Generalized Anxiety Disorder
Conditions
Keywords
Generalized Anxiety Disorder, Mood Disorder, Affective Disorder, Anxiety Disorder, Drug Therapy
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.
Interventions
DRUGVortioxetine
Encapsulated vortioxetine immediate-release tablets
DRUGPlacebo
Vortioxetine placebo-matching capsules
Sponsors
H. Lundbeck A/S
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score | Baseline and Week 8 | 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
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Responders in HAM-A Total Score at Week 8 | Baseline and 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 | 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 | Baseline and Weeks 1, 2, 4, 6 and 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 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) | Baseline and Weeks 1, 2, 4, 6 and 8. | 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 Hamilton Anxiety Scale (HAM-A) Total Score at Other Weeks Assessed | Baseline and Weeks 1, 2, 4 and 6 | 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. |
| Change From Baseline in Sheehan Disability Scale (SDS) at Week 8 | Baseline and 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) | Baseline and Week 8 | 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 | Baseline and Week 8 | 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. |
| Change From Baseline in Hospital Anxiety and Depression (HAD) Scales | Baseline and Weeks 1, 4 and 8. | 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. |
Countries
United States
Participant flow
Recruitment details
Participants took part in the study at 41 investigative sites in the United States from 17 June 2008 to 16 February 2009.
Pre-assignment details
Participants with a diagnosis of generalized anxiety disorder were enrolled equally in one of three treatment groups, once a day placebo or 2.5 or 10 mg vortioxetine.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Vortioxetine placebo-matching capsules, orally, once daily for up to 8 weeks. | 153 |
| Vortioxetine 2.5 mg Vortioxetine 2.5 mg encapsulated tablets, orally, once daily for up to 8 weeks | 152 |
| Vortioxetine 10 mg Vortioxetine 10 mg encapsulated tablets, orally, once daily for up to 8 weeks. | 152 |
| Total | 457 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 7 | 6 | 8 |
| Overall Study | Lack of Efficacy | 4 | 5 | 4 |
| Overall Study | Lost to Follow-up | 10 | 15 | 17 |
| Overall Study | Noncompliance with Study Drug | 3 | 3 | 1 |
| Overall Study | Other | 4 | 0 | 1 |
| Overall Study | Protocol Deviations | 1 | 6 | 1 |
| Overall Study | Withdrawal of Consent | 13 | 8 | 4 |
Baseline characteristics
| Characteristic | Vortioxetine 10 mg | Placebo | Vortioxetine 2.5 mg | Total |
|---|---|---|---|---|
| Age Continuous | 43.3 years STANDARD_DEVIATION 14.99 | 39.5 years STANDARD_DEVIATION 13.45 | 40.8 years STANDARD_DEVIATION 13.81 | 41.2 years STANDARD_DEVIATION 14.15 |
| Age, Customized ≤55 years | 120 participants | 136 participants | 127 participants | 383 participants |
| Age, Customized >55 years | 32 participants | 17 participants | 25 participants | 74 participants |
| Alcohol Consumption 2 to 6 times per week | 22 participants | 17 participants | 23 participants | 62 participants |
| Alcohol Consumption Daily | 1 participants | 1 participants | 5 participants | 7 participants |
| Alcohol Consumption Never | 44 participants | 50 participants | 42 participants | 136 participants |
