Back to resultsSafety and Tolerability of Vortioxetine (Lu AA21004) in Adults With Major Depressive Disorder
Primary Purpose
Major Depressive Disorder
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Vortioxetine
Sponsored by
About this trial
This is an interventional treatment trial for Major Depressive Disorder focused on measuring Major Depressive Disorder, Depression, Melancholia, Mood Disorder, Dysthymic Disorder, Drug Therapy
Eligibility Criteria
Inclusion Criteria:
- Has completed the double blind treatment period of either study Lu AA21004_304 (NCT00672620) or LuAA21004_305 (NCT00735709) immediately prior to enrollment in the extension study (ie, the baseline visit is the same visit as the completion visit of the double blind treatment of the preceding protocol).
- 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 (classification code 296.xx) at entry into the prior Lu AA21004_304 or Lu AA21004_305 study.
Exclusion Criteria:
In addition to meeting the exclusion criteria for studies Lu AA21004_304 or Lu AA21004_305 at the time of enrollment into those studies respectively, with the exception of the criteria prohibiting previous exposure to Lu AA21004 and investigational drugs, and the criteria prohibiting patients with increased intraocular pressure, or risk of acute narrow-angle glaucoma, the following exclusion criteria apply:
- Has Major Depressive Disorder for whom other psychiatric disorders (mania, bipolar disorder, schizophrenia, or any psychotic disorder) have been diagnosed during the prior study.
- The participant, in the investigator's opinion, has a significant risk of suicide and/or a score of ≥5 points on item 10 (suicidal thoughts) of the Montgomery Åsberg Depression Rating Scale.
- The participant, in the opinion of the investigator, is unlikely to comply with the clinical study protocol or is unsuitable for any reason.
- Has a clinically significant moderate or severe ongoing adverse event related to study medication from the prior study.
- Has used/uses disallowed concomitant medication.
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Vortioxetine
Arm Description
Vortioxetine 2.5 mg, 5 mg or 10 mg, encapsulated tablets, orally, once daily for up to 52 weeks. For the first week of treatment all participants received 5 mg/day vortioxetine, thereafter, the dose could be increased to 10 mg/day or decreased to 2.5 mg/day, based on participant's response and tolerability as judged by the investigator.
Outcomes
Primary Outcome Measures
Physical Examination Findings
Physical examination consisted of the following body systems: (1) appearance; (2) extremities; (3) skin; (4) head and neck; (5) eyes, ears, nose, and throat; (6) lungs and chest; (7) heart and cardiovascular system; (8) abdomen; and (9) musculoskeletal system. An assessment of the nervous system was conducted; any findings were captured under the appropriate body area.
Each system was assessed as normal or abnormal.
Number of Participants With Potentially Clinically Significant Laboratory Evaluation Findings
Participants with at least one post-baseline potentially clinically significant (as defined in the table below) serum chemistry, hematology or urinalysis result. ULN = upper limit of normal; LLN = Lower limit of normal.
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings
A standard 12-lead ECG was performed at the designated study visits. The central reader reviewed and recorded the intervals (PR, QRS, RR, QT, and corrected QT interval [QTc]), and interpreted the ECG using 1 of the following categories: within normal limits or abnormal. The number of participants with at least one post-baseline potentially clinically significant ECG finding is reported. bpm = beats per minute; QTcB = QT interval corrected using Bazett's formula; QTcF = QT interval corrected using Fridericia's formula.
Number of Participants With Adverse Events (AEs)
The intensity (severity) of each AE was defined as:
Mild: caused minimal discomfort and did not interfere in a significant manner with normal activities.
Moderate: sufficiently uncomfortable to produce some impairment of normal activities.
Severe: incapacitating, preventing the patient from participating in normal activities.
The causal relationship between an AE and study drug was assessed by the investigator as Probable, Possible or Not Related; Related=AEs with causality of Possibly or Probably. A serious AE (SAE) was defined as any untoward medical occurrence that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, led to a congenital anomaly/birth defect, or was an important medical event that either jeopardized the patient, required intervention to prevent any of the SAEs defined above, a suicide attempt or an abortion.
