Back to resultsStudy of Efficacy and Safety of Vortioxetine (Lu AA21004) in Treating Generalized Anxiety Disorder
Primary Purpose
Generalized Anxiety Disorder
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 Generalized Anxiety Disorder focused on measuring Generalized Anxiety Disorder, Mood Disorder, Affective Disorder, Anxiety Disorder, Drug Therapy
Eligibility Criteria
Inclusion Criteria:
- Has a primary diagnosis of Generalized Anxiety Disorder according to Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR®) criteria (classification code 300.02).
- Has a Hamilton Anxiety Scale total score ≥ 20.
- Has a Hamilton Anxiety Scale score ≥ 2 on both item 1 (anxious mood) and item 2 (tension).
- Has a Montgomery-Åsberg Depression Rating Scale total score ≤16.
Exclusion Criteria:
Has 1 or more of the following:
- Any current psychiatric disorder other than Generalized Anxiety Disorder as defined in the DSM-IV-TR (as assessed by the Mini International Neuropsychiatric Interview [MINI]).
- 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 and participant must have a negative urine drug screen prior to Baseline.
- 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.
- Is taking excluded medications.
- 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 or has made a suicide attempt in the previous 6 months.
- Has previously failed to respond to adequate treatment with selective serotonin reuptake inhibitors and/or serotonin-norepinephrine reuptake inhibitors.
- 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.
- Has a clinically significant unstable illness.
- Has an alanine aminotransferase, aspartate aminotransferase, or total bilirubin level > 1.5 times the upper limit of normal.
- Has a serum creatinine of > 1.5 × the upper limit of normal.
- Has a previous history of cancer that had been in remission for less than 5 years.
- Has thyroid stimulating hormone value outside the normal range.
- Has an abnormal electrocardiogram.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Placebo Comparator
Experimental
Experimental
Arm Label
Placebo
Vortioxetine 2.5 mg
Vortioxetine 10 mg
Arm Description
Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.
Vortioxetine 2.5 mg encapsulated tablets, orally, once daily for up to 8 weeks.
Vortioxetine 10 mg encapsulated tablets, orally, once daily for up to 8 weeks.
Outcomes
Primary Outcome Measures
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. Least Squares (LS) means were from an analysis of covariance (ANCOVA) model with treatment and center as fixed factors and the Baseline value as a covariate.
Secondary Outcome Measures
Change From Baseline in Hamilton Anxiety Scale (HAM-A) Total Score at Other Weeks Assessed
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 were from an ANCOVA model with treatment and center as fixed factors and the Baseline value as a covariate.
Percentage of Responders in HAM-A Total Score at Week 8
Response was defined as a participant with a ≥50% decrease from Baseline in the 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 (symptoms absent) to 56 (maximum severity).
Percentage of Participants in HAM-A Remission at Week 8
Remission is defined as a Hamilton Anxiety Scale (HAM-A) total score ≤ 7. 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 (symptoms absent) to 56 (maximum severity).
Clinical Global Impression Scale-Global Improvement (CGI-I) at Each Week Assessed
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 adjusting for Baseline CGI-S score, center, and treatment.
Change From Baseline in Clinical Global Impression Scale-Severity of Illness (CGI-S)
The Clinical Global Impression - Severity scale (CGI-S) is a 7-point scale that requires the clinician to rate the severity of the participant'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 adjusting for Baseline score, center, and treatment.
Change From Baseline in Hospital Anxiety and Depression (HAD) Scales
The HAD scale is completed by the participant and comprises two subscales, one measuring depression (focusing on the state of lost interest and diminished pleasure response) and one measuring anxiety (including anxious mood, restlessness, anxious thoughts, panic attacks). Each subscale is made up of 7 items that are assessed on a scale of 0 = no anxiety/depression to 3 = severe feeling of anxiety/depression. Participants are required to indicate the response which most accurately reflects the way they have felt over the last few days. Scores for the depression and anxiety subscales are summed separately and not combined, with each score ranging from 0 to 21 (maximal severity). 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) 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.