| Alcohol Consumption Once a week | 29 participants | 33 participants | 28 participants | 90 participants |
| Alcohol Consumption Once monthly or less often | 56 participants | 52 participants | 54 participants | 162 participants |
| Body Mass Index (BMI) | 30.04 kg/m^2 STANDARD_DEVIATION 7.792 | 29.10 kg/m^2 STANDARD_DEVIATION 6.595 | 29.69 kg/m^2 STANDARD_DEVIATION 7.817 | 29.61 kg/m^2 STANDARD_DEVIATION 7.415 |
| Clinical Global Impression - Severity scale score | 4.3 scores on a scale STANDARD_DEVIATION 0.47 | 4.4 scores on a scale STANDARD_DEVIATION 0.54 | 4.3 scores on a scale STANDARD_DEVIATION 0.49 | 4.3 scores on a scale STANDARD_DEVIATION 0.5 |
| Hamilton Anxiety Scale Total Score | 24.5 scores on a scale STANDARD_DEVIATION 3.71 | 25.2 scores on a scale STANDARD_DEVIATION 3.86 | 25.0 scores on a scale STANDARD_DEVIATION 3.6 | 24.9 scores on a scale STANDARD_DEVIATION 3.73 |
| Height | 168.86 cm STANDARD_DEVIATION 10.032 | 168.31 cm STANDARD_DEVIATION 9.994 | 168.63 cm STANDARD_DEVIATION 8.932 | 168.60 cm STANDARD_DEVIATION 9.649 |
| Hospital Anxiety and Depression - Anxiety subscale | 13.2 scores on a scale STANDARD_DEVIATION 3.17 | 13.9 scores on a scale STANDARD_DEVIATION 3.27 | 13.2 scores on a scale STANDARD_DEVIATION 3.56 | 13.4 scores on a scale STANDARD_DEVIATION 3.35 |
| Hospital Anxiety and Depression - Depression subscale | 8.0 scores on a scale STANDARD_DEVIATION 3.6 | 8.7 scores on a scale STANDARD_DEVIATION 3.67 | 8.0 scores on a scale STANDARD_DEVIATION 3.8 | 8.3 scores on a scale STANDARD_DEVIATION 3.7 |
| Montgomery Åsberg Depression Rating Scale (MADRS) total score | 13.04 scores on a scale STANDARD_DEVIATION 2.521 | 12.73 scores on a scale STANDARD_DEVIATION 2.417 | 12.64 scores on a scale STANDARD_DEVIATION 2.502 | 12.80 scores on a scale STANDARD_DEVIATION 2.481 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 participants | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Asian | 2 participants | 2 participants | 3 participants | 7 participants |
| Race/Ethnicity, Customized Black | 38 participants | 46 participants | 38 participants | 122 participants |
| Race/Ethnicity, Customized Caucasian (White, including Hispanic) | 112 participants | 105 participants | 110 participants | 327 participants |
| Race/Ethnicity, Customized Hispanic/Latino | 15 participants | 13 participants | 18 participants | 46 participants |
| Race/Ethnicity, Customized Non-Hispanic/Non-Latino | 137 participants | 140 participants | 134 participants | 411 participants |
| Region of Enrollment United States | 152 participants | 153 participants | 152 participants | 457 participants |
| Sex: Female, Male Female | 96 Participants | 105 Participants | 103 Participants | 304 Participants |
| Sex: Female, Male Male | 56 Participants | 48 Participants | 49 Participants | 153 Participants |
| Smoking Classification Current smoker | 46 participants | 44 participants | 51 participants | 141 participants |
| Smoking Classification Ex-smoker | 22 participants | 22 participants | 29 participants | 73 participants |
| Smoking Classification Never Smoked | 84 participants | 87 participants | 72 participants | 243 participants |
| Weight | 85.67 kg STANDARD_DEVIATION 23.249 | 82.66 kg STANDARD_DEVIATION 20.731 | 84.48 kg STANDARD_DEVIATION 22.727 | 84.27 kg STANDARD_DEVIATION 22.245 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 70 / 153 | 72 / 151 | 83 / 152 |
| serious Total, serious adverse events | 1 / 153 | 2 / 151 | 1 / 152 |
Outcome results
Primary
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.
