Major Depressive Disorder
Conditions
Brief summary
To evaluate the efficacy of SPD489 when used as augmentation to an antidepressant in the treatment of major depressive disorder (MDD) as measured by mean change in total Montgomery-Ǻsberg Depression Rating Scale (MADRS) scores.
Interventions
DRUGAntidepressant + SPD489 (lisdexamfetamine dimesylate)
Escitalopram oxalate (antidepressant) 20 mg/day oral + 20, 30, or 50 mg SPD489 oral once daily for 6 weeks
Escitalopram oxalate (antidepressant) 20 mg/day oral + placebo oral once daily for 6 weeks
Sponsors
Shire
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* Adults aged 18-55 with a primary diagnosis of nonpsychotic MDD
Exclusion criteria
* History of non-response to multiple antidepressants
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Augmentation Baseline for Non-Remitters in Montgomery-Ǻsberg Depression Rating Scale (MADRS) Total Score at Week 6 - Last Observation Carried Forward (LOCF) | Augmentation Baseline, 6 weeks | MADRS is a validated, 10-item rating scale with each item being scored on a scale from 0-6 with a total score ranging from 0-60. Lower scores indicate a decreased severity of depression. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Augmentation Baseline for Non-Remitters in the Sheehan Disability Scale (SDS) Total Score at Week 6 | Augmentation Baseline, 6 weeks | Designed to evaluate the extent to which illness symptoms impact a subject's life in 3 areas: work/school, social, and family/home. Each area is scored on a scale from 0 (no impairment) to 10 (highly impaired) with a total score ranging from 0 (unimpaired) to 30 (highly impaired). Lower scores translate into less impairment. |
| Percentage of Non-Remitters With Improvement on Clinical Global Impression-Improvement (CGI-I) at Week 6 - LOCF | 6 weeks | Clinical Global Impression-Improvement (CGI-I) consists of a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved) or 2 (much improved) on the scale. |
| Assessment in Non-Remitters of Clinical Global Impression-Severity of Illness (CGI-S) at Augmentation Baseline | Augmentation baseline | CGI-S assesses the severity of the subject's condition on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill) |
| Assessment in Non-Remitters of Clinical Global Impression-Severity of Illness (CGI-S) at Week 6 | 6 weeks | CGI-S assesses the severity of the subject's condition on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill) |
| Change From Augmentation Baseline for Non-Remitters in the Behavior Rating Inventory of Executive Function - Adult Version (BRIEF-A) Scale Total Score at Week 6 | Augmentation Baseline and 6 weeks | BRIEF-A is a validated 75-item questionnaire composed of three scales (Global Executive Composite, Behavioral Recognition Index, and Metacognition Index). Items are rated 1 (never), 2 (sometimes), and 3 (often). There is no range for a total score. Raw scale scores are used to develop interpretive reports. Lower scores reflect better functioning. |
| Change From Augmentation Baseline for Non-Remitters in the Multidimensional Assessment of Fatigue (MAF) Scale Total Score at Week 6 | Augmentation Baseline and 6 weeks | MAF contains 16 items scored on a scale from 1 (not at all) to 10 (a great deal). Answers are converted to a Global Fatigue Index with total scores ranging from 1 (no fatigue) to 50 (severe fatigue). Lower scores indicate less fatigue. |
| Change From Augmentation Baseline for Non-Remitters in the Quick Inventory of Depressive Symptomatology - Self-Report (QIDS-SR) Scale Total Score at Week 6 | Augmentation Baseline and 6 weeks | QIDS-SR is a validated, self-reported rating scale that contains 16 items scored on a scale from 0-3 with total scores ranging from 0 (no depression) to 27 (very severe depression). Lower scores indicate less depression. |
| Change From Augmentation Baseline for Remitters in MADRS Total Score at Week 6 - LOCF | Augmentation Baseline and 6 weeks | MADRS is a validated, 10-item rating scale with each item being scored on a scale from 0-6 with a total score ranging from 0-60. Lower scores indicate a decreased severity of depression. |
| Change From Augmentation Baseline for Non-Remitters in the Hamilton Depression Scale (HAM-D) Total Score at Week 6 - LOCF | Augmentation Baseline, 6 weeks | The HAM-D is a validated rating scale which consists of 17 items. Nine of the items are scored on a scale of 0-4 and 8 items are scored on a scale of 0-2 for a total scoring range of 0-52. A score of 0-7 is generally accepted to be within the normal range (or in clinical remission), while a score of 20 or higher indicates increased severity of depression. In general, the lower the total score the less severe the depression. |
| Change From Augmentation Baseline for Remitters in the SDS Total Score at Week 6 | Augmentation Baseline and 6 weeks | Designed to evaluate the extent to which illness symptoms impact a subject's life in 3 areas: work/school, social, and family/home. Each area is scored on a scale from 0 (no impairment) to 10 (highly impaired) with a total score ranging from 0 (unimpaired) to 30 (highly impaired). Lower scores translate into less impairment. |
