo | Change in CDRS-R Somatic Score | -5.78 units on a scale | Standard Error 0.44 |
Secondary
Change in CDRS-R Subjective Score
Change in Children Depression Rating Scale - Revised (CDRS-R): Subjective. The CDRS-R has been widely used for the evaluation of children and adolescents with major depressive disorder (MDD). The CDRS-R total score is the sum of the responses to 17 items. Each item is graded on a 5- or 7-point scale. Subjective is one of four subscores defined in the CDRS-R: sum of items 9, 10, 12, 13; score ranges from 4 to 28. The highest possible score indicates the most severe measure of depression.
Time frame: From Randomization to Week 8
Population: Double-blind treatment period. There where overall numbers of participants analyzed are not consistent with numbers provided in the participant flow can be due to particpant flow module total number of patients also includes patients that were enrolled but not treated and other reasons of discontinuation from the study.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Vortioxetine 10 mg/Day | Change in CDRS-R Subjective Score | -2.41 units on a scale | Standard Error 0.22 |
| Vortioxetine 20 mg/Day | Change in CDRS-R Subjective Score | -2.63 units on a scale | Standard Error 0.21 |
| Fluoxetine 20 mg/Day, | Change in CDRS-R Subjective Score | -3.23 units on a scale | Standard Error 0.21 |
| Placebo | Change in CDRS-R Subjective Score | -2.66 units on a scale | Standard Error 0.21 |
Secondary
Change in CDRS-R Total Score During Treatment (at Week 2)
The CDRS-R is a clinician-rated scale to measure the severity of depression of children and adolescents. The CDRS-R consists of 17 items: 14 items rate verbal observations, and three items rate nonverbal observations (tempo of language, hypoactivity, and nonverbal expression of depressed affect). Depression symptoms are rated on a 5-point scale from 1 to 5 for the verbal observations, and a 7-point scale from 1 to 7 for the nonverbal observations. The total score ranges from 17 (normal) to 113 (severe depression).Children and parents answer separately. Rater judges and selects 'Best'.
Time frame: At week 2
Population: Double-blind treatment period. There where overall numbers of participants analyzed are not consistent with numbers provided in the participant flow can be due to particpant flow module total number of patients also includes patients that were enrolled but not treated and other reasons of discontinuation from the study.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Vortioxetine 10 mg/Day | Change in CDRS-R Total Score During Treatment (at Week 2) | -9.58 units on a scale | Standard Error 1.02 |
| Vortioxetine 20 mg/Day | Change in CDRS-R Total Score During Treatment (at Week 2) | -10.15 units on a scale | Standard Error 0.99 |
| Fluoxetine 20 mg/Day, | Change in CDRS-R Total Score During Treatment (at Week 2) | -10.34 units on a scale | Standard Error 1 |
| Placebo | Change in CDRS-R Total Score During Treatment (at Week 2) | -8.83 units on a scale | Standard Error 0.98 |
Secondary
Change in CDRS-R Total Score During Treatment (at Week 4)
The CDRS-R is a clinician-rated scale to measure the severity of depression of children and adolescents. The CDRS-R consists of 17 items: 14 items rate verbal observations, and three items rate nonverbal observations (tempo of language, hypoactivity, and nonverbal expression of depressed affect). Depression symptoms are rated on a 5-point scale from 1 to 5 for the verbal observations, and a 7-point scale from 1 to 7 for the nonverbal observations. The total score ranges from 17 (normal) to 113 (severe depression).
