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 determine the safety and efficacy of 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, 5 mg or 10 mg of vortioxetine, once daily, 60 mg of duloxetine once daily, or a placebo once daily for eight weeks. 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. Participants who complete the 8-week treatment period will enter a 2-week discontinuation period in order to assess potential discontinuation symptoms. Total commitment time is up to 12 weeks.
Interventions
DRUGPlacebo
Placebo-matching capsules
DRUGVortioxetine
Encapsulated vortioxetine immediate release tablets
DRUGDuloxetine
Overencapsulated duloxetine 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 65 Years
Healthy volunteers
No
Inclusion criteria
* Has a primary diagnosis of generalized anxiety disorder according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth 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
* Had received any investigational compound \<30 days before Screening or 5 half-lives prior to Screening, whichever is longer. * Received Lu AA21004 in a previous clinical study. * Was a study site employee, or an immediate family member (ie, spouse, parent, child, or sibling) of a study site employee involved in conduct of this study. * 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 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. * Has known sensitivity to duloxetine. * 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 inhibitor 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 known history of or currently has increased intraocular pressure or is at risk of acute narrow-angle glaucoma. * Has a clinically significant unstable illness, for example, hepatic impairment or renal insufficiency, or a cardiovascular, pulmonary, gastrointestinal, endocrine, neurological, rheumatologic, immunologic, infectious, skin and subcutaneous tissue disorders, or metabolic disturbance. * Has an alanine aminotransferase, aspartate aminotransferase, or total bilirubin level \>1.5 times the upper limit of normal. * Has a serum creatinine level \>1.5 upper limit of normal. * Has a previous history of cancer that had been in remission for less than 5 years. * Hasclinically significant abnormal vital signs as determined by the investigator. * Has a history of lack of response to previous adequate treatment with duloxetine for any Generalized Anxiety Disorder episode. * Has 1 or more laboratory values outside the normal range, based on the blood or urine samples taken at the Screening Visit * Has a thyroid stimulating hormone value outside the normal range. * Has an abnormal electrocardiogram. * has a disease or was taking medications that, in the opinion of the investigator, could have interfered with the assessments of safety, tolerability, or efficacy. * The patient, in the opinion of the investigator, was unlikely to comply with the clinical study protocol or was unsuitable for any reason. * Had previously been enrolled in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Hamilton Anxiety (HAM-A) Scale Total Score at Week 8 | Baseline to 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 a mixed model for repeated measurements (MMRM) with week, Baseline score-by-week and treatment-by-week interaction as factors. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Clinical Global Impression Scale-Global Improvement (CGI-I) at Week 8 | Baseline to Week 8 | The Clinical Global Impression - Global Improvement scale measures the participant's improvement (or worsening) as assessed by the investigator relative to Baseline on a 7-point scale: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse. LS means were from a mixed model for repeated measurements (MMRM) with week, Baseline score-by-week and treatment-by-week interaction as factors. |
| Change From Baseline in Sheehan Disability Scale (SDS) at Week 8 | Baseline to 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 a mixed model for repeated measurements (MMRM) with week, Baseline score-by-week and treatment-by-week interaction as factors. |
| Percentage of Responders in HAM-A Total Score at Week 8 | Week 8 | Response was defined as participants 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). |
| Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score at Week 8 in Participants With Baseline HAM-A ≥25 | Baseline to 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. LS means were from a mixed model for repeated measurements (MMRM) with week, Baseline score-by-week and treatment-by-week interaction as factors. |
| Change From Baseline in Hamilton Anxiety Scale (HAM-A) Total Score at Other Weeks Assessed | Baseline to 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 a mixed model for repeated measurements (MMRM) with week, Baseline score-by-week and treatment-by-week interaction as factors. |
| Change From Baseline in Hospital Anxiety and Depression (HAD) - Anxiety Subscale at Other Weeks Assessed | Baseline to Weeks 1 and 4 | The HAD-Anxiety subscale is completed by the participant and measures anxiety, including anxious mood, restlessness, anxious thoughts, and panic attacks. The subscale is made up of 7 items that are assessed on a scale from 0 (no anxiety) to 3 (severe feeling of anxiety). Participants are required to indicate the response which most accurately reflects the way they have felt over the last few days. Scores are summed and range from 0 to 21 (maximal severity). LS means were from a mixed model for repeated measurements (MMRM) with week, Baseline score-by-week and treatment-by-week interaction as factors. |
| Mean Clinical Global Impression Scale-Global Improvement (CGI-I) at Other Weeks Assessed | Baseline to Weeks 1, 2, 4 and 6 | The Clinical Global Impression - Global Improvement scale measures the participant's improvement (or worsening) as assessed by the clinician relative to Baseline on a 7-point scale: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse. LS means were from a mixed model for repeated measurements (MMRM) with week, Baseline score-by-week and treatment-by-week interaction as factors. |
| Change From Baseline in Hospital Anxiety and Depression (HAD) - Anxiety Subscale at Week 8 | Baseline to Week 8 | The HAD-Anxiety subscale is completed by the participant and measures anxiety, including anxious mood, restlessness, anxious thoughts, and panic attacks. The subscale is made up of 7 items that are assessed on a scale from 0 (no anxiety) to 3 (severe feeling of anxiety). Participants are required to indicate the response which most accurately reflects the way they have felt over the last few days. Scores are summed and range from 0 to 21 (maximal severity). LS means were from a mixed model for repeated measurements (MMRM) with week, Baseline score-by-week and treatment-by-week interaction as factors. |
| Percentage of Responders in HAM-A Total Score at Other Weeks Assessed | Baseline and Weeks 1, 2, 4 and 6 | Response was defined as participants 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). |
| Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score at Other Weeks Assessed in Participants With Baseline HAM-A ≥25 | Baseline to 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 a mixed model for repeated measurements (MMRM) with week, Baseline score-by-week and treatment-by-week interaction as factors. |
| Percentage of Participants in HAM-A Remission at Each Week Assessed | Weeks 1, 2, 4, 6 and 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). |
| Change From Baseline in Clinical Global Impression Scale-Severity of Illness (CGI-S) | Baseline to 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 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. LS means were from a mixed model for repeated measurements (MMRM) with week, Baseline score-by-week and treatment-by-week interaction as factors. |
| Change From Baseline in Hospital Anxiety and Depression (HAD) - Depression Subscale at All Weeks Assessed | Baseline to Weeks 1, 4 and 8 | The HAD-Depression subscale is completed by the participant and measures depression, focusing on the state of lost interest and diminished pleasure response. The subscale is made up of 7 items that are assessed on a scale from 0 (no depression) to 3 (severe feeling of depression). Participants are required to indicate the response which most accurately reflects the way they have felt over the last few days. The item scores are summed and the total subscore ranges from 0 to 21 (maximal severity). LS means were from a mixed model for repeated measurements (MMRM) model with week, Baseline score-by-week and treatment-by-week interaction as factors. |
| 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 the 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 Sheehan Disability Scale (SDS) at Other Weeks Assessed | Baseline to Weeks 1, 2 and 4 | 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 a mixed model for repeated measurements (MMRM) with week, Baseline score-by-week and treatment-by-week interaction as factors. |
Countries
United States
Participant flow
Recruitment details
Participants took part in the study at 71 investigative sites in the United States from 20 June 2008 to 27 February 2009.