| Percentage of Remitters With Improvement on CGI-I at Week 6 - LOCF | 6 weeks | Clinical Global Impression-Improvement (CGI-I) consists of a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved) or 2 (much improved) on the scale. |
| Assessment in Remitters of CGI-S at Augmentation Baseline | Augmentation Baseline | CGI-S assesses the severity of the subject's condition on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill) |
| Assessment in Remitters of CGI-S at Week 6 | 6 weeks | CGI-S assesses the severity of the subject's condition on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill) |
| Change From Augmentation Baseline for Remitters in the BRIEF-A Scale Total Score at Week 6 | Augmentation baseline and 6 weeks | BRIEF-A is a validated 86-item questionnaire composed of three scales (Global Executive Composite, Behavioral Recognition Index, and Metacognition Index). Items are rated 1 (never), 2 (sometimes), and 3 (often). Lower scores reflect better functioning. |
| Change From Augmentation Baseline for Remitters in the MAF Scale Total Score at Week 6 | Augmentation baseline and 6 weeks | MAF contains 16 items scored on a scale from 1 (not at all) to 10 (a great deal). Answers are converted to a Global Fatigue Index with total scores ranging from 1 (no fatigue) to 50 (severe fatigue). Lower scores indicate less fatigue. |
| Change From Augmentation Baseline for Remitters in the QIDS-SR Scale Total Score at Week 6 | Augmentation baseline and 6 weeks | QIDS-SR is a validated, self-reported rating scale that contains 16 items scored on a scale from 0-3 with total scores ranging from 0 (no depression) to 27 (very severe depression). Lower scores indicate less depression. |
| Change From Augmentation Baseline for Remitters in the HAM-D Total Score at Week 6 - LOCF | Augmentation Baseline and 6 weeks | The HAM-D is a validated rating scale which consists of 17 items. Nine of the items are scored on a scale of 0-4 and 8 items are scored on a scale of 0-2 for a total scoring range of 0-52. A score of 0-7 is generally accepted to be within the normal range (or in clinical remission), while a score of 20 or higher indicates increased severity of depression. In general, the lower the total score the less severe the depression. |
Countries
United States
Participant flow
Pre-assignment details
246 subjects entered the antidepressant lead-in phase receiving escitalopram oxalate (antidepressant) 20 mg/day for 8 weeks. After 8 weeks, subjects with residual depressive symptoms (n = 177) were randomly assigned (stratified by remission, either remitters or non-remitters) to receive augmentation therapy (either SPD489 or placebo).
Participants by arm
| Arm | Count |
|---|---|
| Antidepressant + SPD489 Subjects with residual depressive symptoms (symptoms of depression that remain after initial antidepressant treatment) after the 8-week lead-in period with antidepressant (escitalopram @ 20 mg/day) were randomly assigned to receive augmentation therapy (antidepressant @ 20 mg/day + SPD489 @ either 20, 30, or 50 mg/day) for 6 weeks. This includes both non-remitters (Montgomery-Ǻsberg Depression Rating Scale \[MADRS\] total score greater than 10 at augmentation baseline) and remitters (MADRS total score of less than or equal to 10 at augmentation baseline). | 88 |
| Antidepressant + Placebo . Subjects with residual depressive symptoms after the 8-week lead-in period with antidepressant were randomly assigned to receive augmentation therapy (antidepressant @ 20 mg/day + placebo) for 6 weeks. This includes both non-remitters and remitters. | 85 |
| Total | 173 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 2 |
| Overall Study | Lost to Follow-up | 3 | 3 |
| Overall Study | Non-adherence to visit schedule | 0 | 1 |
| Overall Study | Non-compliance with study medication | 2 | 0 |
| Overall Study | Positive urine drug screen | 0 | 1 |
| Overall Study | Sponsor decision | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | Antidepressant + SPD489 | Antidepressant + Placebo . | Total |
|---|---|---|---|
| Age, Continuous | 39.4 years STANDARD_DEVIATION 9.65 | 38.6 years STANDARD_DEVIATION 10.38 | 39.0 years STANDARD_DEVIATION 9.99 |
| Age, Customized 18-40 years | 44 Participants | 49 Participants | 93 Participants |
| Age, Customized 41-55 years | 44 Participants | 36 Participants | 80 Participants |
| Region of Enrollment United States | 88 Participants | 85 Participants | 173 Participants |
| Sex: Female, Male Female | 53 Participants | 54 Participants | 107 Participants |
| Sex: Female, Male Male | 35 Participants | 31 Participants | 66 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 35 / 88 | 15 / 85 |
| serious Total, serious adverse events | 0 / 88 | 1 / 85 |
Outcome results
Primary
Change From Augmentation Baseline for Non-Remitters in Montgomery-Ǻsberg Depression Rating Scale (MADRS) Total Score at Week 6 - Last Observation Carried Forward (LOCF)
MADRS is a validated, 10-item rating scale with each item being scored on a scale from 0-6 with a total score ranging from 0-60. Lower scores indicate a decreased severity of depression.
