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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02709655
Recruitment Status : Completed
First Posted : March 16, 2016
Results First Posted : September 22, 2022
Last Update Posted : September 22, 2022
Sponsor:
Collaborator:
Takeda
Information provided by (Responsible Party):
H. Lundbeck A/S

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

Condition or disease Intervention/treatment Phase
Depressive Disorder, Major Drug: Vortioxetine 10 mg/day Drug: Vortioxetine 20 mg/day Drug: Fluoxetine 20mg/day Other: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 683 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: 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)
Actual Study Start Date : May 18, 2016
Actual Primary Completion Date : January 21, 2022
Actual Study Completion Date : January 21, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Vortioxetine 10 mg/day Drug: Vortioxetine 10 mg/day

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

Other Names:
  • Brintellix ®
  • Lu AA21004

Experimental: Vortioxetine 20 mg/day Drug: Vortioxetine 20 mg/day

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

Other Names:
  • Brintellix ®
  • Lu AA21004

Active Comparator: Fluoxetine 20 mg/day,
A decision has been taken to stop recruitment into this treatment arm.
Drug: Fluoxetine 20mg/day

20 mg/day, encapsulated tablet, orally (with addition of lower initial dose levels).

Based on tolerability the dose may be reduced by 10 mg/day. No dose increase will be allowed


Placebo Comparator: Placebo Other: Placebo
Encapsulated tablet, orally




Primary Outcome Measures :
  1. Change From Baseline in Children Depression Rating Scale - Revised (CDRS-R) Total Score at Week 8 of Phase B [ Time Frame: Baseline (Week 4 of Phase A), Week 8 of Phase B ]
    The CDRS-R is a clinician-rated scale to measure the severity of depression in children and adolescents. The CDRS-R was rated by a clinician following interviews with the child and parent and consisted of 17 items out of which 3 items rated nonverbal observations (listless speech, hypoactivity, and depressed affect). Fourteen items were rated on a 7-point scale from 1 to 7, and 3 items (sleep disturbance, appetite disturbance, and listless speech) were scored on a 5-point scale from 1 to 5. A rating of 1 indicated normal functioning and a higher number indicated a greater degree of depression. The total score ranged from 17 (normal) to 113 (severe depression). Least square (LS) mean was estimated using a restricted maximum likelihood (REML)-based Mixed Model Repeated Measurements (MMRM) approach.


Secondary Outcome Measures :
  1. Change From Baseline in CDRS-R Total Score at Weeks 2, 4, and 6 of Phase B [ Time Frame: Baseline (Week 4 of Phase A), Weeks 2, 4, and 6 of Phase B ]
    The CDRS-R is a clinician-rated scale to measure the severity of depression in children and adolescents. The CDRS-R was rated by a clinician following interviews with the child and parent and consisted of 17 items out of which 3 items rated nonverbal observations (listless speech, hypoactivity, and depressed affect). Fourteen items were rated on a 7-point scale from 1 to 7, and 3 items (sleep disturbance, appetite disturbance, and listless speech) were scored on a 5-point scale from 1 to 5. A rating of 1 indicated normal functioning and a higher number indicated a greater degree of depression. The total score ranged from 17 (normal) to 113 (severe depression).

  2. Change From Baseline in CDRS-R Subscores (Mood, Somatic, Subjective, and Behaviour) at Weeks 2, 4, 6, and 8 of Phase B [ Time Frame: Baseline (Week 4 of Phase A), Weeks 2, 4, 6, and 8 of Phase B ]
    The CDRS-R was rated by a clinician following interviews with the child and parent and consisted of 17 items out of which 3 items rated nonverbal observations (listless speech, hypoactivity, and depressed affect). Fourteen items were rated on a 7-point scale from 1 to 7, and 3 items (sleep disturbance, appetite disturbance, and listless speech) were scored on a 5-point scale from 1 to 5. A rating of 1 indicated normal functioning and a higher number indicated a greater degree of depression. The total score ranged from 17 (normal) to 113 (severe depression). Four subscores were defined based on the CDRS-R: Mood: sum of items 8, 11, 14, 15; score range 4 to 28, Somatic: sum of items 4, 5, 6, 7, 16, 17; score range 6 to 36, Subjective: sum of items 9, 10, 12, 13; score range 4 to 28, and Behaviour: sum of items 1, 2, 3; score range 3 to 21. Higher scores indicated the most severe measure of depression.

