Back to resultsEfficacy and Safety of Vortioxetine (Lu AA21004) in the Treatment of Patients With Major Depressive Disorder
Primary Purpose
Major Depressive Disorder
Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Vortioxetine
Duloxetine
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Major Depressive Disorder focused on measuring Major Depressive Disorder, Depression, Drug Therapy, Major Depressive Episode
Eligibility Criteria
Inclusion Criteria:
- Suffers from a major depressive episode as the primary diagnosis according to Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) criteria.
- The reported duration of the current major depressive episode is at least 3 months.
Exclusion Criteria:
Has 1 or more the following:
- Any current psychiatric disorder other than major depressive disorder as defined in the DSM-IV-TR.
- Current or past history of: manic or hypomanic episode, schizophrenia, or any other psychotic disorder, including major depression with psychotic features, mental retardation, organic mental disorders, or mental disorders due to a general medical condition as defined in the DSM-IV-TR.
- Any substance disorder (except nicotine and caffeine) within the previous 6 months as defined in the DSM-IV-TR.
- Presence or history of a clinically significant neurological disorder (including epilepsy).
- Neurodegenerative disorder (Alzheimer disease, Parkinson disease, multiple sclerosis, Huntington disease, etc).
- Any Axis II disorder that might compromise the study.
- Has a significant risk of suicide according to the investigator's opinion or has a score ≥5 on item 10 (suicidal thoughts) of the Montgomery Åsberg Depression Rating Scale (MADRS) or has made a suicide attempt in the previous 6 months.
- The current depressive symptoms of the patient are considered by the investigator to have been resistant to 2 adequate antidepressant treatments of at least 6 weeks duration each.
- Has received electroconvulsive therapy within 6 months prior to Screening.
- Is currently receiving formal cognitive or behavioral therapy, systematic psychotherapy, or plans to initiate such therapy during the study.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Active Comparator
Placebo Comparator
Arm Label
Vortioxetine 2.5 mg
Vortioxetine 5 mg
Duloxetine 60 mg
Placebo
Arm Description
Vortioxetine 2.5 mg, encapsulated tablets, orally, once daily for up to 8 weeks, then placebo-matching capsules, orally, once daily, for 1 week following the treatment period.
Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up to 8 weeks, then placebo-matching capsules, orally, once daily, for 1 week following the treatment period.
Duloxetine 60 mg, capsules, orally, once daily for up to 8 weeks, then duloxetine 30 mg capsules, orally, once daily for 1 week after the treatment period.
Placebo-matching capsules, orally, once daily for up to 9 weeks.
Outcomes
Primary Outcome Measures
Change From Baseline in the 24-item Hamilton Depression Scale Total Score at Week 8
The HAM-D24 is a clinician-rated 24-item scale for assessing the severity of depression symptoms. The scores for each item range from 0 to 4 or 0 to 2, where 0 represents no symptoms. The rating is based on the past 7 days prior to the time of assessment. The total score ranges from 0 to 74 where a higher score indicates a greater depressive state. Least squares (LS) means were from an Analysis of Covariance (ANCOVA) model with terms for treatment and center as factors and the Baseline rank value as a covariate.
Secondary Outcome Measures
Change From Baseline in the 24-item Hamilton Depression Scale Total Score at Other Weeks Assessed
The HAM-D24 is a clinician-rated 24-item scale for assessing the severity of depression symptoms. The scores for each item range from 0 to 4 or 0 to 2, where 0 represents no symptoms. The rating is based on the past 7 days prior to the time of assessment. The total score ranges from 0 to 74 where a higher score indicates a greater depressive state. LS means were from an ANCOVA model with terms for treatment and center as factors and the Baseline rank value as a covariate.
Percentage of Responders in HAM-D 24 Total Score by Study Visit
A responder is defined as a participant with a ≥50% decrease from Baseline in HAM-D24 total score. The HAM-D24 is a clinician-rated 24-item scale for assessing the severity of depression symptoms. The scores for each item range from 0 to 4 or 0 to 2, where 0 represents no symptoms. The rating is based on the past 7 days prior to the time of assessment. The total score ranges from 0 to 74, where a higher score indicates a greater depressive state.
Percentage of Participants With a Sustained Response in HAM-D24
A sustained response is defined as a ≥ 20% decrease from Baseline in HAM-D24 total score obtained at Week 1 and sustained through Week 7 and at least 50% decrease from Baseline at Week 8.
