Efficacy Study of Vortioxetine (Lu AA21004) for Treatment of Major Depressive Disorder

Study Overview
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Brief Summary
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The purpose of this study is to assess the efficacy, safety and tolerability of 8-week treatment with Vortioxetine (Lu AA21004), once daily (QD), in Japanese participants with major depressive disorder. The purpose of this study is to assess the efficacy, safety and tolerability of 8-week treatment with Lu AA21004, once daily (QD), in Japanese participants with major depressive disorder.

Detailed Description
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Lu AA21004 was discovered by H. Lundbeck A/S, and is under co-development by H. Lundbeck A/S and Takeda for the treatment of major depressive disorder and general anxiety disorder. Major depressive disorder (MDD) is a chronic, recurring disease with considerable morbidity in the general population. The estimated lifetime prevalence of major depression in the adult population is 5 to 25%, with approximately 2-fold higher prevalence in women than in men. The hallmark of the disease is a depressed mood, with additional symptoms including sleep disturbances, psychomotor agitation or retardation, sexual dysfunction, weight loss, concentration difficulties and delusional ideas. In addition to direct ill effects, MDD causes suicide or job loss and exerts indirect influence on social economy. This study will assess the efficacy and the safety of Lu AA21004. This study consists of a 1-week screening period, an 8-week double-blind treatment period, 4-week safety follow-up.The duration of the study is 13 weeks in total. Blood samples will be collected from participants, and a safety follow-up contact (visit or phone call) will be made 4 weeks after completion of the 8-week double-blind treatment period. Subjects who complete the 8-week double-blind treatment period can successively enter a long-term extension study (Lu AA21004/OCT-001; NCT01395147; hereinafter, OCT-001), if they meet all inclusion criteria and none of exclusion criteria of the OCT-001 study and are willing to participate in the OCT-001 study. Subjects who will enter the OCT-001 will not be requested to safety follow-up after completion of the 8-week double-blind treatment period. Lu AA21004 was discovered by H. Lundbeck A/S, and is under co-development by H. Lundbeck A/S and Takeda for the treatment of major depressive disorder and general anxiety disorder. Major depressive disorder (MDD) is a chronic, recurring disease with considerable morbidity in the general population. The estimated lifetime prevalence of major depression in the adult population is 5 to 25%, with approximately 2-fold higher prevalence in women than in men. The hallmark of the disease is a depressed mood, with additional symptoms including sleep disturbances, psychomotor agitation or retardation, sexual dysfunction, weight loss, concentration difficulties and delusional ideas. In addition to direct ill effects, MDD causes suicide or job loss and exerts indirect influence on social economy. This study will assess the efficacy and the safety of Lu AA21004. This study consists of a 1-week screening period, an 8-week double-blind treatment period, 4-week s safety follow-up.The duration of the study is 13 weeks in total. Blood samples will be collected from participants, and a safety follow-up contact (visit or phone call) will be made 4 weeks after completion of the 8-week double-blind treatment period. Subjects who complete the 8-week double-blind treatment period can successively enter a long-term extension study (Lu AA21004/OCT-001; NCT01395147; hereinafter, OCT-001), if they meet all inclusion criteria and none of exclusion criteria of the OCT-001 study and are willing to participate in the OCT-001 study. Subjects who will enter the OCT-001 will not be requested to safety follow-up after completion of the 8-week double-blind treatment period.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Phase III Study to Assess the Efficacy and Safety of Lu AA21004 in Patients With Major Depressive Disorder

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Drug: Vortioxetine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The subject suffers from Major Depressive Disorder (MDD) as the primary diagnosis according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) criteria (classification code 296.2x and 296.3x). The reported duration of the current major depressive episode is at least 3 months at the Screening Visit. The subject has a Montgomery-Åsberg Depression Rating Scale (MADRS) total score ≥26 at the Screening and Baseline Visits. The subject has a Clinical Global Impression Scale-Severity (CGI-S) score ≥4 at the Screening and Baseline Visits Exclusion Criteria: The subject has one or more of the following conditions: Any current psychiatric disorder other than MDD as defined in the DSM-IV-TR. A subject who exhibits symptoms of anxiety is eligible unless the subject fulfills the diagnostic criteria for a current anxiety disorder per 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 any substance-related disorder (except nicotine and caffeine-related disorders) as defined in the DSM-IV-TR. Presence or history of a clinically significant neurological disorder (including epilepsy). Neurodegenerative disorder (Alzheimer's disease, Parkinson's disease, multiple sclerosis, Huntington's disease, etc.). Any DSM-IV-TR axis II disorder that might compromise the study. The current depressive symptoms of the subject are considered by the investigator to have been resistant to 2 adequate antidepressant treatments of at least 6 weeks duration each. The subject is at significant risk of suicide or has a score ≥5 on Item 10 (suicidal thoughts) of the MADRS at the Screening and Baseline Visit, or has attempted suicide within 6 months prior to the Screening Visit.

