Attention Deficit Hyperactivity Disorder
Conditions
Brief summary
The purpose is to determine the effect of vortioxetine treatment on ADHD symptoms in adult patients with ADHD in a 12 weeks study.
Detailed description
The study employed the Sequential Parallel Comparison Design (SPCD), a clinical study design which intend to increase signal detection by using two stages of treatment: * Stage 1 - first 6 weeks of the 12-weeks treatment period (Visit 2/Baseline 1 to Visit 5/Week 6) * Stage 2 - last 6 weeks of the 12-weeks treatment period (Visit 5/Baseline 2 to Visit 8/Week 12) In Stage 1, patients were randomized to placebo or vortioxetine 10 or 20mg. Patients on vortioxetine 10 or 20mg/day during Stage 1 remained on the same treatment in Stage 2. Responders to placebo in Stage 1 remained on Placebo in Stage 2. Patients who were placebo non-responders during Stage 1, defined as patients with a \<30% reduction in AISRS total score from Baseline 1, were re-randomized to placebo or vortioxetine 10 or 20mg/day in Stage 2.
Interventions
DRUGvortioxetine 10 mg tablet
Oral tablets, once daily
DRUGvortioxetine 20 mg tablet
Oral tablets, once daily
OTHERPlacebo tablet
Oral tablets, once daily
Sponsors
H. Lundbeck A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* The patient is willing and able to attend study appointments within the specified time windows. * The patient is an outpatient. * The patient is diagnosed with a primary diagnosis of ADHD according to the DSM-5™ classification. * The patient has an AISRS total score ≥24. * The patient has a CGI-S rating ≥4 (moderately ill or worse).
Exclusion criteria
* The patient has previously been treated with vortioxetine. * The patient has any current psychiatric disorder (DSM-IV-TR™ criteria), other than ADHD, as assessed using the Mini International Neuropsychiatric Interview (MINI). * The patient has a known first-degree relative with bipolar disorder. * The patient suffers from intellectual disability as evaluated by the Wechsler Abbreviated Scale of Intelligence (WASI) II vocabulary and matrix. * The patient suffers from organic mental disorders, or mental disorders due to a general medical condition (DSM-5™ criteria). * The patient has reported current use of, or has tested positive for, drugs of abuse (opiates, methadone, cocaine, amphetamines \[including ecstasy\], barbiturates, benzodiazepines, and cannabinoids). If a patient tests positive for opiates due to incidental use of codeine containing medication, as assessed in a clinical interview, the drug screen may be repeated up to three weeks later but the retest result must be available from the central laboratory latest at Visit 2 and has to be negative for this patient to be eligible for enrolment. If a patient tests positive for amphetamines due to his/her ADHD current treatment, as confirmed by a clinical interview, the patient is eligible for enrolment provided this treatment is discontinued two weeks prior to the Baseline Visit. * The patient has a history of two prior failed (\<50% improvement in symptoms) adequate trials of ADHD treatment. * The patient has any other disorder for which the treatment takes priority over treatment of ADHD or is likely to interfere with study treatment or impair treatment compliance. * The patient has a history of moderate or severe head trauma or other neurological disorders or systemic medical diseases that are, in the investigator's opinion, likely to affect central nervous system functioning. * The patient has attempted suicide within the last 6 months or is at significant risk of suicide (either in the opinion of the Investigator or defined as a yes to suicidal ideation questions 4 or 5 or answering yes to suicidal behaviour on the Columbia-Suicide Rating Scale (C-SSRS) within the last 12 months). Other protocol defined inclusion and
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in ADHD Investigator Symptom Rating Scale (AISRS) Total Score | Baseline to Week 6 | AISRS: an 18-item scale administered by the investigator. It included 9 items that evaluated symptoms of inattention and 9 items that evaluated symptoms of impulsivity and hyperactivity. Each item was rated from 0 (none) to 3 (severe). AISRS total score was calculated as sum of all the items on the scale and ranged from 0 to 54. A higher score corresponded to a worse severity of ADHD. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cognitive Function/Global Executive Function: Change in BRIEF-A Using the Global Executive Composite Score | Baseline to Week 6 | BRIEF-A is a validated questionnaire composed of 75-item within nine non-overlapping scales: 4 scales in the Behavioral Regulation Index (BRI) (inhibit, shift, emotional control, and self-monitor), and 5 scales in the Metacognition Index (MI) (initiate, working memory, plan/organise, task monitor, and organization of materials). Each item is rated on a 3-point scale with the numeric score of 1 to 3. The BRIEF-A yields an overall score (Global Executive Composite) composed of two index scores, the MI and the BRI. Raw scale scores are used to generate T-scores. A reduction in score indicates less impairment. |
| Overall Functioning: Change in Sheehan Disability Scale (SDS) Total Score | Baseline to Week 6 | The SDS comprises a series of patient rated scales designed to measure impairment. The patient rates the extent to which his or her (1) work, (2) social life or leisure activities and 3) home life or family responsibilities are impaired on a 10-point visual analogue scale, on which 0 = normal functioning and 10 = severe functional impairment. The number of days lost and the number of underproductive days last from work/school due to symptoms are also captured. The total score is calculated as a sum of the 3 visual analogue scales, ranges from 0 to 30. A higher score represents more severe functional impairment. A reduction in score indicates less impairment. |
| Productivity: Change in Work Limitations Questionnaire (WLQ) Productivity Loss Score | Baseline to Week 6 | The WLQ is a patient self-rated scale designed to assess on-the-job impact of chronic health problems and/or treatment. The WLQ consists of 25 items in 4 dimensions: limitations handling time (5 items), physical work demands (6 items), mental-interpersonal work demands (9 items), and output demands (5 items). Each item is rated on a 5-point scale from All of the Time (score 5) to None of the Time (score 0), or Does Not Apply to My Job. The WLQ Productivity Loss Score is derived from the Global Productivity Index, which is calculated as a weighed sum of the 4 dimensions. Reduction in WLQ Productivity Loss score indicates less work limitation and represents the estimated percentage of productivity loss in the past two weeks due to presenteeism relative to a healthy benchmark sample. WLQ Productivity Loss Score ranges from 0% to 24,9%. |
| Change in AISRS Inattention Sub-score | Baseline to Week 6 | The AISRS inattentive subscale score consists of 9 items from the AISRS which address inattention. Each item is rated from 0 to 3. The AISRS inattentive subscale score can range from 0 to 27. A higher score corresponds to a worse severity of ADHD inattentiveness. |
| Change AISRS Hyperactivity/Impulsivity Sub-score | Baseline to Week 6 | The AISRS hyperactive/impulsive subscale score consists of 9 items from the AISRS which address hyperactivity and impulsivity. Each item is rated from 0 to 3. The AISRS hyperactive/impulsive subscale score can range from 0 to 27. A higher score corresponds to a worse severity of ADHD hyperactivity/impulsivity. |
| Percentage of Patients Responding (Response Defined as 30% or Greater Reduction From Baseline in AISRS Total Score) | Baseline to Week 6 | AISRS: an 18-item scale administered by the investigator. It included 9 items that evaluated symptoms of inattention and 9 items that evaluated symptoms of impulsivity and hyperactivity. Each item was rated from 0 (none) to 3 (severe). AISRS total score was calculated as sum of all the items on the scale and ranged from 0 to 54. A higher score corresponded to a worse severity of ADHD. |
| Change in Adult ADHD Self-Report Scale (ASRS) Total Score | Baseline to Week 6 | The Adult ADHD Self-Report Scale (ASRS) is a patient-rated scale designed to assess the ADHD symptoms in adults based on the diagnostic criteria of DSM-IVTM. The ASRS consist of 18 items, each rated on a 5-point scale from Never to Very Often. The categories Never and Rarely were combined when calculating the total score to mirror the scoring of the AISRS, with 0 representing Never/Rarely and 3 representing Very Often. The Total Score ranges from 0 to 54. A reduction in score indicates less severity of ADHD. |