  3. Percentage of Participants With CDRS-R Response [ Time Frame: Weeks 2, 4, 6, and 8 of Phase B ]
    CDRS-R response was defined as a ≥50% decrease in CDRS-R total score, calculated as: (change from baseline [Randomization])/(baseline value - 17). The CDRS-R is a clinician-rated scale to measure the severity of depression in children and adolescents. The CDRS-R was rated by a clinician following interviews with the child and parent and consisted of 17 items out of which 3 items rated nonverbal observations (listless speech, hypoactivity, and depressed affect). Fourteen items were rated on a 7-point scale from 1 to 7, and 3 items (sleep disturbance, appetite disturbance, and listless speech) were scored on a 5-point scale from 1 to 5. A rating of 1 indicated normal functioning and a higher number indicated a greater degree of depression. The total score ranged from 17 (normal) to 113 (severe depression).

  4. Percentage of Participants With CDRS-R Remission [ Time Frame: Weeks 2, 4, 6, and 8 of Phase B ]
    CDRS-R remission was defined as a CDRS-R total score ≤28. The CDRS-R is a clinician-rated scale to measure the severity of depression in children and adolescents. The CDRS-R was rated by a clinician following interviews with the child and parent and consisted of 17 items out of which 3 items rated nonverbal observations (listless speech, hypoactivity, and depressed affect). Fourteen items were rated on a 7-point scale from 1 to 7, and 3 items (sleep disturbance, appetite disturbance, and listless speech) were scored on a 5-point scale from 1 to 5. A rating of 1 indicated normal functioning and a higher number indicated a greater degree of depression. The total score ranged from 17 (normal) to 113 (severe depression).

  5. 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 [ Time Frame: Baseline (Week 4 of Phase A), Weeks 2, 4, 6, and 8 of Phase B ]
    The GBI 10-item depression scale was developed to screen for depressive symptoms in children and adolescents. Two versions of the GBI 10-item depression scale were used, the child rated version (CGBI) and the parent rated version (PGBI). The 10 depression items were rated on a 4-point scale from 0 (never or hardly ever) to 3 (very often or almost constantly). The total score ranged from 0 to 30, with higher scores indicating greater pathology.

  6. Parent Global Assessment (PGA) Score [ Time Frame: Weeks 2, 4, 6, and 8 of Phase B ]
    The PGA is a parent-rated variation of the CGI-I to evaluate the severity of the child's symptoms. The PGA reflects assessments of symptoms using a 7-point scale ranging from 1 (very much improved) to 7 (very much worse).

  7. 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 [ Time Frame: Baseline (Week 4 of Phase A), Weeks 1, 2, 3, 4, 6, and 8 of Phase B ]
    The CGI-S provides the clinician's impression of the participant's current state of mental illness. The clinician uses his or her clinical experience of this participant population to rate the severity of the participant's current mental illness on a 7-point scale ranging from 1 (normal - not at all ill) to 7 (among the most extremely ill participants).

  8. Clinical Global Impression - Global Improvement (CGI-I) Score [ Time Frame: Weeks 1, 2, 3, 4, 6, and 8 of Phase B ]
    The CGI-I provides the clinician's impression of the participant's improvement (or worsening). The clinician assesses the participant's condition relative to a baseline on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse).

  9. Percentage of Participants With CGI-S Remission [ Time Frame: Weeks 1, 2, 3, 4, 6, and 8 of Phase B ]
    CGI-S remission was defined as a CGI-S score of 1 or 2. The CGI-S provides the clinician's impression of the participant's current state of mental illness. The clinician uses his or her clinical experience of this participant population to rate the severity of the participant's current mental illness on a 7-point scale ranging from 1 (normal - not at all ill) to 7 (among the most extremely ill participants).

  10. Change From Baseline in Children's Global Assessment Scale (CGAS) Score at Weeks 4 and 8 of Phase B [ Time Frame: Baseline (Week 4 of Phase A), Weeks 4 and 8 of Phase B ]
    The CGAS is a clinician-rated global scale to measure the lowest level of functioning for a child (4 to 16 years) during a specified time period. The CGAS contains behaviourally-oriented descriptors at each anchor point that depict behaviours and life situations applicable to a child. The score ranges from 1 (most functionally impaired child) to 100 (the healthiest). A score greater than 70 indicates normal function.