Time frame: Augmentation Baseline, 6 weeks
Population: Primary Efficacy Analysis Set defined as all non-remitters (MADRS total score greater than 10 at augmentation baseline) who take at least 1 dose of randomized augmentation treatment and have at least 1 primary efficacy measurement after randomization.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Antidepressant + SPD489 (Non-remitters) | Change From Augmentation Baseline for Non-Remitters in Montgomery-Ǻsberg Depression Rating Scale (MADRS) Total Score at Week 6 - Last Observation Carried Forward (LOCF) | -7.1 Units on a scale | Standard Error 0.93 |
| Antidepressant + Placebo (Non-remitters) | Change From Augmentation Baseline for Non-Remitters in Montgomery-Ǻsberg Depression Rating Scale (MADRS) Total Score at Week 6 - Last Observation Carried Forward (LOCF) | -4.9 Units on a scale | Standard Error 0.94 |
p-value: 0.090290% CI: [-4.5, -0.1]ANCOVA
Secondary
Assessment in Non-Remitters of Clinical Global Impression-Severity of Illness (CGI-S) at Augmentation Baseline
CGI-S assesses the severity of the subject's condition on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill)
Time frame: Augmentation baseline
Population: Primary Efficacy Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Antidepressant + SPD489 (Non-remitters) | Assessment in Non-Remitters of Clinical Global Impression-Severity of Illness (CGI-S) at Augmentation Baseline | Mildly ill | 40.0 Percent of participants |
| Antidepressant + SPD489 (Non-remitters) | Assessment in Non-Remitters of Clinical Global Impression-Severity of Illness (CGI-S) at Augmentation Baseline | Markedly ill | 6.2 Percent of participants |
| Antidepressant + SPD489 (Non-remitters) | Assessment in Non-Remitters of Clinical Global Impression-Severity of Illness (CGI-S) at Augmentation Baseline | Borderline mentally ill | 20.0 Percent of participants |
| Antidepressant + SPD489 (Non-remitters) | Assessment in Non-Remitters of Clinical Global Impression-Severity of Illness (CGI-S) at Augmentation Baseline | Severely ill | 0 Percent of participants |
| Antidepressant + SPD489 (Non-remitters) | Assessment in Non-Remitters of Clinical Global Impression-Severity of Illness (CGI-S) at Augmentation Baseline | Moderately ill | 32.3 Percent of participants |
| Antidepressant + SPD489 (Non-remitters) | Assessment in Non-Remitters of Clinical Global Impression-Severity of Illness (CGI-S) at Augmentation Baseline | Among the most extremely ill | 0 Percent of participants |
| Antidepressant + SPD489 (Non-remitters) | Assessment in Non-Remitters of Clinical Global Impression-Severity of Illness (CGI-S) at Augmentation Baseline | Normal, not at all ill | 1.5 Percent of participants |
| Antidepressant + Placebo (Non-remitters) | Assessment in Non-Remitters of Clinical Global Impression-Severity of Illness (CGI-S) at Augmentation Baseline | Among the most extremely ill | 0 Percent of participants |
| Antidepressant + Placebo (Non-remitters) | Assessment in Non-Remitters of Clinical Global Impression-Severity of Illness (CGI-S) at Augmentation Baseline | Normal, not at all ill | 1.6 Percent of participants |
| Antidepressant + Placebo (Non-remitters) | Assessment in Non-Remitters of Clinical Global Impression-Severity of Illness (CGI-S) at Augmentation Baseline | Borderline mentally ill | 12.5 Percent of participants |
| Antidepressant + Placebo (Non-remitters) | Assessment in Non-Remitters of Clinical Global Impression-Severity of Illness (CGI-S) at Augmentation Baseline | Mildly ill | 34.4 Percent of participants |
| Antidepressant + Placebo (Non-remitters) | Assessment in Non-Remitters of Clinical Global Impression-Severity of Illness (CGI-S) at Augmentation Baseline | Moderately ill | 48.4 Percent of participants |
| Antidepressant + Placebo (Non-remitters) | Assessment in Non-Remitters of Clinical Global Impression-Severity of Illness (CGI-S) at Augmentation Baseline | Markedly ill | 3.1 Percent of participants |
| Antidepressant + Placebo (Non-remitters) | Assessment in Non-Remitters of Clinical Global Impression-Severity of Illness (CGI-S) at Augmentation Baseline | Severely ill | 0 Percent of participants |