| Change in Clinical Global Impression - Severity of Illness (CGI-S) Score | Baseline to Week 6 | The Clinical Global Impression - Severity of Illness (CGI-S) provides the clinician's impression of the patient's current state of mental illness. The clinician uses his or her clinical experience of this patient population to rate the severity of the patient's current mental illness on a 7-point scale ranging from 1 (Normal - not at all ill) to 7 (among the most extremely ill patients). Higher scores indicate worsening. |
| Clinical Global Impression - Global Improvement (CGI-I) Score | Week 6 | The Clinical Global Impression - Global Improvement (CGI-I) provides the clinician's impression of the patient's improvement (or worsening). The clinician assesses the patient's condition relative to a baseline on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). Higher scores indicate worsening. |
| Response (Defined as a CGI-I Score of 1 or 2), Stage 1 | Week 6 | The Clinical Global Impression - Global Improvement (CGI-I) provides the clinician's impression of the patient's improvement (or worsening). The clinician assesses the patient's condition relative to a baseline on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). Higher scores indicate worsening. |
| Change in BRIEF-A Using the Behavioural Regulation Index | Baseline to Week 6 | The Behavioral Regulation Index (BRI) is an index score of the BRIEF-A and consists of 4 scales: inhibit, shift, emotional control, and self-monitor). Each item is rated on a 3-point scale with the numeric score of 1 to 3. Raw scale scores are used to generate T-scores. A reduction in score indicates less impairment. |
| Change in BRIEF-A Subscales - Inhibit | Baseline to Week 6 | The BRIEF-A subscale Inhibit is a subscale within the Behavioural Regulation Index (BRI). Each item is rated on a 3-point scale ranging from 1 (never) to 3 (often). Raw scale scores are used to generate T-scores. A reduction in score indicates less impairment. |
| Change BRIEF-A Subscales - Initiate | Baseline to Week 6 | The BRIEF-A subscale Initiate is a subscale within the Behavioural Regulation Index (BRI). Each item is rated on a 3-point scale ranging from 1 (never) to 3 (often). Raw scale scores are used to generate T-scores. A reduction in score indicates less impairment. |
| Change in BRIEF-A Subscales - Organization of Materials | Baseline to Week 6 | The BRIEF-A subscale Organization of Materials is a subscale within the Behavioural Regulation Index (BRI). Each item is rated on a 3-point scale ranging from 1 (never) to 3 (often). Raw scale scores are used to generate T-scores. A reduction in score indicates less impairment. |
| Change in BRIEF-A Subscales - Planning/Organize | Baseline to Week 6 | The BRIEF-A subscale Planning/Organize is a subscale within the Behavioural Regulation Index (BRI). Each item is rated on a 3-point scale ranging from 1 (never) to 3 (often). Raw scale scores are used to generate T-scores. A reduction in score indicates less impairment. |
| Change in BRIEF-A Subscales - Shift | Baseline to Week 6 | The BRIEF-A subscale Shift is a subscale within the Behavioural Regulation Index (BRI). Each item is rated on a 3-point scale ranging from 1 (never) to 3 (often). Raw scale scores are used to generate T-scores. A reduction in score indicates less impairment. |
| Change in BRIEF-A Subscales - Self Monitor | Baseline to Week 6 | The BRIEF-A subscale Self Monitor is a subscale within the Behavioural Regulation Index (BRI). Each item is rated on a 3-point scale ranging from 1 (never) to 3 (often). Raw scale scores are used to generate T-scores. A reduction in score indicates less impairment. |
| Change in BRIEF-A Subscales - Task Monitor | Baseline to Week 6 | The BRIEF-A subscale Task Monitor is a subscale within the Behavioural Regulation Index (BRI). Each item is rated on a 3-point scale ranging from 1 (never) to 3 (often). Raw scale scores are used to generate T-scores. A reduction in score indicates less impairment. |
| Change in BRIEF-A Subscales - Working Memory | Baseline to Week 6 | The BRIEF-A subscale Working Memory is a subscale within the Behavioural Regulation Index (BRI). Each item is rated on a 3-point scale ranging from 1 (never) to 3 (often). Raw scale scores are used to generate T-scores. A reduction in score indicates less impairment. |
| Change in BRIEF-A Subscales - Emotional Control | Baseline to Week 6 | The BRIEF-A subscale Emotional Control is a subscale within the Behavioural Regulation Index (BRI). Each item is rated on a 3-point scale ranging from 1 (never) to 3 (often). Raw scale scores are used to generate T-scores. A reduction in score indicates less impairment. |
| Change in Perceived Deficits Questionnaire - Depression (PDQ-D) Total Score | Baseline to Week 6 | The PDQ-D is a patient-rated scale designed to assess cognitive impairment/dysfunction adapted for MDD. Each item is rated on a scale from 0 (never) to 4 (almost always). The total score of the 20 items ranges from 0 to 80 with higher scores reflect greater subjective cognitive impairment. A reduction in score indicates less impairment. |
| Change in PDQ-D Subscales - Attention and Concentration Sub-score | Baseline to Week 6 | The PDQ-D attention/concentration sub-score consists of items 1, 5, 9, 13, and 17 of the PDQ with a score ranging from 0 to 20. A higher score reflects greater subjective cognitive impairment. A reduction in score indicates less cognitive impairment. |
| Change in PDQ-D Sub-scales - Retrospective Memory Sub-score | Baseline to Week 6 | The PDQ-D retrospective memory sub-score consists of items 2, 6, 10, 14, and 18 of the PDQ (see Outcome 23) with a score ranging from 0 to 20. A higher score reflects greater subjective cognitive impairment. A reduction in score indicates less cognitive impairment. |
| Change in PDQ-D Sub-scales - Prospective Memory Sub-score | Baseline to Week 6 | The PDQ-D prospective memory sub-score consists of items 3, 7, 11, 15, and 19 of the PDQ (see Outcome 23) with a score ranging from 0 to 20. A higher score reflects greater subjective cognitive impairment. A reduction in score indicates less cognitive impairment. |
| Change in PDQ-D Sub-scales - Planning and Organisation Sub-score | Baseline to Week 6 | The PDQ-D planning and organisation sub-score consists of items 4, 8, 12, 16, and 20 of the PDQ (see Outcome 23) with a score ranging from 0 to 20. A higher score reflects greater subjective cognitive impairment. A reduction in score indicates less cognitive impairment. |
| Change in SDS Item Scores - Family | Baseline to Week 6 | The SDS item family is rated from 0 = normal functioning to 10 = severe functional impairment (see outcome 4). A higher score represents more severe functional impairment. A reduction in score indicates less impairment. |
| Change in SDS Item Scores - Work | Baseline to Week 6 | The SDS item work is rated from 0 = normal functioning to 10 = severe functional impairment (see outcome 4). A higher score represents more severe functional impairment. A reduction in score indicates less impairment. |
| Change in SDS Item Scores - Social Life | Baseline to Week 6 | The SDS item social life is rated from 0 = normal functioning to 10 = severe functional impairment (see outcome 4). A higher score represents more severe functional impairment. A reduction in score indicates less impairment. |
| Change in SDS Item Scores - Number of Days Lost | Baseline to Week 6 | This SDS item captures days lost from school or work (see outcome 4). |
| Change in SDS Item Scores - Number of Underproductive Days | Baseline to Week 6 | This SDS item captures the number of underproductive days (see outcome 4) |
| Change in WLQ Using the Global Productivity Index | Baseline to Week 6 | The WLQ is a patient self-rated scale designed to assess on-the-job impact of chronic health problems and/or treatment. The WLQ consists of 25 items in 4 dimensions: limitations handling time (5 items), physical work demands (6 items), mental-interpersonal work demands (9 items), and output demands (5 items). Each item is rated on a 5-point scale from All of the Time (score 5) to None of the Time (score 0), or Does Not Apply to My Job. The Global Productivity Index is calculated as a weighed sum of the 4 dimensions, and ranges from 0.000 to 0.286. Reduction in score indicates less work limitation. |