Time frame: Baseline and Week 8
Population: The full analysis set (FAS) included all randomized patients who received at least 1 dose of study drug, and had at least 1 post-baseline value for assessment of primary efficacy. Last observation carried forward (LOCF) was used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score | -9.87 scores on a scale | Standard Error 0.584 |
| Vortioxetine 2.5 mg | Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score | -10.75 scores on a scale | Standard Error 0.569 |
| Vortioxetine 10 mg | Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score | -10.68 scores on a scale | Standard Error 0.581 |
Comparison: P-values were tested at the 5% significance level (ie, statistical significance if P\<0.05). To control for multiplicity, a pre-specified sequential testing procedure was applied to compare 10 mg and 2.5 mg vortioxetine to placebo; as soon as an endpoint was non-significant at 0.05, the testing procedure stopped for all subsequent endpoints.p-value: 0.27995% CI: [-2.45, 0.71]ANCOVA
p-value: 0.30695% CI: [-2.36, 0.74]ANCOVA
Secondary
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.
Time frame: Baseline and Week 8
Population: Full analysis set with a Baseline SF-36 measurement; LOCF was used.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in 36-item Short-form Health Survey (SF-36) | Physical functioning subscore | 0.46 scores on a scale | Standard Error 1.513 |
| Placebo | Change From Baseline in 36-item Short-form Health Survey (SF-36) | Role - physical subscore | 4.44 scores on a scale | Standard Error 2.018 |
| Placebo | Change From Baseline in 36-item Short-form Health Survey (SF-36) | Bodily pain subscore | 5.90 scores on a scale | Standard Error 1.901 |
| Placebo | Change From Baseline in 36-item Short-form Health Survey (SF-36) | General health subscore | 4.44 scores on a scale | Standard Error 1.289 |
| Placebo | Change From Baseline in 36-item Short-form Health Survey (SF-36) | Vitality subscore | 12.35 scores on a scale | Standard Error 1.782 |
| Placebo | Change From Baseline in 36-item Short-form Health Survey (SF-36) | Social functioning subscore | 15.35 scores on a scale | Standard Error 2.075 |
| Placebo | Change From Baseline in 36-item Short-form Health Survey (SF-36) | Role-emotional subscore | 15.16 scores on a scale | Standard Error 2.076 |
| Placebo | Change From Baseline in 36-item Short-form Health Survey (SF-36) | Mental health subscore | 12.93 scores on a scale | Standard Error 1.642 |
| Vortioxetine 2.5 mg | Change From Baseline in 36-item Short-form Health Survey (SF-36) | Bodily pain subscore | 10.67 scores on a scale | Standard Error 1.855 |
| Vortioxetine 2.5 mg | Change From Baseline in 36-item Short-form Health Survey (SF-36) | Role-emotional subscore | 21.72 scores on a scale | Standard Error 2.028 |
| Vortioxetine 2.5 mg | Change From Baseline in 36-item Short-form Health Survey (SF-36) | General health subscore | 7.01 scores on a scale | Standard Error 1.258 |
| Vortioxetine 2.5 mg | Change From Baseline in 36-item Short-form Health Survey (SF-36) | Vitality subscore | 15.62 scores on a scale | Standard Error 1.74 |
| Vortioxetine 2.5 mg | Change From Baseline in 36-item Short-form Health Survey (SF-36) | Social functioning subscore | 18.38 scores on a scale | Standard Error 2.025 |
| Vortioxetine 2.5 mg | Change From Baseline in 36-item Short-form Health Survey (SF-36) | Physical functioning subscore | 2.69 scores on a scale | Standard Error 1.478 |
| Vortioxetine 2.5 mg | Change From Baseline in 36-item Short-form Health Survey (SF-36) | Role - physical subscore | 8.17 scores on a scale | Standard Error 1.972 |
| Vortioxetine 2.5 mg | Change From Baseline in 36-item Short-form Health Survey (SF-36) | Mental health subscore | 17.25 scores on a scale | Standard Error 1.608 |
| Vortioxetine 10 mg | Change From Baseline in 36-item Short-form Health Survey (SF-36) | Bodily pain subscore | 8.12 scores on a scale | Standard Error 1.905 |
| Vortioxetine 10 mg | Change From Baseline in 36-item Short-form Health Survey (SF-36) | Role - physical subscore | 6.17 scores on a scale | Standard Error 2.026 |
| Vortioxetine 10 mg | Change From Baseline in 36-item Short-form Health Survey (SF-36) | Physical functioning subscore | 2.07 scores on a scale | Standard Error 1.517 |
| Vortioxetine 10 mg | Change From Baseline in 36-item Short-form Health Survey (SF-36) | General health subscore | 5.90 scores on a scale | Standard Error 1.292 |
| Vortioxetine 10 mg | Change From Baseline in 36-item Short-form Health Survey (SF-36) | Role-emotional subscore | 16.60 scores on a scale | Standard Error 2.081 |
| Vortioxetine 10 mg | Change From Baseline in 36-item Short-form Health Survey (SF-36) | Social functioning subscore | 17.56 scores on a scale | Standard Error 2.07 |
| Vortioxetine 10 mg | Change From Baseline in 36-item Short-form Health Survey (SF-36) | Vitality subscore | 14.33 scores on a scale | Standard Error 1.783 |
| Vortioxetine 10 mg | Change From Baseline in 36-item Short-form Health Survey (SF-36) | Mental health subscore | 14.74 scores on a scale | Standard Error 1.643 |
Secondary
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.
