Active Reference (Fluoxetine) Fixed-dose Study of Vortioxetine in Paediatric Participants Aged 7 to 11 Years With Major Depressive Disorder (MDD)

Study Overview
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Brief Summary
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Investigation of the efficacy and safety of a new potential treatment of Major depressive disorder (MDD) in paediatric participants (age 7 to 11 years).

Official Title
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Interventional, Randomized, Double-blind, Placebo-controlled, Active-reference (Fluoxetine), Fixed-dose Study of Vortioxetine in Paediatric Patients Aged 7 to 11 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 20mg/day
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The participant has MDD, diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5™). The participant has a CDRS-R total score ≥45 at the Screening Visit and the Baseline. The participant has a CGI-S score ≥4 at the Screening Visit and the Baseline. The participant is a boy or girl, aged ≥7 and <12 years at Screening Visit The participant has provided assent to participation and parent(s)/legal representative (s) signed the Informed Consent Form. Exclusion Criteria: The participant has participated in a clinical study <30 days prior to the Screening Visit. The participant has previously participated in a study with vortioxetine. Other protocol defined inclusion and exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 7 Years
Maximum Age: 11 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, 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<br>* Other names: Lu AA21004;|
| Experimental: Vortioxetine 20 mg/day<br> | Drug: Vortioxetine 20 mg/day<br>* 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<br>* Other names: Lu AA21004;|
| Active Comparator: Fluoxetine 20 mg/day,<br>A decision has been taken to stop recruitment into this treatment arm. | Drug: Fluoxetine 20mg/day<br>* 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<br>|
| Placebo Comparator: Placebo<br> | Other: Placebo<br>* Encapsulated tablet, orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline (Week 4 of Phase A), Week 8 of Phase B | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | Baseline (Week 4 of Phase A), Weeks 2, 4, and 6 of Phase B | 
| 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. | Baseline (Week 4 of Phase A), Weeks 2, 4, 6, and 8 of Phase B | 
| 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). | Weeks 2, 4, 6, and 8 of Phase B | 
| 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). | Weeks 2, 4, 6, and 8 of Phase B | 
| 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. | Baseline (Week 4 of Phase A), Weeks 2, 4, 6, and 8 of Phase B | 
| 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). | Weeks 2, 4, 6, and 8 of Phase B | 
| 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). | Baseline (Week 4 of Phase A), Weeks 1, 2, 3, 4, 6, and 8 of Phase B | 
| 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). | Weeks 1, 2, 3, 4, 6, and 8 of Phase B | 
| 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). | Weeks 1, 2, 3, 4, 6, and 8 of Phase B | 
| 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. | Baseline (Week 4 of Phase A), Weeks 4 and 8 of Phase B | 
| 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. | Baseline (Week 4 of Phase A), Weeks 4 and 8 of Phase B | 
| 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. | Baseline (Week 4 of Phase A), Weeks 4 and 8 of Phase B | 
| 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. | Baseline (Week 4 of Phase A), Weeks 4 and 8 of Phase B | 
| 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. | Baseline (Week 4 of Phase A), Weeks 4 and 8 of Phase B | 
| 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. | Baseline (Week 4 of Phase A), Weeks 4 and 8 of Phase B | 
| 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. | Baseline (Week 4 of Phase A), Weeks 4 and 8 of Phase B | 
| 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. | Baseline (Week 4 of Phase A), Weeks 4 and 8 of Phase B | 
| 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. | Baseline (Week 4 of Phase A), Weeks 4 and 8 of Phase B | 
| 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. | Baseline (Week 4 of Phase A), Weeks 4 and 8 of Phase B | 
| 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). | Baseline (Week 4 of Phase A), Weeks 4 and 8 of Phase B | 

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