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

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

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

Study Overview

• Status: Completed
• Conditions: Depressive Disorder, Major
• Intervention / Treatment: Drug: Vortioxetine (IV); Drug: Vortioxetine (tablet); Other: Placebo (IV)

• Study Type: Interventional
• Enrollment (Actual): 55
• Phase: Phase 2

Contacts and Locations

Study Locations

• Estonia
  • Tallinn, Estonia
    • EE1019
  • Tallinn, Estonia
    • EE1020
• Finland
  • Helsinki, Finland
    • FI1040
  • Helsinki, Finland
    • FI1041
  • Kuopio, Finland
    • FI1030
  • Pori, Finland
    • FI1009
  • Turku, Finland
    • FI1027

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IV vortioxetine	Drug: Vortioxetine (IV); 17 mg, solution for infusion, administered, over 2 hours as single dose; Drug: Vortioxetine (tablet); 10 mg, tablets, oral administration once daily for 15 days (open labelled)
Placebo Comparator: IV placebo	Drug: Vortioxetine (tablet); 10 mg, tablets, oral administration once daily for 15 days (open labelled); Other: Placebo (IV); Saline: isotonic sodium chloride, administered, over 2 hours as single dose

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: H. Lundbeck A/S
• Collaborators: Takeda

Publications and helpful links

General Publications

• Vieta E, Florea I, Schmidt SN, Areberg J, Ettrup A. Intravenous vortioxetine to accelerate onset of effect in major depressive disorder: a 2-week, randomized, double-blind, placebo-controlled study. Int Clin Psychopharmacol. 2019 Jul;34(4):153-160. doi: 10.1097/YIC.0000000000000271.

Helpful Links

• Results EudraCT 2015-005081-30

Study record dates

Study Major Dates

• Study Start (Actual): September 27, 2016
• Primary Completion (Actual): April 27, 2017
• Study Completion (Actual): April 27, 2017

Study Registration Dates

• First Submitted: September 28, 2016
• First Submitted That Met QC Criteria: September 28, 2016
• First Posted (Estimate): September 29, 2016

Study Record Updates

• Last Update Posted (Actual): June 20, 2018
• Last Update Submitted That Met QC Criteria: June 18, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Tranquilizing Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Serotonin 5-HT1 Receptor Agonists; Serotonin Receptor Agonists; Serotonin Antagonists; Anti-Anxiety Agents; Serotonin 5-HT3 Receptor Antagonists; Vortioxetine
• Other Study ID Numbers: 16903A; 2015-005081-30 (EudraCT Number)