Time frame: Baseline and Weeks 1, 2, 4, 6 and 8.
Population: Full analysis set; LOCF was used. n indicates the number of patients included in the analysis at each time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Clinical Global Impression Scale-Severity of Illness (CGI-S) | Week 1 (n=146, 140, 143) | -0.40 scores on a scale | Standard Error 0.054 |
| Placebo | Change From Baseline in Clinical Global Impression Scale-Severity of Illness (CGI-S) | Week 6 (n=148, 144, 146) | -0.93 scores on a scale | Standard Error 0.083 |
| Placebo | Change From Baseline in Clinical Global Impression Scale-Severity of Illness (CGI-S) | Week 4 (n=148, 144, 146) | -0.82 scores on a scale | Standard Error 0.081 |
| Placebo | Change From Baseline in Clinical Global Impression Scale-Severity of Illness (CGI-S) | Week 8 (n=148, 144, 146) | -1.10 scores on a scale | Standard Error 0.09 |
| Placebo | Change From Baseline in Clinical Global Impression Scale-Severity of Illness (CGI-S) | Week 2 (n=148, 143, 146) | -0.68 scores on a scale | Standard Error 0.072 |
| Vortioxetine 2.5 mg | Change From Baseline in Clinical Global Impression Scale-Severity of Illness (CGI-S) | Week 4 (n=148, 144, 146) | -1.01 scores on a scale | Standard Error 0.079 |
| Vortioxetine 2.5 mg | Change From Baseline in Clinical Global Impression Scale-Severity of Illness (CGI-S) | Week 1 (n=146, 140, 143) | -0.47 scores on a scale | Standard Error 0.053 |
| Vortioxetine 2.5 mg | Change From Baseline in Clinical Global Impression Scale-Severity of Illness (CGI-S) | Week 2 (n=148, 143, 146) | -0.82 scores on a scale | Standard Error 0.07 |
| Vortioxetine 2.5 mg | Change From Baseline in Clinical Global Impression Scale-Severity of Illness (CGI-S) | Week 6 (n=148, 144, 146) | -1.14 scores on a scale | Standard Error 0.081 |
| Vortioxetine 2.5 mg | Change From Baseline in Clinical Global Impression Scale-Severity of Illness (CGI-S) | Week 8 (n=148, 144, 146) | -1.21 scores on a scale | Standard Error 0.088 |
| Vortioxetine 10 mg | Change From Baseline in Clinical Global Impression Scale-Severity of Illness (CGI-S) | Week 8 (n=148, 144, 146) | -1.14 scores on a scale | Standard Error 0.09 |
| Vortioxetine 10 mg | Change From Baseline in Clinical Global Impression Scale-Severity of Illness (CGI-S) | Week 6 (n=148, 144, 146) | -1.03 scores on a scale | Standard Error 0.082 |
| Vortioxetine 10 mg | Change From Baseline in Clinical Global Impression Scale-Severity of Illness (CGI-S) | Week 1 (n=146, 140, 143) | -0.37 scores on a scale | Standard Error 0.054 |
| Vortioxetine 10 mg | Change From Baseline in Clinical Global Impression Scale-Severity of Illness (CGI-S) | Week 4 (n=148, 144, 146) | -0.93 scores on a scale | Standard Error 0.081 |
| Vortioxetine 10 mg | Change From Baseline in Clinical Global Impression Scale-Severity of Illness (CGI-S) | Week 2 (n=148, 143, 146) | -0.69 scores on a scale | Standard Error 0.071 |
Secondary
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.