Pre-assignment details
Participants with a diagnosis of generalized anxiety disorder were enrolled equally in 1 of 5 treatment groups, once a day placebo, 2.5 mg, 5 mg or 10 mg vortioxetine, or 60 mg duloxetine.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo-matching capsules, orally, once daily for up to 9 weeks. | 157 |
| Vortioxetine 2.5 mg Vortioxetine 2.5 mg encapsulated tablets, orally, once daily, for 8 weeks, followed by placebo-matching capsules, orally, once daily, for 1 week. | 156 |
| Vortioxetine 5 mg Vortioxetine 5 mg encapsulated tablets, orally, once daily, for 8 weeks, followed by placebo-matching capsule, orally, once daily, for 1 week. | 156 |
| Vortioxetine 10 mg Vortioxetine 10 mg encapsulated tablets, orally, once daily, for 8 weeks, followed by placebo-matching capsules, orally, once daily, for 1 week. | 156 |
| Duloxetine 60 mg Duloxetine 60 mg capsules, orally, once daily, for 8 weeks, followed by duloxetine 30 mg capsules, orally, once daily, for 1 week. | 156 |
| Total | 781 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 4 | 8 | 11 | 11 | 23 |
| Overall Study | Lack of Efficacy | 4 | 4 | 2 | 1 | 1 |
| Overall Study | Lost to Follow-up | 11 | 8 | 13 | 15 | 13 |
| Overall Study | Non-compliance with Study Drug | 6 | 1 | 6 | 3 | 3 |
| Overall Study | Other | 1 | 1 | 1 | 2 | 2 |
| Overall Study | Protocol Deviations | 3 | 5 | 3 | 7 | 5 |
| Overall Study | Withdrawal of Consent | 7 | 9 | 3 | 6 | 3 |
Baseline characteristics
| Characteristic | Vortioxetine 2.5 mg | Total | Placebo | Duloxetine 60 mg | Vortioxetine 10 mg | Vortioxetine 5 mg |
|---|---|---|---|---|---|---|
| Age Continuous | 39.2 years STANDARD_DEVIATION 11.9 | 38.6 years STANDARD_DEVIATION 12.14 | 36.8 years STANDARD_DEVIATION 12.12 | 39.5 years STANDARD_DEVIATION 12.28 | 39.8 years STANDARD_DEVIATION 12.33 | 37.7 years STANDARD_DEVIATION 11.96 |
| Age, Customized ≤55 years | 140 participants | 704 participants | 143 participants | 137 participants | 137 participants | 147 participants |
| Age, Customized >55 years | 16 participants | 77 participants | 14 participants | 19 participants | 19 participants | 9 participants |
| Alcohol Consumption 2 to 6 times per week | 30 participants | 108 participants | 17 participants | 22 participants | 22 participants | 17 participants |
| Alcohol Consumption Daily | 2 participants | 15 participants | 1 participants | 7 participants | 3 participants | 2 participants |
| Alcohol Consumption Never | 49 participants | 226 participants | 40 participants | 44 participants | 53 participants | 40 participants |
| Alcohol Consumption Once a week | 25 participants | 131 participants | 27 participants | 19 participants | 29 participants | 31 participants |
| Alcohol Consumption Once monthly or less often | 50 participants | 300 participants | 71 participants | 64 participants | 49 participants | 66 participants |
| Body Mass Index (BMI) | 28.19 kg/m^2 STANDARD_DEVIATION 6.651 | 28.51 kg/m^2 STANDARD_DEVIATION 7.064 | 29.54 kg/m^2 STANDARD_DEVIATION 8.478 | 28.10 kg/m^2 STANDARD_DEVIATION 6.325 | 28.49 kg/m^2 STANDARD_DEVIATION 7.058 | 28.24 kg/m^2 STANDARD_DEVIATION 6.589 |
| Clinical Global Impression - Severity scale score | 4.4 scores on a scale STANDARD_DEVIATION 0.63 | 4.4 scores on a scale STANDARD_DEVIATION 0.6 | 4.3 scores on a scale STANDARD_DEVIATION 0.56 | 4.4 scores on a scale STANDARD_DEVIATION 0.62 | 4.4 scores on a scale STANDARD_DEVIATION 0.59 | 4.4 scores on a scale STANDARD_DEVIATION 0.59 |
| Hamilton Anxiety Scale Total Score | 25.3 scores on a scale STANDARD_DEVIATION 4.25 | 25.0 scores on a scale STANDARD_DEVIATION 3.9 | 24.4 scores on a scale STANDARD_DEVIATION 3.73 | 25.0 scores on a scale STANDARD_DEVIATION 3.94 | 25.3 scores on a scale STANDARD_DEVIATION 3.96 | 25.0 scores on a scale STANDARD_DEVIATION 3.57 |
| Height | 167.87 cm STANDARD_DEVIATION 9.139 | 168.28 cm STANDARD_DEVIATION 9.147 | 168.74 cm STANDARD_DEVIATION 9.605 | 167.94 cm STANDARD_DEVIATION 9.3 | 167.61 cm STANDARD_DEVIATION 8.378 | 169.25 cm STANDARD_DEVIATION 9.282 |
| Hospital Anxiety and Depression - Anxiety subscale | 13.8 scores on a scale STANDARD_DEVIATION 3.4 | 13.8 scores on a scale STANDARD_DEVIATION 3.41 | 13.9 scores on a scale STANDARD_DEVIATION 3.23 | 13.4 scores on a scale STANDARD_DEVIATION 3.7 | 14.0 scores on a scale STANDARD_DEVIATION 3.02 | 13.8 scores on a scale STANDARD_DEVIATION 3.7 |
| Hospital Anxiety and Depression - Depression subscale | 8.2 scores on a scale STANDARD_DEVIATION 3.83 | 8.2 scores on a scale STANDARD_DEVIATION 3.89 | 8.2 scores on a scale STANDARD_DEVIATION 4.12 | 8.2 scores on a scale STANDARD_DEVIATION 4 | 8.5 scores on a scale STANDARD_DEVIATION 3.59 | 8.2 scores on a scale STANDARD_DEVIATION 3.94 |
| Montgomery Åsberg Depression Rating Scale (MADRS) total score | 12.24 scores on a scale STANDARD_DEVIATION 3.279 | 12.16 scores on a scale STANDARD_DEVIATION 2.989 | 11.83 scores on a scale STANDARD_DEVIATION 2.787 | 11.99 scores on a scale STANDARD_DEVIATION 3.087 | 12.47 scores on a scale STANDARD_DEVIATION 2.868 | 12.24 scores on a scale STANDARD_DEVIATION 2.895 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 participants | 3 participants | 0 participants | 0 participants | 2 participants | 0 participants |
| Race/Ethnicity, Customized Asian | 0 participants | 14 participants | 4 participants | 4 participants | 0 participants | 6 participants |
| Race/Ethnicity, Customized Black | 31 participants | 156 participants | 35 participants | 31 participants | 33 participants | 26 participants |
| Race/Ethnicity, Customized Caucasian (White, including Hispanic) | 121 participants | 604 participants | 118 participants | 121 participants | 120 participants | 124 participants |
| Race/Ethnicity, Customized Native Hawaiian/ Other Pacific Islander | 1 participants | 2 participants | 0 participants | 0 participants | 1 participants | 0 participants |
| Region of Enrollment United States | 156 participants | 781 participants | 157 participants | 156 participants | 156 participants | 156 participants |
| Sex: Female, Male Female | 109 Participants | 529 Participants | 102 Participants | 113 Participants | 105 Participants | 100 Participants |
| Sex: Female, Male Male | 47 Participants | 252 Participants | 55 Participants | 43 Participants | 51 Participants | 56 Participants |
| Smoking Classification Current Smoker | 43 participants | 214 participants | 41 participants | 43 participants | 43 participants | 44 participants |
| Smoking Classification Ex-smoker | 28 participants | 141 participants | 23 participants | 31 participants | 28 participants | 31 participants |
| Smoking Classification Never Smoked | 85 participants | 425 participants | 92 participants | 82 participants | 85 participants | 81 participants |
| Weight | 79.47 kg STANDARD_DEVIATION 19.893 | 80.91 kg STANDARD_DEVIATION 21.558 | 84.40 kg STANDARD_DEVIATION 25.426 | 79.51 kg STANDARD_DEVIATION 20.09 | 80.17 kg STANDARD_DEVIATION 21.42 | 80.98 kg STANDARD_DEVIATION 20.312 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 85 / 155 | 100 / 156 | 104 / 155 | 111 / 156 | 116 / 154 |
| serious Total, serious adverse events | 0 / 155 | 1 / 156 | 0 / 155 | 1 / 156 | 3 / 154 |
Outcome results
Primary
Change From Baseline in the Hamilton Anxiety (HAM-A) Scale Total Score at 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 a mixed model for repeated measurements (MMRM) with week, Baseline score-by-week and treatment-by-week interaction as factors.
Time frame: Baseline to 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 postbaseline value for assessment of primary efficacy. A mixed model for repeated measurements (MMRM) based on observed cases was used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in the Hamilton Anxiety (HAM-A) Scale Total Score at Week 8 | -11.27 scores on a scale | Standard Error 0.595 |
| Vortioxetine 2.5 mg | Change From Baseline in the Hamilton Anxiety (HAM-A) Scale Total Score at Week 8 | -12.23 scores on a scale | Standard Error 0.6 |
| Vortioxetine 5 mg | Change From Baseline in the Hamilton Anxiety (HAM-A) Scale Total Score at Week 8 | -11.57 scores on a scale | Standard Error 0.606 |
| Vortioxetine 10 mg | Change From Baseline in the Hamilton Anxiety (HAM-A) Scale Total Score at Week 8 | -11.66 scores on a scale | Standard Error 0.606 |
| Duloxetine 60 mg | Change From Baseline in the Hamilton Anxiety (HAM-A) Scale Total Score at Week 8 | -13.87 scores on a scale | Standard Error 0.635 |
Comparison: P-values were tested at the 5% level of significance (ie, statistical significance if P\<0.05) comparing each of the 3 doses of vortioxetine to placebo.p-value: 0.25595% CI: [-2.62, 0.69]Mixed model for repeated measurements
Comparison: To control for multiplicity, a pre-specified sequential testing procedure was applied to compare 10 mg and 5 mg vortioxetine to placebo; as soon as an endpoint was non-significant at 0.025, the testing procedure stopped for all subsequent endpoints.p-value: 0.71995% CI: [-1.96, 1.35]Mixed model for repeated measurements
Comparison: To control for multiplicity, a pre-specified sequential testing procedure was applied to compare 10 mg and 5 mg vortioxetine to placebo; as soon as an endpoint was non-significant at 0.025, the testing procedure stopped for all subsequent endpoints.p-value: 0.64295% CI: [-2.06, 1.27]Mixed model for repeated measurements
p-value: 0.00395% CI: [-4.3, -0.89]Mixed model for repeated measurements
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 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. LS means were from a mixed model for repeated measurements (MMRM) with week, Baseline score-by-week and treatment-by-week interaction as factors.