Number of Participants With Potentially Clinically Significant Vital Sign Findings
Participants with at least one potentially clinically significant post-baseline vital sign finding. The definition of clinically significant is included in the table below for each parameter. SSBP = supine systolic blood pressure; SDBP = supine diastolic blood pressure.
Secondary Outcome Measures
Change From Baseline in Hamilton Depression Scale-24 Item (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. Final Visit includes data from Week 52 or earlier for participants who didn't complete the 52 weeks.
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). Decrease in the total score or on individual items indicates improvement. Final Visit includes data from Week 52 or earlier for participants who didn't complete the 52 weeks.
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. Final Visit includes data from Week 52 or earlier for participants who didn't complete the 52 weeks.
Change From Baseline in the Clinical Global Impression of 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. Final Visit includes data from Week 52 or earlier for participants who didn't complete the 52 weeks.
Change From Baseline to the Final Visit in 36-item Short-form Health Survey (SF-36)
The Medical Outcomes Study SF-36 is a participant self-rated questionnaire that is a general measure of perceived health status comprising 36 questions, which yields an 8-scale health profile. The 8 health concepts are: 1. Limitation in physical activities because of health problems. 2. Limitations in usual role activities because of physical health problems. 3. Bodily pain. 4. Limitations in social activities because of physical or emotional problems. 5. General mental health (psychological distress and well-being). 6. Limitations in usual role activities because of emotional problems. 7. Vitality (energy and fatigue). 8. General health perception. Each scale ranges from 0 (best) - 100 (worst).
Change From Baseline to the Final Visit in the Sheehan Disability Scale
The Sheehan Disability Scale (SDS) 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.
Health Care Resource Utilization 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
NCT00707980
First Posted
June 27, 2008
Last Updated
October 24, 2013
Sponsor
Takeda
Collaborators
H. Lundbeck A/S
1. Study Identification
Unique Protocol Identification Number
NCT00707980
Brief Title
Safety and Tolerability of Vortioxetine (Lu AA21004) in Adults With Major Depressive Disorder
Official Title
A Long-Term, Open-Label, Flexible-Dose, Extension Study Evaluating the Safety and Tolerability of Lu AA21004 in Subjects With Major Depressive Disorder
Study Type
Interventional
2. Study Status
Record Verification Date
October 2013
Overall Recruitment Status
Completed
Study Start Date
June 2008 (undefined)
Primary Completion Date
July 2010 (Actual)
Study Completion Date
August 2010 (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 long-term 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 people who have major depressive disorder (MDD). This study looked at MDD relief in people who took vortioxetine.
The study enrolled 836 patients that had completed one of two other vortioxetine studies. Participants received 5 mg of vortioxetine for the first week of treatment. After completing the first week of treatment, the dose could be increased to 10 mg/day or decreased to 2.5 mg/day based on participant's response as judged by the doctor.
All participants were asked to take one encapsulated tablet at the same time each day throughout the study.
This multi-center trial was conducted worldwide. The overall time to participate in this study was up to 56 weeks. Participants made 13 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, Melancholia, Mood Disorder, Dysthymic Disorder, Drug Therapy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
836 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Vortioxetine
Arm Type
Experimental
Arm Description
Vortioxetine 2.5 mg, 5 mg or 10 mg, encapsulated tablets, orally, once daily for up to 52 weeks. For the first week of treatment all participants received 5 mg/day vortioxetine, thereafter, the dose could be increased to 10 mg/day or decreased to 2.5 mg/day, based on participant's response and tolerability as judged by the investigator.
Intervention Type
Drug
Intervention Name(s)
Vortioxetine
Other Intervention Name(s)
Lu AA21004, Brintellix®
Intervention Description
Encapsulated vortioxetine immediate-release tablets
Primary Outcome Measure Information:
Title
Physical Examination Findings
Description
Physical examination consisted of the following body systems: (1) appearance; (2) extremities; (3) skin; (4) head and neck; (5) eyes, ears, nose, and throat; (6) lungs and chest; (7) heart and cardiovascular system; (8) abdomen; and (9) musculoskeletal system. An assessment of the nervous system was conducted; any findings were captured under the appropriate body area.