Time frame: Baseline and Weeks 1, 2, 4 and 6
Population: Full analysis set; LOCF was used. n indicates the number of patients included in the analysis at each time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Hamilton Anxiety Scale (HAM-A) Total Score at Other Weeks Assessed | Week 1 (n=147, 142, 143) | -5.07 scores on a scale | Standard Error 0.433 |
| Placebo | Change From Baseline in Hamilton Anxiety Scale (HAM-A) Total Score at Other Weeks Assessed | Week 2 (n=148, 144, 146) | -7.41 scores on a scale | Standard Error 0.501 |
| Placebo | Change From Baseline in Hamilton Anxiety Scale (HAM-A) Total Score at Other Weeks Assessed | Week 4 (n=148, 144, 146) | -8.88 scores on a scale | Standard Error 0.566 |
| Placebo | Change From Baseline in Hamilton Anxiety Scale (HAM-A) Total Score at Other Weeks Assessed | Week 6 (n=148, 144, 146) | -9.54 scores on a scale | Standard Error 0.565 |
| Vortioxetine 2.5 mg | Change From Baseline in Hamilton Anxiety Scale (HAM-A) Total Score at Other Weeks Assessed | Week 6 (n=148, 144, 146) | -10.35 scores on a scale | Standard Error 0.55 |
| Vortioxetine 2.5 mg | Change From Baseline in Hamilton Anxiety Scale (HAM-A) Total Score at Other Weeks Assessed | Week 1 (n=147, 142, 143) | -5.29 scores on a scale | Standard Error 0.423 |
| Vortioxetine 2.5 mg | Change From Baseline in Hamilton Anxiety Scale (HAM-A) Total Score at Other Weeks Assessed | Week 4 (n=148, 144, 146) | -9.45 scores on a scale | Standard Error 0.551 |
| Vortioxetine 2.5 mg | Change From Baseline in Hamilton Anxiety Scale (HAM-A) Total Score at Other Weeks Assessed | Week 2 (n=148, 144, 146) | -8.11 scores on a scale | Standard Error 0.488 |
| Vortioxetine 10 mg | Change From Baseline in Hamilton Anxiety Scale (HAM-A) Total Score at Other Weeks Assessed | Week 6 (n=148, 144, 146) | -10.50 scores on a scale | Standard Error 0.563 |
| Vortioxetine 10 mg | Change From Baseline in Hamilton Anxiety Scale (HAM-A) Total Score at Other Weeks Assessed | Week 2 (n=148, 144, 146) | -8.05 scores on a scale | Standard Error 0.499 |
| Vortioxetine 10 mg | Change From Baseline in Hamilton Anxiety Scale (HAM-A) Total Score at Other Weeks Assessed | Week 4 (n=148, 144, 146) | -9.54 scores on a scale | Standard Error 0.564 |
| Vortioxetine 10 mg | Change From Baseline in Hamilton Anxiety Scale (HAM-A) Total Score at Other Weeks Assessed | Week 1 (n=147, 142, 143) | -5.30 scores on a scale | Standard Error 0.433 |
Secondary
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.
Time frame: Baseline and Weeks 1, 4 and 8.