Time frame: Baseline to Weeks 1, 2, 4, 6 and 8
Population: Full analysis set with available data at Baseline. A mixed model for repeated measurements (MMRM) based on observed cases 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 6 (n=127, 123, 121, 120, 112) | -1.22 scores on a scale | Standard Error 0.083 |
| Placebo | Change From Baseline in Clinical Global Impression Scale-Severity of Illness (CGI-S) | Week 1 (n=151, 148, 141, 149, 142) | -0.42 scores on a scale | Standard Error 0.055 |
| Placebo | Change From Baseline in Clinical Global Impression Scale-Severity of Illness (CGI-S) | Week 8 (n=120, 118, 114, 111, 106) | -1.42 scores on a scale | Standard Error 0.095 |
| Placebo | Change From Baseline in Clinical Global Impression Scale-Severity of Illness (CGI-S) | Week 2 (n=147, 145, 142, 147, 130) | -0.71 scores on a scale | Standard Error 0.066 |
| Placebo | Change From Baseline in Clinical Global Impression Scale-Severity of Illness (CGI-S) | Week 4 (n=140, 135, 132, 134, 115) | -0.95 scores on a scale | Standard Error 0.076 |
| Vortioxetine 2.5 mg | Change From Baseline in Clinical Global Impression Scale-Severity of Illness (CGI-S) | Week 6 (n=127, 123, 121, 120, 112) | -1.32 scores on a scale | Standard Error 0.084 |
| Vortioxetine 2.5 mg | Change From Baseline in Clinical Global Impression Scale-Severity of Illness (CGI-S) | Week 4 (n=140, 135, 132, 134, 115) | -1.12 scores on a scale | Standard Error 0.077 |
| Vortioxetine 2.5 mg | Change From Baseline in Clinical Global Impression Scale-Severity of Illness (CGI-S) | Week 2 (n=147, 145, 142, 147, 130) | -0.74 scores on a scale | Standard Error 0.066 |
| Vortioxetine 2.5 mg | Change From Baseline in Clinical Global Impression Scale-Severity of Illness (CGI-S) | Week 8 (n=120, 118, 114, 111, 106) | -1.50 scores on a scale | Standard Error 0.096 |
| Vortioxetine 2.5 mg | Change From Baseline in Clinical Global Impression Scale-Severity of Illness (CGI-S) | Week 1 (n=151, 148, 141, 149, 142) | -0.37 scores on a scale | Standard Error 0.055 |
| Vortioxetine 5 mg | Change From Baseline in Clinical Global Impression Scale-Severity of Illness (CGI-S) | Week 4 (n=140, 135, 132, 134, 115) | -1.02 scores on a scale | Standard Error 0.077 |
| Vortioxetine 5 mg | Change From Baseline in Clinical Global Impression Scale-Severity of Illness (CGI-S) | Week 1 (n=151, 148, 141, 149, 142) | -0.39 scores on a scale | Standard Error 0.056 |
| Vortioxetine 5 mg | Change From Baseline in Clinical Global Impression Scale-Severity of Illness (CGI-S) | Week 2 (n=147, 145, 142, 147, 130) | -0.80 scores on a scale | Standard Error 0.067 |
| Vortioxetine 5 mg | Change From Baseline in Clinical Global Impression Scale-Severity of Illness (CGI-S) | Week 6 (n=127, 123, 121, 120, 112) | -1.31 scores on a scale | Standard Error 0.084 |
| Vortioxetine 5 mg | Change From Baseline in Clinical Global Impression Scale-Severity of Illness (CGI-S) | Week 8 (n=120, 118, 114, 111, 106) | -1.38 scores on a scale | Standard Error 0.097 |
| Vortioxetine 10 mg | Change From Baseline in Clinical Global Impression Scale-Severity of Illness (CGI-S) | Week 8 (n=120, 118, 114, 111, 106) | -1.44 scores on a scale | Standard Error 0.097 |
| Vortioxetine 10 mg | Change From Baseline in Clinical Global Impression Scale-Severity of Illness (CGI-S) | Week 1 (n=151, 148, 141, 149, 142) | -0.42 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 6 (n=127, 123, 121, 120, 112) | -1.35 scores on a scale | Standard Error 0.084 |
| Vortioxetine 10 mg | Change From Baseline in Clinical Global Impression Scale-Severity of Illness (CGI-S) | Week 4 (n=140, 135, 132, 134, 115) | -1.11 scores on a scale | Standard Error 0.076 |
| Vortioxetine 10 mg | Change From Baseline in Clinical Global Impression Scale-Severity of Illness (CGI-S) | Week 2 (n=147, 145, 142, 147, 130) | -0.75 scores on a scale | Standard Error 0.065 |
| Duloxetine 60 mg | Change From Baseline in Clinical Global Impression Scale-Severity of Illness (CGI-S) | Week 4 (n=140, 135, 132, 134, 115) | -1.28 scores on a scale | Standard Error 0.082 |
| Duloxetine 60 mg | Change From Baseline in Clinical Global Impression Scale-Severity of Illness (CGI-S) | Week 6 (n=127, 123, 121, 120, 112) | -1.55 scores on a scale | Standard Error 0.088 |
| Duloxetine 60 mg | Change From Baseline in Clinical Global Impression Scale-Severity of Illness (CGI-S) | Week 1 (n=151, 148, 141, 149, 142) | -0.54 scores on a scale | Standard Error 0.057 |
| Duloxetine 60 mg | Change From Baseline in Clinical Global Impression Scale-Severity of Illness (CGI-S) | Week 8 (n=120, 118, 114, 111, 106) | -1.77 scores on a scale | Standard Error 0.101 |
| Duloxetine 60 mg | Change From Baseline in Clinical Global Impression Scale-Severity of Illness (CGI-S) | Week 2 (n=147, 145, 142, 147, 130) | -0.97 scores on a scale | Standard Error 0.069 |
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 a mixed model for repeated measurements (MMRM) with week, Baseline score-by-week and treatment-by-week interaction as factors.
Time frame: Baseline to Weeks 1, 2, 4 and 6
Population: Full analysis set. A mixed model for repeated measurements (MMRM) based on observed cases 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= 151, 149, 142, 149, 143) | -4.70 scores on a scale | Standard Error 0.423 |
| Placebo | Change From Baseline in Hamilton Anxiety Scale (HAM-A) Total Score at Other Weeks Assessed | Week 2 (n=147, 145, 143, 147, 130) | -7.30 scores on a scale | Standard Error 0.472 |
| Placebo | Change From Baseline in Hamilton Anxiety Scale (HAM-A) Total Score at Other Weeks Assessed | Week 4 (n= 139, 135, 132, 133, 116) | -8.66 scores on a scale | Standard Error 0.518 |
| Placebo | Change From Baseline in Hamilton Anxiety Scale (HAM-A) Total Score at Other Weeks Assessed | Week 6 (n= 127, 123, 122, 120, 112) | -10.28 scores on a scale | Standard Error 0.547 |
| Vortioxetine 2.5 mg | Change From Baseline in Hamilton Anxiety Scale (HAM-A) Total Score at Other Weeks Assessed | Week 1 (n= 151, 149, 142, 149, 143) | -4.56 scores on a scale | Standard Error 0.421 |
| Vortioxetine 2.5 mg | Change From Baseline in Hamilton Anxiety Scale (HAM-A) Total Score at Other Weeks Assessed | Week 6 (n= 127, 123, 122, 120, 112) | -10.82 scores on a scale | Standard Error 0.553 |
| Vortioxetine 2.5 mg | Change From Baseline in Hamilton Anxiety Scale (HAM-A) Total Score at Other Weeks Assessed | Week 2 (n=147, 145, 143, 147, 130) | -7.28 scores on a scale | Standard Error 0.471 |
| Vortioxetine 2.5 mg | Change From Baseline in Hamilton Anxiety Scale (HAM-A) Total Score at Other Weeks Assessed | Week 4 (n= 139, 135, 132, 133, 116) | -9.77 scores on a scale | Standard Error 0.52 |
| Vortioxetine 5 mg | Change From Baseline in Hamilton Anxiety Scale (HAM-A) Total Score at Other Weeks Assessed | Week 6 (n= 127, 123, 122, 120, 112) | -11.26 scores on a scale | Standard Error 0.556 |
| Vortioxetine 5 mg | Change From Baseline in Hamilton Anxiety Scale (HAM-A) Total Score at Other Weeks Assessed | Week 2 (n=147, 145, 143, 147, 130) | -8.22 scores on a scale | Standard Error 0.476 |
| Vortioxetine 5 mg | Change From Baseline in Hamilton Anxiety Scale (HAM-A) Total Score at Other Weeks Assessed | Week 4 (n= 139, 135, 132, 133, 116) | -9.84 scores on a scale | Standard Error 0.525 |
| Vortioxetine 5 mg | Change From Baseline in Hamilton Anxiety Scale (HAM-A) Total Score at Other Weeks Assessed | Week 1 (n= 151, 149, 142, 149, 143) | -4.90 scores on a scale | Standard Error 0.43 |