Each system was assessed as normal or abnormal.
Time Frame
Baseline and Week 52
Title
Number of Participants With Potentially Clinically Significant Laboratory Evaluation Findings
Description
Participants with at least one post-baseline potentially clinically significant (as defined in the table below) serum chemistry, hematology or urinalysis result. ULN = upper limit of normal; LLN = Lower limit of normal.
Time Frame
Weeks 4, 8, 12, 20, 28, 36, 44 and 52
Title
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings
Description
A standard 12-lead ECG was performed at the designated study visits. The central reader reviewed and recorded the intervals (PR, QRS, RR, QT, and corrected QT interval [QTc]), and interpreted the ECG using 1 of the following categories: within normal limits or abnormal. The number of participants with at least one post-baseline potentially clinically significant ECG finding is reported. bpm = beats per minute; QTcB = QT interval corrected using Bazett's formula; QTcF = QT interval corrected using Fridericia's formula.
Time Frame
Weeks 4, 12, 24, 36 and 52
Title
Number of Participants With Adverse Events (AEs)
Description
The intensity (severity) of each AE was defined as:
Mild: caused minimal discomfort and did not interfere in a significant manner with normal activities.
Moderate: sufficiently uncomfortable to produce some impairment of normal activities.
Severe: incapacitating, preventing the patient from participating in normal activities.
The causal relationship between an AE and study drug was assessed by the investigator as Probable, Possible or Not Related; Related=AEs with causality of Possibly or Probably. A serious AE (SAE) was defined as any untoward medical occurrence that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, led to a congenital anomaly/birth defect, or was an important medical event that either jeopardized the patient, required intervention to prevent any of the SAEs defined above, a suicide attempt or an abortion.
Time Frame
From the first dose of open-label study drug until 4 weeks after the last dose (up to 56 weeks)
Title
Number of Participants With Potentially Clinically Significant Vital Sign Findings
Description
Participants with at least one potentially clinically significant post-baseline vital sign finding. The definition of clinically significant is included in the table below for each parameter. SSBP = supine systolic blood pressure; SDBP = supine diastolic blood pressure.
Time Frame
Weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 36, 44 and 52
Secondary Outcome Measure Information:
Title
Change From Baseline in Hamilton Depression Scale-24 Item (HAM-D24) Total Score
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. Final Visit includes data from Week 52 or earlier for participants who didn't complete the 52 weeks.
Time Frame
Baseline and Weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 36, 44 and 52.
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). Decrease in the total score or on individual items indicates improvement. Final Visit includes data from Week 52 or earlier for participants who didn't complete the 52 weeks.
Time Frame
Baseline and Weeks 4, 24 and 52
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. Final Visit includes data from Week 52 or earlier for participants who didn't complete the 52 weeks.
Time Frame
Baseline and Weeks 4, 24 and 52
Title
Change From Baseline in the Clinical Global Impression of 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. Final Visit includes data from Week 52 or earlier for participants who didn't complete the 52 weeks.
Time Frame
Baseline and Weeks 4, 24 and 52
Title
Change From Baseline to the Final Visit in 36-item Short-form Health Survey (SF-36)
Description
The Medical Outcomes Study SF-36 is a participant self-rated questionnaire that is a general measure of perceived health status comprising 36 questions, which yields an 8-scale health profile. The 8 health concepts are: 1. Limitation in physical activities because of health problems. 2. Limitations in usual role activities because of physical health problems. 3. Bodily pain. 4. Limitations in social activities because of physical or emotional problems. 5. General mental health (psychological distress and well-being). 6. Limitations in usual role activities because of emotional problems. 7. Vitality (energy and fatigue). 8. General health perception. Each scale ranges from 0 (best) - 100 (worst).