Time frame: At week 4
Population: Double-blind treatment period. There where overall numbers of participants analyzed are not consistent with numbers provided in the participant flow can be due to particpant flow module total number of patients also includes patients that were enrolled but not treated and other reasons of discontinuation from the study.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Vortioxetine 10 mg/Day | Change in CDRS-R Total Score During Treatment (at Week 4) | -14.32 units on a scale | Standard Error 1.14 |
| Vortioxetine 20 mg/Day | Change in CDRS-R Total Score During Treatment (at Week 4) | -15.03 units on a scale | Standard Error 1.1 |
| Fluoxetine 20 mg/Day, | Change in CDRS-R Total Score During Treatment (at Week 4) | -16.25 units on a scale | Standard Error 1.11 |
| Placebo | Change in CDRS-R Total Score During Treatment (at Week 4) | -13.71 units on a scale | Standard Error 1.09 |
Secondary
Change in CDRS-R Total Score During Treatment (at Week 6)
The CDRS-R is a clinician-rated scale to measure the severity of depression of children and adolescents. The CDRS-R consists of 17 items: 14 items rate verbal observations, and three items rate nonverbal observations (tempo of language, hypoactivity, and nonverbal expression of depressed affect). Depression symptoms are rated on a 5-point scale from 1 to 5 for the verbal observations, and a 7-point scale from 1 to 7 for the nonverbal observations. The total score ranges from 17 (normal) to 113 (severe depression).
Time frame: At week 6
Population: Double-blind treatment period. There where overall numbers of participants analyzed are not consistent with numbers provided in the participant flow can be due to particpant flow module total number of patients also includes patients that were enrolled but not treated and other reasons of discontinuation from the study.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Vortioxetine 10 mg/Day | Change in CDRS-R Total Score During Treatment (at Week 6) | -15.43 units on a scale | Standard Error 1.24 |
| Vortioxetine 20 mg/Day | Change in CDRS-R Total Score During Treatment (at Week 6) | -17.78 units on a scale | Standard Error 1.19 |
| Fluoxetine 20 mg/Day, | Change in CDRS-R Total Score During Treatment (at Week 6) | -19.20 units on a scale | Standard Error 1.2 |
| Placebo | Change in CDRS-R Total Score During Treatment (at Week 6) | -16.71 units on a scale | Standard Error 1.19 |
Secondary
Change in Children's Global Assessment Scale (CGAS) Score
The Children's Global Assessment Score (CGAS) is a rating scale which measures psychological, social and school functioning for children. 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 items range in value from 1 (most functionally impaired child) to 100 (the healthiest). A total score above 70 indicates normal function.
Time frame: From Randomization to Week 8
Population: Double-blind treatment period. There where overall numbers of participants analyzed are not consistent with numbers provided in the participant flow can be due to particpant flow module total number of patients also includes patients that were enrolled but not treated and other reasons of discontinuation from the study.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Vortioxetine 10 mg/Day | Change in Children's Global Assessment Scale (CGAS) Score | 12.24 units on a scale | Standard Error 1.25 |
| Vortioxetine 20 mg/Day | Change in Children's Global Assessment Scale (CGAS) Score | 13.89 units on a scale | Standard Error 1.2 |
| Fluoxetine 20 mg/Day, | Change in Children's Global Assessment Scale (CGAS) Score | 16.43 units on a scale | Standard Error 1.2 |
| Placebo | Change in Children's Global Assessment Scale (CGAS) Score | 14.52 units on a scale | Standard Error 1.19 |
Secondary
Change in Clinical Global Impression Severity of Illness (CGI-S) Score
The CGI-S provides the clinician's impression of the patient's current state of mental illness. The clinician uses his or her clinical experience of this patient population to rate the severity of the patient's current mental illness on a 7-point scale ranging from 1 (normal - not at all ill) to 7 (among the most extremely ill patients).
Time frame: From Randomization to Week 8
Population: Double-blind treatment period. There where overall numbers of participants analyzed are not consistent with numbers provided in the participant flow can be due to particpant flow module total number of patients also includes patients that were enrolled but not treated and other reasons of discontinuation from the study.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Vortioxetine 10 mg/Day | Change in Clinical Global Impression Severity of Illness (CGI-S) Score | -1.23 units on a scale | Standard Error 0.1 |
| Vortioxetine 20 mg/Day | Change in Clinical Global Impression Severity of Illness (CGI-S) Score | -1.38 units on a scale | Standard Error 0.1 |
| Fluoxetine 20 mg/Day, | Change in Clinical Global Impression Severity of Illness (CGI-S) Score | -1.59 units on a scale | Standard Error 0.1 |
| Placebo | Change in Clinical Global Impression Severity of Illness (CGI-S) Score | -1.21 units on a scale | Standard Error 0.1 |
Secondary
Change in General Behaviour Inventory (GBI) Depression Sub Scale Score Assessed by the Parents
Using the 10-item depression subscale, assessed by parent (PGBI-10D). Change from randomization to Week 8 in GBI Total Parent/Guardian Version Depression score. GBI is a self-report inventory with 73 items focused on mood-related behaviors including depressive, hypomanic, and biphasic symptoms. One 20-item subscale completed by parent/guardian. Symptoms rated on 4-point Likert scale from 0 (never/hardly ever) to 3 (often/almost constantly). Minimum score 0=better outcome, maximum score 60=worse outcome.