| Vortioxetine 10 mg | Change From Baseline in Hamilton Anxiety Scale (HAM-A) Total Score at Other Weeks Assessed | Week 1 (n= 151, 149, 142, 149, 143) | -5.04 scores on a scale | Standard Error 0.419 |
| Vortioxetine 10 mg | Change From Baseline in Hamilton Anxiety Scale (HAM-A) Total Score at Other Weeks Assessed | Week 2 (n=147, 145, 143, 147, 130) | -7.63 scores on a scale | Standard Error 0.468 |
| Vortioxetine 10 mg | Change From Baseline in Hamilton Anxiety Scale (HAM-A) Total Score at Other Weeks Assessed | Week 6 (n= 127, 123, 122, 120, 112) | -11.05 scores on a scale | Standard Error 0.552 |
| Vortioxetine 10 mg | Change From Baseline in Hamilton Anxiety Scale (HAM-A) Total Score at Other Weeks Assessed | Week 4 (n= 139, 135, 132, 133, 116) | -9.73 scores on a scale | Standard Error 0.519 |
| Duloxetine 60 mg | Change From Baseline in Hamilton Anxiety Scale (HAM-A) Total Score at Other Weeks Assessed | Week 6 (n= 127, 123, 122, 120, 112) | -12.66 scores on a scale | Standard Error 0.583 |
| Duloxetine 60 mg | Change From Baseline in Hamilton Anxiety Scale (HAM-A) Total Score at Other Weeks Assessed | Week 4 (n= 139, 135, 132, 133, 116) | -11.13 scores on a scale | Standard Error 0.553 |
| Duloxetine 60 mg | Change From Baseline in Hamilton Anxiety Scale (HAM-A) Total Score at Other Weeks Assessed | Week 2 (n=147, 145, 143, 147, 130) | -9.29 scores on a scale | Standard Error 0.494 |
| Duloxetine 60 mg | Change From Baseline in Hamilton Anxiety Scale (HAM-A) Total Score at Other Weeks Assessed | Week 1 (n= 151, 149, 142, 149, 143) | -5.48 scores on a scale | Standard Error 0.435 |
Secondary
Change From Baseline in Hospital Anxiety and Depression (HAD) - Anxiety Subscale at Other Weeks Assessed
The HAD-Anxiety subscale is completed by the participant and measures anxiety, including anxious mood, restlessness, anxious thoughts, and panic attacks. The subscale is made up of 7 items that are assessed on a scale from 0 (no anxiety) to 3 (severe feeling of anxiety). Participants are required to indicate the response which most accurately reflects the way they have felt over the last few days. Scores are summed and range from 0 to 21 (maximal severity). LS means were from a mixed model for repeated measurements (MMRM) with week, Baseline score-by-week and treatment-by-week interaction as factors.
Time frame: Baseline to Weeks 1 and 4
Population: Full analysis set with available data at Baseline. A mixed model for repeated measurements (MMRM) based on observed cases 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 Hospital Anxiety and Depression (HAD) - Anxiety Subscale at Other Weeks Assessed | Week 1 (n=150, 149, 141, 149, 141) | -1.81 scores on a scale | Standard Error 0.273 |
| Placebo | Change From Baseline in Hospital Anxiety and Depression (HAD) - Anxiety Subscale at Other Weeks Assessed | Week 4 (n=141, 142, 139, 141, 126) | -3.24 scores on a scale | Standard Error 0.31 |
| Vortioxetine 2.5 mg | Change From Baseline in Hospital Anxiety and Depression (HAD) - Anxiety Subscale at Other Weeks Assessed | Week 1 (n=150, 149, 141, 149, 141) | -1.85 scores on a scale | Standard Error 0.274 |
| Vortioxetine 2.5 mg | Change From Baseline in Hospital Anxiety and Depression (HAD) - Anxiety Subscale at Other Weeks Assessed | Week 4 (n=141, 142, 139, 141, 126) | -3.34 scores on a scale | Standard Error 0.31 |
| Vortioxetine 5 mg | Change From Baseline in Hospital Anxiety and Depression (HAD) - Anxiety Subscale at Other Weeks Assessed | Week 1 (n=150, 149, 141, 149, 141) | -1.89 scores on a scale | Standard Error 0.28 |
| Vortioxetine 5 mg | Change From Baseline in Hospital Anxiety and Depression (HAD) - Anxiety Subscale at Other Weeks Assessed | Week 4 (n=141, 142, 139, 141, 126) | -3.60 scores on a scale | Standard Error 0.313 |
| Vortioxetine 10 mg | Change From Baseline in Hospital Anxiety and Depression (HAD) - Anxiety Subscale at Other Weeks Assessed | Week 4 (n=141, 142, 139, 141, 126) | -4.01 scores on a scale | Standard Error 0.31 |
| Vortioxetine 10 mg | Change From Baseline in Hospital Anxiety and Depression (HAD) - Anxiety Subscale at Other Weeks Assessed | Week 1 (n=150, 149, 141, 149, 141) | -2.22 scores on a scale | Standard Error 0.272 |
| Duloxetine 60 mg | Change From Baseline in Hospital Anxiety and Depression (HAD) - Anxiety Subscale at Other Weeks Assessed | Week 1 (n=150, 149, 141, 149, 141) | -2.91 scores on a scale | Standard Error 0.285 |
| Duloxetine 60 mg | Change From Baseline in Hospital Anxiety and Depression (HAD) - Anxiety Subscale at Other Weeks Assessed | Week 4 (n=141, 142, 139, 141, 126) | -5.11 scores on a scale | Standard Error 0.328 |
Secondary
Change From Baseline in Hospital Anxiety and Depression (HAD) - Anxiety Subscale at Week 8
The HAD-Anxiety subscale is completed by the participant and measures anxiety, including anxious mood, restlessness, anxious thoughts, and panic attacks. The subscale is made up of 7 items that are assessed on a scale from 0 (no anxiety) to 3 (severe feeling of anxiety). Participants are required to indicate the response which most accurately reflects the way they have felt over the last few days. Scores are summed and range from 0 to 21 (maximal severity). LS means were from a mixed model for repeated measurements (MMRM) with week, Baseline score-by-week and treatment-by-week interaction as factors.
Time frame: Baseline to Week 8
Population: Full analysis set. A mixed model for repeated measurements (MMRM) based on observed cases was used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Hospital Anxiety and Depression (HAD) - Anxiety Subscale at Week 8 | -4.00 scores on a scale | Standard Error 0.361 |
| Vortioxetine 2.5 mg | Change From Baseline in Hospital Anxiety and Depression (HAD) - Anxiety Subscale at Week 8 | -3.89 scores on a scale | Standard Error 0.364 |
| Vortioxetine 5 mg | Change From Baseline in Hospital Anxiety and Depression (HAD) - Anxiety Subscale at Week 8 | -4.24 scores on a scale | Standard Error 0.366 |
| Vortioxetine 10 mg | Change From Baseline in Hospital Anxiety and Depression (HAD) - Anxiety Subscale at Week 8 | -5.09 scores on a scale | Standard Error 0.372 |
| Duloxetine 60 mg | Change From Baseline in Hospital Anxiety and Depression (HAD) - Anxiety Subscale at Week 8 | -5.54 scores on a scale | Standard Error 0.385 |
p-value: 0.8395% CI: [-0.89, 1.11]Mixed model for repeated measurements
p-value: 0.64395% CI: [-1.24, 0.77]Mixed model for repeated measurements
p-value: 0.03695% CI: [-2.1, -0.07]Mixed model for repeated measurements
p-value: 0.00495% CI: [-2.58, -0.5]Mixed model for repeated measurements
Secondary
Change From Baseline in Hospital Anxiety and Depression (HAD) - Depression Subscale at All Weeks Assessed
The HAD-Depression subscale is completed by the participant and measures depression, focusing on the state of lost interest and diminished pleasure response. The subscale is made up of 7 items that are assessed on a scale from 0 (no depression) to 3 (severe feeling of depression). Participants are required to indicate the response which most accurately reflects the way they have felt over the last few days. The item scores are summed and the total subscore ranges from 0 to 21 (maximal severity). LS means were from a mixed model for repeated measurements (MMRM) model with week, Baseline score-by-week and treatment-by-week interaction as factors.