Secondary
Assessment in Non-Remitters of Clinical Global Impression-Severity of Illness (CGI-S) at Week 6
CGI-S assesses the severity of the subject's condition on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill)
Time frame: 6 weeks
Population: Primary Efficacy Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Antidepressant + SPD489 (Non-remitters) | Assessment in Non-Remitters of Clinical Global Impression-Severity of Illness (CGI-S) at Week 6 | Normal, not at all ill | 27.0 Percent of participants |
| Antidepressant + SPD489 (Non-remitters) | Assessment in Non-Remitters of Clinical Global Impression-Severity of Illness (CGI-S) at Week 6 | Borderline mentally ill | 31.7 Percent of participants |
| Antidepressant + SPD489 (Non-remitters) | Assessment in Non-Remitters of Clinical Global Impression-Severity of Illness (CGI-S) at Week 6 | Moderately ill | 9.5 Percent of participants |
| Antidepressant + SPD489 (Non-remitters) | Assessment in Non-Remitters of Clinical Global Impression-Severity of Illness (CGI-S) at Week 6 | Markedly ill | 1.6 Percent of participants |
| Antidepressant + SPD489 (Non-remitters) | Assessment in Non-Remitters of Clinical Global Impression-Severity of Illness (CGI-S) at Week 6 | Severely ill | 0 Percent of participants |
| Antidepressant + SPD489 (Non-remitters) | Assessment in Non-Remitters of Clinical Global Impression-Severity of Illness (CGI-S) at Week 6 | Among the most extremely ill | 0 Percent of participants |
| Antidepressant + SPD489 (Non-remitters) | Assessment in Non-Remitters of Clinical Global Impression-Severity of Illness (CGI-S) at Week 6 | Mildly ill | 30.2 Percent of participants |
| Antidepressant + Placebo (Non-remitters) | Assessment in Non-Remitters of Clinical Global Impression-Severity of Illness (CGI-S) at Week 6 | Borderline mentally ill | 24.2 Percent of participants |
| Antidepressant + Placebo (Non-remitters) | Assessment in Non-Remitters of Clinical Global Impression-Severity of Illness (CGI-S) at Week 6 | Normal, not at all ill | 14.5 Percent of participants |
| Antidepressant + Placebo (Non-remitters) | Assessment in Non-Remitters of Clinical Global Impression-Severity of Illness (CGI-S) at Week 6 | Severely ill | 0 Percent of participants |
| Antidepressant + Placebo (Non-remitters) | Assessment in Non-Remitters of Clinical Global Impression-Severity of Illness (CGI-S) at Week 6 | Mildly ill | 22.6 Percent of participants |
| Antidepressant + Placebo (Non-remitters) | Assessment in Non-Remitters of Clinical Global Impression-Severity of Illness (CGI-S) at Week 6 | Moderately ill | 29.0 Percent of participants |
| Antidepressant + Placebo (Non-remitters) | Assessment in Non-Remitters of Clinical Global Impression-Severity of Illness (CGI-S) at Week 6 | Among the most extremely ill | 0 Percent of participants |
| Antidepressant + Placebo (Non-remitters) | Assessment in Non-Remitters of Clinical Global Impression-Severity of Illness (CGI-S) at Week 6 | Markedly ill | 9.7 Percent of participants |
Secondary
Assessment in Remitters of CGI-S at Augmentation Baseline
CGI-S assesses the severity of the subject's condition on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill)
Time frame: Augmentation Baseline
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Antidepressant + SPD489 (Non-remitters) | Assessment in Remitters of CGI-S at Augmentation Baseline | Mildly ill | 21.7 Percent of participants |
| Antidepressant + SPD489 (Non-remitters) | Assessment in Remitters of CGI-S at Augmentation Baseline | Markedly ill | 0 Percent of participants |
| Antidepressant + SPD489 (Non-remitters) | Assessment in Remitters of CGI-S at Augmentation Baseline | Borderline mentally ill | 47.8 Percent of participants |
| Antidepressant + SPD489 (Non-remitters) | Assessment in Remitters of CGI-S at Augmentation Baseline | Severely ill | 0 Percent of participants |
| Antidepressant + SPD489 (Non-remitters) | Assessment in Remitters of CGI-S at Augmentation Baseline | Moderately ill | 4.3 Percent of participants |