Percentage of Participants in MADRS Remission at Week 8
Remission is defined as a participant with a Montgomery Åsberg Depression Rating Scale (MADRS) total score ≤10. The MADRS is a depression rating scale consisting of 10 items, each rated 0 to 6. The 10 items represent the core symptoms of depressive illness. The overall score ranges from 0 (symptoms absent) to 60 (severe depression). Decrease in the total score or on individual items indicates improvement.
Change From Baseline in the Montgomery Åsberg Depression Rating Scale (MADRS) Total Score
The MADRS is a depression rating scale consisting of 10 items, each rated 0 to 6. The 10 items represent the core symptoms of depressive illness. The overall score ranges from 0 (symptoms absent) to 60 (severe depression). A decrease in the total score or on individual items indicates improvement. LS means are from an ANCOVA model with treatment and center as fixed factors and the Baseline value as a covariate.
Clinical Global Impression Scale-Global Improvement Scale
The Clinical Global Impression - Global Improvement scale assesses the participant's improvement (or worsening) as assessed by the clinician relative to Baseline on a 7-point scale: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse. LS means were from an ANCOVA model with treatment and center as fixed factors and the CGI-S Baseline value as a covariate.
Change From Baseline in Montgomery-Åsberg Depression Rating Scale - Self-assessment (MADRS-S)
The MADRS-S is a patient-reported outcome measure based on MADRS, administered to evaluate treatment effectiveness in depression. This scale consists of 9 items assessing patients' mood, feelings of unease, sleep, appetite, ability to concentrate, initiative, emotional involvement, pessimism and zest for life. Each item is scored between 0 (best) and 3 (worst). The total score is calculated by summing the answers of the nine items, ranging between 0 and 27 (higher scores indicate increased impairment). LS means are from an ANCOVA model with treatment and center as fixed factors and the Baseline value as a covariate.
Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score
The HAM-A is an anxiety rating scale consisting of 14 items that assess anxious mood, tension, fear, insomnia, intellectual (cognitive) symptoms, depressed mood, behavior at interview, somatic (sensory), cardiovascular, respiratory, gastrointestinal, genitourinary, autonomic and somatic (muscular) symptoms. Each symptom is rated from 0 (absent) to 4 (maximum severity). Total scores range from 0 to 56, where <17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe. Total scores above 30 are rare, but indicate very severe anxiety. LS means are from an ANCOVA model with treatment and center as fixed factors and the Baseline value as a covariate.
Change From Baseline in the Clinical Global Impression Scale-Severity of Illness Scale
The Clinical Global Impression - Severity scale (CGI-S) is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. Considering total clinical experience, a patient is assessed on severity of mental illness on the following scale: 1, normal, not at all ill; 2, borderline mentally ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7, extremely ill. LS means were from an ANCOVA model with treatment and center as fixed factors and the Baseline value as a covariate.
Change From Baseline in Sheehan Disability Scale (SDS) Total Score at Week 8
The Sheehan Disability Scale assesses functional impairment in 3 domains: work/school, social life or leisure activities, and home life or family responsibilities. The participant rates the extent to which each aspect is impaired on a 10-point visual analog scale, from 0 (not at all) to 10 (extremely). The 3 scores are added together to calculate the total score, which ranges from 0 to 30, with higher scores indicating more impairment. LS means were from an ANCOVA model with treatment and center as fixed factors and the Baseline value as a covariate.
Healthcare Resource Utilization as Assessed by the Health Economic Assessment Questionnaire
Healthcare resource utilization was assessed by the Health Economic Assessment (HEA) questionnaire, which monitors participants absenteeism from work, as well as resource use such as visits to a general practitioner, outpatient and inpatient services, hospitalization, medications, and other relevant services over the past 8 weeks.
Full Information
NCT ID
NCT00672620
First Posted
May 2, 2008
Last Updated
October 25, 2013
Sponsor
Takeda
Collaborators
H. Lundbeck A/S
1. Study Identification
Unique Protocol Identification Number
NCT00672620
Brief Title
Efficacy and Safety of Vortioxetine (Lu AA21004) in the Treatment of Patients With Major Depressive Disorder
Official Title
A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, Active-Referenced, Fixed-Dose Study Comparing the Efficacy and Safety of 2 Doses of Lu AA21004 in Acute Treatment of Adults With Major Depressive Disorder
Study Type
Interventional
2. Study Status
Record Verification Date
October 2013
Overall Recruitment Status
Completed
Study Start Date
April 2008 (undefined)
Primary Completion Date
November 2008 (Actual)
Study Completion Date
December 2008 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Takeda
Collaborators
H. Lundbeck A/S
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to determine the efficacy and safety of vortioxetine, once daily (QD), in adults with major depressive disorder.
