Active Reference (Fluoxetine) Fixed-dose Study of Vortioxetine in Paediatric Patients Aged 12 to 17 Years With Major Depressive Disorder (MDD)

Study Overview
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Brief Summary
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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).

Official Title
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Interventional, Randomised, Double-blind, Placebo-controlled, Active Reference (Fluoxetine), Fixed-dose Study of Vortioxetine in Paediatric Patients Aged 12 to 17 Years, With Major Depressive Disorder (MDD)

Conditions
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Depressive Disorder, Major

Intervention / Treatment
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* Drug: Vortioxetine 10 mg/day
* Drug: Vortioxetine 20 mg/day
* Drug: Fluoxetine 20 mg/day
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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 exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vortioxetine 10 mg/day<br> | Drug: Vortioxetine 10 mg/day<br>* 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<br>* Other names: Lu AA21004;|
| Experimental: Vortioxetine 20 mg/day<br> | Drug: Vortioxetine 20 mg/day<br>* 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<br>* Other names: Lu AA21004;|
| Active Comparator: Fluoxetine 20 mg/day,<br> | Drug: Fluoxetine 20 mg/day<br>* 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<br>|
| Placebo Comparator: Placebo<br> | Other: Placebo<br>* Encapsulated tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | From Randomization to Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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'. | At week 2 | 
| 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). | At week 4 | 
| 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). | At week 6 | 
| 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. | From randomization to Week 8 | 
| 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. | From Randomization to Week 8 | 
| 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. | From Randomization to Week 8 | 
| 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. | From Randomization to Week 8 | 
| 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). | From Randomization to Week 8 | 
| CDRS-R Remission | Remission is defined as a CDRS-R total score <= 28. | From Randomization to Week 8 | 
| 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. | From randomization to week 8 | 
| 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. | From randomization to Week 8 | 
| 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). | From Randomization to Week 8 | 
| 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). | From Randomization to Week 8 | 
| 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). | From Randomization to Week 8 | 
| 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. | From Randomization to Week 8 | 
| CGI-S Remission | Remission defined as CGI-S score of 1 or 2. | From Randomization to Week 8 | 
| 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. | From Randomization to Week 8 | 
| 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. | From Randomization to Week 8 | 
| 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. | From Randomization to Week 8 | 
| 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. | From Randomization to Week 8 | 
| 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. | From Randomization to Week 8 | 
| 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. | From Randomization to week 8 | 
| 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. | From Randomization to Week 8 | 
| 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. | From Randomization to week 8 | 
| 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. | From Randomization to week 8 | 
| 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. | From Randomization to Week 8 | 
| 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). | From Randomization to Week 8 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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paediatric patients