  11. 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 [ Time Frame: Baseline (Week 4 of Phase A), Weeks 4 and 8 of Phase B ]
    The PedsQL™ VAS is designed to measure at-that-moment functioning in children and adolescents. The PedsQL VAS consists of 6 domains: anxiety, sadness, anger, worry, fatigue and pain using visual analogue scales. The functionality for each domain is measured on a 10 cm line with a happy face at one end and a sad face at the other (0-10 points). The participants are asked to mark on the line how they feel. A lower value represents a better outcome.

  12. Change From Baseline in PedsQL VAS: Sad or Blue (Sadness) Score at Weeks 4 and 8 of Phase B [ Time Frame: Baseline (Week 4 of Phase A), Weeks 4 and 8 of Phase B ]
    The PedsQL™ VAS is designed to measure at-that-moment functioning in children and adolescents. The PedsQL VAS consists of 6 domains: anxiety, sadness, anger, worry, fatigue and pain using visual analogue scales. The functionality for each domain is measured on a 10 cm line with a happy face at one end and a sad face at the other (0-10 points). The participants are asked to mark on the line how they feel. A lower value represents a better outcome.

  13. Change From Baseline in PedsQL VAS: Angry Score at Weeks 4 and 8 of Phase B [ Time Frame: Baseline (Week 4 of Phase A), Weeks 4 and 8 of Phase B ]
    The PedsQL™ VAS is designed to measure at-that-moment functioning in children and adolescents. The PedsQL VAS consists of 6 domains: anxiety, sadness, anger, worry, fatigue and pain using visual analogue scales. The functionality for each domain is measured on a 10 cm line with a happy face at one end and a sad face at the other (0-10 points). The participants are asked to mark on the line how they feel. A lower value represents a better outcome.

  14. Change From Baseline in PedsQL VAS: Worry Score at Weeks 4 and 8 of Phase B [ Time Frame: Baseline (Week 4 of Phase A), Weeks 4 and 8 of Phase B ]
    The PedsQL™ VAS is designed to measure at-that-moment functioning in children and adolescents. The PedsQL VAS consists of 6 domains: anxiety, sadness, anger, worry, fatigue and pain using visual analogue scales. The functionality for each domain is measured on a 10 cm line with a happy face at one end and a sad face at the other (0-10 points). The participants are asked to mark on the line how they feel. A lower value represents a better outcome.

  15. Change From Baseline in PedsQL VAS: Tired (Fatigue) Score at Weeks 4 and 8 of Phase B [ Time Frame: Baseline (Week 4 of Phase A), Weeks 4 and 8 of Phase B ]
    The PedsQL™ VAS is designed to measure at-that-moment functioning in children and adolescents. The PedsQL VAS consists of 6 domains: anxiety, sadness, anger, worry, fatigue and pain using visual analogue scales. The functionality for each domain is measured on a 10 cm line with a happy face at one end and a sad face at the other (0-10 points). The participants are asked to mark on the line how they feel. A lower value represents a better outcome.

  16. Change From Baseline in PedsQL VAS: Pain or Hurt Score at Weeks 4 and 8 of Phase B [ Time Frame: Baseline (Week 4 of Phase A), Weeks 4 and 8 of Phase B ]
    The PedsQL™ VAS is designed to measure at-that-moment functioning in children and adolescents. The PedsQL VAS consists of 6 domains: anxiety, sadness, anger, worry, fatigue and pain using visual analogue scales. The functionality for each domain is measured on a 10 cm line with a happy face at one end and a sad face at the other (0-10 points). The participants are asked to mark on the line how they feel. A lower value represents a better outcome.

  17. Change From Baseline in PedsQL VAS Total Average Score at Weeks 4 and 8 of Phase B [ Time Frame: Baseline (Week 4 of Phase A), Weeks 4 and 8 of Phase B ]
    The PedsQL™ VAS is designed to measure at-that-moment functioning in children and adolescents. The PedsQL™ VAS consists of 6 domains: anxiety, sadness, anger, worry, fatigue, and pain using visual analogue scales. The functionality for each domain is measured on a 10cm line with a happy face at one end and a sad face at the other (0-10 points). The participants are asked to mark on the line how they feel. The total score is the average of all 6 items. A lower value represents a better outcome.