Time frame: Baseline to Weeks 1, 4 and 8
Population: Full analysis set with available data at Baseline. A mixed model for repeated measurements (MMRM) based on observed cases 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 Hospital Anxiety and Depression (HAD) - Depression Subscale at All Weeks Assessed | Week 1 (n=150, 149, 141, 149, 141) | -0.81 scores on a scale | Standard Error 0.226 |
| Placebo | Change From Baseline in Hospital Anxiety and Depression (HAD) - Depression Subscale at All Weeks Assessed | Week 8 (n=123, 120, 119, 111, 108) | -2.21 scores on a scale | Standard Error 0.3 |
| Placebo | Change From Baseline in Hospital Anxiety and Depression (HAD) - Depression Subscale at All Weeks Assessed | Week 4 (n=141, 142, 139, 141, 126) | -1.32 scores on a scale | Standard Error 0.268 |
| Vortioxetine 2.5 mg | Change From Baseline in Hospital Anxiety and Depression (HAD) - Depression Subscale at All Weeks Assessed | Week 4 (n=141, 142, 139, 141, 126) | -1.83 scores on a scale | Standard Error 0.268 |
| Vortioxetine 2.5 mg | Change From Baseline in Hospital Anxiety and Depression (HAD) - Depression Subscale at All Weeks Assessed | Week 1 (n=150, 149, 141, 149, 141) | -0.83 scores on a scale | Standard Error 0.226 |
| Vortioxetine 2.5 mg | Change From Baseline in Hospital Anxiety and Depression (HAD) - Depression Subscale at All Weeks Assessed | Week 8 (n=123, 120, 119, 111, 108) | -1.82 scores on a scale | Standard Error 0.303 |
| Vortioxetine 5 mg | Change From Baseline in Hospital Anxiety and Depression (HAD) - Depression Subscale at All Weeks Assessed | Week 4 (n=141, 142, 139, 141, 126) | -1.70 scores on a scale | Standard Error 0.271 |
| Vortioxetine 5 mg | Change From Baseline in Hospital Anxiety and Depression (HAD) - Depression Subscale at All Weeks Assessed | Week 1 (n=150, 149, 141, 149, 141) | -0.88 scores on a scale | Standard Error 0.231 |
| Vortioxetine 5 mg | Change From Baseline in Hospital Anxiety and Depression (HAD) - Depression Subscale at All Weeks Assessed | Week 8 (n=123, 120, 119, 111, 108) | -1.96 scores on a scale | Standard Error 0.305 |
| Vortioxetine 10 mg | Change From Baseline in Hospital Anxiety and Depression (HAD) - Depression Subscale at All Weeks Assessed | Week 1 (n=150, 149, 141, 149, 141) | -1.25 scores on a scale | Standard Error 0.225 |
| Vortioxetine 10 mg | Change From Baseline in Hospital Anxiety and Depression (HAD) - Depression Subscale at All Weeks Assessed | Week 8 (n=123, 120, 119, 111, 108) | -1.94 scores on a scale | Standard Error 0.31 |
| Vortioxetine 10 mg | Change From Baseline in Hospital Anxiety and Depression (HAD) - Depression Subscale at All Weeks Assessed | Week 4 (n=141, 142, 139, 141, 126) | -1.61 scores on a scale | Standard Error 0.268 |
| Duloxetine 60 mg | Change From Baseline in Hospital Anxiety and Depression (HAD) - Depression Subscale at All Weeks Assessed | Week 4 (n=141, 142, 139, 141, 126) | -2.62 scores on a scale | Standard Error 0.283 |
| Duloxetine 60 mg | Change From Baseline in Hospital Anxiety and Depression (HAD) - Depression Subscale at All Weeks Assessed | Week 1 (n=150, 149, 141, 149, 141) | -1.19 scores on a scale | Standard Error 0.235 |
| Duloxetine 60 mg | Change From Baseline in Hospital Anxiety and Depression (HAD) - Depression Subscale at All Weeks Assessed | Week 8 (n=123, 120, 119, 111, 108) | -2.77 scores on a scale | Standard Error 0.32 |
Secondary
Change From Baseline in Sheehan Disability Scale (SDS) at Other Weeks Assessed
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 a mixed model for repeated measurements (MMRM) with week, Baseline score-by-week and treatment-by-week interaction as factors.
Time frame: Baseline to Weeks 1, 2 and 4
Population: Full analysis set with available data at Baseline. A mixed model for repeated measurements (MMRM) based on observed cases 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 Sheehan Disability Scale (SDS) at Other Weeks Assessed | Week 1 (n=116, 111, 109, 125, 112) | -3.22 scores on a scale | Standard Error 0.506 |
| Placebo | Change From Baseline in Sheehan Disability Scale (SDS) at Other Weeks Assessed | Week 4 (n=108, 106, 106, 115, 91) | -4.55 scores on a scale | Standard Error 0.59 |
| Placebo | Change From Baseline in Sheehan Disability Scale (SDS) at Other Weeks Assessed | Week 2 (n=116, 114, 116, 123, 103) | -4.53 scores on a scale | Standard Error 0.536 |
| Vortioxetine 2.5 mg | Change From Baseline in Sheehan Disability Scale (SDS) at Other Weeks Assessed | Week 2 (n=116, 114, 116, 123, 103) | -4.18 scores on a scale | Standard Error 0.547 |
| Vortioxetine 2.5 mg | Change From Baseline in Sheehan Disability Scale (SDS) at Other Weeks Assessed | Week 1 (n=116, 111, 109, 125, 112) | -2.74 scores on a scale | Standard Error 0.521 |
| Vortioxetine 2.5 mg | Change From Baseline in Sheehan Disability Scale (SDS) at Other Weeks Assessed | Week 4 (n=108, 106, 106, 115, 91) | -4.98 scores on a scale | Standard Error 0.604 |
| Vortioxetine 5 mg | Change From Baseline in Sheehan Disability Scale (SDS) at Other Weeks Assessed | Week 2 (n=116, 114, 116, 123, 103) | -5.02 scores on a scale | Standard Error 0.542 |
| Vortioxetine 5 mg | Change From Baseline in Sheehan Disability Scale (SDS) at Other Weeks Assessed | Week 1 (n=116, 111, 109, 125, 112) | -3.28 scores on a scale | Standard Error 0.521 |
| Vortioxetine 5 mg | Change From Baseline in Sheehan Disability Scale (SDS) at Other Weeks Assessed | Week 4 (n=108, 106, 106, 115, 91) | -5.92 scores on a scale | Standard Error 0.6 |
| Vortioxetine 10 mg | Change From Baseline in Sheehan Disability Scale (SDS) at Other Weeks Assessed | Week 1 (n=116, 111, 109, 125, 112) | -4.11 scores on a scale | Standard Error 0.483 |
| Vortioxetine 10 mg | Change From Baseline in Sheehan Disability Scale (SDS) at Other Weeks Assessed | Week 4 (n=108, 106, 106, 115, 91) | -6.47 scores on a scale | Standard Error 0.568 |
| Vortioxetine 10 mg | Change From Baseline in Sheehan Disability Scale (SDS) at Other Weeks Assessed | Week 2 (n=116, 114, 116, 123, 103) | -5.46 scores on a scale | Standard Error 0.514 |
| Duloxetine 60 mg | Change From Baseline in Sheehan Disability Scale (SDS) at Other Weeks Assessed | Week 2 (n=116, 114, 116, 123, 103) | -7.09 scores on a scale | Standard Error 0.563 |
| Duloxetine 60 mg | Change From Baseline in Sheehan Disability Scale (SDS) at Other Weeks Assessed | Week 1 (n=116, 111, 109, 125, 112) | -4.74 scores on a scale | Standard Error 0.521 |
| Duloxetine 60 mg | Change From Baseline in Sheehan Disability Scale (SDS) at Other Weeks Assessed | Week 4 (n=108, 106, 106, 115, 91) | -7.95 scores on a scale | Standard Error 0.632 |
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 a mixed model for repeated measurements (MMRM) with week, Baseline score-by-week and treatment-by-week interaction as factors.
Time frame: Baseline to Week 8
Population: Full analysis set. A mixed model for repeated measurements (MMRM) based on observed cases was used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Sheehan Disability Scale (SDS) at Week 8 | -6.35 scores on a scale | Standard Error 0.631 |
| Vortioxetine 2.5 mg | Change From Baseline in Sheehan Disability Scale (SDS) at Week 8 | -6.15 scores on a scale | Standard Error 0.647 |
| Vortioxetine 5 mg | Change From Baseline in Sheehan Disability Scale (SDS) at Week 8 | -6.68 scores on a scale | Standard Error 0.642 |
| Vortioxetine 10 mg | Change From Baseline in Sheehan Disability Scale (SDS) at Week 8 | -7.95 scores on a scale | Standard Error 0.623 |
| Duloxetine 60 mg | Change From Baseline in Sheehan Disability Scale (SDS) at Week 8 | -8.81 scores on a scale | Standard Error 0.675 |
p-value: 0.65295% CI: [-1.16, 1.85]Mixed model for repeated measurements
p-value: 0.51195% CI: [-1.98, 0.98]Mixed model for repeated measurements
p-value: 0.20495% CI: [-2.38, 0.51]Mixed model for repeated measurements
p-value: 0.00195% CI: [-4.1, -1.03]Mixed model for repeated measurements
Secondary
Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score at Other Weeks Assessed in Participants With Baseline HAM-A ≥25
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 a mixed model for repeated measurements (MMRM) with week, Baseline score-by-week and treatment-by-week interaction as factors.