Time Frame
Baseline and Week 52
Title
Change From Baseline to the Final Visit in the Sheehan Disability Scale
Description
The Sheehan Disability Scale (SDS) 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.
Time Frame
Baseline and Week 52
Title
Health Care Resource Utilization 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 52
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
76 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Has completed the double blind treatment period of either study Lu AA21004_304 (NCT00672620) or LuAA21004_305 (NCT00735709) immediately prior to enrollment in the extension study (ie, the baseline visit is the same visit as the completion visit of the double blind treatment of the preceding protocol).
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 (classification code 296.xx) at entry into the prior Lu AA21004_304 or Lu AA21004_305 study.
Exclusion Criteria:
In addition to meeting the exclusion criteria for studies Lu AA21004_304 or Lu AA21004_305 at the time of enrollment into those studies respectively, with the exception of the criteria prohibiting previous exposure to Lu AA21004 and investigational drugs, and the criteria prohibiting patients with increased intraocular pressure, or risk of acute narrow-angle glaucoma, the following exclusion criteria apply:
Has Major Depressive Disorder for whom other psychiatric disorders (mania, bipolar disorder, schizophrenia, or any psychotic disorder) have been diagnosed during the prior study.
The participant, in the investigator's opinion, has a significant risk of suicide and/or a score of ≥5 points on item 10 (suicidal thoughts) of the Montgomery Åsberg Depression Rating Scale.
The participant, in the opinion of the investigator, is unlikely to comply with the clinical study protocol or is unsuitable for any reason.
Has a clinically significant moderate or severe ongoing adverse event related to study medication from the prior study.
Has used/uses disallowed concomitant medication.
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
City
Elizabeth Vale
Country
Australia
City
Richmond
Country
Australia
City
Southport
Country
Australia
City
Osijek
Country
Croatia
City
Zagreb
Country
Croatia
City
Bully les Mines
Country
France
City
Marseille
Country
France
City
Strasbourg
Country
France
City
Berlin
Country
Germany
City
Bochum
Country
Germany
City
Chemnitz
Country
Germany
City
Huettenberg
Country
Germany
City
Leipzig
Country
Germany
City
München
Country
Germany
City
Nuernberg
Country
Germany
City
Wiesbaden
Country
Germany
City
Buchon
Country
Korea, Republic of
City
Gyeonggi-do
Country
Korea, Republic of
City
Incheon
Country
Korea, Republic of
City
Seoul
Country
Korea, Republic of
City
Liepaja
Country
Latvia
City
Riga
Country
Latvia
City
Sigulda
Country
Latvia
City
Siauliai
Country
Lithuania
City
Vilnius
Country
Lithuania
City
Kuala Lumpur
Country
Malaysia
City
SchHoogfliet
Country
Netherlands
City
Wildervank
Country
Netherlands
City
Zwijndrecht
Country
Netherlands
City
Białystok
Country
Poland
City
Leszno
Country
Poland
City
Pruszków
Country
Poland
City
Skórzewo
Country
Poland
City
Toruń
Country
Poland
City
Tuszyn
Country
Poland
City
Moscow
Country
Russian Federation
City
Nizhny Novgorod
Country
Russian Federation
City
Novosibirsk
Country
Russian Federation
City
Omsk
Country
Russian Federation
City
St. Petersburg
Country
Russian Federation
City
Stavropol
Country
Russian Federation
City
Tomsk
Country
Russian Federation
City
Belgrade
Country
Serbia
City
Bryanston
Country
South Africa
City
Durban
Country
South Africa
City
Lyttelton
Country
South Africa
City
NoordHeuwel
Country
South Africa
City
Pretoria
Country
South Africa
City
Kaohsiung
Country
Taiwan
City
Dnepropetrovsk
Country
Ukraine
City
Kiev
Country
Ukraine
City
Lugansk
Country
Ukraine
City
Simferopol
Country
Ukraine
City
Glasgow
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
Safety and Tolerability of Vortioxetine (Lu AA21004) in Adults With Major Depressive Disorder
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