Vortioxetine Intravenous Infusion at Initiation of Oral Treatment With Vortioxetine in Patients With Depression

Interventional, Randomized, Double-blind, Placebo-controlled Study of the Efficacy and Safety of Initial Administration of 25 mg Vortioxetine Intravenously With 10 mg/Day Vortioxetine Orally in Patients With Major Depressive Disorder

The purpose of this study is to evaluate the efficacy and safety of vortioxetine given as a single intravenous dose of 25 mg at initiation of an oral vortioxetine regimen of 10 mg/day for 7 days

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: Vortioxetine infusion 25 mg; Drug: Vortioxetine tablets 10 mg/day; Drug: Placebo infusion; Drug: Placebo tablets

Detailed Description

The study consists of a 7-day double-blind Treatment Period (Day 0 to Day 6)

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 2

Contacts and Locations

Study Locations

• Bulgaria
  • Burgas, Bulgaria
    • Mental Health Centre 'Prof. Dr. Ivan Temkov', EOOD (BG1004)
  • Kardzhali, Bulgaria
    • SPH - Kardzhali, EOOD (BG1005)
  • Kazanlak, Bulgaria
    • MHAT "Dr. Hristo Stambolski", EOOD (BG1001)
  • Novi Iskar, Bulgaria
    • State Psychiatric Hospital "Sv. Ivan Rilski" (BG1009)
  • Pleven, Bulgaria
    • UMHAT 'Dr. Georgi Stranski', EAD (BG1006)
  • Ruse, Bulgaria
    • MHC - Ruse, EOOD (BG1007)
  • Tsarev Brod, Bulgaria
    • State Psychiatric Hospital (BG1008)
  • Vratsa, Bulgaria
    • Mental Health Center-Vratsa EOOD (BG1002)
• Estonia
  • Tallinn, Estonia
    • Marienthali Kliinik (EE2001)
  • Tartu, Estonia
    • Tartu University Hospital (EE2002)
• Latvia
  • Daugavpils, Latvia
    • Psychoneurological Hospital of Daugavpils (LV3003)
  • Riga, Latvia
    • Riga Centre of Psychiatry and Narcology (LV3002)
  • Strenči, Latvia
    • Psychoneurological Hospital of Strenci (LV3001)

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 MDD, diagnosed according to DSM-5® and confirmed using the Mini-International Neuropsychiatric Interview (MINI).
• The patient has a MADRS total score ≥ 30 at the Screening Visit.
• As part of standard of care treatment, the patient is to be admitted to hospital due to the severity of the depressive symptoms and is willing to remain hospitalized for the duration of the study treatment period.
• The patient has had the current MDE for ≥3 months but less than 12 months.
• The patient has received treatment for the current episode with an SSRI/SNRI monotherapy (citalopram, escitalopram, paroxetine, duloxetine, venlafaxine, sertraline) at an approved dose for at least 6 weeks.

Exclusion criteria:

-The patient has any current psychiatric disorder or Axis I disorder (DSM-5® criteria), established as the primary diagnosis, other than MDD, as assessed using the MINI or another diagnostic interview

