Back to resultsEfficacy and Safety Study of Vortioxetine (Lu AA21004) in Adults With Major Depressive Disorder
Primary Purpose
Depressive Disorder, Major
Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Vortioxetine
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Depressive Disorder, Major focused on measuring Major Depressive Disorder, Depression, Melancholia, Drug Therapy
Eligibility Criteria
Inclusion Criteria:
- Suffers from a major depressive episode recurrent as the primary diagnosis according to the American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria.
- Has a Montgomery Åsberg Depression Rating Scale (MADRS) total score of 26 or greater at Screening and Baseline Visits.
- Has a Clinical Global Impression - Severity of Illness (CGI-S) score of 4 or greater at Screening and Baseline Visits.
Exclusion Criteria:
- Has previously participated in a Lu AA21004 clinical study.
Has 1 or more the following:
- Any current psychiatric disorder other than Major Depressive Disorder as defined in the DSM-IV
- Current or past history of: manic or hypomanic episode, schizophrenia or any other psychotic disorder defined in the DSM-IV-TR.
- Diagnosis of alcohol or other substance disorder (except nicotine and caffeine) as defined in the DSM-IV-TR that has not been in sustained full remission for at least years prior to screening (participant must also have negative urine drug screen prior to Baseline).
- Presence or history of a clinically significant neurological disorder (including epilepsy)
- Neurodegenerative disorder.
- Any Axis II disorder that might compromise the study.
- Has a thyroid stimulating hormone value outside the normal range at the Screening Visit that is deemed clinically significant by the investigator.
- Has clinically significant abnormal vital signs as determined by the investigator.
- Has an abnormal Electrocardiogram.
- Has an alanine aminotransferase, aspartate aminotransferase or total bilirubin level greater than 1.5 times the upper limits of normal.
- Has a previous history of cancer that had been in remission for less than 5 years prior to the first dose of study medication.
- Has a disease or takes medication that, in the opinion of the investigator, could interfere with the assessments of safety, tolerability, or efficacy.
- Has a known history of or currently has increased intraocular pressure or is at risk of acute narrow-angle glaucoma.
- Has a clinically significant unstable illness, for example, hepatic impairment or renal insufficiency, or a cardiovascular, pulmonary, gastrointestinal, endocrine, neurological, rheumatologic, immunologic, infectious, skin and subcutaneous tissue disorders, or metabolic disturbance. For the purposes of this protocol the following conditions are considered unstable due to the potential impact on assessment of MDD response: pain disorder, chronic fatigue syndrome, fibromyalgia, and obstructive sleep apnea.
- Has a significant risk of suicide according to the investigator's opinion.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Placebo Comparator
Experimental
Experimental
Arm Label
Placebo
Vortioxetine 10 mg
Vortioxetine 20 mg
Arm Description
Placebo-matching capsules, orally, once daily for up to 8 weeks.
Vortioxetine 10 mg, encapsulated tablets, orally, once daily for up to 8 weeks.
Vortioxetine 10 mg, encapsulated tablets, orally, once daily for one week then vortioxetine 20 mg, encapsulated tablets, orally, once daily for up to 7 weeks.
Outcomes
Primary Outcome Measures
Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score
The MADRS is a depression rating scale consisting of 10 items, each rated 0 (normal) to 6 (most abnormal). 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. Least squares (LS) means are from a mixed model for repeated measurements (MMRM) analysis of covariance (ANCOVA) with treatment, center, week, treatment-by-week interaction, Baseline MADRS total score-by-week as fixed effects.
Secondary Outcome Measures
Percentage of Participants With a MADRS Response at Week 8
Response is defined as a participant with a ≥50% decrease in Montgomery Åsberg Depression Rating Scale (MADRS) total score from Baseline. 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.
Mean Clinical Global Impression Scale-Improvement (CGI-I) Score at Week 8
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 a mixed model for repeated measurements (MMRM) ANCOVA with treatment, center, week, treatment-by-week interaction, Baseline Clinical Global Impression Scale-Severity of Illness Scale (CGI-S) score-by-week as fixed effects.
Change From Baseline in MADRS Total Score at Week 8 in Participants With Baseline Hamilton Anxiety Scale (HAM-A) Total Score ≥20
The MADRS is a depression rating scale consisting of 10 items, each rated 0 (normal) to 6 (most abnormal). 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 a mixed model for repeated measurements (MMRM) ANCOVA with treatment, center, week, treatment-by-week interaction, Baseline MADRS total score-by-week as fixed effects.