Time frame: Baseline to weeks 1, 2, 4 and 6
Population: Full analysis set patients with a HAM-A Baseline score ≥25. A mixed model for repeated measurements (MMRM) based on observed cases 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 the Hamilton Anxiety Scale (HAM-A) Total Score at Other Weeks Assessed in Participants With Baseline HAM-A ≥25 | Week 1 (n=63, 76, 70, 70, 66) | -5.32 scores on a scale | Standard Error 0.787 |
| Placebo | Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score at Other Weeks Assessed in Participants With Baseline HAM-A ≥25 | Week 2 (n=62, 73, 70, 68, 62) | -7.55 scores on a scale | Standard Error 0.856 |
| Placebo | Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score at Other Weeks Assessed in Participants With Baseline HAM-A ≥25 | Week 4 (n=60, 68, 67, 63, 54) | -8.61 scores on a scale | Standard Error 0.901 |
| Placebo | Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score at Other Weeks Assessed in Participants With Baseline HAM-A ≥25 | Week 6 (n=58, 63, 62, 54, 51) | -10.72 scores on a scale | Standard Error 0.937 |
| Vortioxetine 2.5 mg | Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score at Other Weeks Assessed in Participants With Baseline HAM-A ≥25 | Week 1 (n=63, 76, 70, 70, 66) | -6.07 scores on a scale | Standard Error 0.719 |
| Vortioxetine 2.5 mg | Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score at Other Weeks Assessed in Participants With Baseline HAM-A ≥25 | Week 6 (n=58, 63, 62, 54, 51) | -12.86 scores on a scale | Standard Error 0.88 |
| Vortioxetine 2.5 mg | Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score at Other Weeks Assessed in Participants With Baseline HAM-A ≥25 | Week 2 (n=62, 73, 70, 68, 62) | -8.82 scores on a scale | Standard Error 0.785 |
| Vortioxetine 2.5 mg | Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score at Other Weeks Assessed in Participants With Baseline HAM-A ≥25 | Week 4 (n=60, 68, 67, 63, 54) | -11.61 scores on a scale | Standard Error 0.837 |
| Vortioxetine 5 mg | Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score at Other Weeks Assessed in Participants With Baseline HAM-A ≥25 | Week 6 (n=58, 63, 62, 54, 51) | -14.11 scores on a scale | Standard Error 0.895 |
| Vortioxetine 5 mg | Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score at Other Weeks Assessed in Participants With Baseline HAM-A ≥25 | Week 2 (n=62, 73, 70, 68, 62) | -10.18 scores on a scale | Standard Error 0.81 |
| Vortioxetine 5 mg | Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score at Other Weeks Assessed in Participants With Baseline HAM-A ≥25 | Week 4 (n=60, 68, 67, 63, 54) | -12.87 scores on a scale | Standard Error 0.854 |
| Vortioxetine 5 mg | Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score at Other Weeks Assessed in Participants With Baseline HAM-A ≥25 | Week 1 (n=63, 76, 70, 70, 66) | -5.96 scores on a scale | Standard Error 0.749 |
| Vortioxetine 10 mg | Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score at Other Weeks Assessed in Participants With Baseline HAM-A ≥25 | Week 1 (n=63, 76, 70, 70, 66) | -5.94 scores on a scale | Standard Error 0.74 |
| Vortioxetine 10 mg | Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score at Other Weeks Assessed in Participants With Baseline HAM-A ≥25 | Week 2 (n=62, 73, 70, 68, 62) | -8.51 scores on a scale | Standard Error 0.808 |
| Vortioxetine 10 mg | Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score at Other Weeks Assessed in Participants With Baseline HAM-A ≥25 | Week 6 (n=58, 63, 62, 54, 51) | -12.75 scores on a scale | Standard Error 0.918 |
| Vortioxetine 10 mg | Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score at Other Weeks Assessed in Participants With Baseline HAM-A ≥25 | Week 4 (n=60, 68, 67, 63, 54) | -10.98 scores on a scale | Standard Error 0.862 |
| Duloxetine 60 mg | Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score at Other Weeks Assessed in Participants With Baseline HAM-A ≥25 | Week 6 (n=58, 63, 62, 54, 51) | -14.35 scores on a scale | Standard Error 0.961 |
| Duloxetine 60 mg | Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score at Other Weeks Assessed in Participants With Baseline HAM-A ≥25 | Week 4 (n=60, 68, 67, 63, 54) | -12.56 scores on a scale | Standard Error 0.914 |
| Duloxetine 60 mg | Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score at Other Weeks Assessed in Participants With Baseline HAM-A ≥25 | Week 2 (n=62, 73, 70, 68, 62) | -10.40 scores on a scale | Standard Error 0.844 |
| Duloxetine 60 mg | Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score at Other Weeks Assessed in Participants With Baseline HAM-A ≥25 | Week 1 (n=63, 76, 70, 70, 66) | -6.78 scores on a scale | Standard Error 0.77 |
Secondary
Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score at Week 8 in Participants With Baseline HAM-A ≥25
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 a mixed model for repeated measurements (MMRM) with week, Baseline score-by-week and treatment-by-week interaction as factors.
Time frame: Baseline to Week 8
Population: Full analysis set patients with a HAM-A Baseline score ≥25. A mixed model for repeated measurements (MMRM) based on observed cases was used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score at Week 8 in Participants With Baseline HAM-A ≥25 | -11.61 scores on a scale | Standard Error 1.008 |
| Vortioxetine 2.5 mg | Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score at Week 8 in Participants With Baseline HAM-A ≥25 | -14.12 scores on a scale | Standard Error 0.945 |
| Vortioxetine 5 mg | Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score at Week 8 in Participants With Baseline HAM-A ≥25 | -13.87 scores on a scale | Standard Error 0.955 |
| Vortioxetine 10 mg | Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score at Week 8 in Participants With Baseline HAM-A ≥25 | -13.22 scores on a scale | Standard Error 0.999 |
| Duloxetine 60 mg | Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score at Week 8 in Participants With Baseline HAM-A ≥25 | -16.15 scores on a scale | Standard Error 1.039 |
p-value: 0.06495% CI: [-5.15, 0.14]Mixed model for repeated measurements
p-value: 0.09695% CI: [-4.92, 0.4]Mixed model for repeated measurements
p-value: 0.2595% CI: [-4.36, 1.14]Mixed model for repeated measurements
p-value: 0.00295% CI: [-7.34, -1.73]Mixed model for repeated measurements
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 the 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: Sick leave related to anxiety | 5 participants |
| Placebo | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Baseline: Hospitalization related to anxiety | 0 participants |
| Placebo | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Baseline: Any sick leave | 14 participants |
| Placebo | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Week 8: Sick leave related to anxiety | 2 participants |
| Placebo | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Week 8: Any sick leave | 13 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 | Baseline: Any hospitalization-related services | 0 participants |
| Placebo | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Baseline: Any resource use | 34 participants |
| Placebo | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Week 8: Any hospitalization-related service | 0 participants |
| Placebo | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Week 8: Any resource use | 26 participants |
| Vortioxetine 2.5 mg | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Baseline: Hospitalization related to anxiety | 2 participants |
| Vortioxetine 2.5 mg | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Baseline: Any resource use | 36 participants |
| Vortioxetine 2.5 mg | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Baseline: Any hospitalization-related services | 3 participants |
| Vortioxetine 2.5 mg | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Baseline: Any sick leave | 16 participants |
| Vortioxetine 2.5 mg | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Baseline: Sick leave related to anxiety | 10 participants |
| Vortioxetine 2.5 mg | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Week 8: Any resource use | 24 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 | Week 8: Hospitalization related to anxiety | 0 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 | Week 8: Sick leave related to anxiety | 2 participants |
| Vortioxetine 5 mg | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Week 8: Any resource use | 29 participants |
| Vortioxetine 5 mg | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Week 8: Any sick leave | 7 participants |
| Vortioxetine 5 mg | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Baseline: Hospitalization related to anxiety | 1 participants |
| Vortioxetine 5 mg | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Baseline: Any sick leave | 13 participants |
| Vortioxetine 5 mg | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Baseline: Any hospitalization-related services | 1 participants |
| Vortioxetine 5 mg | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Baseline: Sick leave related to anxiety | 9 participants |
| Vortioxetine 5 mg | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Week 8: Any hospitalization-related service | 0 participants |
| Vortioxetine 5 mg | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Baseline: Any resource use | 26 participants |
| Vortioxetine 5 mg | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Week 8: Sick leave related to anxiety | 3 participants |
| Vortioxetine 5 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 hospitalization-related services | 0 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 resource use | 43 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: Hospitalization related to anxiety | 0 participants |
| Vortioxetine 10 mg | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Week 8: Any resource use | 23 participants |
| Vortioxetine 10 mg | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Baseline: Sick leave related to anxiety | 9 participants |
| Vortioxetine 10 mg | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Week 8: Any sick leave | 7 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 sick leave | 15 participants |
| Duloxetine 60 mg | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Baseline: Any resource use | 38 participants |
| Duloxetine 60 mg | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Week 8: Any sick leave | 11 participants |
| Duloxetine 60 mg | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Baseline: Sick leave related to anxiety | 7 participants |
| Duloxetine 60 mg | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Week 8: Any resource use | 22 participants |
| Duloxetine 60 mg | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Week 8: Sick leave related to anxiety | 4 participants |
| Duloxetine 60 mg | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Week 8: Any hospitalization-related service | 3 participants |
| Duloxetine 60 mg | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Baseline: Any hospitalization-related services | 2 participants |
| Duloxetine 60 mg | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Week 8: Hospitalization related to anxiety | 1 participants |
| Duloxetine 60 mg | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Baseline: Hospitalization related to anxiety | 0 participants |
| Duloxetine 60 mg | Health Care Resource Utilization Assessed by the Health Economic Assessment Questionnaire | Baseline: Any sick leave | 12 participants |
Secondary
Mean Clinical Global Impression Scale-Global Improvement (CGI-I) at Other Weeks Assessed
The Clinical Global Impression - Global Improvement scale measures the participant's improvement (or worsening) as assessed by the clinician relative to Baseline on a 7-point scale: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse. LS means were from a mixed model for repeated measurements (MMRM) with week, Baseline score-by-week and treatment-by-week interaction as factors.