| Antidepressant + SPD489 (Non-remitters) | Assessment in Remitters of CGI-S at Augmentation Baseline | Among the most extremely ill | 0 Percent of participants |
| Antidepressant + SPD489 (Non-remitters) | Assessment in Remitters of CGI-S at Augmentation Baseline | Normal, not at all ill | 26.1 Percent of participants |
| Antidepressant + Placebo (Non-remitters) | Assessment in Remitters of CGI-S at Augmentation Baseline | Among the most extremely ill | 0 Percent of participants |
| Antidepressant + Placebo (Non-remitters) | Assessment in Remitters of CGI-S at Augmentation Baseline | Normal, not at all ill | 23.8 Percent of participants |
| Antidepressant + Placebo (Non-remitters) | Assessment in Remitters of CGI-S at Augmentation Baseline | Borderline mentally ill | 71.4 Percent of participants |
| Antidepressant + Placebo (Non-remitters) | Assessment in Remitters of CGI-S at Augmentation Baseline | Mildly ill | 4.8 Percent of participants |
| Antidepressant + Placebo (Non-remitters) | Assessment in Remitters of CGI-S at Augmentation Baseline | Moderately ill | 0 Percent of participants |
| Antidepressant + Placebo (Non-remitters) | Assessment in Remitters of CGI-S at Augmentation Baseline | Markedly ill | 0 Percent of participants |
| Antidepressant + Placebo (Non-remitters) | Assessment in Remitters of CGI-S at Augmentation Baseline | Severely ill | 0 Percent of participants |
Secondary
Assessment in Remitters of CGI-S at Week 6
CGI-S assesses the severity of the subject's condition on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill)
Time frame: 6 weeks
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Antidepressant + SPD489 (Non-remitters) | Assessment in Remitters of CGI-S at Week 6 | Mildly ill | 13.6 Percent of participants |
| Antidepressant + SPD489 (Non-remitters) | Assessment in Remitters of CGI-S at Week 6 | Markedly ill | 0 Percent of participants |
| Antidepressant + SPD489 (Non-remitters) | Assessment in Remitters of CGI-S at Week 6 | Borderline mentally ill | 36.4 Percent of participants |
| Antidepressant + SPD489 (Non-remitters) | Assessment in Remitters of CGI-S at Week 6 | Severely ill | 0 Percent of participants |
| Antidepressant + SPD489 (Non-remitters) | Assessment in Remitters of CGI-S at Week 6 | Moderately ill | 0 Percent of participants |
| Antidepressant + SPD489 (Non-remitters) | Assessment in Remitters of CGI-S at Week 6 | Among the most extremely ill | 0 Percent of participants |
| Antidepressant + SPD489 (Non-remitters) | Assessment in Remitters of CGI-S at Week 6 | Normal, not at all ill | 50.0 Percent of participants |
| Antidepressant + Placebo (Non-remitters) | Assessment in Remitters of CGI-S at Week 6 | Among the most extremely ill | 0 Percent of participants |
| Antidepressant + Placebo (Non-remitters) | Assessment in Remitters of CGI-S at Week 6 | Normal, not at all ill | 61.9 Percent of participants |
| Antidepressant + Placebo (Non-remitters) | Assessment in Remitters of CGI-S at Week 6 | Borderline mentally ill | 23.8 Percent of participants |
| Antidepressant + Placebo (Non-remitters) | Assessment in Remitters of CGI-S at Week 6 | Mildly ill | 9.5 Percent of participants |
| Antidepressant + Placebo (Non-remitters) | Assessment in Remitters of CGI-S at Week 6 | Moderately ill | 4.8 Percent of participants |
| Antidepressant + Placebo (Non-remitters) | Assessment in Remitters of CGI-S at Week 6 | Markedly ill | 0 Percent of participants |
| Antidepressant + Placebo (Non-remitters) | Assessment in Remitters of CGI-S at Week 6 | Severely ill | 0 Percent of participants |
Secondary
Change From Augmentation Baseline for Non-Remitters in the Behavior Rating Inventory of Executive Function - Adult Version (BRIEF-A) Scale Total Score at Week 6
BRIEF-A is a validated 75-item questionnaire composed of three scales (Global Executive Composite, Behavioral Recognition Index, and Metacognition Index). Items are rated 1 (never), 2 (sometimes), and 3 (often). There is no range for a total score. Raw scale scores are used to develop interpretive reports. Lower scores reflect better functioning.