  18. Change From Baseline in PedsQL Emotional Distress Summary Average Score at Weeks 4 and 8 of Phase B [ Time Frame: Baseline (Week 4 of Phase A), Weeks 4 and 8 of Phase B ]
    The PedsQL™ VAS is designed to measure at-that-moment functioning in children and adolescents. The PedsQL VAS consists of 6 domains: anxiety, sadness, anger, worry, fatigue and pain using visual analogue scales. The functionality for each domain is measured on a 10 cm line with a happy face at one end and a sad face at the other (0-10 points). The participants are asked to mark on the line how they feel. The average emotional distress summary score is the mean of the anxiety, sadness, anger, and worry items. A lower value represents a better outcome.

  19. 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 [ Time Frame: Baseline (Week 4 of Phase A), Weeks 4 and 8 of Phase B ]
    The PQ-LES-Q is a patient-rated scale designed to assess satisfaction with life. It is an adaptation of the Quality of Life Enjoyment and Satisfaction Questionnaire, which is used to measure quality of life in adults. The PQ-LES-Q consist of 15 items, item 1 to 14 assess the degree of satisfaction experienced by participants in various areas of daily functioning, and item 15 allows subjects to summarise their experience in a global rating. Each item is rated on a 5-point scale from 1 (very poor) to 5 (very good). The total score range of item 1 to 14 is 14 to 70, with higher scores indicating greater satisfaction.

  20. Change From Baseline in PQ-LES-Q Overall Evaluation Score (Item 15) at Weeks 4 and 8 of Phase B [ Time Frame: Baseline (Week 4 of Phase A), Weeks 4 and 8 of Phase B ]
    The PQ-LES-Q is a patient-rated scale designed to assess satisfaction with life. It is an adaptation of the Quality of Life Enjoyment and Satisfaction Questionnaire, which is used to measure quality of life in adults. The PQ-LES-Q consist of 15 items, item 1 to 14 assess the degree of satisfaction experienced by participants in various areas of daily functioning, and item 15 allows subjects to summarize their experience in a global rating. Item 15 is rated on a 5-point scale from 1 (very poor) to 5 (very good).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   7 Years to 11 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. The participant has MDD, diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5™).
  2. The participant has a CDRS-R total score ≥45 at the Screening Visit and the Baseline.
  3. The participant has a CGI-S score ≥4 at the Screening Visit and the Baseline.
  4. The participant is a boy or girl, aged ≥7 and <12 years at Screening Visit
  5. The participant has provided assent to participation and parent(s)/legal representative (s) signed the Informed Consent Form.

Exclusion Criteria:

  1. The participant has participated in a clinical study <30 days prior to the Screening Visit.
  2. The participant has previously participated in a study with vortioxetine.

Other protocol defined inclusion and exclusion criteria may apply


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02709655


Locations
Show Show 98 study locations
Sponsors and Collaborators
H. Lundbeck A/S
Takeda
Investigators
Layout table for investigator information
Study Director: Email contact via Lundbeck A/S LundbeckClinicalTrials@Lundbeck.com
  Study Documents (Full-Text)

Documents provided by H. Lundbeck A/S:
Study Protocol  [PDF] August 21, 2018
Statistical Analysis Plan  [PDF] February 8, 2022

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Responsible Party: H. Lundbeck A/S
ClinicalTrials.gov Identifier: NCT02709655    
Other Study ID Numbers: 12709A
2008-005353-38 ( EudraCT Number )
First Posted: March 16, 2016    Key Record Dates
Results First Posted: September 22, 2022
Last Update Posted: September 22, 2022
Last Verified: August 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by H. Lundbeck A/S:
paediatric
Additional relevant MeSH terms:
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Depressive Disorder
Depression
Depressive Disorder, Major
Mood Disorders
Mental Disorders
Behavioral Symptoms
Vortioxetine
Fluoxetine
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Serotonin Agents
Physiological Effects of Drugs
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Cytochrome P-450 CYP2D6 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Anti-Anxiety Agents
Tranquilizing Agents
Central Nervous System Depressants
Serotonin 5-HT1 Receptor Agonists
Serotonin Receptor Agonists
Serotonin 5-HT3 Receptor Antagonists
Serotonin Antagonists