Randomised Placebo-controlled Duloxetine-referenced Study of Efficacy and Safety of 15 and 20 mg of Vortioxetine (Lu AA21004) in Acute Treatment of Major Depressive Disorder in Adults

Study Overview
=================
Brief Summary
-----------------
The purpose of the study is to evaluate the efficacy, tolerability and the safety of two fixed doses of vortioxetine in the treatment of major depressive disorder.

Official Title
-----------------
A Randomised, Double-blind, Parallel-group, Placebo-controlled, Duloxetine-referenced, Fixed-dose Study Evaluating the Efficacy and Safety of Lu AA21004 (15 and 20 mg/Day) in the Acute Treatment of Adult Patients With Major Depressive Disorder

Conditions
-----------------
Major Depressive Disorder

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: The patient has recurrent MDD as the primary diagnosis according to DSM-IV-TR™ criteria (classification code 296.3x) The patient has a MADRS total score >=26 The patient has a CGI-S score >=4 The patient has had the current episode of MDE for >3 months Exclusion Criteria: Any current anxiety psychiatric disorder as defined in the DSM-IV TR Current diagnosis or 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 Current diagnosis or history of alcohol or other substance abuse or dependence (excluding nicotine or caffeine) as defined in the DSM-IV TR Use of any psychoactive medication 2 weeks prior to screening and during the study The patient is at significant risk of suicide or has a score >=5 on Item 10 (suicidal thoughts) of the MADRS, or has attempted suicide within 6 months prior to the Screening Visit Other protocol-defined inclusion and exclusion criteria may apply.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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: 15 mg<br> | Drug: Vortioxetine (Lu AA21004)<br>* encapsulated tablets, daily, orally<br>* Other names: Brintellix;|
| Experimental: Vortioxetine: 20 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 capsules, daily, orally<br>* Other names: Cymbalta®;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Responders at Week 8 (Response Defined as a >=50% Decrease in the MADRS Total Score From Baseline) |  | 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 MADRS Total Score After 8 Weeks of Treatment in Patients With Baseline HAM-A Total Score ≥20 |  | Baseline and Week 8 | 
| Proportion of Remitters at Week 8 (Remission Defined as a MADRS Total Score <=10) |  | Week 8 | 
| Change From Baseline in SDS Total Score After 8 Weeks of Treatment | The Sheehan Disability Scale (SDS) comprises self-rated items designed to measure impairment. The patient rates the extent to which his or her (1) work, (2) social life or leisure activities and (3) home life or family responsibilities are impaired on a 10-point visual analogue scales, on which 0 = normal functioning and 10 = severe functional impairment. The three items may be summed into a single dimensional measure of global functional impairment that ranges from 0 (unimpaired) to 30 (highly impaired). The higher the score, the more severe. | Baseline and Week 8 | 
| Change From Baseline in ASEX Total Score After 8 Weeks of Treatment | The Arizona Sexual Experience Scale (ASEX) is a 5-item, patient self-rated scale that evaluates a patient's recent sexual experience. Patients are asked to assess their own experience over the last week (for example, How strong is your sex drive?, Are your orgasms satisfying?) and respond on a 6-point scale for each item. The ASEX is used to identify individuals with sexual dysfunction. Possible total score ranges from 5 to 30, with the higher score indicating more patient sexual dysfunction. A negative change indicates a lower sexual dysfunction. | Baseline and Week 8 | 
| Potential Discontinuation Symptoms After Abrupt Discontinuation of Treatment With Vortioxetine | The Discontinuation-Emergent Signs and Symptoms Scale (DESS) was designed to evaluate possible effects of discontinuation of antidepressant therapy. It is a clinician-rated instrument that queries for signs and symptoms on a 43-item checklist (for example, agitation, insomnia, fatigue, and dizziness) to assess whether the item (event) is discontinuation-emergent. A new or worsened event reported after discontinuation of therapy scores 1 point on the checklist, and the DESS total score is the sum of all positive scores on the checklist. A higher score indicates more symptoms. | Change from Week 8 in DESS total score analyzed at Week 10 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Major depressive disorder, Placebo-controlled, Active reference, Multicenter study, Randomised study, Acute treatment