Other in- and exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: Placebo infusion; concentrate for solution for infusion, 25 mL administered in 250 mL saline over 2 hours as single dose; Drug: Placebo tablets; oral administration once daily
EXPERIMENTAL: Vortioxetine	Drug: Vortioxetine infusion 25 mg; 1 mg/mL, concentrate for solution for infusion, 25 mL (25 mg) administered in 250 mL saline over 2 hours as single dose for 7 days; Drug: Vortioxetine tablets 10 mg/day; 10 mg, tablets, oral administration once daily; Other Names: Brintellix ®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline (Day 0) to Day 1 (24 h post-infusion) in MADRS-6 subscale score	The Montgomery and Åsberg Depression Rating Scale (MADRS) is a ten-item rating scale designed to assess the severity of the symptoms in depressive illness and to be sensitive to treatment effects. Items in the scale assess apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts and suicidal thoughts. Symptoms are rated on a 7-point scale from 0 (no symptom) to 6 (severe symptom). Definitions of severity are provided at two-point intervals. The total score of the ten items ranges from 0 to 60. The primary endpoint will be evaluated with MADRS-6 subscale score, calculated based on the scores on MADRS items 1, 2, 3, 7, 8, and 9 which cover core symptoms (apparent sadness, reported sadness, inner tension, lassitude, inability to feel, and pessimistic thoughts) and is more sensitive to the effect of treatment.	From baseline (Day 0) to Day 1 (24 h post-infusion)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline (Day 0) to Day 3 in MADRS-6 subscale score	The Montgomery and Åsberg Depression Rating Scale (MADRS) is a ten-item rating scale designed to assess the severity of the symptoms in depressive illness and to be sensitive to treatment effects. Items in the scale assess apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts and suicidal thoughts. Symptoms are rated on a 7-point scale from 0 (no symptom) to 6 (severe symptom). Definitions of severity are provided at two-point intervals. The total score of the ten items ranges from 0 to 60. The endpoint will be evaluated with MADRS-6 subscale score, calculated based on the scores on MADRS items 1, 2, 3, 7, 8, and 9 which cover core symptoms (apparent sadness, reported sadness, inner tension, lassitude, inability to feel, and pessimistic thoughts) and is more sensitive to the effect of treatment.	From baseline (Day 0) to Day 3
Change from baseline (Day 0) to Day 7 in MADRS-6 subscale score	The Montgomery and Åsberg Depression Rating Scale (MADRS) is a ten-item rating scale designed to assess the severity of the symptoms in depressive illness and to be sensitive to treatment effects. Items in the scale assess apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts and suicidal thoughts. Symptoms are rated on a 7-point scale from 0 (no symptom) to 6 (severe symptom). Definitions of severity are provided at two-point intervals. The total score of the ten items ranges from 0 to 60. The endpoint will be evaluated with MADRS-6 subscale score, calculated based on the scores on MADRS items 1, 2, 3, 7, 8, and 9 which cover core symptoms (apparent sadness, reported sadness, inner tension, lassitude, inability to feel, and pessimistic thoughts) and is more sensitive to the effect of treatment.	From baseline (Day 0) to Day 7
Change in MADRS total score from baseline to Day 1, Day 3, Day 7	The Montgomery and Åsberg Depression Rating Scale (MADRS) is a ten-item rating scale designed to assess the severity of the symptoms in depressive illness and to be sensitive to treatment effects. Items in the scale assess apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts and suicidal thoughts. Symptoms are rated on a 7-point scale from 0 (no symptom) to 6 (severe symptom). Definitions of severity are provided at two-point intervals. The total score of the ten items ranges from 0 to 60.	From baseline to Day 1, Day 3, Day 7
≥50% decrease in MADRS total score from baseline on Day 1 and Day 3	The Montgomery and Åsberg Depression Rating Scale (MADRS) is a ten-item rating scale designed to assess the severity of the symptoms in depressive illness and to be sensitive to treatment effects. Items in the scale assess apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts and suicidal thoughts. Symptoms are rated on a 7-point scale from 0 (no symptom) to 6 (severe symptom). Definitions of severity are provided at two-point intervals. The total score of the ten items ranges from 0 to 60.	On Day 1 and Day 3
CGI-I score at Day 1, Day 3, Day 7	The Clinical Global Impression (CGI) provides an overall clinician-determined summary measure that takes into account all available information, including knowledge of the patient's history, psychosocial circumstances, symptoms, behavior, and the impact of the symptoms on the patient's ability to function. The CGI consists of two clinician-rated subscales: severity of illness (CGI-S) and global improvement (CGI-I). The 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). In all cases, the assessment should be made independent of whether the rater believes the improvement is drug-related or not.	At Day 1, Day 3, Day 7
CGI-I response (defined as CGI-I score ≤2) on Day 1 and 3	The Clinical Global Impression (CGI) provides an overall clinician-determined summary measure that takes into account all available information, including knowledge of the patient's history, psychosocial circumstances, symptoms, behavior, and the impact of the symptoms on the patient's ability to function. The CGI consists of two clinician-rated subscales: severity of illness (CGI-S) and global improvement (CGI-I). The 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). In all cases, the assessment should be made independent of whether the rater believes the improvement is drug-related or not.	At Day 1 and 3
Change from baseline in CGI-S score to Day 1, Day 3, Day 7	The Clinical Global Impression (CGI) provides an overall clinician-determined summary measure that takes into account all available information, including knowledge of the patient's history, psychosocial circumstances, symptoms, behavior, and the impact of the symptoms on the patient's ability to function. The CGI consists of two clinician-rated subscales: severity of illness (CGI-S) and global improvement (CGI-I). The 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).	From baseline to Day 1, Day 3, Day 7
CL/F of vortioxetine	Total plasma clearance of vortioxetine	Day 0, Day 1, Day 7
Cav	average plasma concentration during a steady-state day	Day 0, Day 1, Day 7

Collaborators and Investigators

• Sponsor: H. Lundbeck A/S

Publications and helpful links

General Publications

• Rancans E, Zambori J, Dalsgaard M, Baayen C, Areberg J, Ettrup A, Florea I. Intravenous vortioxetine to accelerate onset of effect in major depressive disorder: a 7-day randomized, double-blind, placebo-controlled exploratory study. Int Clin Psychopharmacol. 2020 Nov;35(6):305-312. doi: 10.1097/YIC.0000000000000326.

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 3, 2018
• Primary Completion (ACTUAL): July 31, 2019
• Study Completion (ACTUAL): August 28, 2019

Study Registration Dates

• First Submitted: December 5, 2018
• First Submitted That Met QC Criteria: December 5, 2018
• First Posted (ACTUAL): December 6, 2018

Study Record Updates

• Last Update Posted (ACTUAL): August 29, 2019
• Last Update Submitted That Met QC Criteria: August 28, 2019
• Last Verified: June 1, 2019

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: 17915A

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No