Time frame: From randomization to week 8
Population: Double-blind treatment period. There where overall numbers of participants analyzed are not consistent with numbers provided in the participant flow can be due to particpant flow module total number of patients also includes patients that were enrolled but not treated and other reasons of discontinuation from the study.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Vortioxetine 10 mg/Day | Change in General Behaviour Inventory (GBI) Depression Sub Scale Score Assessed by the Parents | -6.23 units on a scale | Standard Deviation 0.56 |
| Vortioxetine 20 mg/Day | Change in General Behaviour Inventory (GBI) Depression Sub Scale Score Assessed by the Parents | -6.48 units on a scale | Standard Deviation 0.54 |
| Fluoxetine 20 mg/Day, | Change in General Behaviour Inventory (GBI) Depression Sub Scale Score Assessed by the Parents | -8.00 units on a scale | Standard Deviation 0.54 |
| Placebo | Change in General Behaviour Inventory (GBI) Depression Sub Scale Score Assessed by the Parents | -6.62 units on a scale | Standard Deviation 0.53 |
Secondary
Change in Paediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q) Total Scores
PQ-LES-Q total score (items 1 to 14). 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 (Q-LES-Q), which is used to measure quality of life in adults. The PQ LES Q consist of 15 items, item 1-14 assess the degree of satisfaction experienced by subjects in various areas of daily functioning (and item 15 allows subjects to summarize 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 1-14 (this outcome measurement) is 14 to 70, with higher scores indicating greater satisfaction.
Time frame: From Randomization to Week 8
Population: Double-blind treatment period. There where overall numbers of participants analyzed are not consistent with numbers provided in the participant flow can be due to particpant flow module total number of patients also includes patients that were enrolled but not treated and other reasons of discontinuation from the study.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Vortioxetine 10 mg/Day | Change in Paediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q) Total Scores | 7.62 units on a scale | Standard Error 0.97 |
| Vortioxetine 20 mg/Day | Change in Paediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q) Total Scores | 7.56 units on a scale | Standard Error 0.93 |
| Fluoxetine 20 mg/Day, | Change in Paediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q) Total Scores | 9.26 units on a scale | Standard Error 0.94 |
| Placebo | Change in Paediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q) Total Scores | 7.06 units on a scale | Standard Error 0.92 |
Secondary
Change in Pediatric Quality of Life Inventory (PedsQL) Visual Analogue Scales (VAS): Afraid or Scared (Anxiety) Score
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 patients are asked to mark on the line how they feel. A lower value represents a better outcome.
