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

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ClinicalTrials.gov Identifier: NCT02709746
Recruitment Status : Completed
First Posted : March 16, 2016
Results First Posted : August 19, 2020
Last Update Posted : August 19, 2020
Sponsor:
Collaborator:
Takeda
Information provided by (Responsible Party):
H. Lundbeck A/S

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).

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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 784 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: 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)
Study Start Date : May 2016
Actual Primary Completion Date : July 2, 2019
Actual Study Completion Date : July 30, 2019

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 (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 (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, Drug: Fluoxetine 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

Placebo Comparator: Placebo Other: Placebo
Encapsulated tablet




Primary Outcome Measures :
  1. Change in Children Depression Rating Scale - Revised (CDRS-R) Total Score After Treatment [ Time Frame: 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 Outcome Measures :
  1. Change in CDRS-R Total Score During Treatment (at Week 2) [ Time Frame: 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'.

  2. Change in CDRS-R Total Score During Treatment (at Week 4) [ Time Frame: 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).

  3. Change in CDRS-R Total Score During Treatment (at Week 6) [ Time Frame: 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).

  4. Change in CDRS-R Mood Score [ Time Frame: 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.

  5. Change in CDRS-R Somatic Score [ Time Frame: 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.

  6. Change in CDRS-R Subjective Score [ Time Frame: 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.

  7. Change in CDRS-R Behaviour Score [ Time Frame: 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.

  8. CDRS-R Response [ Time Frame: 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).

  9. CDRS-R Remission [ Time Frame: From Randomization to Week 8 ]
    Remission is defined as a CDRS-R total score <= 28.

  10. Change in General Behaviour Inventory (GBI) Depression Sub Scale Score Assessed by the Parents [ Time Frame: 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.

  11. Change General Behaviour Inventory (GBI) Depression Subscale Score Assessed by the Child [ Time Frame: 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.

  12. Parent Global Assessment-Global Improvement (PGA) Score [ Time Frame: 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).

  13. Change in Symbol Digit Modalities Test (SDMT) [ Time Frame: 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).

  14. Change in Clinical Global Impression Severity of Illness (CGI-S) Score [ Time Frame: 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).

  15. Clinical Global Impression - Global Improvement (CGI-I) Score [ Time Frame: 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.

  16. CGI-S Remission [ Time Frame: From Randomization to Week 8 ]
    Remission defined as CGI-S score of 1 or 2.

  17. Change in Children's Global Assessment Scale (CGAS) Score [ Time Frame: 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.

  18. Change in Pediatric Quality of Life Inventory (PedsQL) Visual Analogue Scales (VAS): Afraid or Scared (Anxiety) Score [ Time Frame: 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.

  19. Change in PedsQL VAS: Sad or Blue (Sadness) Score [ Time Frame: 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.

  20. Change in PedsQL VAS: Angry Score [ Time Frame: 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.

  21. Change in PedsQL VAS: Worry Score [ Time Frame: 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.

  22. Change in PedsQL VAS: Tired (Fatigue) Score [ Time Frame: 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.

  23. Change in PedsQL VAS: Pain or Hurt Score [ Time Frame: 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.

  24. Change in PedsQL VAS Total Average Score [ Time Frame: 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.

  25. Change in PedsQL Emotional Distress Summary Average Score [ Time Frame: 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.

  26. Change in Paediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q) Total Scores [ Time Frame: 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.

  27. Change in PQ-LES-Q Overall Score [ Time Frame: 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).



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.


Layout table for eligibility information
Ages Eligible for Study:   12 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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


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): NCT02709746


Locations
Show Show 124 study locations
Sponsors and Collaborators
H. Lundbeck A/S
Takeda
Investigators
Layout table for investigator information
Study Director: Email contact via H. Lundbeck A/S LundbeckClinicalTrials@Lundbeck.com
  Study Documents (Full-Text)

Documents provided by H. Lundbeck A/S:
Study Protocol  [PDF] July 5, 2018
Statistical Analysis Plan  [PDF] August 15, 2019

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Responsible Party: H. Lundbeck A/S
ClinicalTrials.gov Identifier: NCT02709746    
Other Study ID Numbers: 12710A
2008-005354-20 ( EudraCT Number )
First Posted: March 16, 2016    Key Record Dates
Results First Posted: August 19, 2020
Last Update Posted: August 19, 2020
Last Verified: August 2020
Keywords provided by H. Lundbeck A/S:
paediatric patients
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