Vortioxetine Intravenous Infusion at Initiation of Oral Treatment With Vortioxetine in Patients With Depression
Primary Purpose
Major Depressive Disorder
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Vortioxetine infusion 25 mg
Vortioxetine tablets 10 mg/day
Placebo infusion
Placebo tablets
Sponsored by
About this trial
This is an interventional treatment trial for Major Depressive Disorder
Eligibility Criteria
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
Sites / Locations
- Mental Health Centre 'Prof. Dr. Ivan Temkov', EOOD (BG1004)
- SPH - Kardzhali, EOOD (BG1005)
- MHAT "Dr. Hristo Stambolski", EOOD (BG1001)
- State Psychiatric Hospital "Sv. Ivan Rilski" (BG1009)
- UMHAT 'Dr. Georgi Stranski', EAD (BG1006)
- MHC - Ruse, EOOD (BG1007)
- State Psychiatric Hospital (BG1008)
- Mental Health Center-Vratsa EOOD (BG1002)
- Marienthali Kliinik (EE2001)
- Tartu University Hospital (EE2002)
- Psychoneurological Hospital of Daugavpils (LV3003)
- Riga Centre of Psychiatry and Narcology (LV3002)
- Psychoneurological Hospital of Strenci (LV3001)
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Vortioxetine
Placebo
Arm Description
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
≥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.
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.
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.
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).
CL/F of vortioxetine
Total plasma clearance of vortioxetine
Cav
average plasma concentration during a steady-state day
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03766867
Brief Title
Vortioxetine Intravenous Infusion at Initiation of Oral Treatment With Vortioxetine in Patients With Depression
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
June 2019
Overall Recruitment Status
Completed
Study Start Date
December 3, 2018 (Actual)
Primary Completion Date
July 31, 2019 (Actual)
Study Completion Date
August 28, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
H. Lundbeck A/S
4. Oversight
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
5. Study Description
Brief Summary
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
Detailed Description
The study consists of a 7-day double-blind Treatment Period (Day 0 to Day 6)
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Major Depressive Disorder
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
80 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Vortioxetine
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Vortioxetine infusion 25 mg
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Vortioxetine tablets 10 mg/day
Other Intervention Name(s)
Brintellix ®
Intervention Description
10 mg, tablets, oral administration once daily
Intervention Type
Drug
Intervention Name(s)
Placebo infusion
Intervention Description
concentrate for solution for infusion, 25 mL administered in 250 mL saline over 2 hours as single dose
Intervention Type
Drug
Intervention Name(s)
Placebo tablets
Intervention Description
oral administration once daily
Primary Outcome Measure Information:
Title
Change from baseline (Day 0) to Day 1 (24 h post-infusion) in MADRS-6 subscale score
Description
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.
Time Frame
From baseline (Day 0) to Day 1 (24 h post-infusion)
Secondary Outcome Measure Information:
Title
Change from baseline (Day 0) to Day 3 in MADRS-6 subscale score
Description
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.
Time Frame
From baseline (Day 0) to Day 3
Title
Change from baseline (Day 0) to Day 7 in MADRS-6 subscale score
Description
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.
Time Frame
From baseline (Day 0) to Day 7
Title
Change in MADRS total score from baseline to Day 1, Day 3, Day 7
Description
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.
Time Frame
From baseline to Day 1, Day 3, Day 7
Title
≥50% decrease in MADRS total score from baseline on Day 1 and Day 3
Description
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.
Time Frame
On Day 1 and Day 3
Title
CGI-I score at Day 1, Day 3, Day 7
Description
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.
Time Frame
At Day 1, Day 3, Day 7
Title
CGI-I response (defined as CGI-I score ≤2) on Day 1 and 3
Description
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.
Time Frame
At Day 1 and 3
Title
Change from baseline in CGI-S score to Day 1, Day 3, Day 7
Description
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).
Time Frame
From baseline to Day 1, Day 3, Day 7
Title
CL/F of vortioxetine
Description
Total plasma clearance of vortioxetine
Time Frame
Day 0, Day 1, Day 7
Title
Cav
Description
average plasma concentration during a steady-state day
Time Frame
Day 0, Day 1, Day 7
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Email contact via H. Lundbeck A/S
Organizational Affiliation
LundbeckClinicalTrials@Lundbeck.com
Official's Role
Study Director
Facility Information:
Facility Name
Mental Health Centre 'Prof. Dr. Ivan Temkov', EOOD (BG1004)
City
Burgas
Country
Bulgaria
Facility Name
SPH - Kardzhali, EOOD (BG1005)
City
Kardzhali
Country
Bulgaria
Facility Name
MHAT "Dr. Hristo Stambolski", EOOD (BG1001)
City
Kazanlak
Country
Bulgaria
Facility Name
State Psychiatric Hospital "Sv. Ivan Rilski" (BG1009)
City
Novi Iskar
Country
Bulgaria
Facility Name
UMHAT 'Dr. Georgi Stranski', EAD (BG1006)
City
Pleven
Country
Bulgaria
Facility Name
MHC - Ruse, EOOD (BG1007)
City
Ruse
Country
Bulgaria
Facility Name
State Psychiatric Hospital (BG1008)
City
Tsarev Brod
Country
Bulgaria
Facility Name
Mental Health Center-Vratsa EOOD (BG1002)
City
Vratsa
Country
Bulgaria
Facility Name
Marienthali Kliinik (EE2001)
City
Tallinn
Country
Estonia
Facility Name
Tartu University Hospital (EE2002)
City
Tartu
Country
Estonia
Facility Name
Psychoneurological Hospital of Daugavpils (LV3003)
City
Daugavpils
Country
Latvia
Facility Name
Riga Centre of Psychiatry and Narcology (LV3002)
City
Riga
Country
Latvia
Facility Name
Psychoneurological Hospital of Strenci (LV3001)
City
Strenči
Country
Latvia
12. IPD Sharing Statement
Citations:
PubMed Identifier
32784346
Citation
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.
Results Reference
derived
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Vortioxetine Intravenous Infusion at Initiation of Oral Treatment With Vortioxetine in Patients With Depression
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