Trial Outcomes & Findings for Exploratory Study of SPD489 in Adults With Major Depressive Disorder (MDD) as Augmentation Therapy to an Antidepressant (NCT NCT00905424)

NCT ID: NCT00905424

Last Updated: 2021-06-14

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 246 participants
• Primary outcome timeframe: Augmentation Baseline, 6 weeks
• Results posted on: 2021-06-14

Participant Flow

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).

Participant milestones

Measure	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).	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.
Overall Study STARTED	89	88
Overall Study COMPLETED	78	79
Overall Study NOT COMPLETED	11	9

Reasons for withdrawal

Measure	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).	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.
Overall Study Lost to Follow-up	3	3
Overall Study Withdrawal by Subject	1	2
Overall Study Adverse Event	4	2
Overall Study Non-compliance with study medication	2	0
Overall Study Sponsor decision	1	0
Overall Study Positive urine drug screen	0	1
Overall Study Non-adherence to visit schedule	0	1

Baseline Characteristics

Exploratory Study of SPD489 in Adults With Major Depressive Disorder (MDD) as Augmentation Therapy to an Antidepressant

Baseline characteristics by cohort

Measure	Antidepressant + SPD489 n=88 Participants 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).	Antidepressant + Placebo . n=85 Participants 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.	Total n=173 Participants Total of all reporting groups
Age, Continuous	39.4 years STANDARD_DEVIATION 9.65 • n=5 Participants	38.6 years STANDARD_DEVIATION 10.38 • n=7 Participants	39.0 years STANDARD_DEVIATION 9.99 • n=5 Participants
Age, Customized 18-40 years	44 Participants n=5 Participants	49 Participants n=7 Participants	93 Participants n=5 Participants
Age, Customized 41-55 years	44 Participants n=5 Participants	36 Participants n=7 Participants	80 Participants n=5 Participants
Sex: Female, Male Female	53 Participants n=5 Participants	54 Participants n=7 Participants	107 Participants n=5 Participants
Sex: Female, Male Male	35 Participants n=5 Participants	31 Participants n=7 Participants	66 Participants n=5 Participants
Region of Enrollment United States	88 Participants n=5 Participants	85 Participants n=7 Participants	173 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Antidepressant + SPD489 (Non-remitters) n=65 Participants Subjects with residual depressive symptoms after the 8-week lead-in period with antidepressant were randomly assigned to receive augmentation therapy (SPD489). At augmentation baseline, randomization was stratified by Non-remitters and remitters. Non-remitters were defined as subjects who had an MADRS total score of greater than 10 at augmentation baseline. Subjects received antidepressant (escitalopram @ 20 mg/day) + an optimal dose of SPD489 (either 20, 30, or 50 mg/day) for 6 weeks.	Antidepressant + Placebo (Non-remitters) n=64 Participants Subjects with residual depressive symptoms after the 8-week lead-in period with antidepressant were randomly assigned to receive augmentation therapy (placebo). At augmentation baseline, randomization was stratified by Non-remitters and remitters. Non-remitters were defined as subjects who had an MADRS total score of greater than 10 at augmentation baseline. Subjects received antidepressant (escitalopram @ 20 mg/day) + placebo for 6 weeks.
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	-4.9 Units on a scale Standard Error 0.94

SECONDARY outcome

Timeframe: Augmentation Baseline, 6 weeks

Population: Primary Efficacy Analysis Set

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.

Outcome measures

Measure	Antidepressant + SPD489 (Non-remitters) n=65 Participants Subjects with residual depressive symptoms after the 8-week lead-in period with antidepressant were randomly assigned to receive augmentation therapy (SPD489). At augmentation baseline, randomization was stratified by Non-remitters and remitters. Non-remitters were defined as subjects who had an MADRS total score of greater than 10 at augmentation baseline. Subjects received antidepressant (escitalopram @ 20 mg/day) + an optimal dose of SPD489 (either 20, 30, or 50 mg/day) for 6 weeks.	Antidepressant + Placebo (Non-remitters) n=64 Participants Subjects with residual depressive symptoms after the 8-week lead-in period with antidepressant were randomly assigned to receive augmentation therapy (placebo). At augmentation baseline, randomization was stratified by Non-remitters and remitters. Non-remitters were defined as subjects who had an MADRS total score of greater than 10 at augmentation baseline. Subjects received antidepressant (escitalopram @ 20 mg/day) + placebo for 6 weeks.
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	-4.0 Units on a scale Standard Error 0.65

SECONDARY outcome

Timeframe: Augmentation Baseline, 6 weeks

Population: Primary Efficacy Analysis Set

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.