Population: Full analysis set; LOCF was used. n indicates the number of patients included in the analysis at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Hospital Anxiety and Depression (HAD) Scales | Anxiety Scale at Week 1 (n=147, 142, 143) | -1.64 scores on a scale | Standard Deviation 0.266 |
| Placebo | Change From Baseline in Hospital Anxiety and Depression (HAD) Scales | Anxiety Scale at Week 4 (n=148, 144, 146) | -2.81 scores on a scale | Standard Deviation 0.343 |
| Placebo | Change From Baseline in Hospital Anxiety and Depression (HAD) Scales | Anxiety Scale at Week 8 (n=148, 144, 146) | -3.63 scores on a scale | Standard Deviation 0.365 |
| Placebo | Change From Baseline in Hospital Anxiety and Depression (HAD) Scales | Depression Scale at Week 1 (n=147, 142, 143) | -0.71 scores on a scale | Standard Deviation 0.226 |
| Placebo | Change From Baseline in Hospital Anxiety and Depression (HAD) Scales | Depression Scale at Week 4 (n=148, 144, 146) | -1.66 scores on a scale | Standard Deviation 0.272 |
| Placebo | Change From Baseline in Hospital Anxiety and Depression (HAD) Scales | Depression Scale at Week 8 (n=148, 144, 146) | -1.76 scores on a scale | Standard Deviation 0.308 |
| Vortioxetine 2.5 mg | Change From Baseline in Hospital Anxiety and Depression (HAD) Scales | Depression Scale at Week 8 (n=148, 144, 146) | -2.56 scores on a scale | Standard Deviation 0.3 |
| Vortioxetine 2.5 mg | Change From Baseline in Hospital Anxiety and Depression (HAD) Scales | Anxiety Scale at Week 1 (n=147, 142, 143) | -2.07 scores on a scale | Standard Deviation 0.258 |
| Vortioxetine 2.5 mg | Change From Baseline in Hospital Anxiety and Depression (HAD) Scales | Depression Scale at Week 1 (n=147, 142, 143) | -1.35 scores on a scale | Standard Deviation 0.22 |
| Vortioxetine 2.5 mg | Change From Baseline in Hospital Anxiety and Depression (HAD) Scales | Depression Scale at Week 4 (n=148, 144, 146) | -2.23 scores on a scale | Standard Deviation 0.265 |
| Vortioxetine 2.5 mg | Change From Baseline in Hospital Anxiety and Depression (HAD) Scales | Anxiety Scale at Week 4 (n=148, 144, 146) | -3.66 scores on a scale | Standard Deviation 0.333 |
| Vortioxetine 2.5 mg | Change From Baseline in Hospital Anxiety and Depression (HAD) Scales | Anxiety Scale at Week 8 (n=148, 144, 146) | -4.29 scores on a scale | Standard Deviation 0.354 |
| Vortioxetine 10 mg | Change From Baseline in Hospital Anxiety and Depression (HAD) Scales | Anxiety Scale at Week 4 (n=148, 144, 146) | -3.39 scores on a scale | Standard Deviation 0.339 |
| Vortioxetine 10 mg | Change From Baseline in Hospital Anxiety and Depression (HAD) Scales | Anxiety Scale at Week 8 (n=148, 144, 146) | -4.20 scores on a scale | Standard Deviation 0.361 |
| Vortioxetine 10 mg | Change From Baseline in Hospital Anxiety and Depression (HAD) Scales | Depression Scale at Week 8 (n=148, 144, 146) | -2.21 scores on a scale | Standard Deviation 0.306 |
| Vortioxetine 10 mg | Change From Baseline in Hospital Anxiety and Depression (HAD) Scales | Depression Scale at Week 1 (n=147, 142, 143) | -1.15 scores on a scale | Standard Deviation 0.225 |
| Vortioxetine 10 mg | Change From Baseline in Hospital Anxiety and Depression (HAD) Scales | Anxiety Scale at Week 1 (n=147, 142, 143) | -2.03 scores on a scale | Standard Deviation 0.264 |
| Vortioxetine 10 mg | Change From Baseline in Hospital Anxiety and Depression (HAD) Scales | Depression Scale at Week 4 (n=148, 144, 146) | -2.10 scores on a scale | Standard Deviation 0.271 |
Secondary
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.