| Change in WLQ Domain Scores - Limitations Handling Time | Baseline to Week 6 | Limitations Handling Time is scored on a scale of 0 (limited at work none of the time) to 100 (limited at work all of the time) based on a converted mean score. A reduction in score indicates less work limitation. |
| Change in WLQ Domain Scores - Mental-Interpersonal Work Demands | Baseline to Week 6 | Mental-Interpersonal Work Demands is scored on a scale of 0 (limited at work none of the time) to 100 (limited at work all of the time) based on a converted mean score. A reduction in score indicates less work limitation. |
| Change in WLQ Domain Scores - Physical Demands | Baseline to Week 6 | Physical Demands is scored on a scale of 0 (limited at work none of the time) to 100 (limited at work all of the time) based on a converted mean score. A reduction in score indicates less work limitation. |
| Change in WLQ Domain Scores - Output Demands | Baseline to Week 6 | Output Demands is scored on a scale of 0 (limited at work none of the time) to 100 (limited at work all of the time) based on a converted mean score. A reduction in score indicates less work limitation. |
| Inattention/Meta-cognition: Change in Behavior Rating Inventory of Executive Function - Adult Version (BRIEF-A) Using Metacognition Index | Baseline to Week 6 | The Metacognition Index (MI) is an index score of the BRIEF-A consisting of 5 scales: initiate, working memory, plan/organise, task monitor, and organization of materials. Each item is rated on a 3-point scale with the numeric score of 1 to 3. Raw scale scores are used to generate T-scores. A reduction in score indicates less impairment. |
| Change in AAQoL Subscales - Life Productivity Sub-score | Baseline to Week 6 | The AAQoL is a patient-rated scale designed to assess health-related quality of life in adults with ADHD. The AAQoL consists of 29 items, each item is rated on a 5-point scale from 1 (not at all/never) to 5 (extremely/very often). The AAQoL Life productivity subscale is based on 11 items and ranges from 11 to 55. A reduction in score indicates less impairment. |
| Change in AAQoL Subscales - Psychological Health Sub-score | Baseline to Week 6 | The AAQoL is a patient-rated scale designed to assess health-related quality of life in adults with ADHD. The AAQoL consists of 29 items, each item is rated on a 5-point scale from 1 (not at all/never) to 5 (extremely/very often). The AAQoL Psychological Health subscale is based on 6 items and ranges from 6 to 30. A reduction in score indicates less impairment. |
| Change in AAQoL Subscales - Life Outlook Sub-score | Baseline to Week 6 | The AAQoL is a patient-rated scale designed to assess health-related quality of life in adults with ADHD. The AAQoL consists of 29 items, each item is rated on a 5-point scale from 1 (not at all/never) to 5 (extremely/very often). The AAQoL Life Outlook subscale is based on 7 items and ranges from 7 to 35. A reduction in score indicates less impairment. |
| Change in AAQoL Subscales - Relationships Sub-score | Baseline to Week 6 | The AAQoL is a patient-rated scale designed to assess health-related quality of life in adults with ADHD. The AAQoL consists of 29 items, each item is rated on a 5-point scale from 1 (not at all/never) to 5 (extremely/very often). The AAQoL Relationship subscale is based on 5 items and ranges from 5 to 25. A reduction in score indicates less impairment. |
| Change in Adult ADHD Quality of Life Measure (AAQoL) Total Score | Baseline to Week 6 | The AAQoL is a patient-rated scale designed to assess health-related quality of life in adults with ADHD. The AAQoL consists of 29 items, each item is rated on a 5-point scale from 1 (not at all/never) to 5 (extremely/very often). The AAQoL Total score is based on all 29 items and ranges from 29 to 145. A reduction in score indicates less impairment. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo (Stage 1) Patients treated wtih placebo in Stage 1. | 128 |
| Vortioxetine 10mg (Stage 1) Patients treated with vortioxetine 10mg in Stage 1. | 47 |
| Vortioxetine 20mg (Stage 1) Patients treated with vortioxetine 20mg in Stage 1. | 44 |
| Total | 219 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Administrative or other reason(s) | 1 | 5 | 11 | 1 | 1 |
| Overall Study | Adverse Event | 4 | 4 | 3 | 0 | 1 |
| Overall Study | Lack of Efficacy | 2 | 0 | 5 | 0 | 1 |
| Overall Study | Lost to Follow-up | 2 | 4 | 5 | 0 | 0 |
| Overall Study | Non-compliance with IMP | 1 | 2 | 7 | 0 | 0 |
| Overall Study | Protocol Violation | 0 | 0 | 3 | 0 | 1 |
| Overall Study | Withdrawal before treatment | 2 | 1 | 5 | 0 | 0 |
| Overall Study | Withdrawal of Consent | 1 | 0 | 3 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo (Stage 1) | Vortioxetine 10mg (Stage 1) | Vortioxetine 20mg (Stage 1) | Total |
|---|---|---|---|---|
| Age, Continuous | 37.1 years STANDARD_DEVIATION 10.3 | 35.8 years STANDARD_DEVIATION 9.6 | 37.2 years STANDARD_DEVIATION 10.4 | 36.9 years STANDARD_DEVIATION 10.2 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 8 Participants | 4 Participants | 1 Participants | 13 Participants |
| Race (NIH/OMB) Black or African American | 15 Participants | 3 Participants | 8 Participants | 26 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants | 1 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 6 Participants | 2 Participants | 4 Participants | 12 Participants |
| Race (NIH/OMB) White | 97 Participants | 37 Participants | 31 Participants | 165 Participants |
| Sex: Female, Male Female | 66 Participants | 24 Participants | 19 Participants | 109 Participants |
| Sex: Female, Male Male | 62 Participants | 23 Participants | 25 Participants | 110 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 91 | 0 / 68 | 0 / 60 |
| other Total, other adverse events | 39 / 91 | 34 / 68 | 36 / 60 |
| serious Total, serious adverse events | 1 / 91 | 1 / 68 | 0 / 60 |
Outcome results
Primary
Change in ADHD Investigator Symptom Rating Scale (AISRS) Total Score
AISRS: an 18-item scale administered by the investigator. It included 9 items that evaluated symptoms of inattention and 9 items that evaluated symptoms of impulsivity and hyperactivity. Each item was rated from 0 (none) to 3 (severe). AISRS total score was calculated as sum of all the items on the scale and ranged from 0 to 54. A higher score corresponded to a worse severity of ADHD.
Time frame: Baseline to Week 6
Population: Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo, Stage 1 | Change in ADHD Investigator Symptom Rating Scale (AISRS) Total Score | -12.4 units on a scale | Standard Error 1.25 |
| Vortioxetine 10mg, Stage 1 | Change in ADHD Investigator Symptom Rating Scale (AISRS) Total Score | -12.8 units on a scale | Standard Error 1.99 |
| Vortioxetine 20mg, Stage 1 | Change in ADHD Investigator Symptom Rating Scale (AISRS) Total Score | -11.6 units on a scale | Standard Error 2.17 |
| Placebo, Stage 2 | Change in ADHD Investigator Symptom Rating Scale (AISRS) Total Score | -4.1 units on a scale | Standard Error 1.92 |
| Vortioxetine 10mg, Stage 2 | Change in ADHD Investigator Symptom Rating Scale (AISRS) Total Score | -3.9 units on a scale | Standard Error 1.98 |
| Vortioxetine 20mg, Stage 2 | Change in ADHD Investigator Symptom Rating Scale (AISRS) Total Score | -2.9 units on a scale | Standard Error 2.35 |
| Placebo, Combined | Change in ADHD Investigator Symptom Rating Scale (AISRS) Total Score | -8.3 units on a scale | Standard Error 1.1 |
| Vortioxetine 10mg, Combined | Change in ADHD Investigator Symptom Rating Scale (AISRS) Total Score | -8.3 units on a scale | Standard Error 1.4 |
| Vortioxetine 20mg, Combined | Change in ADHD Investigator Symptom Rating Scale (AISRS) Total Score | -7.3 units on a scale | Standard Error 1.6 |
Comparison: The mean difference between treatment groups was estimated based on LS means for the treatment-by-visit interaction in stagewise MMRM analyses. In each stage, the REML-based MMRM model included site ID (stage 1 only), visit, treatment (placebo, vortioxetine 10mg, vortioxetine 20mg), baseline (for the stage) AISRS total score, treatment-by-visit interaction, and baseline (stage) AISRS total score-by-visit interaction, with an unstructured covariance structure to model the within-patient errors.p-value: 0.972395% CI: [-3.6, 3.5]weighed z-score
p-value: 0.60195% CI: [-2.8, 4.8]weighed z-score
Secondary
Change AISRS Hyperactivity/Impulsivity Sub-score
The AISRS hyperactive/impulsive subscale score consists of 9 items from the AISRS which address hyperactivity and impulsivity. Each item is rated from 0 to 3. The AISRS hyperactive/impulsive subscale score can range from 0 to 27. A higher score corresponds to a worse severity of ADHD hyperactivity/impulsivity.