Detailed Description
The drug that was tested in this study is called Vortioxetine. Vortioxetine is being tested to treat depression in adults who have major depressive disorder (MDD). This study looked at MDD relief in people who took varying dosages of vortioxetine.
The study enrolled 611 patients. Participants were randomly assigned (by chance, like flipping a coin) to one of the four treatment groups-which remained undisclosed to the patient and study doctor during the study (unless there was an urgent medical need):
Vortioxetine 2.5 mg
Vortioxetine 5 mg
Duloxetine 10 mg
Placebo (dummy inactive capsule) - this was a capsule that looked like the study drug but had no active ingredient.
All participants were asked to take one capsule at the same time each day throughout the study.
This multi-center trial was conducted in the United States. The overall time to participate in this study was up to 12 weeks. Participants made 8 visits to the clinic, and were contacted by telephone 4 weeks after the last dose of study drug for a follow-up assessment.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Major Depressive Disorder
Keywords
Major Depressive Disorder, Depression, Drug Therapy, Major Depressive Episode
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
611 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Vortioxetine 2.5 mg
Arm Type
Experimental
Arm Description
Vortioxetine 2.5 mg, encapsulated tablets, orally, once daily for up to 8 weeks, then placebo-matching capsules, orally, once daily, for 1 week following the treatment period.
Arm Title
Vortioxetine 5 mg
Arm Type
Experimental
Arm Description
Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up to 8 weeks, then placebo-matching capsules, orally, once daily, for 1 week following the treatment period.
Arm Title
Duloxetine 60 mg
Arm Type
Active Comparator
Arm Description
Duloxetine 60 mg, capsules, orally, once daily for up to 8 weeks, then duloxetine 30 mg capsules, orally, once daily for 1 week after the treatment period.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo-matching capsules, orally, once daily for up to 9 weeks.
Intervention Type
Drug
Intervention Name(s)
Vortioxetine
Other Intervention Name(s)
Lu AA21004, Brintellix®
Intervention Description
Encapsulated vortioxetine immediate-release tablets
Intervention Type
Drug
Intervention Name(s)
Duloxetine
Other Intervention Name(s)
Cymbalta®
Intervention Description
Duloxetine capsules
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo-matching capsules
Primary Outcome Measure Information:
Title
Change From Baseline in the 24-item Hamilton Depression Scale Total Score at Week 8
Description
The HAM-D24 is a clinician-rated 24-item scale for assessing the severity of depression symptoms. The scores for each item range from 0 to 4 or 0 to 2, where 0 represents no symptoms. The rating is based on the past 7 days prior to the time of assessment. The total score ranges from 0 to 74 where a higher score indicates a greater depressive state. Least squares (LS) means were from an Analysis of Covariance (ANCOVA) model with terms for treatment and center as factors and the Baseline rank value as a covariate.
Time Frame
Baseline and Week 8
Secondary Outcome Measure Information:
Title
Change From Baseline in the 24-item Hamilton Depression Scale Total Score at Other Weeks Assessed
Description
The HAM-D24 is a clinician-rated 24-item scale for assessing the severity of depression symptoms. The scores for each item range from 0 to 4 or 0 to 2, where 0 represents no symptoms. The rating is based on the past 7 days prior to the time of assessment. The total score ranges from 0 to 74 where a higher score indicates a greater depressive state. LS means were from an ANCOVA model with terms for treatment and center as factors and the Baseline rank value as a covariate.
Time Frame
Baseline and Weeks 1, 2, 4, and 6
Title
Percentage of Responders in HAM-D 24 Total Score by Study Visit
Description
A responder is defined as a participant with a ≥50% decrease from Baseline in HAM-D24 total score. The HAM-D24 is a clinician-rated 24-item scale for assessing the severity of depression symptoms. The scores for each item range from 0 to 4 or 0 to 2, where 0 represents no symptoms. The rating is based on the past 7 days prior to the time of assessment. The total score ranges from 0 to 74, where a higher score indicates a greater depressive state.
Time Frame
Baseline and Weeks 1, 2, 4, 6 and 8.