Time frame: From Randomization to Week 8
Population: Double-blind treatment period. There where overall numbers of participants analyzed are not consistent with numbers provided in the participant flow can be due to particpant flow module total number of patients also includes patients that were enrolled but not treated and other reasons of discontinuation from the study.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Vortioxetine 10 mg/Day | Change in Pediatric Quality of Life Inventory (PedsQL) Visual Analogue Scales (VAS): Afraid or Scared (Anxiety) Score | -0.47 units on a scale | Standard Error 0.19 |
| Vortioxetine 20 mg/Day | Change in Pediatric Quality of Life Inventory (PedsQL) Visual Analogue Scales (VAS): Afraid or Scared (Anxiety) Score | -0.76 units on a scale | Standard Error 0.18 |
| Fluoxetine 20 mg/Day, | Change in Pediatric Quality of Life Inventory (PedsQL) Visual Analogue Scales (VAS): Afraid or Scared (Anxiety) Score | -0.78 units on a scale | Standard Error 0.18 |
| Placebo | Change in Pediatric Quality of Life Inventory (PedsQL) Visual Analogue Scales (VAS): Afraid or Scared (Anxiety) Score | -0.71 units on a scale | Standard Error 0.18 |
Secondary
Change in PedsQL Emotional Distress Summary Average Score
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 patients 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: From Randomization to week 8
Population: Double-blind treatment period. There where overall numbers of participants analyzed are not consistent with numbers provided in the participant flow can be due to particpant flow module total number of patients also includes patients that were enrolled but not treated and other reasons of discontinuation from the study.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Vortioxetine 10 mg/Day | Change in PedsQL Emotional Distress Summary Average Score | -0.93 units on a scale | Standard Error 0.18 |
| Vortioxetine 20 mg/Day | Change in PedsQL Emotional Distress Summary Average Score | -1.09 units on a scale | Standard Error 0.17 |
| Fluoxetine 20 mg/Day, | Change in PedsQL Emotional Distress Summary Average Score | -1.33 units on a scale | Standard Error 0.17 |
| Placebo | Change in PedsQL Emotional Distress Summary Average Score | -1.18 units on a scale | Standard Error 0.17 |
Secondary
Change in PedsQL VAS: Angry Score
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 patients are asked to mark on the line how they feel. A lower value represents a better outcome.
Time frame: From Randomization to Week 8
Population: Double-blind treatment period. There where overall numbers of participants analyzed are not consistent with numbers provided in the participant flow can be due to particpant flow module total number of patients also includes patients that were enrolled but not treated and other reasons of discontinuation from the study.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Vortioxetine 10 mg/Day | Change in PedsQL VAS: Angry Score | -0.51 units on a scale | Standard Error 0.23 |
| Vortioxetine 20 mg/Day | Change in PedsQL VAS: Angry Score | -0.70 units on a scale | Standard Error 0.23 |
| Fluoxetine 20 mg/Day, | Change in PedsQL VAS: Angry Score | -1.01 units on a scale | Standard Error 0.23 |
| Placebo | Change in PedsQL VAS: Angry Score | -0.59 units on a scale | Standard Error 0.23 |
Secondary
Change in PedsQL VAS: Pain or Hurt Score
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 patients are asked to mark on the line how they feel. A lower value represents a better outcome.
Time frame: From Randomization to Week 8
Population: Double-blind treatment period. There where overall numbers of participants analyzed are not consistent with numbers provided in the participant flow can be due to particpant flow module total number of patients also includes patients that were enrolled but not treated and other reasons of discontinuation from the study.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Vortioxetine 10 mg/Day | Change in PedsQL VAS: Pain or Hurt Score | -1.12 units on a scale | Standard Error 0.22 |
| Vortioxetine 20 mg/Day | Change in PedsQL VAS: Pain or Hurt Score | -0.97 units on a scale | Standard Error 0.21 |
| Fluoxetine 20 mg/Day, | Change in PedsQL VAS: Pain or Hurt Score | -0.83 units on a scale | Standard Error 0.21 |
| Placebo | Change in PedsQL VAS: Pain or Hurt Score | -0.76 units on a scale | Standard Error 0.21 |
Secondary
Change in PedsQL VAS: Sad or Blue (Sadness) Score
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 patients are asked to mark on the line how they feel. A lower value represents a better outcome.
Time frame: From Randomization to Week 8
Population: Double-blind treatment period. There where overall numbers of participants analyzed are not consistent with numbers provided in the participant flow can be due to particpant flow module total number of patients also includes patients that were enrolled but not treated and other reasons of discontinuation from the study.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Vortioxetine 10 mg/Day | Change in PedsQL VAS: Sad or Blue (Sadness) Score | -1.90 units on a scale | Standard Error 0.26 |
| Vortioxetine 20 mg/Day | Change in PedsQL VAS: Sad or Blue (Sadness) Score | -1.71 units on a scale | Standard Error 0.25 |
| Fluoxetine 20 mg/Day, | Change in PedsQL VAS: Sad or Blue (Sadness) Score | -2.45 units on a scale | Standard Error 0.25 |
| Placebo | Change in PedsQL VAS: Sad or Blue (Sadness) Score | -2.12 units on a scale | Standard Error 0.24 |
Secondary
Change in PedsQL VAS: Tired (Fatigue) Score
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 patients are asked to mark on the line how they feel. A lower value represents a better outcome.