The HAM-A is a 14 item rating scale to quantify anxiety severity rated on a 5-point scale from 0 (not present) to 4 (severe) with a total score range from 0 to 56, where lower scores indicate mild severity.
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 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 mixed model for repeated measurements (MMRM) ANCOVA with treatment, center, week, treatment-by-week interaction, Baseline SDS total score-by-week as fixed effects.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01163266
Brief Title
Efficacy and Safety Study of Vortioxetine (Lu AA21004) in Adults With Major Depressive Disorder
Official Title
A Phase 3, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, Fixed-Dose Study Comparing the Efficacy and Safety of 2 Doses (10 and 20 mg) 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
July 2010 (undefined)
Primary Completion Date
January 2012 (Actual)
Study Completion Date
January 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Takeda
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to evaluate the efficacy of vortioxetine, once daily (QD), compared with placebo 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 462 patients. Participants were randomly assigned (by chance, like flipping a coin) to one of the three treatment groups-which remained undisclosed to the patient and study doctor during the study (unless there was an urgent medical need):
Vortioxetine 10 mg
Vortioxetine 20 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 13 weeks. Participants made 9 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
Depressive Disorder, Major
Keywords
Major Depressive Disorder, Depression, Melancholia, Drug Therapy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
462 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo-matching capsules, orally, once daily for up to 8 weeks.
Arm Title
Vortioxetine 10 mg
Arm Type
Experimental
Arm Description
Vortioxetine 10 mg, encapsulated tablets, orally, once daily for up to 8 weeks.
Arm Title
Vortioxetine 20 mg
Arm Type
Experimental
Arm Description
Vortioxetine 10 mg, encapsulated tablets, orally, once daily for one week then vortioxetine 20 mg, encapsulated tablets, orally, once daily for up to 7 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)
Placebo
Intervention Description
Vortioxetine placebo-matching capsules
Primary Outcome Measure Information:
Title
Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score
Description
The MADRS is a depression rating scale consisting of 10 items, each rated 0 (normal) to 6 (most abnormal). 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. Least squares (LS) means are from a mixed model for repeated measurements (MMRM) analysis of covariance (ANCOVA) with treatment, center, week, treatment-by-week interaction, Baseline MADRS total score-by-week as fixed effects.
Time Frame
Baseline and Week 8
Secondary Outcome Measure Information:
Title
Percentage of Participants With a MADRS Response at Week 8
Description
Response is defined as a participant with a ≥50% decrease in Montgomery Åsberg Depression Rating Scale (MADRS) total score from Baseline. 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
Baseline and Week 8
Title
Mean Clinical Global Impression Scale-Improvement (CGI-I) Score at Week 8
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 a mixed model for repeated measurements (MMRM) ANCOVA with treatment, center, week, treatment-by-week interaction, Baseline Clinical Global Impression Scale-Severity of Illness Scale (CGI-S) score-by-week as fixed effects.
Time Frame
Week 8
Title
Change From Baseline in MADRS Total Score at Week 8 in Participants With Baseline Hamilton Anxiety Scale (HAM-A) Total Score ≥20
Description
The MADRS is a depression rating scale consisting of 10 items, each rated 0 (normal) to 6 (most abnormal). 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 a mixed model for repeated measurements (MMRM) ANCOVA with treatment, center, week, treatment-by-week interaction, Baseline MADRS total score-by-week as fixed effects.
The HAM-A is a 14 item rating scale to quantify anxiety severity rated on a 5-point scale from 0 (not present) to 4 (severe) with a total score range from 0 to 56, where lower scores indicate mild severity.
Time Frame
Baseline and 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 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 mixed model for repeated measurements (MMRM) ANCOVA with treatment, center, week, treatment-by-week interaction, Baseline SDS total score-by-week as fixed effects.
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 recurrent as the primary diagnosis according to the American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria.
Has a Montgomery Åsberg Depression Rating Scale (MADRS) total score of 26 or greater at Screening and Baseline Visits.
Has a Clinical Global Impression - Severity of Illness (CGI-S) score of 4 or greater at Screening and Baseline Visits.
Exclusion Criteria:
Has previously participated in a Lu AA21004 clinical study.
Has 1 or more the following:
Any current psychiatric disorder other than Major Depressive Disorder as defined in the DSM-IV
Current or past history of: manic or hypomanic episode, schizophrenia or any other psychotic disorder defined in the DSM-IV-TR.
Diagnosis of alcohol or other substance disorder (except nicotine and caffeine) as defined in the DSM-IV-TR that has not been in sustained full remission for at least years prior to screening (participant must also have negative urine drug screen prior to Baseline).