Time frame: Baseline to Week 6
Population: Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo, Stage 1 | Change AISRS Hyperactivity/Impulsivity Sub-score | -5.9 units on a scale | Standard Error 0.62 |
| Vortioxetine 10mg, Stage 1 | Change AISRS Hyperactivity/Impulsivity Sub-score | -7.0 units on a scale | Standard Error 0.99 |
| Vortioxetine 20mg, Stage 1 | Change AISRS Hyperactivity/Impulsivity Sub-score | -5.7 units on a scale | Standard Error 1.08 |
| Placebo, Stage 2 | Change AISRS Hyperactivity/Impulsivity Sub-score | -2.1 units on a scale | Standard Error 0.93 |
| Vortioxetine 10mg, Stage 2 | Change AISRS Hyperactivity/Impulsivity Sub-score | -2.0 units on a scale | Standard Error 0.97 |
| Vortioxetine 20mg, Stage 2 | Change AISRS Hyperactivity/Impulsivity Sub-score | -1.2 units on a scale | Standard Error 1.15 |
| Placebo, Combined | Change AISRS Hyperactivity/Impulsivity Sub-score | -4.0 units on a scale | Standard Error 0.6 |
| Vortioxetine 10mg, Combined | Change AISRS Hyperactivity/Impulsivity Sub-score | -4.5 units on a scale | Standard Error 0.7 |
| Vortioxetine 20mg, Combined | Change AISRS Hyperactivity/Impulsivity Sub-score | -3.4 units on a scale | Standard Error 0.8 |
Secondary
Change BRIEF-A Subscales - Initiate
The BRIEF-A subscale Initiate is a subscale within the Behavioural Regulation Index (BRI). Each item is rated on a 3-point scale ranging from 1 (never) to 3 (often). Raw scale scores are used to generate T-scores. A reduction in score indicates less impairment.
Time frame: Baseline to Week 6
Population: Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo, Stage 1 | Change BRIEF-A Subscales - Initiate | -6.2 T-score | Standard Error 1.4 |
| Vortioxetine 10mg, Stage 1 | Change BRIEF-A Subscales - Initiate | -5.8 T-score | Standard Error 1.6 |
| Vortioxetine 20mg, Stage 1 | Change BRIEF-A Subscales - Initiate | -4.2 T-score | Standard Error 1.8 |
Secondary
Change in AAQoL Subscales - Life Outlook Sub-score
The AAQoL is a patient-rated scale designed to assess health-related quality of life in adults with ADHD. The AAQoL consists of 29 items, each item is rated on a 5-point scale from 1 (not at all/never) to 5 (extremely/very often). The AAQoL Life Outlook subscale is based on 7 items and ranges from 7 to 35. A reduction in score indicates less impairment.
Time frame: Baseline to Week 6
Population: Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo, Stage 1 | Change in AAQoL Subscales - Life Outlook Sub-score | 3.7 units on a scale | Standard Error 1.3 |
| Vortioxetine 10mg, Stage 1 | Change in AAQoL Subscales - Life Outlook Sub-score | 5.0 units on a scale | Standard Error 1.7 |
| Vortioxetine 20mg, Stage 1 | Change in AAQoL Subscales - Life Outlook Sub-score | 3.0 units on a scale | Standard Error 1.8 |
Secondary
Change in AAQoL Subscales - Life Productivity Sub-score
The AAQoL is a patient-rated scale designed to assess health-related quality of life in adults with ADHD. The AAQoL consists of 29 items, each item is rated on a 5-point scale from 1 (not at all/never) to 5 (extremely/very often). The AAQoL Life productivity subscale is based on 11 items and ranges from 11 to 55. A reduction in score indicates less impairment.
Time frame: Baseline to Week 6
Population: Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo, Stage 1 | Change in AAQoL Subscales - Life Productivity Sub-score | 10.9 units on a scale | Standard Error 2.4 |
| Vortioxetine 10mg, Stage 1 | Change in AAQoL Subscales - Life Productivity Sub-score | 11.6 units on a scale | Standard Error 2.8 |
| Vortioxetine 20mg, Stage 1 | Change in AAQoL Subscales - Life Productivity Sub-score | 6.4 units on a scale | Standard Error 3.1 |
Secondary
Change in AAQoL Subscales - Psychological Health Sub-score
The AAQoL is a patient-rated scale designed to assess health-related quality of life in adults with ADHD. The AAQoL consists of 29 items, each item is rated on a 5-point scale from 1 (not at all/never) to 5 (extremely/very often). The AAQoL Psychological Health subscale is based on 6 items and ranges from 6 to 30. A reduction in score indicates less impairment.
Time frame: Baseline to Week 6
Population: Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo, Stage 1 | Change in AAQoL Subscales - Psychological Health Sub-score | 6.7 units on a scale | Standard Error 2.2 |
| Vortioxetine 10mg, Stage 1 | Change in AAQoL Subscales - Psychological Health Sub-score | 10.3 units on a scale | Standard Error 2.5 |
| Vortioxetine 20mg, Stage 1 | Change in AAQoL Subscales - Psychological Health Sub-score | 5.7 units on a scale | Standard Error 2.7 |
Secondary
Change in AAQoL Subscales - Relationships Sub-score
The AAQoL is a patient-rated scale designed to assess health-related quality of life in adults with ADHD. The AAQoL consists of 29 items, each item is rated on a 5-point scale from 1 (not at all/never) to 5 (extremely/very often). The AAQoL Relationship subscale is based on 5 items and ranges from 5 to 25. A reduction in score indicates less impairment.
Time frame: Baseline to Week 6
Population: Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo, Stage 1 | Change in AAQoL Subscales - Relationships Sub-score | 7.4 units on a scale | Standard Error 2.1 |
| Vortioxetine 10mg, Stage 1 | Change in AAQoL Subscales - Relationships Sub-score | 8.1 units on a scale | Standard Error 2.5 |
| Vortioxetine 20mg, Stage 1 | Change in AAQoL Subscales - Relationships Sub-score | 6.0 units on a scale | Standard Error 2.7 |
Secondary
Change in Adult ADHD Quality of Life Measure (AAQoL) Total Score
The AAQoL is a patient-rated scale designed to assess health-related quality of life in adults with ADHD. The AAQoL consists of 29 items, each item is rated on a 5-point scale from 1 (not at all/never) to 5 (extremely/very often). The AAQoL Total score is based on all 29 items and ranges from 29 to 145. A reduction in score indicates less impairment.
Time frame: Baseline to Week 6
Population: Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo, Stage 1 | Change in Adult ADHD Quality of Life Measure (AAQoL) Total Score | 7.7 units on a scale | Standard Error 1.7 |
| Vortioxetine 10mg, Stage 1 | Change in Adult ADHD Quality of Life Measure (AAQoL) Total Score | 9.1 units on a scale | Standard Error 2.1 |
| Vortioxetine 20mg, Stage 1 | Change in Adult ADHD Quality of Life Measure (AAQoL) Total Score | 5.4 units on a scale | Standard Error 2.3 |
Secondary
Change in Adult ADHD Self-Report Scale (ASRS) Total Score
The Adult ADHD Self-Report Scale (ASRS) is a patient-rated scale designed to assess the ADHD symptoms in adults based on the diagnostic criteria of DSM-IVTM. The ASRS consist of 18 items, each rated on a 5-point scale from Never to Very Often. The categories Never and Rarely were combined when calculating the total score to mirror the scoring of the AISRS, with 0 representing Never/Rarely and 3 representing Very Often. The Total Score ranges from 0 to 54. A reduction in score indicates less severity of ADHD.
Time frame: Baseline to Week 6
Population: Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo, Stage 1 | Change in Adult ADHD Self-Report Scale (ASRS) Total Score | -4.9 units on a scale | Standard Error 1 |
| Vortioxetine 10mg, Stage 1 | Change in Adult ADHD Self-Report Scale (ASRS) Total Score | -6.5 units on a scale | Standard Error 1.3 |
| Vortioxetine 20mg, Stage 1 | Change in Adult ADHD Self-Report Scale (ASRS) Total Score | -3.4 units on a scale | Standard Error 1.4 |
Secondary
Change in AISRS Inattention Sub-score
The AISRS inattentive subscale score consists of 9 items from the AISRS which address inattention. Each item is rated from 0 to 3. The AISRS inattentive subscale score can range from 0 to 27. A higher score corresponds to a worse severity of ADHD inattentiveness.