Time frame: Baseline and Week 8
Population: Full analysis set with available data at Baseline; LOCF was used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Sheehan Disability Scale (SDS) at Week 8 | -4.26 scores on a scale | Standard Error 0.617 |
| Vortioxetine 2.5 mg | Change From Baseline in Sheehan Disability Scale (SDS) at Week 8 | -5.73 scores on a scale | Standard Error 0.623 |
| Vortioxetine 10 mg | Change From Baseline in Sheehan Disability Scale (SDS) at Week 8 | -5.24 scores on a scale | Standard Error 0.657 |
Secondary
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.
Time frame: Baseline and Weeks 1, 2, 4, 6 and 8.
Population: Full analysis set; LOCF was used. n indicates the number of patients included in the analysis at each time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Clinical Global Impression Scale-Global Improvement (CGI-I) at Each Week Assessed | Week 6 (n=148, 144, 146) | 2.68 scores on a scale | Standard Error 0.089 |
| Placebo | Clinical Global Impression Scale-Global Improvement (CGI-I) at Each Week Assessed | Week 4 (n=148, 144, 146) | 2.87 scores on a scale | Standard Error 0.089 |
| Placebo | Clinical Global Impression Scale-Global Improvement (CGI-I) at Each Week Assessed | Week 1 (n=146, 141, 143) | 3.35 scores on a scale | Standard Error 0.071 |
| Placebo | Clinical Global Impression Scale-Global Improvement (CGI-I) at Each Week Assessed | Week 2 (n=148, 143, 146) | 2.99 scores on a scale | Standard Error 0.083 |
| Placebo | Clinical Global Impression Scale-Global Improvement (CGI-I) at Each Week Assessed | Week 8 (n=148, 144, 146) | 2.60 scores on a scale | Standard Error 0.095 |
| Vortioxetine 2.5 mg | Clinical Global Impression Scale-Global Improvement (CGI-I) at Each Week Assessed | Week 4 (n=148, 144, 146) | 2.75 scores on a scale | Standard Error 0.086 |
| Vortioxetine 2.5 mg | Clinical Global Impression Scale-Global Improvement (CGI-I) at Each Week Assessed | Week 1 (n=146, 141, 143) | 3.30 scores on a scale | Standard Error 0.07 |
| Vortioxetine 2.5 mg | Clinical Global Impression Scale-Global Improvement (CGI-I) at Each Week Assessed | Week 2 (n=148, 143, 146) | 2.91 scores on a scale | Standard Error 0.081 |
| Vortioxetine 2.5 mg | Clinical Global Impression Scale-Global Improvement (CGI-I) at Each Week Assessed | Week 6 (n=148, 144, 146) | 2.58 scores on a scale | Standard Error 0.087 |
| Vortioxetine 2.5 mg | Clinical Global Impression Scale-Global Improvement (CGI-I) at Each Week Assessed | Week 8 (n=148, 144, 146) | 2.56 scores on a scale | Standard Error 0.093 |
| Vortioxetine 10 mg | Clinical Global Impression Scale-Global Improvement (CGI-I) at Each Week Assessed | Week 8 (n=148, 144, 146) | 2.51 scores on a scale | Standard Error 0.095 |
| Vortioxetine 10 mg | Clinical Global Impression Scale-Global Improvement (CGI-I) at Each Week Assessed | Week 6 (n=148, 144, 146) | 2.60 scores on a scale | Standard Error 0.088 |
| Vortioxetine 10 mg | Clinical Global Impression Scale-Global Improvement (CGI-I) at Each Week Assessed | Week 1 (n=146, 141, 143) | 3.38 scores on a scale | Standard Error 0.071 |
| Vortioxetine 10 mg | Clinical Global Impression Scale-Global Improvement (CGI-I) at Each Week Assessed | Week 4 (n=148, 144, 146) | 2.69 scores on a scale | Standard Error 0.088 |
| Vortioxetine 10 mg | Clinical Global Impression Scale-Global Improvement (CGI-I) at Each Week Assessed | Week 2 (n=148, 143, 146) | 2.92 scores on a scale | Standard Error 0.083 |
Secondary
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.