Change From Baseline 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). LS means were from an ANCOVA model with treatment and center as fixed factors and the baseline value as a covariate.
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
NCT00731120
First Posted
August 6, 2008
Last Updated
October 25, 2013
Sponsor
Takeda
Collaborators
H. Lundbeck A/S
1. Study Identification
Unique Protocol Identification Number
NCT00731120
Brief Title
Study of Efficacy and Safety of Vortioxetine (Lu AA21004) in Treating Generalized Anxiety Disorder
Official Title
A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, Fixed-Dose Study Comparing the Efficacy and Safety of 2 Doses of Lu AA21004 in Acute Treatment of Adults With Generalized Anxiety 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
January 2009 (Actual)
Study Completion Date
February 2009 (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 evaluate the safety and efficacy of 2.5 mg and 10 mg vortioxetine, once daily (QD), in adults with generalized anxiety disorder.
Detailed Description
Participants in this study will be randomly assigned to receive either 2.5 mg or 10 mg of vortioxetine or a placebo once daily for an eight week treatment period.
Participants will be seen weekly during the first 2 weeks of treatment, and then every 2 weeks up to the end of the 8-week treatment period. Total commitment time is up to 12 weeks.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Generalized Anxiety Disorder
Keywords
Generalized Anxiety Disorder, Mood Disorder, Affective Disorder, Anxiety Disorder, Drug Therapy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
457 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks.
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.
Arm Title
Vortioxetine 10 mg
Arm Type
Experimental
Arm Description
Vortioxetine 10 mg encapsulated tablets, orally, once daily for up to 8 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 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. Least Squares (LS) means were from an analysis of covariance (ANCOVA) model with treatment and center as fixed factors and the Baseline value as a covariate.
Time Frame
Baseline and Week 8
Secondary Outcome Measure Information:
Title
Change From Baseline in Hamilton Anxiety Scale (HAM-A) Total Score at Other Weeks Assessed
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 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 and 6
Title
Percentage of Responders in HAM-A Total Score at Week 8
Description
Response was defined as a participant with a ≥50% decrease from Baseline in the 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 (symptoms absent) to 56 (maximum severity).
Time Frame
Baseline and Week 8
Title
Percentage of Participants in HAM-A Remission at Week 8
Description
Remission is defined as a Hamilton Anxiety Scale (HAM-A) total score ≤ 7. 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 (symptoms absent) to 56 (maximum severity).
Time Frame
Week 8
Title
Clinical Global Impression Scale-Global Improvement (CGI-I) at Each Week Assessed
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 adjusting for Baseline CGI-S score, center, and treatment.
Time Frame
Baseline and Weeks 1, 2, 4, 6 and 8.
Title
Change From Baseline in Clinical Global Impression Scale-Severity of Illness (CGI-S)
Description
The Clinical Global Impression - Severity scale (CGI-S) is a 7-point scale that requires the clinician to rate the severity of the participant'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 adjusting for Baseline score, center, and treatment.
Time Frame
Baseline and Weeks 1, 2, 4, 6 and 8.
Title
Change From Baseline in Hospital Anxiety and Depression (HAD) Scales
Description
The HAD scale is completed by the participant and comprises two subscales, one measuring depression (focusing on the state of lost interest and diminished pleasure response) and one measuring anxiety (including anxious mood, restlessness, anxious thoughts, panic attacks). Each subscale is made up of 7 items that are assessed on a scale of 0 = no anxiety/depression to 3 = severe feeling of anxiety/depression. Participants are required to indicate the response which most accurately reflects the way they have felt over the last few days. Scores for the depression and anxiety subscales are summed separately and not combined, with each score ranging from 0 to 21 (maximal severity). 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, 4 and 8.
Title
Change From Baseline in Sheehan Disability Scale (SDS) 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
Change From Baseline 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). 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
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 8
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Has a primary diagnosis of Generalized Anxiety Disorder according to Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR®) criteria (classification code 300.02).