Time frame: Baseline to Week 6
Population: Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo, Stage 1 | Change in AISRS Inattention Sub-score | -6.5 units on a scale | Standard Error 0.71 |
| Vortioxetine 10mg, Stage 1 | Change in AISRS Inattention Sub-score | -6.0 units on a scale | Standard Error 1.14 |
| Vortioxetine 20mg, Stage 1 | Change in AISRS Inattention Sub-score | -5.9 units on a scale | Standard Error 1.24 |
| Placebo, Stage 2 | Change in AISRS Inattention Sub-score | -1.9 units on a scale | Standard Error 1.2 |
| Vortioxetine 10mg, Stage 2 | Change in AISRS Inattention Sub-score | -2.0 units on a scale | Standard Error 1.21 |
| Vortioxetine 20mg, Stage 2 | Change in AISRS Inattention Sub-score | -1.6 units on a scale | Standard Error 1.48 |
| Placebo, Combined | Change in AISRS Inattention Sub-score | -4.2 units on a scale | Standard Error 0.7 |
| Vortioxetine 10mg, Combined | Change in AISRS Inattention Sub-score | -4.0 units on a scale | Standard Error 0.8 |
| Vortioxetine 20mg, Combined | Change in AISRS Inattention Sub-score | -3.8 units on a scale | Standard Error 1 |
Secondary
Change in BRIEF-A Subscales - Emotional Control
The BRIEF-A subscale Emotional Control is a subscale within the Behavioural Regulation Index (BRI). Each item is rated on a 3-point scale ranging from 1 (never) to 3 (often). Raw scale scores are used to generate T-scores. A reduction in score indicates less impairment.
Time frame: Baseline to Week 6
Population: Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo, Stage 1 | Change in BRIEF-A Subscales - Emotional Control | -3.4 T-score | Standard Error 1 |
| Vortioxetine 10mg, Stage 1 | Change in BRIEF-A Subscales - Emotional Control | -4.8 T-score | Standard Error 1.1 |
| Vortioxetine 20mg, Stage 1 | Change in BRIEF-A Subscales - Emotional Control | -3.5 T-score | Standard Error 1.4 |
Secondary
Change in BRIEF-A Subscales - Inhibit
The BRIEF-A subscale Inhibit is a subscale within the Behavioural Regulation Index (BRI). Each item is rated on a 3-point scale ranging from 1 (never) to 3 (often). Raw scale scores are used to generate T-scores. A reduction in score indicates less impairment.
Time frame: Baseline to Week 6
Population: Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo, Stage 1 | Change in BRIEF-A Subscales - Inhibit | -5.5 T-score | Standard Error 1.4 |
| Vortioxetine 10mg, Stage 1 | Change in BRIEF-A Subscales - Inhibit | -8.6 T-score | Standard Error 1.5 |
| Vortioxetine 20mg, Stage 1 | Change in BRIEF-A Subscales - Inhibit | -3.2 T-score | Standard Error 1.8 |
Secondary
Change in BRIEF-A Subscales - Organization of Materials
The BRIEF-A subscale Organization of Materials is a subscale within the Behavioural Regulation Index (BRI). Each item is rated on a 3-point scale ranging from 1 (never) to 3 (often). Raw scale scores are used to generate T-scores. A reduction in score indicates less impairment.
Time frame: Baseline to Week 6
Population: Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo, Stage 1 | Change in BRIEF-A Subscales - Organization of Materials | -4.4 T-score | Standard Error 1.1 |
| Vortioxetine 10mg, Stage 1 | Change in BRIEF-A Subscales - Organization of Materials | -6.3 T-score | Standard Error 1.3 |
| Vortioxetine 20mg, Stage 1 | Change in BRIEF-A Subscales - Organization of Materials | -3.2 T-score | Standard Error 1.5 |
Secondary
Change in BRIEF-A Subscales - Planning/Organize
The BRIEF-A subscale Planning/Organize is a subscale within the Behavioural Regulation Index (BRI). Each item is rated on a 3-point scale ranging from 1 (never) to 3 (often). Raw scale scores are used to generate T-scores. A reduction in score indicates less impairment.
Time frame: Baseline to Week 6
Population: Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo, Stage 1 | Change in BRIEF-A Subscales - Planning/Organize | -8.2 T-score | Standard Error 1.6 |
| Vortioxetine 10mg, Stage 1 | Change in BRIEF-A Subscales - Planning/Organize | -8.7 T-score | Standard Error 1.8 |
| Vortioxetine 20mg, Stage 1 | Change in BRIEF-A Subscales - Planning/Organize | -6.8 T-score | Standard Error 2.1 |
Secondary
Change in BRIEF-A Subscales - Self Monitor
The BRIEF-A subscale Self Monitor is a subscale within the Behavioural Regulation Index (BRI). Each item is rated on a 3-point scale ranging from 1 (never) to 3 (often). Raw scale scores are used to generate T-scores. A reduction in score indicates less impairment.
Time frame: Baseline to Week 6
Population: Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo, Stage 1 | Change in BRIEF-A Subscales - Self Monitor | -6.5 T-score | Standard Error 1.4 |
| Vortioxetine 10mg, Stage 1 | Change in BRIEF-A Subscales - Self Monitor | -11.0 T-score | Standard Error 1.6 |
| Vortioxetine 20mg, Stage 1 | Change in BRIEF-A Subscales - Self Monitor | -4.8 T-score | Standard Error 1.8 |
Secondary
Change in BRIEF-A Subscales - Shift
The BRIEF-A subscale Shift is a subscale within the Behavioural Regulation Index (BRI). Each item is rated on a 3-point scale ranging from 1 (never) to 3 (often). Raw scale scores are used to generate T-scores. A reduction in score indicates less impairment.
Time frame: Baseline to Week 6
Population: Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo, Stage 1 | Change in BRIEF-A Subscales - Shift | -5.6 T-score | Standard Error 1.4 |
| Vortioxetine 10mg, Stage 1 | Change in BRIEF-A Subscales - Shift | -9.1 T-score | Standard Error 1.6 |
| Vortioxetine 20mg, Stage 1 | Change in BRIEF-A Subscales - Shift | -3.5 T-score | Standard Error 1.9 |
Secondary
Change in BRIEF-A Subscales - Task Monitor
The BRIEF-A subscale Task Monitor is a subscale within the Behavioural Regulation Index (BRI). Each item is rated on a 3-point scale ranging from 1 (never) to 3 (often). Raw scale scores are used to generate T-scores. A reduction in score indicates less impairment.
Time frame: Baseline to Week 6
Population: Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo, Stage 1 | Change in BRIEF-A Subscales - Task Monitor | -6.4 T-score | Standard Error 1.5 |
| Vortioxetine 10mg, Stage 1 | Change in BRIEF-A Subscales - Task Monitor | -7.8 T-score | Standard Error 1.7 |
| Vortioxetine 20mg, Stage 1 | Change in BRIEF-A Subscales - Task Monitor | -4.9 T-score | Standard Error 2 |
Secondary
Change in BRIEF-A Subscales - Working Memory
The BRIEF-A subscale Working Memory is a subscale within the Behavioural Regulation Index (BRI). Each item is rated on a 3-point scale ranging from 1 (never) to 3 (often). Raw scale scores are used to generate T-scores. A reduction in score indicates less impairment.
Time frame: Baseline to Week 6
Population: Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo, Stage 1 | Change in BRIEF-A Subscales - Working Memory | -7.6 T-score | Standard Error 1.6 |
| Vortioxetine 10mg, Stage 1 | Change in BRIEF-A Subscales - Working Memory | -9.9 T-score | Standard Error 1.8 |
| Vortioxetine 20mg, Stage 1 | Change in BRIEF-A Subscales - Working Memory | -3.8 T-score | Standard Error 2.1 |
Secondary
Change in BRIEF-A Using the Behavioural Regulation Index
The Behavioral Regulation Index (BRI) is an index score of the BRIEF-A and consists of 4 scales: inhibit, shift, emotional control, and self-monitor). Each item is rated on a 3-point scale with the numeric score of 1 to 3. Raw scale scores are used to generate T-scores. A reduction in score indicates less impairment.
Time frame: Baseline to Week 6
Population: Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo, Stage 1 | Change in BRIEF-A Using the Behavioural Regulation Index | -5.3 T-score | Standard Error 1.1 |
| Vortioxetine 10mg, Stage 1 | Change in BRIEF-A Using the Behavioural Regulation Index | -7.9 T-score | Standard Error 1.3 |
| Vortioxetine 20mg, Stage 1 | Change in BRIEF-A Using the Behavioural Regulation Index | -3.9 T-score | Standard Error 1.6 |
Secondary
Change in Clinical Global Impression - Severity of Illness (CGI-S) Score
The Clinical Global Impression - Severity of Illness (CGI-S) provides the clinician's impression of the patient's current state of mental illness. The clinician uses his or her clinical experience of this patient population to rate the severity of the patient's current mental illness on a 7-point scale ranging from 1 (Normal - not at all ill) to 7 (among the most extremely ill patients). Higher scores indicate worsening.