Title
Percentage of Participants With a Sustained Response in HAM-D24
Description
A sustained response is defined as a ≥ 20% decrease from Baseline in HAM-D24 total score obtained at Week 1 and sustained through Week 7 and at least 50% decrease from Baseline at Week 8.
Time Frame
Baseline to Week 8
Title
Percentage of Participants in MADRS Remission at Week 8
Description
Remission is defined as a participant with a Montgomery Åsberg Depression Rating Scale (MADRS) total score ≤10. The MADRS is a depression rating scale consisting of 10 items, each rated 0 to 6. The 10 items represent the core symptoms of depressive illness. The overall score ranges from 0 (symptoms absent) to 60 (severe depression). Decrease in the total score or on individual items indicates improvement.
Time Frame
Week 8
Title
Change From Baseline in the Montgomery Åsberg Depression Rating Scale (MADRS) Total Score
Description
The MADRS is a depression rating scale consisting of 10 items, each rated 0 to 6. The 10 items represent the core symptoms of depressive illness. The overall score ranges from 0 (symptoms absent) to 60 (severe depression). A decrease in the total score or on individual items indicates improvement. LS means are from an ANCOVA model with treatment and center as fixed factors and the Baseline value as a covariate.
Time Frame
Baseline and Weeks 1, 2, 4, 6 and 8
Title
Clinical Global Impression Scale-Global Improvement Scale
Description
The Clinical Global Impression - Global Improvement scale assesses the participant's improvement (or worsening) as assessed by the clinician relative to Baseline on a 7-point scale: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse. LS means were from an ANCOVA model with treatment and center as fixed factors and the CGI-S Baseline value as a covariate.
Time Frame
Baseline and Weeks 1, 2, 4, 6 and 8.
Title
Change From Baseline in Montgomery-Åsberg Depression Rating Scale - Self-assessment (MADRS-S)
Description
The MADRS-S is a patient-reported outcome measure based on MADRS, administered to evaluate treatment effectiveness in depression. This scale consists of 9 items assessing patients' mood, feelings of unease, sleep, appetite, ability to concentrate, initiative, emotional involvement, pessimism and zest for life. Each item is scored between 0 (best) and 3 (worst). The total score is calculated by summing the answers of the nine items, ranging between 0 and 27 (higher scores indicate increased impairment). LS means are from an ANCOVA model with treatment and center as fixed factors and the Baseline value as a covariate.
Time Frame
Baseline and Weeks 1, 4 and 8
Title
Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score
Description
The HAM-A is an anxiety rating scale consisting of 14 items that assess anxious mood, tension, fear, insomnia, intellectual (cognitive) symptoms, depressed mood, behavior at interview, somatic (sensory), cardiovascular, respiratory, gastrointestinal, genitourinary, autonomic and somatic (muscular) symptoms. Each symptom is rated from 0 (absent) to 4 (maximum severity). Total scores range from 0 to 56, where <17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe. Total scores above 30 are rare, but indicate very severe anxiety. LS means are from an ANCOVA model with treatment and center as fixed factors and the Baseline value as a covariate.
Time Frame
Baseline and Weeks 1, 2, 4, 6 and 8.
Title
Change From Baseline in the Clinical Global Impression Scale-Severity of Illness Scale
Description
The Clinical Global Impression - Severity scale (CGI-S) is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. Considering total clinical experience, a patient is assessed on severity of mental illness on the following scale: 1, normal, not at all ill; 2, borderline mentally ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7, extremely ill. LS means were from an ANCOVA model with treatment and center as fixed factors and the Baseline value as a covariate.
Time Frame
Baseline and Weeks 1, 2, 4, 6 and 8.
Title
Change From Baseline in Sheehan Disability Scale (SDS) Total Score at Week 8
Description
The Sheehan Disability Scale assesses functional impairment in 3 domains: work/school, social life or leisure activities, and home life or family responsibilities. The participant rates the extent to which each aspect is impaired on a 10-point visual analog scale, from 0 (not at all) to 10 (extremely). The 3 scores are added together to calculate the total score, which ranges from 0 to 30, with higher scores indicating more impairment. LS means were from an ANCOVA model with treatment and center as fixed factors and the Baseline value as a covariate.
Time Frame
Baseline and Week 8
Title
Healthcare Resource Utilization as Assessed by the Health Economic Assessment Questionnaire
Description
Healthcare resource utilization was assessed by the Health Economic Assessment (HEA) questionnaire, which monitors participants absenteeism from work, as well as resource use such as visits to a general practitioner, outpatient and inpatient services, hospitalization, medications, and other relevant services over the past 8 weeks.
