Randomised Placebo-controlled Duloxetine-referenced Study of Efficacy and Safety of 5 mg of Vortioxetine (Lu AA21004) in Acute Treatment of Major Depressive Disorder in Elderly Patients

Study Overview
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Brief Summary
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To assess the efficacy of Vortioxetine (5 mg daily) versus placebo in the acute treatment of depression by means of the change from baseline in the 24-item Hamilton Depression Scale (HAM-D24) total score after 8 weeks of double-blind treatment in elderly patients.

Official Title
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Randomised, Double-blind, Parallel-group, Placebo-controlled, Duloxetine-referenced, Fixed Dose Study Comparing the Efficacy and Safety of [Vortioxetine] Lu AA21004 in Acute Treatment of Major Depressive Disorder in Elderly Patients

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Drug: Placebo
* Drug: Vortioxetine (Lu AA21004)
* Drug: Duloxetine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical Diagnosis of recurrent Major Depressive Episode (MDE) according the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) criteria with: Reported duration of the current episode of at least 4 weeks MADRS total score >=26 At least one previous MDE before the age of 60 years Exclusion Criteria: Mini Mental State Exam (MMSE) <24 Any current anxiety disorder as defined in the DSM-IV-TR Current or past history of manic or hypomanic episode, schizophrenia, or any other psychotic disorder, including major depression with psychotic features, mental retardation, organic mental disorders, or mental disorders due to a general medical condition as defined in the DSM-IV-TR Any substance disorder (except nicotine and caffeine) within the previous 6 months as defined in the DSM-IV-TR Presence or history of a clinically significant neurological disorder (including epilepsy) Neurodegenerative disorder (Alzheimer's disease, Parkinson disease, multiple sclerosis, Huntington disease, etc) Any Axis II disorder that might compromise the study Significant risk of suicide according to the investigator's opinion, or has a score >=5 on item 10 of the MADRS or has made a suicide attempt in the previous 6 months Other inclusion and exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 65 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 |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* capsules; daily; orally<br>|
| Experimental: Vortioxetine 5 mg<br> | Drug: Vortioxetine (Lu AA21004)<br>* encapsulated tablets; daily; orally<br>* Other names: Brintellix;|
| Other: Duloxetine 60 mg<br>Active reference | Drug: Duloxetine<br>* encapsulated tablets; daily; orally<br>* Other names: Cymbalta®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in HAM-D-24 Total Score After 8 Weeks of Treatment | The Hamilton Depression Scale - 24 Items (HAM-D-24) measures depression severity. Items are rated on a scale from 0 (symptoms not present) to a maximum of 2 to 4 (symptom extremely severe) for a total score range of 0 to 76. The higher the score, the more severe. | Baseline and Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in HAM-D-24 Total Score After 6 Weeks of Treatment |  | Baseline and Week 6 | 
| Change From Baseline in HAM-D-24 Total Score After 4 Weeks of Treatment |  | Baseline and Week 4 | 
| Change From Baseline in HAM-D-24 Total Score After 2 Weeks of Treatment |  | Baseline and Week 2 | 
| Change From Baseline in HAM-D-24 Total Score After 1 Week of Treatment |  | Baseline and Week 1 | 
| Change From Baseline in MADRS Total Score After 8 Weeks of Treatment | The Montgomery Åsberg Depression Rating Scale (MADRS) is a depression rating scale consisting of 10 items, each rated 0 (no symptom) to 6 (severe symptom). The 10 items represent the core symptoms of depressive illness. The rating should be based on a clinical interview with the patient, moving from broadly phrased questions about symptoms to more detailed ones, which allow a precise rating of severity, covering the last 7 days. Total score from 0 to 60. The higher the score, the more severe. | Baseline and Week 8 | 
| Change From Baseline in HAM-A Total Score After 8 Weeks of Treatment | The Hamilton Anxiety Rating Scale (HAM-A) consists of 14 items that assess anxious mood, tension, fear, insomnia, intellectual (cognitive) symptoms, depressed mood, behaviour at interview, somatic (sensory), cardiovascular, respiratory, gastrointestinal, genitourinary, autonomic, and somatic (muscular) symptoms. Each symptom is rated from 0 (absent) to 4 (maximum severity). Total score from 0 to 56. The higher the score, the more severe. | Baseline and Week 8 | 
| Change From Baseline in CGI-S Score After 8 Weeks of Treatment | The Clinical Global Impression - Severity of Illness (CGI-S) is a 7-point scale rated from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). The investigator should use his/her total clinical experience with this patient population to judge how mentally ill the patient is at the time of rating. | Baseline and Week 8 | 
| Change in Clinical Status Using CGI-I Score at Week 8 | The Clinical Global Impression - Global Improvement (CGI-I) is a 7-point scale rated from 1 (very much improved) to 7 (very much worse). The investigator rated the patient's overall improvement relative to baseline, whether or not, in the opinion of the investigator, this was entirely due to the drug treatment. | Week 8 | 
| Change From Baseline in GDS Total Score After 8 Weeks of Treatment | The Geriatric Depression Scale (GDS) is a patient self-rating scale designed for the screening of depression in the elderly. It has also been validated as a measure of depression severity. The original version consists of 30 questions with a yes/no answer. In this study, the short 15-item version was used. The total score ranges from 0 to 15, with 15 representing maximum severity. | Baseline and Week 8 | 
| Proportion of Responders at Week 8 (Response Defined as a >=50% Reduction in the HAM-D-24 Total Score) |  | Week 8 | 
| Proportion of Remitters at Week 8 (Remission Defined as a MADRS Total Score <=10) |  | Week 8 | 
| Risk of Suicidality Using C-SSRS Scores | The Columbia-Suicide Severity Rating Scale (C-SSRS) was developed by researchers at Columbia University as a tool to systematically assess suicidal ideation and behaviour in patients during participation in a clinical study. The C-SSRS is composed of questions that address suicidal behaviour and questions that address suicidal ideation, with sub-questions that assess severity. The tool was administered via an interview with the patient. | Up to 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Depression, Elderly, Acute treatment