Time frame: Baseline to Week 6
Population: Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo, Stage 1 | Change in Clinical Global Impression - Severity of Illness (CGI-S) Score | -0.5 units on a scale | Standard Error 0.1 |
| Vortioxetine 10mg, Stage 1 | Change in Clinical Global Impression - Severity of Illness (CGI-S) Score | -0.7 units on a scale | Standard Error 0.1 |
| Vortioxetine 20mg, Stage 1 | Change in Clinical Global Impression - Severity of Illness (CGI-S) Score | -0.6 units on a scale | Standard Error 0.1 |
Secondary
Change in PDQ-D Subscales - Attention and Concentration Sub-score
The PDQ-D attention/concentration sub-score consists of items 1, 5, 9, 13, and 17 of the PDQ with a score ranging from 0 to 20. A higher score reflects greater subjective cognitive impairment. A reduction in score indicates less cognitive impairment.
Time frame: Baseline to Week 6
Population: Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo, Stage 1 | Change in PDQ-D Subscales - Attention and Concentration Sub-score | -1.7 units on a scale | Standard Error 0.4 |
| Vortioxetine 10mg, Stage 1 | Change in PDQ-D Subscales - Attention and Concentration Sub-score | -2.3 units on a scale | Standard Error 0.5 |
| Vortioxetine 20mg, Stage 1 | Change in PDQ-D Subscales - Attention and Concentration Sub-score | -1.8 units on a scale | Standard Error 0.6 |
Secondary
Change in PDQ-D Sub-scales - Planning and Organisation Sub-score
The PDQ-D planning and organisation sub-score consists of items 4, 8, 12, 16, and 20 of the PDQ (see Outcome 23) with a score ranging from 0 to 20. A higher score reflects greater subjective cognitive impairment. A reduction in score indicates less cognitive impairment.
Time frame: Baseline to Week 6
Population: Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo, Stage 1 | Change in PDQ-D Sub-scales - Planning and Organisation Sub-score | -2.4 units on a scale | Standard Error 0.5 |
| Vortioxetine 10mg, Stage 1 | Change in PDQ-D Sub-scales - Planning and Organisation Sub-score | -2.5 units on a scale | Standard Error 0.6 |
| Vortioxetine 20mg, Stage 1 | Change in PDQ-D Sub-scales - Planning and Organisation Sub-score | -1.9 units on a scale | Standard Error 0.7 |
Secondary
Change in PDQ-D Sub-scales - Prospective Memory Sub-score
The PDQ-D prospective memory sub-score consists of items 3, 7, 11, 15, and 19 of the PDQ (see Outcome 23) with a score ranging from 0 to 20. A higher score reflects greater subjective cognitive impairment. A reduction in score indicates less cognitive impairment.
Time frame: Baseline to Week 6
Population: Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo, Stage 1 | Change in PDQ-D Sub-scales - Prospective Memory Sub-score | -1.5 units on a scale | Standard Error 0.4 |
| Vortioxetine 10mg, Stage 1 | Change in PDQ-D Sub-scales - Prospective Memory Sub-score | -2.3 units on a scale | Standard Error 0.5 |
| Vortioxetine 20mg, Stage 1 | Change in PDQ-D Sub-scales - Prospective Memory Sub-score | -0.9 units on a scale | Standard Error 0.6 |
Secondary
Change in PDQ-D Sub-scales - Retrospective Memory Sub-score
The PDQ-D retrospective memory sub-score consists of items 2, 6, 10, 14, and 18 of the PDQ (see Outcome 23) with a score ranging from 0 to 20. A higher score reflects greater subjective cognitive impairment. A reduction in score indicates less cognitive impairment.
Time frame: Baseline to Week 6
Population: Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo, Stage 1 | Change in PDQ-D Sub-scales - Retrospective Memory Sub-score | -1.8 units on a scale | Standard Error 0.5 |
| Vortioxetine 10mg, Stage 1 | Change in PDQ-D Sub-scales - Retrospective Memory Sub-score | -2.4 units on a scale | Standard Error 0.6 |
| Vortioxetine 20mg, Stage 1 | Change in PDQ-D Sub-scales - Retrospective Memory Sub-score | -1.5 units on a scale | Standard Error 0.6 |
Secondary
Change in Perceived Deficits Questionnaire - Depression (PDQ-D) Total Score
The PDQ-D is a patient-rated scale designed to assess cognitive impairment/dysfunction adapted for MDD. Each item is rated on a scale from 0 (never) to 4 (almost always). The total score of the 20 items ranges from 0 to 80 with higher scores reflect greater subjective cognitive impairment. A reduction in score indicates less impairment.
Time frame: Baseline to Week 6
Population: Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo, Stage 1 | Change in Perceived Deficits Questionnaire - Depression (PDQ-D) Total Score | -7.6 units on a scale | Standard Error 1.6 |
| Vortioxetine 10mg, Stage 1 | Change in Perceived Deficits Questionnaire - Depression (PDQ-D) Total Score | -9.3 units on a scale | Standard Error 2 |
| Vortioxetine 20mg, Stage 1 | Change in Perceived Deficits Questionnaire - Depression (PDQ-D) Total Score | -6.3 units on a scale | Standard Error 2.2 |
Secondary
Change in SDS Item Scores - Family
The SDS item family is rated from 0 = normal functioning to 10 = severe functional impairment (see outcome 4). A higher score represents more severe functional impairment. A reduction in score indicates less impairment.
Time frame: Baseline to Week 6
Population: Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo, Stage 1 | Change in SDS Item Scores - Family | -1.5 units on a scale | Standard Error 0.3 |
| Vortioxetine 10mg, Stage 1 | Change in SDS Item Scores - Family | -1.8 units on a scale | Standard Error 0.3 |
| Vortioxetine 20mg, Stage 1 | Change in SDS Item Scores - Family | -1.5 units on a scale | Standard Error 0.4 |
Secondary
Change in SDS Item Scores - Number of Days Lost
This SDS item captures days lost from school or work (see outcome 4).
Time frame: Baseline to Week 6
Population: Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo, Stage 1 | Change in SDS Item Scores - Number of Days Lost | -0.3 days | Standard Error 0.1 |
| Vortioxetine 10mg, Stage 1 | Change in SDS Item Scores - Number of Days Lost | -0.2 days | Standard Error 0.1 |
| Vortioxetine 20mg, Stage 1 | Change in SDS Item Scores - Number of Days Lost | -0.1 days | Standard Error 0.2 |
Secondary
Change in SDS Item Scores - Number of Underproductive Days
This SDS item captures the number of underproductive days (see outcome 4)
Time frame: Baseline to Week 6
Population: Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo, Stage 1 | Change in SDS Item Scores - Number of Underproductive Days | -1.2 days | Standard Error 0.3 |
| Vortioxetine 10mg, Stage 1 | Change in SDS Item Scores - Number of Underproductive Days | -1.0 days | Standard Error 0.3 |
| Vortioxetine 20mg, Stage 1 | Change in SDS Item Scores - Number of Underproductive Days | -1.2 days | Standard Error 0.3 |
Secondary
Change in SDS Item Scores - Social Life
The SDS item social life is rated from 0 = normal functioning to 10 = severe functional impairment (see outcome 4). A higher score represents more severe functional impairment. A reduction in score indicates less impairment.
Time frame: Baseline to Week 6
Population: Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo, Stage 1 | Change in SDS Item Scores - Social Life | -1.1 units on a scale | Standard Error 0.3 |
| Vortioxetine 10mg, Stage 1 | Change in SDS Item Scores - Social Life | -1.7 units on a scale | Standard Error 0.3 |
| Vortioxetine 20mg, Stage 1 | Change in SDS Item Scores - Social Life | -1.5 units on a scale | Standard Error 0.4 |
Secondary
Change in SDS Item Scores - Work
The SDS item work is rated from 0 = normal functioning to 10 = severe functional impairment (see outcome 4). A higher score represents more severe functional impairment. A reduction in score indicates less impairment.
Time frame: Baseline to Week 6
Population: Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo, Stage 1 | Change in SDS Item Scores - Work | -1.2 units on a scale | Standard Error 0.3 |
| Vortioxetine 10mg, Stage 1 | Change in SDS Item Scores - Work | -2.0 units on a scale | Standard Error 0.4 |
| Vortioxetine 20mg, Stage 1 | Change in SDS Item Scores - Work | -2.1 units on a scale | Standard Error 0.4 |
Secondary
Change in WLQ Domain Scores - Limitations Handling Time
Limitations Handling Time is scored on a scale of 0 (limited at work none of the time) to 100 (limited at work all of the time) based on a converted mean score. A reduction in score indicates less work limitation.
