Study of the Efficacy and Safety of Initial Administration of 17 mg Vortioxetine Intravenously With 10 mg/Day Vortioxetine Orally in Patients With Major Depressive Disorder

Study Overview
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Brief Summary
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To evaluate the early onset of efficacy of vortioxetine 17 mg intravenously (IV) and vortioxetine 10 mg/day oral dose regimen versus placebo IV and vortioxetine 10 mg/day oral dose regimen on depressive symptoms

Official Title
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Interventional, Randomised, Double-blind, Parallel-group Study of the Efficacy and Safety of Initial Administration of 17 mg Vortioxetine Intravenously With 10 mg/Day Vortioxetine Orally in Patients With Major Depressive Disorder

Conditions
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Depressive Disorder, Major

Intervention / Treatment
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* Drug: Vortioxetine (IV)
* Other: Placebo (IV)
* Drug: Vortioxetine (tablet)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patient has recurrent Major Depressive Disorder (MDD), diagnosed according to Diagnostic and Statistical Manual for Mental Disorders, 5th Edition (DSM-5™), classification code (296.3x). The recurrent Major Depressive Episode (MDE) should be confirmed using the Mini-International Neuropsychiatric Interview (MINI). The patient has a Montgomery Åsberg Depression Rating Scale (MADRS) total score ≥30 at both Screening and Baseline Visits. The patient has had the current MDE for ≥3 months Exclusion Criteria: The patient has any current psychiatric disorder or Axis I disorder (DSM-5™ criteria), other than MDD, as assessed using the Mini International Neuropsychiatric Interview (MINI). The patient has a current diagnosis of history of manic or hypomanic episode, schizophrenia or any other psychotic disorder, including major depression with psychotic features (DSM-5™ criteria). The patient suffers from personality disorders, intellectual disability, pervasive development disorder, attention deficit/hyperactivity disorder, organic mental disorders, or mental disorders due to a general medical condition (DSM-5™ criteria). The patient has a history of lack of response to previous treatment with vortioxetine (including current episode). Other Protocol defined inclusion and exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum 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 |
| --- | --- |
| Experimental: IV vortioxetine<br> | Drug: Vortioxetine (IV)<br>* 17 mg, solution for infusion, administered, over 2 hours as single dose<br>Drug: Vortioxetine (tablet)<br>* 10 mg, tablets, oral administration once daily for 15 days (open labelled)<br>|
| Placebo Comparator: IV placebo<br> | Other: Placebo (IV)<br>* Saline: isotonic sodium chloride, administered, over 2 hours as single dose<br>Drug: Vortioxetine (tablet)<br>* 10 mg, tablets, oral administration once daily for 15 days (open labelled)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline to Week 1 in MADRS total score | 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, thus, a negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms. | Baseline to Week 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline to Week 2 in MADRS total score | 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, thus, a negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms. | Baseline to Week 2 | 
| Change from baseline to Day 3 in MADRS total score | 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, thus, a negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms. | Baseline to Day 3 | 
| Change from baseline to Day 1 in MADRS total score | 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, thus, a negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms. | Baseline to Day 1 | 
| Response (defined as a ≥ 50% decrease in MADRS total score from baseline) at Week 1 |  | Week 1 | 
| Remission at Week 1 (defined as a MADRS total score ≤ 10) |  | Week 1 | 
| Change from baseline to Week 1 in HADS depression subscale | The Hospital Anxiety and Depression Scale (HADS) is a patient-rated scale designed to screen for anxiety and depressive states in medical patients. It consists of two sub-scales: the D-scale measures depression and the A-scale measures anxiety. Each sub-scale contains 7 items, and each item is rated from 0 (absent) to 3 (maximum severity). The score of each sub-scale ranges from 0 to 21. | baseline to Week 1 | 
| Global clinical impression -Global Improvement | The Clinical Global Impression - global improvement CGI-I provides the clinician's impression of the patient's improvement (or worsening). The clinician assesses the patient's condition relative to a baseline on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). | At Week 1 | 
| Change from baseline in Global clinical impression -Severity | The Clinical Global Impression severity of illness (CGI-S) provides the clinician's impression of the patient's current state of mental illness. The clinician uses his or her clinical experience of this patient population to rate the severity of the patient's current mental illness on a 7-point scale ranging from 1 (normal - not at all ill) to 7 (among the most extremely ill patients | Baseline to Week 1 | 
| Oral clearance (CL/F) |  | 2, 8 and 24 hours postdose (day 1) and day 14 | 
| Average Plasma Concentration (Cav) |  | 2, 8 and 24 hours postdose (day 1) and day 14 | 
| Change from baseline to Week 1 in HADS anxiety subscale | The HADS is a patient-rated scale designed to screen for anxiety and depressive states in medical patients. It consists of two sub-scales: the D-scale measures depression and the A-scale measures anxiety. Each sub-scale contains 7 items, and each item is rated from 0 (absent) to 3 (maximum severity). The score of each sub-scale ranges from 0 to 21. | Baseline to Week 1 |