Randomised Placebo-controlled Duloxetine-referenced Efficacy and Safety Study of 2.5, 5 and 10 mg of Vortioxetine (Lu AA21004) in Acute Treatment of Major Depressive Disorder

Study Overview
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Brief Summary
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The purpose of the study is to evaluate the efficacy and the tolerability of three fixed doses of Vortioxetine in order to establish the appropriate clinical effective dose range in the treatment of Major Depressive Disorder (MDD).

Official Title
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A Randomised, Double-blind, Parallel-group, Placebo-controlled, Duloxetine-referenced, Fixed-dose Study Evaluating the Efficacy and Safety of Three Dosages of [Vortioxetine] Lu AA21004, in Acute Treatment of Major Depressive Disorder

Conditions
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Major Depressive Disorder

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: MDE as primary diagnosis according to DSM-IV-TR criteria (classification code 296.xx) Moderate to severe depression Current MDE duration of at least 3 months Exclusion Criteria: Any current psychiatric disorder other than MDD as defined in the DSM-IV TR Any substance disorder within the previous 6 months Female patients of childbearing potential who are not using effective contraception Use of any psychoactive medication 2 weeks prior to screening and during the study Other protocol-defined inclusion and exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: 2.5 mg<br> | Drug: Vortioxetine (Lu AA21004)<br>* 2.5 mg/day; encapsulated tablets; orally<br>* Other names: Brintellix;|
| Experimental: Vortioxetine: 5 mg<br> | Drug: Vortioxetine (Lu AA21004)<br>* 5 mg/day; encapsulated tablets; orally<br>* Other names: Brintellix;|
| Experimental: Vortioxetine: 10 mg<br> | Drug: Vortioxetine (Lu AA21004)<br>* 10 mg/day; encapsulated tablets; orally<br>* Other names: Brintellix;|
| Other: Duloxetine: 60 mg<br>Active reference | Drug: Duloxetine<br>* 60 mg/day; encapsulated capsules; 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 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 |
| --- | --- | --- |
| 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 | 
| 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 HAM-D-24 Total Score After 8 Weeks of Treatment in Patients With Baseline HAM-A Total Score >=20 |  | Baseline and 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 | 
| Proportion of Remitters at Week 8 (Remission Defined as a MADRS Total Score <=10) |  | 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 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 | 

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