Study of Efficacy and Safety of Vortioxetine (Lu AA21004) in Treating Generalized Anxiety Disorder

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Generalized Anxiety Disorder

Intervention / Treatment
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* Drug: Vortioxetine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks. | Drug: Placebo<br>* Vortioxetine placebo-matching capsules<br>|
| Experimental: Vortioxetine 2.5 mg<br>Vortioxetine 2.5 mg encapsulated tablets, orally, once daily for up to 8 weeks. | Drug: Vortioxetine<br>* Encapsulated vortioxetine immediate-release tablets<br>* Other names: Brintellix®;|
| Experimental: Vortioxetine 10 mg<br>Vortioxetine 10 mg encapsulated tablets, orally, once daily for up to 8 weeks. | Drug: Vortioxetine<br>* Encapsulated vortioxetine immediate-release tablets<br>* Other names: Brintellix®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline and Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline and Weeks 1, 2, 4 and 6 | 
| 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). | Baseline and Week 8 | 
| 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). | Week 8 | 
| 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. | Baseline and Weeks 1, 2, 4, 6 and 8. | 
| 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. | Baseline and Weeks 1, 2, 4, 6 and 8. | 
| 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. | Baseline and Weeks 1, 4 and 8. | 
| 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. | Baseline and Week 8 | 
| 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. | Baseline and Week 8 | 
| 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. | Baseline and Week 8 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Generalized Anxiety Disorder, Mood Disorder, Affective Disorder, Anxiety Disorder, Drug Therapy