Time frame: From Randomization to week 8
Population: Double-blind treatment period. There where overall numbers of participants analyzed are not consistent with numbers provided in the participant flow can be due to particpant flow module total number of patients also includes patients that were enrolled but not treated and other reasons of discontinuation from the study.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Vortioxetine 10 mg/Day | Change in PedsQL VAS: Tired (Fatigue) Score | -1.18 units on a scale | Standard Error 0.29 |
| Vortioxetine 20 mg/Day | Change in PedsQL VAS: Tired (Fatigue) Score | -1.40 units on a scale | Standard Error 0.28 |
| Fluoxetine 20 mg/Day, | Change in PedsQL VAS: Tired (Fatigue) Score | -1.55 units on a scale | Standard Error 0.28 |
| Placebo | Change in PedsQL VAS: Tired (Fatigue) Score | -1.27 units on a scale | Standard Error 0.28 |
Secondary
Change in PedsQL VAS Total Average Score
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 patients 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: From Randomization to week 8
Population: Double-blind treatment period. There where overall numbers of participants analyzed are not consistent with numbers provided in the participant flow can be due to particpant flow module total number of patients also includes patients that were enrolled but not treated and other reasons of discontinuation from the study.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Vortioxetine 10 mg/Day | Change in PedsQL VAS Total Average Score | -1.00 units on a scale | Standard Error 0.17 |
| Vortioxetine 20 mg/Day | Change in PedsQL VAS Total Average Score | -1.13 units on a scale | Standard Error 0.16 |
| Fluoxetine 20 mg/Day, | Change in PedsQL VAS Total Average Score | -1.33 units on a scale | Standard Error 0.16 |
| Placebo | Change in PedsQL VAS Total Average Score | -1.14 units on a scale | Standard Error 0.16 |
Secondary
Change in PedsQL VAS: Worry Score
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 patients are asked to mark on the line how they feel. A lower value represents a better outcome.
Time frame: From Randomization to Week 8
Population: Double-blind treatment period. There where overall numbers of participants analyzed are not consistent with numbers provided in the participant flow can be due to particpant flow module total number of patients also includes patients that were enrolled but not treated and other reasons of discontinuation from the study.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Vortioxetine 10 mg/Day | Change in PedsQL VAS: Worry Score | -0.96 units on a scale | Standard Error 0.25 |
| Vortioxetine 20 mg/Day | Change in PedsQL VAS: Worry Score | -1.17 units on a scale | Standard Error 0.24 |
| Fluoxetine 20 mg/Day, | Change in PedsQL VAS: Worry Score | -0.91 units on a scale | Standard Error 0.24 |
| Placebo | Change in PedsQL VAS: Worry Score | -1.33 units on a scale | Standard Error 0.24 |
Secondary
Change in PQ-LES-Q Overall Score
PQ-LES-Q overall evaluation score (item 15). 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 (Q-LES-Q), which is used to measure quality of life in adults. The PQ-LES-Q consist of 15 items, item 1-14 assess the degree of satisfaction experienced by subjects in various areas of daily functioning and item 15 allows subjects to summarize their experience in a global rating (this outcome measurement). Item 15 is rated on a 5-point scale from 1 (very poor) to 5 (very good).