Time frame: Augmentation Baseline and 6 weeks
Population: Primary Efficacy Analysis Set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Antidepressant + SPD489 (Non-remitters) | Change From Augmentation Baseline for Non-Remitters in the Behavior Rating Inventory of Executive Function - Adult Version (BRIEF-A) Scale Total Score at Week 6 | Global Executive Composite | -4.7 Units on a scale | Standard Error 1.03 |
| Antidepressant + SPD489 (Non-remitters) | Change From Augmentation Baseline for Non-Remitters in the Behavior Rating Inventory of Executive Function - Adult Version (BRIEF-A) Scale Total Score at Week 6 | Behavioral Regulation Index | -3.7 Units on a scale | Standard Error 0.97 |
| Antidepressant + SPD489 (Non-remitters) | Change From Augmentation Baseline for Non-Remitters in the Behavior Rating Inventory of Executive Function - Adult Version (BRIEF-A) Scale Total Score at Week 6 | Metacognition Index | -4.8 Units on a scale | Standard Error 1.04 |
| Antidepressant + Placebo (Non-remitters) | Change From Augmentation Baseline for Non-Remitters in the Behavior Rating Inventory of Executive Function - Adult Version (BRIEF-A) Scale Total Score at Week 6 | Global Executive Composite | -1.7 Units on a scale | Standard Error 1.04 |
| Antidepressant + Placebo (Non-remitters) | Change From Augmentation Baseline for Non-Remitters in the Behavior Rating Inventory of Executive Function - Adult Version (BRIEF-A) Scale Total Score at Week 6 | Behavioral Regulation Index | -1.7 Units on a scale | Standard Error 0.99 |
| Antidepressant + Placebo (Non-remitters) | Change From Augmentation Baseline for Non-Remitters in the Behavior Rating Inventory of Executive Function - Adult Version (BRIEF-A) Scale Total Score at Week 6 | Metacognition Index | -1.5 Units on a scale | Standard Error 1.06 |
Comparison: Global Executive Compositep-value: 0.046390% CI: [-5.4, -0.5]ANCOVA
Comparison: Behavioral Regulation Indexp-value: 0.143190% CI: [-4.3, 0.3]ANCOVA
Comparison: Metacognition Indexp-value: 0.028190% CI: [-5.8, -0.8]ANCOVA
Secondary
Change From Augmentation Baseline for Non-Remitters in the Hamilton Depression Scale (HAM-D) Total Score at Week 6 - LOCF
The HAM-D is a validated rating scale which consists of 17 items. Nine of the items are scored on a scale of 0-4 and 8 items are scored on a scale of 0-2 for a total scoring range of 0-52. A score of 0-7 is generally accepted to be within the normal range (or in clinical remission), while a score of 20 or higher indicates increased severity of depression. In general, the lower the total score the less severe the depression.
Time frame: Augmentation Baseline, 6 weeks
Population: Primary Efficacy Analysis Set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Antidepressant + SPD489 (Non-remitters) | Change From Augmentation Baseline for Non-Remitters in the Hamilton Depression Scale (HAM-D) Total Score at Week 6 - LOCF | -4.9 Units on a scale | Standard Error 0.64 |
| Antidepressant + Placebo (Non-remitters) | Change From Augmentation Baseline for Non-Remitters in the Hamilton Depression Scale (HAM-D) Total Score at Week 6 - LOCF | -4.0 Units on a scale | Standard Error 0.65 |
p-value: 0.309190% CI: [-2.4, 0.6]ANCOVA
Secondary
Change From Augmentation Baseline for Non-Remitters in the Multidimensional Assessment of Fatigue (MAF) Scale Total Score at Week 6
MAF contains 16 items scored on a scale from 1 (not at all) to 10 (a great deal). Answers are converted to a Global Fatigue Index with total scores ranging from 1 (no fatigue) to 50 (severe fatigue). Lower scores indicate less fatigue.
Time frame: Augmentation Baseline and 6 weeks
Population: Primary Efficacy Analysis Set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Antidepressant + SPD489 (Non-remitters) | Change From Augmentation Baseline for Non-Remitters in the Multidimensional Assessment of Fatigue (MAF) Scale Total Score at Week 6 | -5.3 Units on a scale | Standard Error 1.25 |
| Antidepressant + Placebo (Non-remitters) | Change From Augmentation Baseline for Non-Remitters in the Multidimensional Assessment of Fatigue (MAF) Scale Total Score at Week 6 | -2.3 Units on a scale | Standard Error 1.26 |
p-value: 0.09290% CI: [-6, -0.1]ANCOVA
Secondary
Change From Augmentation Baseline for Non-Remitters in the Quick Inventory of Depressive Symptomatology - Self-Report (QIDS-SR) Scale Total Score at Week 6
QIDS-SR is a validated, self-reported rating scale that contains 16 items scored on a scale from 0-3 with total scores ranging from 0 (no depression) to 27 (very severe depression). Lower scores indicate less depression.
Time frame: Augmentation Baseline and 6 weeks
Population: Primary Efficacy Analysis Set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Antidepressant + SPD489 (Non-remitters) | Change From Augmentation Baseline for Non-Remitters in the Quick Inventory of Depressive Symptomatology - Self-Report (QIDS-SR) Scale Total Score at Week 6 | -2.4 Units on a scale | Standard Error 0.45 |
| Antidepressant + Placebo (Non-remitters) | Change From Augmentation Baseline for Non-Remitters in the Quick Inventory of Depressive Symptomatology - Self-Report (QIDS-SR) Scale Total Score at Week 6 | -1.2 Units on a scale | Standard Error 0.46 |
p-value: 0.077490% CI: [-2.2, -0.1]ANCOVA
Secondary
Change From Augmentation Baseline for Non-Remitters in the Sheehan Disability Scale (SDS) Total Score at Week 6
Designed to evaluate the extent to which illness symptoms impact a subject's life in 3 areas: work/school, social, and family/home. Each area is scored on a scale from 0 (no impairment) to 10 (highly impaired) with a total score ranging from 0 (unimpaired) to 30 (highly impaired). Lower scores translate into less impairment.