Time frame: Baseline to Weeks 1, 2, 4 and 6
Population: Full analysis set with available data at Baseline. A mixed model for repeated measurements (MMRM) based on observed cases 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 | Mean Clinical Global Impression Scale-Global Improvement (CGI-I) at Other Weeks Assessed | Week 4 (n=140, 135, 132, 134, 116) | 2.81 scores on a scale | Standard Error 0.079 |
| Placebo | Mean Clinical Global Impression Scale-Global Improvement (CGI-I) at Other Weeks Assessed | Week 1 (n=151, 148, 141, 149, 141) | 3.44 scores on a scale | Standard Error 0.067 |
| Placebo | Mean Clinical Global Impression Scale-Global Improvement (CGI-I) at Other Weeks Assessed | Week 2 (n=147, 145, 142, 147, 129) | 3.03 scores on a scale | Standard Error 0.072 |
| Placebo | Mean Clinical Global Impression Scale-Global Improvement (CGI-I) at Other Weeks Assessed | Week 6 (n=127, 123, 121, 120, 112) | 2.61 scores on a scale | Standard Error 0.082 |
| Vortioxetine 2.5 mg | Mean Clinical Global Impression Scale-Global Improvement (CGI-I) at Other Weeks Assessed | Week 2 (n=147, 145, 142, 147, 129) | 3.08 scores on a scale | Standard Error 0.072 |
| Vortioxetine 2.5 mg | Mean Clinical Global Impression Scale-Global Improvement (CGI-I) at Other Weeks Assessed | Week 1 (n=151, 148, 141, 149, 141) | 3.46 scores on a scale | Standard Error 0.068 |
| Vortioxetine 2.5 mg | Mean Clinical Global Impression Scale-Global Improvement (CGI-I) at Other Weeks Assessed | Week 6 (n=127, 123, 121, 120, 112) | 2.53 scores on a scale | Standard Error 0.083 |
| Vortioxetine 2.5 mg | Mean Clinical Global Impression Scale-Global Improvement (CGI-I) at Other Weeks Assessed | Week 4 (n=140, 135, 132, 134, 116) | 2.67 scores on a scale | Standard Error 0.08 |
| Vortioxetine 5 mg | Mean Clinical Global Impression Scale-Global Improvement (CGI-I) at Other Weeks Assessed | Week 1 (n=151, 148, 141, 149, 141) | 3.41 scores on a scale | Standard Error 0.069 |
| Vortioxetine 5 mg | Mean Clinical Global Impression Scale-Global Improvement (CGI-I) at Other Weeks Assessed | Week 6 (n=127, 123, 121, 120, 112) | 2.43 scores on a scale | Standard Error 0.084 |
| Vortioxetine 5 mg | Mean Clinical Global Impression Scale-Global Improvement (CGI-I) at Other Weeks Assessed | Week 2 (n=147, 145, 142, 147, 129) | 2.90 scores on a scale | Standard Error 0.073 |
| Vortioxetine 5 mg | Mean Clinical Global Impression Scale-Global Improvement (CGI-I) at Other Weeks Assessed | Week 4 (n=140, 135, 132, 134, 116) | 2.67 scores on a scale | Standard Error 0.081 |
| Vortioxetine 10 mg | Mean Clinical Global Impression Scale-Global Improvement (CGI-I) at Other Weeks Assessed | Week 1 (n=151, 148, 141, 149, 141) | 3.40 scores on a scale | Standard Error 0.067 |
| Vortioxetine 10 mg | Mean Clinical Global Impression Scale-Global Improvement (CGI-I) at Other Weeks Assessed | Week 6 (n=127, 123, 121, 120, 112) | 2.41 scores on a scale | Standard Error 0.083 |
| Vortioxetine 10 mg | Mean Clinical Global Impression Scale-Global Improvement (CGI-I) at Other Weeks Assessed | Week 4 (n=140, 135, 132, 134, 116) | 2.68 scores on a scale | Standard Error 0.08 |
| Vortioxetine 10 mg | Mean Clinical Global Impression Scale-Global Improvement (CGI-I) at Other Weeks Assessed | Week 2 (n=147, 145, 142, 147, 129) | 2.96 scores on a scale | Standard Error 0.072 |
| Duloxetine 60 mg | Mean Clinical Global Impression Scale-Global Improvement (CGI-I) at Other Weeks Assessed | Week 6 (n=127, 123, 121, 120, 112) | 2.25 scores on a scale | Standard Error 0.088 |
| Duloxetine 60 mg | Mean Clinical Global Impression Scale-Global Improvement (CGI-I) at Other Weeks Assessed | Week 1 (n=151, 148, 141, 149, 141) | 3.36 scores on a scale | Standard Error 0.07 |
| Duloxetine 60 mg | Mean Clinical Global Impression Scale-Global Improvement (CGI-I) at Other Weeks Assessed | Week 2 (n=147, 145, 142, 147, 129) | 2.76 scores on a scale | Standard Error 0.077 |
| Duloxetine 60 mg | Mean Clinical Global Impression Scale-Global Improvement (CGI-I) at Other Weeks Assessed | Week 4 (n=140, 135, 132, 134, 116) | 2.44 scores on a scale | Standard Error 0.085 |
Secondary
Mean Clinical Global Impression Scale-Global Improvement (CGI-I) at Week 8
The Clinical Global Impression - Global Improvement scale measures the participant's improvement (or worsening) as assessed by the investigator relative to Baseline on a 7-point scale: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse. LS means were from a mixed model for repeated measurements (MMRM) with week, Baseline score-by-week and treatment-by-week interaction as factors.