Time frame: From Randomization to Week 8
Population: Double-blind treatment period. There where overall numbers of participants analyzed are not consistent with numbers provided in the participant flow can be due to particpant flow module total number of patients also includes patients that were enrolled but not treated and other reasons of discontinuation from the study.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Vortioxetine 10 mg/Day | Change in PQ-LES-Q Overall Score | 0.54 units on a scale | Standard Error 0.08 |
| Vortioxetine 20 mg/Day | Change in PQ-LES-Q Overall Score | 0.43 units on a scale | Standard Error 0.08 |
| Fluoxetine 20 mg/Day, | Change in PQ-LES-Q Overall Score | 0.67 units on a scale | Standard Error 0.08 |
| Placebo | Change in PQ-LES-Q Overall Score | 0.51 units on a scale | Standard Error 0.08 |
Secondary
Change in Symbol Digit Modalities Test (SDMT)
The Symbol Digit Modalities Test (SDMT) is a cognitive test designed to assess speed of performance requiring visual perception, spatial decision-making and psychomotor skills. The SDMT consists of 110 geometric symbols that the patient has to substitute with a corresponding digit in a 90-second period. Each correct digit is counted, and the total score ranges from 0 (less than normal functioning) to 110 (greater than normal functioning).
Time frame: From Randomization to Week 8
Population: Double-blind treatment period. There where overall numbers of participants analyzed are not consistent with numbers provided in the participant flow can be due to particpant flow module total number of patients also includes patients that were enrolled but not treated and other reasons of discontinuation from the study.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Vortioxetine 10 mg/Day | Change in Symbol Digit Modalities Test (SDMT) | 3.75 units on a scale | Standard Error 1.02 |
| Vortioxetine 20 mg/Day | Change in Symbol Digit Modalities Test (SDMT) | 2.64 units on a scale | Standard Error 0.98 |
| Fluoxetine 20 mg/Day, | Change in Symbol Digit Modalities Test (SDMT) | 2.69 units on a scale | Standard Error 0.98 |
| Placebo | Change in Symbol Digit Modalities Test (SDMT) | 2.41 units on a scale | Standard Error 0.97 |
Secondary
Clinical Global Impression - Global Improvement (CGI-I) Score
The CGI-I provides the clinician's impression of the patient's improvement (or worsening). The clinician assesses the patient's condition relative to a baseline on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). In all cases, the assessment should be made independent of whether the rater believes the improvement is drug-related or not.
Time frame: From Randomization to Week 8
Population: Double-blind treatment period. There where overall numbers of participants analyzed are not consistent with numbers provided in the participant flow can be due to particpant flow module total number of patients also includes patients that were enrolled but not treated and other reasons of discontinuation from the study.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Vortioxetine 10 mg/Day | Clinical Global Impression - Global Improvement (CGI-I) Score | 2.81 units on a scale | Standard Error 0.1 |
| Vortioxetine 20 mg/Day | Clinical Global Impression - Global Improvement (CGI-I) Score | 2.69 units on a scale | Standard Error 0.09 |
| Fluoxetine 20 mg/Day, | Clinical Global Impression - Global Improvement (CGI-I) Score | 2.50 units on a scale | Standard Error 0.09 |
| Placebo | Clinical Global Impression - Global Improvement (CGI-I) Score | 2.73 units on a scale | Standard Error 0.09 |
Secondary
Parent Global Assessment-Global Improvement (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 change from Baseline symptoms using a 7 point scale ranging from 1 (very much improved) to 7 (very much worse).
Time frame: From Randomization to Week 8
Population: Double-blind treatment period. There where overall numbers of participants analyzed are not consistent with numbers provided in the participant flow can be due to particpant flow module total number of patients also includes patients that were enrolled but not treated and other reasons of discontinuation from the study.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Vortioxetine 10 mg/Day | Parent Global Assessment-Global Improvement (PGA) Score | 2.80 units on a scale | Standard Error 0.1 |
| Vortioxetine 20 mg/Day | Parent Global Assessment-Global Improvement (PGA) Score | 2.74 units on a scale | Standard Error 0.09 |
| Fluoxetine 20 mg/Day, | Parent Global Assessment-Global Improvement (PGA) Score | 2.49 units on a scale | Standard Error 0.09 |
| Placebo | Parent Global Assessment-Global Improvement (PGA) Score | 2.72 units on a scale | Standard Error 0.09 |