Time frame: Augmentation Baseline, 6 weeks
Population: Primary Efficacy Analysis Set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Antidepressant + SPD489 (Non-remitters) | Change From Augmentation Baseline for Non-Remitters in the Sheehan Disability Scale (SDS) Total Score at Week 6 | -3.7 Units on a scale | Standard Error 0.73 |
| Antidepressant + Placebo (Non-remitters) | Change From Augmentation Baseline for Non-Remitters in the Sheehan Disability Scale (SDS) Total Score at Week 6 | -1.7 Units on a scale | Standard Error 0.74 |
p-value: 0.057390% CI: [-3.7, -0.3]ANCOVA
Secondary
Change From Augmentation Baseline for Remitters in MADRS Total Score at Week 6 - LOCF
MADRS is a validated, 10-item rating scale with each item being scored on a scale from 0-6 with a total score ranging from 0-60. Lower scores indicate a decreased severity of depression.
Time frame: Augmentation Baseline and 6 weeks
Population: Full Analysis Set (FAS) defined as all subjects who take at least 1 dose of randomized augmentation treatment and have at least 1 primary efficacy measurement after randomization.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Antidepressant + SPD489 (Non-remitters) | Change From Augmentation Baseline for Remitters in MADRS Total Score at Week 6 - LOCF | 0.1 Units on a scale | Standard Error 1.13 |
| Antidepressant + Placebo (Non-remitters) | Change From Augmentation Baseline for Remitters in MADRS Total Score at Week 6 - LOCF | -1.1 Units on a scale | Standard Error 1.18 |
p-value: 0.472690% CI: [-1.6, 4]ANCOVA
Secondary
Change From Augmentation Baseline for Remitters in the BRIEF-A Scale Total Score at Week 6
BRIEF-A is a validated 86-item questionnaire composed of three scales (Global Executive Composite, Behavioral Recognition Index, and Metacognition Index). Items are rated 1 (never), 2 (sometimes), and 3 (often). Lower scores reflect better functioning.
Time frame: Augmentation baseline and 6 weeks
Population: FAS
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Antidepressant + SPD489 (Non-remitters) | Change From Augmentation Baseline for Remitters in the BRIEF-A Scale Total Score at Week 6 | Global Executive Composite | -0.9 Units on a scale | Standard Error 1.21 |
| Antidepressant + SPD489 (Non-remitters) | Change From Augmentation Baseline for Remitters in the BRIEF-A Scale Total Score at Week 6 | Behavioral Regulation Index | -0.4 Units on a scale | Standard Error 1.37 |
| Antidepressant + SPD489 (Non-remitters) | Change From Augmentation Baseline for Remitters in the BRIEF-A Scale Total Score at Week 6 | Metacognition Index | -1.1 Units on a scale | Standard Error 1.24 |
| Antidepressant + Placebo (Non-remitters) | Change From Augmentation Baseline for Remitters in the BRIEF-A Scale Total Score at Week 6 | Global Executive Composite | -2.7 Units on a scale | Standard Error 1.21 |
| Antidepressant + Placebo (Non-remitters) | Change From Augmentation Baseline for Remitters in the BRIEF-A Scale Total Score at Week 6 | Metacognition Index | -3.4 Units on a scale | Standard Error 1.24 |
| Antidepressant + Placebo (Non-remitters) | Change From Augmentation Baseline for Remitters in the BRIEF-A Scale Total Score at Week 6 | Behavioral Regulation Index | -1.5 Units on a scale | Standard Error 1.37 |
Comparison: Global Executive Compositep-value: 0.287690% CI: [-1, 4.7]ANCOVA
Comparison: Behavioral Regulation Indexp-value: 0.55990% CI: [-2.1, 4.4]ANCOVA
Comparison: Metacognition Indexp-value: 0.207990% CI: [-0.7, 5.2]ANCOVA
Secondary
Change From Augmentation Baseline for Remitters in the HAM-D Total Score at Week 6 - LOCF
The HAM-D is a validated rating scale which consists of 17 items. Nine of the items are scored on a scale of 0-4 and 8 items are scored on a scale of 0-2 for a total scoring range of 0-52. A score of 0-7 is generally accepted to be within the normal range (or in clinical remission), while a score of 20 or higher indicates increased severity of depression. In general, the lower the total score the less severe the depression.