Time frame: Baseline to Week 6
Population: Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo, Stage 1 | Change in WLQ Domain Scores - Limitations Handling Time | -5.6 units on a scale | Standard Error 2.7 |
| Vortioxetine 10mg, Stage 1 | Change in WLQ Domain Scores - Limitations Handling Time | -7.7 units on a scale | Standard Error 3.1 |
| Vortioxetine 20mg, Stage 1 | Change in WLQ Domain Scores - Limitations Handling Time | -2.2 units on a scale | Standard Error 3.7 |
Secondary
Change in WLQ Domain Scores - Mental-Interpersonal Work Demands
Mental-Interpersonal Work Demands is scored on a scale of 0 (limited at work none of the time) to 100 (limited at work all of the time) based on a converted mean score. A reduction in score indicates less work limitation.
Time frame: Baseline to Week 6
Population: Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo, Stage 1 | Change in WLQ Domain Scores - Mental-Interpersonal Work Demands | -8.4 units on a scale | Standard Error 2.2 |
| Vortioxetine 10mg, Stage 1 | Change in WLQ Domain Scores - Mental-Interpersonal Work Demands | -8.2 units on a scale | Standard Error 2.6 |
| Vortioxetine 20mg, Stage 1 | Change in WLQ Domain Scores - Mental-Interpersonal Work Demands | -6.2 units on a scale | Standard Error 2.9 |
Secondary
Change in WLQ Domain Scores - Output Demands
Output Demands is scored on a scale of 0 (limited at work none of the time) to 100 (limited at work all of the time) based on a converted mean score. A reduction in score indicates less work limitation.
Time frame: Baseline to Week 6
Population: Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo, Stage 1 | Change in WLQ Domain Scores - Output Demands | -8.9 units on a scale | Standard Error 3.1 |
| Vortioxetine 10mg, Stage 1 | Change in WLQ Domain Scores - Output Demands | -7.1 units on a scale | Standard Error 3.5 |
| Vortioxetine 20mg, Stage 1 | Change in WLQ Domain Scores - Output Demands | -7.2 units on a scale | Standard Error 4 |
Secondary
Change in WLQ Domain Scores - Physical Demands
Physical Demands is scored on a scale of 0 (limited at work none of the time) to 100 (limited at work all of the time) based on a converted mean score. A reduction in score indicates less work limitation.
Time frame: Baseline to Week 6
Population: Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo, Stage 1 | Change in WLQ Domain Scores - Physical Demands | -5.5 units on a scale | Standard Error 2.4 |
| Vortioxetine 10mg, Stage 1 | Change in WLQ Domain Scores - Physical Demands | -5.0 units on a scale | Standard Error 2.9 |
| Vortioxetine 20mg, Stage 1 | Change in WLQ Domain Scores - Physical Demands | -4.6 units on a scale | Standard Error 3.2 |
Secondary
Change in WLQ Using the Global Productivity Index
The WLQ is a patient self-rated scale designed to assess on-the-job impact of chronic health problems and/or treatment. The WLQ consists of 25 items in 4 dimensions: limitations handling time (5 items), physical work demands (6 items), mental-interpersonal work demands (9 items), and output demands (5 items). Each item is rated on a 5-point scale from All of the Time (score 5) to None of the Time (score 0), or Does Not Apply to My Job. The Global Productivity Index is calculated as a weighed sum of the 4 dimensions, and ranges from 0.000 to 0.286. Reduction in score indicates less work limitation.
Time frame: Baseline to Week 6
Population: Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo, Stage 1 | Change in WLQ Using the Global Productivity Index | -0.0 Index | Standard Error 0 |
| Vortioxetine 10mg, Stage 1 | Change in WLQ Using the Global Productivity Index | -0.0 Index | Standard Error 0 |
| Vortioxetine 20mg, Stage 1 | Change in WLQ Using the Global Productivity Index | -0.0 Index | Standard Error 0 |
Secondary
Clinical Global Impression - Global Improvement (CGI-I) Score
The Clinical Global Impression - Global Improvement (CGI-I) provides the clinician's impression of the patient's improvement (or worsening). The clinician assesses the patient's condition relative to a baseline on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). Higher scores indicate worsening.
Time frame: Week 6
Population: CGI-I refers to study baseline and was for this reason analyzed for Stage 1 only.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo, Stage 1 | Clinical Global Impression - Global Improvement (CGI-I) Score | 3.01 units on a scale | Standard Error 0.11 |
| Vortioxetine 10mg, Stage 1 | Clinical Global Impression - Global Improvement (CGI-I) Score | 2.93 units on a scale | Standard Error 0.17 |
| Vortioxetine 20mg, Stage 1 | Clinical Global Impression - Global Improvement (CGI-I) Score | 3.15 units on a scale | Standard Error 0.18 |
Secondary
Cognitive Function/Global Executive Function: Change in BRIEF-A Using the Global Executive Composite Score
BRIEF-A is a validated questionnaire composed of 75-item within nine non-overlapping scales: 4 scales in the Behavioral Regulation Index (BRI) (inhibit, shift, emotional control, and self-monitor), and 5 scales in the Metacognition Index (MI) (initiate, working memory, plan/organise, task monitor, and organization of materials). Each item is rated on a 3-point scale with the numeric score of 1 to 3. The BRIEF-A yields an overall score (Global Executive Composite) composed of two index scores, the MI and the BRI. Raw scale scores are used to generate T-scores. A reduction in score indicates less impairment.
Time frame: Baseline to Week 6
Population: Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo, Stage 1 | Cognitive Function/Global Executive Function: Change in BRIEF-A Using the Global Executive Composite Score | -9.9 T-score | Standard Error 1.22 |
| Vortioxetine 10mg, Stage 1 | Cognitive Function/Global Executive Function: Change in BRIEF-A Using the Global Executive Composite Score | -12.5 T-score | Standard Error 1.93 |
| Vortioxetine 20mg, Stage 1 | Cognitive Function/Global Executive Function: Change in BRIEF-A Using the Global Executive Composite Score | -11.4 T-score | Standard Error 2.1 |
| Placebo, Stage 2 | Cognitive Function/Global Executive Function: Change in BRIEF-A Using the Global Executive Composite Score | -3.0 T-score | Standard Error 2.24 |
| Vortioxetine 10mg, Stage 2 | Cognitive Function/Global Executive Function: Change in BRIEF-A Using the Global Executive Composite Score | -3.5 T-score | Standard Error 2.31 |
| Vortioxetine 20mg, Stage 2 | Cognitive Function/Global Executive Function: Change in BRIEF-A Using the Global Executive Composite Score | 2.1 T-score | Standard Error 2.8 |
| Placebo, Combined | Cognitive Function/Global Executive Function: Change in BRIEF-A Using the Global Executive Composite Score | -6.5 T-score | Standard Error 1.3 |
| Vortioxetine 10mg, Combined | Cognitive Function/Global Executive Function: Change in BRIEF-A Using the Global Executive Composite Score | -8.0 T-score | Standard Error 1.5 |
| Vortioxetine 20mg, Combined | Cognitive Function/Global Executive Function: Change in BRIEF-A Using the Global Executive Composite Score | -4.6 T-score | Standard Error 1.8 |
Secondary
Inattention/Meta-cognition: Change in Behavior Rating Inventory of Executive Function - Adult Version (BRIEF-A) Using Metacognition Index
The Metacognition Index (MI) is an index score of the BRIEF-A consisting of 5 scales: initiate, working memory, plan/organise, task monitor, and organization of materials. Each item is rated on a 3-point scale with the numeric score of 1 to 3. Raw scale scores are used to generate T-scores. A reduction in score indicates less impairment.
