Safety and Tolerability of Vortioxetine (LuAA21004) - Open Label Extension Study

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine the long-term safety and tolerability of vortioxetine, once daily (QD), in participants with major depressive disorder.

Detailed Description
-----------------
Depression has been recognized as a chronic illness that imposes a significant burden on individuals, families and society. Major depressive disorder (MDD) is among the most important causes of disability worldwide, in both developing and developed countries. Major depressive disorder is reported to be the most common mood disorder, with a lifetime prevalence of about 15% and as high as 25% in women. Major depressive disorder is characterized by the presence of 1 or more major depressive episodes that presents with depressed mood, loss of interest or pleasure, disturbed sleep or appetite, low energy, feelings of guilt or low self-worth, and poor concentration. This is a multicenter extension study designed to allow eligible patients who have completed short-term efficacy and safety studies LuAA21004_315 (NCT01153009), LuAA21004_316 (NCT01163266) and LuAA21004_317 (NCT01179516) to receive the 52-week treatment with vortioxetine in this open-label extension study. Participants are expected to return to the site for approximately 13 visits. A safety follow-up call will be made 4 weeks after completion of the 52-week treatment period.

Official Title
-----------------
A Phase 3, Long-Term, Open-Label, Flexible-Dose, Extension Study Evaluating the Safety and Tolerability of Lu AA21004 (15 and 20 mg) in Subjects With Major Depressive Disorder

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

Intervention / Treatment
-----------------
* Drug: Vortioxetine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Has completed either study LuAA21004_315 ( NCT01153009), LuAA21004_316 (NCT01163266), or LuAA21004_317 (NCT01179516) immediately prior to enrollment in the extension study (ie, the baseline visit is the same visit as the Week 8 [Lu AA21004_317] or Week 10 [Lu AA21004_315 or Lu AA21004_316] assessment of the preceding protocol). Suffers from a recurrent major depressive episode) as the primary diagnosis according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria (classification code 296.3x) at entry into the prior study. Twelve-month continuation treatment with Lu AA21004 is indicated for the treatment of this participant according to the opinion of the investigator. Females of childbearing potential who are sexually active with a nonsterilized male partner agree to routinely use adequate contraception throughout the duration of the study. Exclusion Criteria: Has Major Depressive Disorder for whom other psychiatric disorders (mania, bipolar disorder, schizophrenia, or any psychotic disorder) have been diagnosed during the prior study. In the investigator's clinical judgment, has a significant risk of suicide and/or a score of ≥5 points on item 10 (suicidal thoughts) of the Montgomery Åsberg Depression Rating Scale (MADRS). In the opinion of the investigator, is unlikely to comply with the clinical study protocol or is unsuitable for any reason. Has a clinically significant moderate or severe ongoing adverse event related to study medication from the prior study. Has used/uses disallowed concomitant medication.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 77 Years

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

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

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

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vortioxetine<br>Vortioxetine 10 mg, capsules, orally, once daily for the first week of treatment; then vortioxetine up-titrated to 15 mg or 20 mg, capsules, orally, once daily for up to 51 weeks. | Drug: Vortioxetine<br>* Vortioxetine tablets<br>* Other names: LuAA21004;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-Emergent Adverse Events at a Frequency Threshold of ≥5% | Treatment-emergent adverse events (TEAE) are adverse events with an onset that occurs after receiving study drug and within 30 days after receiving the last dose of study drug. A TEAE may also be a pretreatment adverse event or a concurrent medical condition diagnosed prior to the date of first dose of study drug that increases in severity after the start of dosing. | Over the 52 week period | 
| Number of Participants With Serious Treatment-Emergent Adverse Events | Serious treatment-emergent adverse events (serious-TEAE) are adverse events with an onset that occurs after receiving study drug and within 30 days after receiving the last dose of study drug. A serious-TEAE may also be a pretreatment adverse event or a concurrent medical condition diagnosed prior to the date of first dose of study drug that increases in severity after the start of dosing. Serious Adverse Events include adverse events that result in death, require either inpatient hospitalization or the prolongation of hospitalization, are life-threatening, result in a persistent or significant disability/incapacity or result in a congenital anomaly/birth defect. Other important medical events, based upon appropriate medical judgment, may also be considered serious adverse events if a trial participant's health is at risk and intervention is required to prevent an outcome mentioned. | Over the 52 week period | 
| Treatment-Emergent Adverse Events Leading to Study Discontinuation | Treatment-emergent adverse events are adverse events with an onset that occurs after receiving study drug and within 30 days after receiving the last dose of study drug. A TEAE may also be a pre-treatment adverse event or a concurrent medical condition diagnosed prior to the date of first dose of study drug that increases in severity after the start of dosing. | Over the 52 week period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score | The change between MADRS total score at each assessed visit and MADRS score at baseline. MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms (i.e., apparent sadness, reported sadness, inner tension, etc.) rated on a 7-point Likert scale from 0 (normal) to 6 (most abnormal) with a total score range from 0 to 60. Higher scores indicate greater severity of symptoms. | Baseline and Weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 36, 44, and 52 | 
| Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score | The change between HAM-A score at each assessed visit and HAM-A score at baseline. HAM-A is a 14 item rating scale to quantify anxiety symptomatology severity (i.e., anxious mood, tension, fear, insomnia, etc.) rated on a 5-point scale from 0 (not present) to 4 (severe) with a total score range from 0 to 56. Higher scores indicate greater severity of symptoms. | Baseline and Weeks 4, 24, and 52 | 
| Change From Baseline in Clinical Global Impression Scale-Severity of Illness (CGI-S) | The change between CGI-S score at each assessed visit and CGI-S score at baseline. The CGI-S assesses the clinician's impression of the subject's current state of mental illness and consists of one question for the investigator: Considering your total clinical experience with this particular population, how mentally ill is the patient at this time? which is rated on a seven-point scale (1=normal, not ill at all; 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=extremely ill). Higher scores indicate greater severity of illness. | Baseline and Weeks 4, 24, and 52 | 
| Change From Baseline in Sheehan Disability Scale (SDS) Total Score | The change between the SDS total score at each assessed visit and the total score collected at baseline. 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. | Baseline and Weeks 12, 24, 36, and 52 | 
| Change From Baseline in SDS Work/School Subscale | The change between the Sheehan Disability work/school subscale score at each assessed visit and work/school subscale score collected at baseline. 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). Higher scores indicate greater severity of impairment. | Baseline and Weeks 12, 24, 36, and 52 | 
| Change From Baseline in SDS Social Life Subscale | The change between the Sheehan Disability social life subscale score at each assessed visit and social life subscale score collected at baseline. 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). Higher scores indicate greater severity of impairment. | Baseline and Weeks 12, 24, 36, and 52 | 
| Change From Baseline in SDS Family Life/Home Responsibilities Subscale | The change between the Sheehan Disability family life/home responsibilities subscale score at each assessed visit and family life/home responsibilities subscale score collected at baseline. 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). Higher scores indicate greater severity of impairment. | Baseline and Weeks 12, 24, 36, and 52 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Depression, Melancholia, Paraphrenia, Drug Therapy