Time frame: Augmentation Baseline and 6 weeks
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Antidepressant + SPD489 (Non-remitters) | Change From Augmentation Baseline for Remitters in the HAM-D Total Score at Week 6 - LOCF | -0.8 Units on a scale | Standard Error 0.92 |
| Antidepressant + Placebo (Non-remitters) | Change From Augmentation Baseline for Remitters in the HAM-D Total Score at Week 6 - LOCF | -1.6 Units on a scale | Standard Error 0.96 |
p-value: 0.518290% CI: [-1.4, 3.1]ANCOVA
Secondary
Change From Augmentation Baseline for Remitters in the MAF Scale Total Score at Week 6
MAF contains 16 items scored on a scale from 1 (not at all) to 10 (a great deal). Answers are converted to a Global Fatigue Index with total scores ranging from 1 (no fatigue) to 50 (severe fatigue). Lower scores indicate less fatigue.
Time frame: Augmentation baseline and 6 weeks
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Antidepressant + SPD489 (Non-remitters) | Change From Augmentation Baseline for Remitters in the MAF Scale Total Score at Week 6 | -4.0 Units on a scale | Standard Error 1.77 |
| Antidepressant + Placebo (Non-remitters) | Change From Augmentation Baseline for Remitters in the MAF Scale Total Score at Week 6 | -0.2 Units on a scale | Standard Error 1.81 |
p-value: 0.148990% CI: [-8, 0.5]ANCOVA
Secondary
Change From Augmentation Baseline for Remitters in the QIDS-SR Scale Total Score at Week 6
QIDS-SR is a validated, self-reported rating scale that contains 16 items scored on a scale from 0-3 with total scores ranging from 0 (no depression) to 27 (very severe depression). Lower scores indicate less depression.
Time frame: Augmentation baseline and 6 weeks
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Antidepressant + SPD489 (Non-remitters) | Change From Augmentation Baseline for Remitters in the QIDS-SR Scale Total Score at Week 6 | -1.9 Units on a scale | Standard Error 0.57 |
| Antidepressant + Placebo (Non-remitters) | Change From Augmentation Baseline for Remitters in the QIDS-SR Scale Total Score at Week 6 | -0.4 Units on a scale | Standard Error 0.58 |
p-value: 0.085290% CI: [-2.8, -0.1]ANCOVA
Secondary
Change From Augmentation Baseline for Remitters in the SDS Total Score at Week 6
Designed to evaluate the extent to which illness symptoms impact a subject's life in 3 areas: work/school, social, and family/home. Each area is scored on a scale from 0 (no impairment) to 10 (highly impaired) with a total score ranging from 0 (unimpaired) to 30 (highly impaired). Lower scores translate into less impairment.
Time frame: Augmentation Baseline and 6 weeks
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Antidepressant + SPD489 (Non-remitters) | Change From Augmentation Baseline for Remitters in the SDS Total Score at Week 6 | -1.6 Units on a scale | Standard Error 0.89 |
| Antidepressant + Placebo (Non-remitters) | Change From Augmentation Baseline for Remitters in the SDS Total Score at Week 6 | -0.6 Units on a scale | Standard Error 0.91 |
p-value: 0.46390% CI: [-3.1, 1.2]ANCOVA
Secondary
Percentage of Non-Remitters With Improvement on Clinical Global Impression-Improvement (CGI-I) at Week 6 - LOCF
Clinical Global Impression-Improvement (CGI-I) consists of a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved) or 2 (much improved) on the scale.
Time frame: 6 weeks
Population: Primary Efficacy Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Antidepressant + SPD489 (Non-remitters) | Percentage of Non-Remitters With Improvement on Clinical Global Impression-Improvement (CGI-I) at Week 6 - LOCF | 60.0 Percent of Participants |
| Antidepressant + Placebo (Non-remitters) | Percentage of Non-Remitters With Improvement on Clinical Global Impression-Improvement (CGI-I) at Week 6 - LOCF | 45.3 Percent of Participants |
p-value: 0.2368Cochran-Mantel-Haenszel
Secondary
Percentage of Remitters With Improvement on CGI-I at Week 6 - LOCF
Clinical Global Impression-Improvement (CGI-I) consists of a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved) or 2 (much improved) on the scale.
Time frame: 6 weeks
Population: FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Antidepressant + SPD489 (Non-remitters) | Percentage of Remitters With Improvement on CGI-I at Week 6 - LOCF | 65.2 Percent of participants |
| Antidepressant + Placebo (Non-remitters) | Percentage of Remitters With Improvement on CGI-I at Week 6 - LOCF | 52.4 Percent of participants |
p-value: 0.523Cochran-Mantel-Haenszel