Has a Hamilton Anxiety Scale total score ≥ 20.
Has a Hamilton Anxiety Scale score ≥ 2 on both item 1 (anxious mood) and item 2 (tension).
Has a Montgomery-Åsberg Depression Rating Scale total score ≤16.
Exclusion Criteria:
Has 1 or more of the following:
Any current psychiatric disorder other than Generalized Anxiety Disorder as defined in the DSM-IV-TR (as assessed by the Mini International Neuropsychiatric Interview [MINI]).
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 and participant must have a negative urine drug screen prior to Baseline.
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.
Is taking excluded medications.
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 or has made a suicide attempt in the previous 6 months.
Has previously failed to respond to adequate treatment with selective serotonin reuptake inhibitors and/or serotonin-norepinephrine reuptake inhibitors.
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.
Has a clinically significant unstable illness.
Has an alanine aminotransferase, aspartate aminotransferase, or total bilirubin level > 1.5 times the upper limit of normal.
Has a serum creatinine of > 1.5 × the upper limit of normal.
Has a previous history of cancer that had been in remission for less than 5 years.
Has thyroid stimulating hormone value outside the normal range.
Has an abnormal electrocardiogram.
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
Birmingham
State/Province
Alabama
Country
United States
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
Orange
State/Province
California
Country
United States
City
Redlands
State/Province
California
Country
United States
City
Cromwell
State/Province
Connecticut
Country
United States
City
Norwich
State/Province
Connecticut
Country
United States
City
Hockessin
State/Province
Delaware
Country
United States
City
Fort Myers
State/Province
Florida
Country
United States
City
Jacksonville
State/Province
Florida
Country
United States
City
Lady Lake
State/Province
Florida
Country
United States
City
Miami
State/Province
Florida
Country
United States
City
Atlanta
State/Province
Georgia
Country
United States
City
Chicago
State/Province
Illinois
Country
United States
City
Libertyville
State/Province
Illinois
Country
United States
City
Valparaiso
State/Province
Indiana
Country
United States
City
Overland Park
State/Province
Kansas
Country
United States
City
Prairie Village
State/Province
Kansas
Country
United States
City
Boston
State/Province
Massachusetts
Country
United States
City
Braintree
State/Province
Massachusetts
Country
United States
City
Pittsfield
State/Province
Massachusetts
Country
United States
City
St Louis
State/Province
Missouri
Country
United States
City
Cherry Hill
State/Province
New Jersey
Country
United States
City
Fresh Meadows
State/Province
New York
Country
United States
City
New York
State/Province
New York
Country
United States
City
Olean
State/Province
New York
Country
United States
City
Cincinnati
State/Province
Ohio
Country
United States
City
Columbus
State/Province
Ohio
Country
United States
City
Middleburg Heights
State/Province
Ohio
Country
United States
City
Oklahoma City
State/Province
Oklahoma
Country
United States
City
Emmaus
State/Province
Pennsylvania
Country
United States
City
Philadelphia
State/Province
Pennsylvania
Country
United States
City
Reading
State/Province
Pennsylvania
Country
United States
City
North Charleston
State/Province
South Carolina
Country
United States
City
Nashville
State/Province
Tennessee
Country
United States
City
Houston
State/Province
Texas
Country
United States
City
San Antonio
State/Province
Texas
Country
United States
City
Midlothian
State/Province
Virginia
Country
United States
City
Waukesha
State/Province
Wisconsin
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
24424707
Citation
Mahableshwarkar AR, Jacobsen PL, Serenko M, Chen Y. A randomized, double-blind, fixed-dose study comparing the efficacy and tolerability of vortioxetine 2.5 and 10 mg in acute treatment of adults with generalized anxiety disorder. Hum Psychopharmacol. 2014 Jan;29(1):64-72. doi: 10.1002/hup.2371.
Results Reference
derived
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Study of Efficacy and Safety of Vortioxetine (Lu AA21004) in Treating Generalized Anxiety Disorder
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