Ages Eligible for Study
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Minimum Age: 20 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vortioxetine 5 mg<br>Vortioxetine 5 mg, tablets, orally, once daily for up to 8 weeks. | Drug: Vortioxetine<br>* Vortioxetine tablets<br>* Other names: BRINTELLIX;|
| Experimental: Vortioxetine 10 mg<br>Vortioxetine 10 mg, tablets, orally, once daily for up to 8 weeks. | Drug: Vortioxetine<br>* Vortioxetine tablets<br>* Other names: BRINTELLIX;|
| Placebo Comparator: Placebo<br>Vortioxetine placebo-matching tablets, orally, once daily for up to 8 weeks. | Drug: Placebo<br>* Vortioxetine placebo<br>* Other names: Vortioxetine placebo-matching tablets;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score After 8 Weeks of Treatment | MADRS is a 10-item clinician rated scale that measures overall severity of depressive symptoms (such as apparent sadness, reported sadness, inner tension) rated on a 7-point Likert scale from 0 (symptoms absent) to 6 (severe depression) with a total possible score range from 0 to 60. Higher scores indicate greater severity of symptoms. A negative change from Baseline indicates that symptoms have improved. An analysis of covariance (ANCOVA) model was used with change in MADRS total score as a dependent variable, treatment as a fixed effect and the baseline MADRS total score as a covariate. | Baseline, Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients With MADRS Response After 8 Weeks of Treatment | MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms (such as apparent sadness, reported sadness, inner tension) rated on a 7-point Likert scale from 0 (symptoms absent) to 6 (severe depression) with a total possible score range from 0 to 60. Higher scores indicate greater severity of symptoms. Response is defined as a ≥50% decrease in the MADRS Total Score from Baseline. | Baseline, Week 8 | 
| Percentage of Patients With MADRS Remission After 8 Weeks of Treatment | MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms (such as apparent sadness, reported sadness, inner tension) rated on a 7-point Likert scale from 0 (symptoms absent) to 6 (severe depression) with a total possible score range from 0 to 60. Higher scores indicate greater severity of symptoms. Remission is defined as a MADRS Total Score ≤10. | Week 8 | 
| Change From Baseline in the Hamilton Depression Scale (HAM-D17) Total Score After 8 Weeks of Treatment | The HAM-D17 is a 17-item rating scale that assesses depressed mood, agitation and somatic symptoms of depression, rated on a 5-point scale from 0 (absent) to 4 (very severe) with a total score range from 0 to 52. Higher scores indicate greater severity of depression symptoms. A negative change from Baseline indicates that symptoms have improved. ANCOVA model was used with treatment as a fixed effect and the baseline HAM-D17 score as a covariate. | Baseline, Week 8 | 
| Clinical Global Impression Scale-Improvement (CGI-I) Score After 8 Weeks of Treatment | The CGI-I assesses the clinician's impression of the participant's state of mental illness improvement and consists of one question for the investigator: Compared to his condition at the start of the study, how much has this patient changed? which is rated on a seven-point scale (1=very much improved; 2=much improved; 3=minimally improved; 4=no change from baseline; 5=minimally worse; 6= much worse; 7=very much worse). Higher scores indicate greater severity of illness. Values closest to 1 for this outcome measure indicate the greatest improvement of symptoms. ANCOVA model was used with treatment as a fixed effect and the baseline CGI-Severity (CGI-S) score as a covariate. | Baseline, Week 8 | 
| Change From Baseline in Sheehan Disability Scale (SDS) Total Score After 8 Weeks of Treatment | The SDS is a 3 item rating scale to assess functional impairment (panic, anxiety, phobic and depressive symptoms) over three inter-related domains (work/school, social life, and family life/home responsibilities) rated on an 11 point scale from 0 (not at all) to 10 (extremely) with a total score range from 0 to 30. Higher scores indicate greater severity of impairment. A negative change from Baseline indicates that symptoms have improved. ANCOVA model was used with treatment as a fixed effect and the Baseline SDS total score as a covariate. | Baseline, Week 8 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Drug Therapy