Time Frame
Baseline and Week 8
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Suffers from a major depressive episode as the primary diagnosis according to Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) criteria.
The reported duration of the current major depressive episode is at least 3 months.
Exclusion Criteria:
Has 1 or more the following:
Any current psychiatric disorder other than major depressive disorder as defined in the DSM-IV-TR.
Current or past history of: manic or hypomanic episode, schizophrenia, or any other psychotic disorder, including major depression with psychotic features, mental retardation, organic mental disorders, or mental disorders due to a general medical condition as defined in the DSM-IV-TR.
Any substance disorder (except nicotine and caffeine) within the previous 6 months as defined in the DSM-IV-TR.
Presence or history of a clinically significant neurological disorder (including epilepsy).
Neurodegenerative disorder (Alzheimer disease, Parkinson disease, multiple sclerosis, Huntington disease, etc).
Any Axis II disorder that might compromise the study.
Has a significant risk of suicide according to the investigator's opinion or has a score ≥5 on item 10 (suicidal thoughts) of the Montgomery Åsberg Depression Rating Scale (MADRS) or has made a suicide attempt in the previous 6 months.
The current depressive symptoms of the patient are considered by the investigator to have been resistant to 2 adequate antidepressant treatments of at least 6 weeks duration each.
Has received electroconvulsive therapy within 6 months prior to Screening.
Is currently receiving formal cognitive or behavioral therapy, systematic psychotherapy, or plans to initiate such therapy during the study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director, Clinical Science
Organizational Affiliation
Takeda
Official's Role
Study Director
Facility Information:
City
Beverly Hills
State/Province
California
Country
United States
City
Irvine,
State/Province
California
Country
United States
City
Santa Ana
State/Province
California
Country
United States
City
Torrance
State/Province
California
Country
United States
City
Upland
State/Province
California
Country
United States
City
Bradenton
State/Province
Florida
Country
United States
City
Coral Springs,
State/Province
Florida
Country
United States
City
Fort Walton Beach
State/Province
Florida
Country
United States
City
Gainesville
State/Province
Florida
Country
United States
City
Jacksonville
State/Province
Florida
Country
United States
City
Maitland
State/Province
Florida
Country
United States
City
Orlando
State/Province
Florida
Country
United States
City
South Miami,
State/Province
Florida
Country
United States
City
West Palm Beach
State/Province
Florida
Country
United States
City
Atlanta
State/Province
Georgia
Country
United States
City
Smyrna
State/Province
Georgia
Country
United States
City
Chicago,
State/Province
Illinois
Country
United States
City
Libertyville
State/Province
Illinois
Country
United States
City
Oak Brook
State/Province
Illinois
Country
United States
City
Prairie Village
State/Province
Kansas
Country
United States
City
Owensboro,
State/Province
Kentucky
Country
United States
City
Baltimore
State/Province
Maryland
Country
United States
City
Pittsfield
State/Province
Massachusetts
Country
United States
City
Worcester,
State/Province
Massachusetts
Country
United States
City
Flowood
State/Province
Mississippi
Country
United States
City
New York
State/Province
New York
Country
United States
City
Olean
State/Province
New York
Country
United States
City
Beachwood
State/Province
Ohio
Country
United States
City
Toledo
State/Province
Ohio
Country
United States
City
Oklahoma City,
State/Province
Oklahoma
Country
United States
City
Allenton
State/Province
Pennsylvania
Country
United States
City
Lancaster
State/Province
Pennsylvania
Country
United States
City
Memphis
State/Province
Tennessee
Country
United States
City
Austin
State/Province
Texas
Country
United States
City
San Antonio
State/Province
Texas
Country
United States
City
Salt Lake City,
State/Province
Utah
Country
United States
City
Seattle
State/Province
Washington
Country
United States
City
Milwaukee
State/Province
Wisconsin
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
23252878
Citation
Mahableshwarkar AR, Jacobsen PL, Chen Y. A randomized, double-blind trial of 2.5 mg and 5 mg vortioxetine (Lu AA21004) versus placebo for 8 weeks in adults with major depressive disorder. Curr Med Res Opin. 2013 Mar;29(3):217-26. doi: 10.1185/03007995.2012.761600. Epub 2013 Jan 17.
Results Reference
result
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Efficacy and Safety of Vortioxetine (Lu AA21004) in the Treatment of Patients With Major Depressive Disorder
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