Time frame: Baseline to Week 6
Population: Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo, Stage 1 | Inattention/Meta-cognition: Change in Behavior Rating Inventory of Executive Function - Adult Version (BRIEF-A) Using Metacognition Index | -10.0 T-score | Standard Error 1.26 |
| Vortioxetine 10mg, Stage 1 | Inattention/Meta-cognition: Change in Behavior Rating Inventory of Executive Function - Adult Version (BRIEF-A) Using Metacognition Index | -11.2 T-score | Standard Error 1.98 |
| Vortioxetine 20mg, Stage 1 | Inattention/Meta-cognition: Change in Behavior Rating Inventory of Executive Function - Adult Version (BRIEF-A) Using Metacognition Index | -10.2 T-score | Standard Error 2.16 |
| Placebo, Stage 2 | Inattention/Meta-cognition: Change in Behavior Rating Inventory of Executive Function - Adult Version (BRIEF-A) Using Metacognition Index | -3.1 T-score | Standard Error 2.28 |
| Vortioxetine 10mg, Stage 2 | Inattention/Meta-cognition: Change in Behavior Rating Inventory of Executive Function - Adult Version (BRIEF-A) Using Metacognition Index | -2.6 T-score | Standard Error 2.34 |
| Vortioxetine 20mg, Stage 2 | Inattention/Meta-cognition: Change in Behavior Rating Inventory of Executive Function - Adult Version (BRIEF-A) Using Metacognition Index | 0.9 T-score | Standard Error 2.84 |
| Placebo, Combined | Inattention/Meta-cognition: Change in Behavior Rating Inventory of Executive Function - Adult Version (BRIEF-A) Using Metacognition Index | -6.5 T-score | Standard Error 1.3 |
| Vortioxetine 10mg, Combined | Inattention/Meta-cognition: Change in Behavior Rating Inventory of Executive Function - Adult Version (BRIEF-A) Using Metacognition Index | -6.9 T-score | Standard Error 1.5 |
| Vortioxetine 20mg, Combined | Inattention/Meta-cognition: Change in Behavior Rating Inventory of Executive Function - Adult Version (BRIEF-A) Using Metacognition Index | -4.6 T-score | Standard Error 1.8 |
Secondary
Overall Functioning: Change in Sheehan Disability Scale (SDS) Total Score
The SDS comprises a series of patient rated scales designed to measure impairment. The patient rates the extent to which his or her (1) work, (2) social life or leisure activities and 3) home life or family responsibilities are impaired on a 10-point visual analogue scale, on which 0 = normal functioning and 10 = severe functional impairment. The number of days lost and the number of underproductive days last from work/school due to symptoms are also captured. The total score is calculated as a sum of the 3 visual analogue scales, ranges from 0 to 30. A higher score represents more severe functional impairment. A reduction in score indicates less impairment.
Time frame: Baseline to Week 6
Population: Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo, Stage 1 | Overall Functioning: Change in Sheehan Disability Scale (SDS) Total Score | -5.3 units on a scale | Standard Error 0.74 |
| Vortioxetine 10mg, Stage 1 | Overall Functioning: Change in Sheehan Disability Scale (SDS) Total Score | -7.9 units on a scale | Standard Error 1.2 |
| Vortioxetine 20mg, Stage 1 | Overall Functioning: Change in Sheehan Disability Scale (SDS) Total Score | -7.4 units on a scale | Standard Error 1.29 |
| Placebo, Stage 2 | Overall Functioning: Change in Sheehan Disability Scale (SDS) Total Score | 0.6 units on a scale | Standard Error 0.91 |
| Vortioxetine 10mg, Stage 2 | Overall Functioning: Change in Sheehan Disability Scale (SDS) Total Score | -0.9 units on a scale | Standard Error 0.95 |
| Vortioxetine 20mg, Stage 2 | Overall Functioning: Change in Sheehan Disability Scale (SDS) Total Score | -1.4 units on a scale | Standard Error 1.14 |
| Placebo, Combined | Overall Functioning: Change in Sheehan Disability Scale (SDS) Total Score | -2.4 units on a scale | Standard Error 0.6 |
| Vortioxetine 10mg, Combined | Overall Functioning: Change in Sheehan Disability Scale (SDS) Total Score | -4.4 units on a scale | Standard Error 0.8 |
| Vortioxetine 20mg, Combined | Overall Functioning: Change in Sheehan Disability Scale (SDS) Total Score | -4.4 units on a scale | Standard Error 0.9 |
Secondary
Percentage of Patients Responding (Response Defined as 30% or Greater Reduction From Baseline in AISRS Total Score)
AISRS: an 18-item scale administered by the investigator. It included 9 items that evaluated symptoms of inattention and 9 items that evaluated symptoms of impulsivity and hyperactivity. Each item was rated from 0 (none) to 3 (severe). AISRS total score was calculated as sum of all the items on the scale and ranged from 0 to 54. A higher score corresponded to a worse severity of ADHD.
Time frame: Baseline to Week 6
Population: Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined response rate was obtained by constructing an equally weighed estimate of the rate combining the two stages.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo, Stage 1 | Percentage of Patients Responding (Response Defined as 30% or Greater Reduction From Baseline in AISRS Total Score) | 30.9 percentage of participants |
| Vortioxetine 10mg, Stage 1 | Percentage of Patients Responding (Response Defined as 30% or Greater Reduction From Baseline in AISRS Total Score) | 27.5 percentage of participants |
| Vortioxetine 20mg, Stage 1 | Percentage of Patients Responding (Response Defined as 30% or Greater Reduction From Baseline in AISRS Total Score) | 23.1 percentage of participants |
Secondary
Productivity: Change in Work Limitations Questionnaire (WLQ) Productivity Loss Score
The WLQ is a patient self-rated scale designed to assess on-the-job impact of chronic health problems and/or treatment. The WLQ consists of 25 items in 4 dimensions: limitations handling time (5 items), physical work demands (6 items), mental-interpersonal work demands (9 items), and output demands (5 items). Each item is rated on a 5-point scale from All of the Time (score 5) to None of the Time (score 0), or Does Not Apply to My Job. The WLQ Productivity Loss Score is derived from the Global Productivity Index, which is calculated as a weighed sum of the 4 dimensions. Reduction in WLQ Productivity Loss score indicates less work limitation and represents the estimated percentage of productivity loss in the past two weeks due to presenteeism relative to a healthy benchmark sample. WLQ Productivity Loss Score ranges from 0% to 24,9%.
Time frame: Baseline to Week 6
Population: Stage 2 dataset includes placebo non-responders from Stage 1 that were re-randomized and treated in Stage 2. The statistical analyses were performed on each stage separately, and the combined analysis was performed by constructing a simple equally weighed least square test-statistic.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo, Stage 1 | Productivity: Change in Work Limitations Questionnaire (WLQ) Productivity Loss Score | -2.4 percentage of days lost | Standard Error 0.54 |
| Vortioxetine 10mg, Stage 1 | Productivity: Change in Work Limitations Questionnaire (WLQ) Productivity Loss Score | -2.5 percentage of days lost | Standard Error 0.84 |
| Vortioxetine 20mg, Stage 1 | Productivity: Change in Work Limitations Questionnaire (WLQ) Productivity Loss Score | -2.4 percentage of days lost | Standard Error 0.96 |
| Placebo, Stage 2 | Productivity: Change in Work Limitations Questionnaire (WLQ) Productivity Loss Score | -0.8 percentage of days lost | Standard Error 1.02 |
| Vortioxetine 10mg, Stage 2 | Productivity: Change in Work Limitations Questionnaire (WLQ) Productivity Loss Score | -0.9 percentage of days lost | Standard Error 0.97 |
| Vortioxetine 20mg, Stage 2 | Productivity: Change in Work Limitations Questionnaire (WLQ) Productivity Loss Score | -0.7 percentage of days lost | Standard Error 1.2 |
| Placebo, Combined | Productivity: Change in Work Limitations Questionnaire (WLQ) Productivity Loss Score | -1.6 percentage of days lost | Standard Error 0.6 |
| Vortioxetine 10mg, Combined | Productivity: Change in Work Limitations Questionnaire (WLQ) Productivity Loss Score | -1.7 percentage of days lost | Standard Error 0.6 |
| Vortioxetine 20mg, Combined | Productivity: Change in Work Limitations Questionnaire (WLQ) Productivity Loss Score | -1.5 percentage of days lost | Standard Error 0.8 |
Secondary
Response (Defined as a CGI-I Score of 1 or 2), Stage 1
The Clinical Global Impression - Global Improvement (CGI-I) provides the clinician's impression of the patient's improvement (or worsening). The clinician assesses the patient's condition relative to a baseline on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). Higher scores indicate worsening.
Time frame: Week 6
Population: CGI-I refers to study baseline and was for this reason analyzed for Stage 1 only.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo, Stage 1 | Response (Defined as a CGI-I Score of 1 or 2), Stage 1 | 43 percentages of participants |
| Vortioxetine 10mg, Stage 1 | Response (Defined as a CGI-I Score of 1 or 2), Stage 1 | 13 percentages of participants |
| Vortioxetine 20mg, Stage 1 | Response (Defined as a CGI-I Score of 1 or 2), Stage 1 | 11 percentages of participants |