Time frame: Baseline to Week 8
Population: Full analysis set. A mixed model for repeated measurements (MMRM) based on observed cases was used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Clinical Global Impression Scale-Global Improvement (CGI-I) at Week 8 | 2.47 scores on a scale | Standard Error 0.091 |
| Vortioxetine 2.5 mg | Mean Clinical Global Impression Scale-Global Improvement (CGI-I) at Week 8 | 2.36 scores on a scale | Standard Error 0.092 |
| Vortioxetine 5 mg | Mean Clinical Global Impression Scale-Global Improvement (CGI-I) at Week 8 | 2.38 scores on a scale | Standard Error 0.093 |
| Vortioxetine 10 mg | Mean Clinical Global Impression Scale-Global Improvement (CGI-I) at Week 8 | 2.38 scores on a scale | Standard Error 0.093 |
| Duloxetine 60 mg | Mean Clinical Global Impression Scale-Global Improvement (CGI-I) at Week 8 | 2.03 scores on a scale | Standard Error 0.098 |
p-value: 0.40795% CI: [-0.36, 0.15]Mixed model for repeated measurements
p-value: 0.53395% CI: [-0.33, 0.17]Mixed model for repeated measurements
p-value: 0.49195% CI: [-0.34, 0.17]Mixed model for repeated measurements
p-value: 0.00195% CI: [-0.7, -0.17]Mixed model for repeated measurements
Secondary
Percentage of Participants in HAM-A Remission at Each Week Assessed
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: 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 (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants in HAM-A Remission at Each Week Assessed | Week 6 (n=154, 154, 148, 154, 149) | 16.2 percentage of participants |
| Placebo | Percentage of Participants in HAM-A Remission at Each Week Assessed | Week 1 (n=151, 149, 142, 149, 143) | 4.0 percentage of participants |
| Placebo | Percentage of Participants in HAM-A Remission at Each Week Assessed | Week 8 (n=154, 154, 148, 154, 149) | 22.1 percentage of participants |
| Placebo | Percentage of Participants in HAM-A Remission at Each Week Assessed | Week 2 (n=154, 154, 147, 154, 149) | 6.5 percentage of participants |
| Placebo | Percentage of Participants in HAM-A Remission at Each Week Assessed | Week 4 (n=154, 154, 148, 154, 149) | 10.4 percentage of participants |
| Vortioxetine 2.5 mg | Percentage of Participants in HAM-A Remission at Each Week Assessed | Week 6 (n=154, 154, 148, 154, 149) | 14.9 percentage of participants |
| Vortioxetine 2.5 mg | Percentage of Participants in HAM-A Remission at Each Week Assessed | Week 4 (n=154, 154, 148, 154, 149) | 13.6 percentage of participants |
| Vortioxetine 2.5 mg | Percentage of Participants in HAM-A Remission at Each Week Assessed | Week 2 (n=154, 154, 147, 154, 149) | 8.4 percentage of participants |
| Vortioxetine 2.5 mg | Percentage of Participants in HAM-A Remission at Each Week Assessed | Week 8 (n=154, 154, 148, 154, 149) | 20.1 percentage of participants |
| Vortioxetine 2.5 mg | Percentage of Participants in HAM-A Remission at Each Week Assessed | Week 1 (n=151, 149, 142, 149, 143) | 2.0 percentage of participants |
| Vortioxetine 5 mg | Percentage of Participants in HAM-A Remission at Each Week Assessed | Week 4 (n=154, 154, 148, 154, 149) | 11.5 percentage of participants |
| Vortioxetine 5 mg | Percentage of Participants in HAM-A Remission at Each Week Assessed | Week 1 (n=151, 149, 142, 149, 143) | 0.7 percentage of participants |
| Vortioxetine 5 mg | Percentage of Participants in HAM-A Remission at Each Week Assessed | Week 2 (n=154, 154, 147, 154, 149) | 7.5 percentage of participants |
| Vortioxetine 5 mg | Percentage of Participants in HAM-A Remission at Each Week Assessed | Week 6 (n=154, 154, 148, 154, 149) | 14.9 percentage of participants |
| Vortioxetine 5 mg | Percentage of Participants in HAM-A Remission at Each Week Assessed | Week 8 (n=154, 154, 148, 154, 149) | 19.6 percentage of participants |
| Vortioxetine 10 mg | Percentage of Participants in HAM-A Remission at Each Week Assessed | Week 8 (n=154, 154, 148, 154, 149) | 20.1 percentage of participants |
| Vortioxetine 10 mg | Percentage of Participants in HAM-A Remission at Each Week Assessed | Week 1 (n=151, 149, 142, 149, 143) | 2.0 percentage of participants |
| Vortioxetine 10 mg | Percentage of Participants in HAM-A Remission at Each Week Assessed | Week 6 (n=154, 154, 148, 154, 149) | 16.9 percentage of participants |
| Vortioxetine 10 mg | Percentage of Participants in HAM-A Remission at Each Week Assessed | Week 4 (n=154, 154, 148, 154, 149) | 13.0 percentage of participants |
| Vortioxetine 10 mg | Percentage of Participants in HAM-A Remission at Each Week Assessed | Week 2 (n=154, 154, 147, 154, 149) | 3.9 percentage of participants |
| Duloxetine 60 mg | Percentage of Participants in HAM-A Remission at Each Week Assessed | Week 4 (n=154, 154, 148, 154, 149) | 17.4 percentage of participants |
| Duloxetine 60 mg | Percentage of Participants in HAM-A Remission at Each Week Assessed | Week 6 (n=154, 154, 148, 154, 149) | 20.8 percentage of participants |
| Duloxetine 60 mg | Percentage of Participants in HAM-A Remission at Each Week Assessed | Week 1 (n=151, 149, 142, 149, 143) | 4.9 percentage of participants |
| Duloxetine 60 mg | Percentage of Participants in HAM-A Remission at Each Week Assessed | Week 8 (n=154, 154, 148, 154, 149) | 28.2 percentage of participants |
| Duloxetine 60 mg | Percentage of Participants in HAM-A Remission at Each Week Assessed | Week 2 (n=154, 154, 147, 154, 149) | 12.1 percentage of participants |
Secondary
Percentage of Responders in HAM-A Total Score at Other Weeks Assessed
Response was defined as participants 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 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 (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Responders in HAM-A Total Score at Other Weeks Assessed | Week 1 (n=151, 149, 142, 149, 143) | 11.3 percentage of participants |
| Placebo | Percentage of Responders in HAM-A Total Score at Other Weeks Assessed | Week 2 (n=154, 154, 147, 154, 149) | 20.8 percentage of participants |
| Placebo | Percentage of Responders in HAM-A Total Score at Other Weeks Assessed | Week 4 (n=154, 154, 148, 154, 149) | 26.0 percentage of participants |
| Placebo | Percentage of Responders in HAM-A Total Score at Other Weeks Assessed | Week 6 (n=154, 154, 148, 154, 149) | 36.4 percentage of participants |
| Vortioxetine 2.5 mg | Percentage of Responders in HAM-A Total Score at Other Weeks Assessed | Week 1 (n=151, 149, 142, 149, 143) | 6.7 percentage of participants |
| Vortioxetine 2.5 mg | Percentage of Responders in HAM-A Total Score at Other Weeks Assessed | Week 6 (n=154, 154, 148, 154, 149) | 37.7 percentage of participants |
| Vortioxetine 2.5 mg | Percentage of Responders in HAM-A Total Score at Other Weeks Assessed | Week 2 (n=154, 154, 147, 154, 149) | 20.1 percentage of participants |
| Vortioxetine 2.5 mg | Percentage of Responders in HAM-A Total Score at Other Weeks Assessed | Week 4 (n=154, 154, 148, 154, 149) | 30.5 percentage of participants |
| Vortioxetine 5 mg | Percentage of Responders in HAM-A Total Score at Other Weeks Assessed | Week 6 (n=154, 154, 148, 154, 149) | 40.5 percentage of participants |
| Vortioxetine 5 mg | Percentage of Responders in HAM-A Total Score at Other Weeks Assessed | Week 2 (n=154, 154, 147, 154, 149) | 21.1 percentage of participants |
| Vortioxetine 5 mg | Percentage of Responders in HAM-A Total Score at Other Weeks Assessed | Week 4 (n=154, 154, 148, 154, 149) | 32.4 percentage of participants |
| Vortioxetine 5 mg | Percentage of Responders in HAM-A Total Score at Other Weeks Assessed | Week 1 (n=151, 149, 142, 149, 143) | 8.5 percentage of participants |
| Vortioxetine 10 mg | Percentage of Responders in HAM-A Total Score at Other Weeks Assessed | Week 1 (n=151, 149, 142, 149, 143) | 10.1 percentage of participants |
| Vortioxetine 10 mg | Percentage of Responders in HAM-A Total Score at Other Weeks Assessed | Week 2 (n=154, 154, 147, 154, 149) | 21.4 percentage of participants |
| Vortioxetine 10 mg | Percentage of Responders in HAM-A Total Score at Other Weeks Assessed | Week 6 (n=154, 154, 148, 154, 149) | 40.9 percentage of participants |
| Vortioxetine 10 mg | Percentage of Responders in HAM-A Total Score at Other Weeks Assessed | Week 4 (n=154, 154, 148, 154, 149) | 35.1 percentage of participants |
| Duloxetine 60 mg | Percentage of Responders in HAM-A Total Score at Other Weeks Assessed | Week 6 (n=154, 154, 148, 154, 149) | 47.7 percentage of participants |
| Duloxetine 60 mg | Percentage of Responders in HAM-A Total Score at Other Weeks Assessed | Week 4 (n=154, 154, 148, 154, 149) | 42.3 percentage of participants |
| Duloxetine 60 mg | Percentage of Responders in HAM-A Total Score at Other Weeks Assessed | Week 2 (n=154, 154, 147, 154, 149) | 28.9 percentage of participants |
| Duloxetine 60 mg | Percentage of Responders in HAM-A Total Score at Other Weeks Assessed | Week 1 (n=151, 149, 142, 149, 143) | 16.8 percentage of participants |
Secondary
Percentage of Responders in HAM-A Total Score at Week 8
Response was defined as participants 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: Week 8
Population: Full analysis set; Last observation carried forward (LOCF) was used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Responders in HAM-A Total Score at Week 8 | 42.2 percentage of participants |
| Vortioxetine 2.5 mg | Percentage of Responders in HAM-A Total Score at Week 8 | 44.8 percentage of participants |
| Vortioxetine 5 mg | Percentage of Responders in HAM-A Total Score at Week 8 | 42.6 percentage of participants |
| Vortioxetine 10 mg | Percentage of Responders in HAM-A Total Score at Week 8 | 44.8 percentage of participants |
| Duloxetine 60 mg | Percentage of Responders in HAM-A Total Score at Week 8 | 51.0 percentage of participants |
p-value: 0.64195% CI: [0.709, 1.75]Regression, Logistic
p-value: 0.94595% CI: [0.643, 1.605]Regression, Logistic
p-value: 0.64195% CI: [0.709, 1.749]Regression, Logistic
p-value: 0.12495% CI: [0.907, 2.246]Regression, Logistic