Time frame: Baseline and Week 8
Population: Full analysis set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Baseline: Any resource use | 32 participants |
| Placebo | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Baseline: Any hospitalization-related services | 2 participants |
| Placebo | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Baseline: Hospitalization related to anxiety | 1 participants |
| Placebo | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Baseline: Any sick leave | 5 participants |
| Placebo | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Baseline: Sick leave related to anxiety | 4 participants |
| Placebo | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Week 8: Any resource use | 14 participants |
| Placebo | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Week 8: Any hospitalization-related service | 3 participants |
| Placebo | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Week 8: Hospitalization related to anxiety | 0 participants |
| Placebo | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Week 8: Any sick leave | 5 participants |
| Placebo | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Week 8: Sick leave related to anxiety | 1 participants |
| Vortioxetine 2.5 mg | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Week 8: Any sick leave | 6 participants |
| Vortioxetine 2.5 mg | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Baseline: Any resource use | 34 participants |
| Vortioxetine 2.5 mg | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Week 8: Any resource use | 23 participants |
| Vortioxetine 2.5 mg | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Baseline: Sick leave related to anxiety | 8 participants |
| Vortioxetine 2.5 mg | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Baseline: Any hospitalization-related services | 1 participants |
| Vortioxetine 2.5 mg | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Week 8: Sick leave related to anxiety | 4 participants |
| Vortioxetine 2.5 mg | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Week 8: Hospitalization related to anxiety | 0 participants |
| Vortioxetine 2.5 mg | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Baseline: Hospitalization related to anxiety | 0 participants |
| Vortioxetine 2.5 mg | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Week 8: Any hospitalization-related service | 0 participants |
| Vortioxetine 2.5 mg | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Baseline: Any sick leave | 13 participants |
| Vortioxetine 10 mg | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Week 8: Hospitalization related to anxiety | 0 participants |
| Vortioxetine 10 mg | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Baseline: Any sick leave | 10 participants |
| Vortioxetine 10 mg | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Baseline: Sick leave related to anxiety | 4 participants |
| Vortioxetine 10 mg | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Week 8: Any resource use | 19 participants |
| Vortioxetine 10 mg | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Week 8: Any sick leave | 8 participants |
| Vortioxetine 10 mg | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Week 8: Any hospitalization-related service | 1 participants |
| Vortioxetine 10 mg | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Baseline: Any resource use | 32 participants |
| Vortioxetine 10 mg | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Week 8: Sick leave related to anxiety | 1 participants |
| Vortioxetine 10 mg | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Baseline: Any hospitalization-related services | 1 participants |
| Vortioxetine 10 mg | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Baseline: Hospitalization related to anxiety | 0 participants |
Secondary
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).
Time frame: Week 8
Population: Full analysis set; LOCF was used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants in HAM-A Remission at Week 8 | 21.6 percentage of participants |
| Vortioxetine 2.5 mg | Percentage of Participants in HAM-A Remission at Week 8 | 21.5 percentage of participants |
| Vortioxetine 10 mg | Percentage of Participants in HAM-A Remission at Week 8 | 19.2 percentage of participants |
Secondary
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).
Time frame: Baseline and Week 8
Population: Full analysis set; LOCF was used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Responders in HAM-A Total Score at Week 8 | 41.9 percentage of participants |
| Vortioxetine 2.5 mg | Percentage of Responders in HAM-A Total Score at Week 8 | 46.5 percentage of participants |
| Vortioxetine 10 mg | Percentage of Responders in HAM-A Total Score at Week 8 | 41.8 percentage of participants |