Presence or history of a clinically significant neurological disorder (including epilepsy)
Neurodegenerative disorder.
Any Axis II disorder that might compromise the study.
Has a thyroid stimulating hormone value outside the normal range at the Screening Visit that is deemed clinically significant by the investigator.
Has clinically significant abnormal vital signs as determined by the investigator.
Has an abnormal Electrocardiogram.
Has an alanine aminotransferase, aspartate aminotransferase or total bilirubin level greater than 1.5 times the upper limits of normal.
Has a previous history of cancer that had been in remission for less than 5 years prior to the first dose of study medication.
Has a disease or takes medication that, in the opinion of the investigator, could interfere with the assessments of safety, tolerability, or efficacy.
Has a known history of or currently has increased intraocular pressure or is at risk of acute narrow-angle glaucoma.
Has a clinically significant unstable illness, for example, hepatic impairment or renal insufficiency, or a cardiovascular, pulmonary, gastrointestinal, endocrine, neurological, rheumatologic, immunologic, infectious, skin and subcutaneous tissue disorders, or metabolic disturbance. For the purposes of this protocol the following conditions are considered unstable due to the potential impact on assessment of MDD response: pain disorder, chronic fatigue syndrome, fibromyalgia, and obstructive sleep apnea.
Has a significant risk of suicide according to the investigator's opinion.
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
Anaheim
State/Province
California
Country
United States
City
Cerritos
State/Province
California
Country
United States
City
Costa Mesa
State/Province
California
Country
United States
City
Encino
State/Province
California
Country
United States
City
Garden Grove
State/Province
California
Country
United States
City
Irvine
State/Province
California
Country
United States
City
Pico Rivera
State/Province
California
Country
United States
City
Riverside
State/Province
California
Country
United States
City
Colorado Springs
State/Province
Colorado
Country
United States
City
Norwich
State/Province
Connecticut
Country
United States
City
Maitland
State/Province
Florida
Country
United States
City
North Miami
State/Province
Florida
Country
United States
City
Orange City
State/Province
Florida
Country
United States
City
Orlando
State/Province
Florida
Country
United States
City
St. Petersburg
State/Province
Florida
Country
United States
City
Smyrna
State/Province
Georgia
Country
United States
City
Chicago
State/Province
Illinois
Country
United States
City
Joliet
State/Province
Illinois
Country
United States
City
Skokie
State/Province
Illinois
Country
United States
City
Wichita
State/Province
Kansas
Country
United States
City
Lake Charles
State/Province
Louisiana
Country
United States
City
Worcester
State/Province
Massachusetts
Country
United States
City
St. Charles
State/Province
Missouri
Country
United States
City
St. Louis
State/Province
Missouri
Country
United States
City
Willingboro
State/Province
New Jersey
Country
United States
City
Buffalo
State/Province
New York
Country
United States
City
New York
State/Province
New York
Country
United States
City
Rochester
State/Province
New York
Country
United States
City
Cinti
State/Province
Ohio
Country
United States
City
Dayton
State/Province
Ohio
Country
United States
City
Middleburg Heights
State/Province
Ohio
Country
United States
City
Portland
State/Province
Oregon
Country
United States
City
Norristown
State/Province
Pennsylvania
Country
United States
City
Philadelphia
State/Province
Pennsylvania
Country
United States
City
Charleston
State/Province
South Carolina
Country
United States
City
Irving
State/Province
Texas
Country
United States
City
Richmond
State/Province
Virginia
Country
United States
City
Seattle
State/Province
Washington
Country
United States
City
Brown Deer
State/Province
Wisconsin
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
31818787
Citation
Christensen MC, Florea I, Loft H, McIntyre RS. Efficacy of vortioxetine in patients with major depressive disorder reporting childhood or recent trauma. J Affect Disord. 2020 Feb 15;263:258-266. doi: 10.1016/j.jad.2019.11.074. Epub 2019 Nov 13.
Results Reference
derived
PubMed Identifier
26035185
Citation
Jacobsen PL, Mahableshwarkar AR, Serenko M, Chan S, Trivedi MH. A randomized, double-blind, placebo-controlled study of the efficacy and safety of vortioxetine 10 mg and 20 mg in adults with major depressive disorder. J Clin Psychiatry. 2015 May;76(5):575-82. doi: 10.4088/JCP.14m09335.
Results Reference
derived
Learn more about this trial
Efficacy and Safety Study of Vortioxetine (Lu AA21004) in Adults With Major Depressive Disorder
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