Outcome measures

Measure	Antidepressant + SPD489 (Non-remitters) n=63 Participants Subjects with residual depressive symptoms after the 8-week lead-in period with antidepressant were randomly assigned to receive augmentation therapy (SPD489). At augmentation baseline, randomization was stratified by Non-remitters and remitters. Non-remitters were defined as subjects who had an MADRS total score of greater than 10 at augmentation baseline. Subjects received antidepressant (escitalopram @ 20 mg/day) + an optimal dose of SPD489 (either 20, 30, or 50 mg/day) for 6 weeks.	Antidepressant + Placebo (Non-remitters) n=62 Participants Subjects with residual depressive symptoms after the 8-week lead-in period with antidepressant were randomly assigned to receive augmentation therapy (placebo). At augmentation baseline, randomization was stratified by Non-remitters and remitters. Non-remitters were defined as subjects who had an MADRS total score of greater than 10 at augmentation baseline. Subjects received antidepressant (escitalopram @ 20 mg/day) + placebo for 6 weeks.
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	-1.7 Units on a scale Standard Error 0.74

SECONDARY outcome

Timeframe: 6 weeks

Population: Primary Efficacy Analysis Set

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.

Outcome measures

Measure	Antidepressant + SPD489 (Non-remitters) n=65 Participants Subjects with residual depressive symptoms after the 8-week lead-in period with antidepressant were randomly assigned to receive augmentation therapy (SPD489). At augmentation baseline, randomization was stratified by Non-remitters and remitters. Non-remitters were defined as subjects who had an MADRS total score of greater than 10 at augmentation baseline. Subjects received antidepressant (escitalopram @ 20 mg/day) + an optimal dose of SPD489 (either 20, 30, or 50 mg/day) for 6 weeks.	Antidepressant + Placebo (Non-remitters) n=64 Participants Subjects with residual depressive symptoms after the 8-week lead-in period with antidepressant were randomly assigned to receive augmentation therapy (placebo). At augmentation baseline, randomization was stratified by Non-remitters and remitters. Non-remitters were defined as subjects who had an MADRS total score of greater than 10 at augmentation baseline. Subjects received antidepressant (escitalopram @ 20 mg/day) + placebo for 6 weeks.
Percentage of Non-Remitters With Improvement on Clinical Global Impression-Improvement (CGI-I) at Week 6 - LOCF	60.0 Percent of Participants	45.3 Percent of Participants

SECONDARY outcome

Timeframe: Augmentation baseline

Population: Primary Efficacy Analysis Set

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)

Outcome measures

Measure	Antidepressant + SPD489 (Non-remitters) n=64 Participants Subjects with residual depressive symptoms after the 8-week lead-in period with antidepressant were randomly assigned to receive augmentation therapy (SPD489). At augmentation baseline, randomization was stratified by Non-remitters and remitters. Non-remitters were defined as subjects who had an MADRS total score of greater than 10 at augmentation baseline. Subjects received antidepressant (escitalopram @ 20 mg/day) + an optimal dose of SPD489 (either 20, 30, or 50 mg/day) for 6 weeks.	Antidepressant + Placebo (Non-remitters) n=64 Participants Subjects with residual depressive symptoms after the 8-week lead-in period with antidepressant were randomly assigned to receive augmentation therapy (placebo). At augmentation baseline, randomization was stratified by Non-remitters and remitters. Non-remitters were defined as subjects who had an MADRS total score of greater than 10 at augmentation baseline. Subjects received antidepressant (escitalopram @ 20 mg/day) + placebo for 6 weeks.
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	1.6 Percent of participants
Assessment in Non-Remitters of Clinical Global Impression-Severity of Illness (CGI-S) at Augmentation Baseline Borderline mentally ill	20.0 Percent of participants	12.5 Percent of participants
Assessment in Non-Remitters of Clinical Global Impression-Severity of Illness (CGI-S) at Augmentation Baseline Mildly ill	40.0 Percent of participants	34.4 Percent of participants
Assessment in Non-Remitters of Clinical Global Impression-Severity of Illness (CGI-S) at Augmentation Baseline Moderately ill	32.3 Percent of participants	48.4 Percent of participants
Assessment in Non-Remitters of Clinical Global Impression-Severity of Illness (CGI-S) at Augmentation Baseline Markedly ill	6.2 Percent of participants	3.1 Percent of participants
Assessment in Non-Remitters of Clinical Global Impression-Severity of Illness (CGI-S) at Augmentation Baseline Severely ill	0 Percent of participants	0 Percent of participants
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	0 Percent of participants

SECONDARY outcome

Timeframe: 6 weeks

Population: Primary Efficacy Analysis Set

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)

Outcome measures

Measure	Antidepressant + SPD489 (Non-remitters) n=63 Participants Subjects with residual depressive symptoms after the 8-week lead-in period with antidepressant were randomly assigned to receive augmentation therapy (SPD489). At augmentation baseline, randomization was stratified by Non-remitters and remitters. Non-remitters were defined as subjects who had an MADRS total score of greater than 10 at augmentation baseline. Subjects received antidepressant (escitalopram @ 20 mg/day) + an optimal dose of SPD489 (either 20, 30, or 50 mg/day) for 6 weeks.	Antidepressant + Placebo (Non-remitters) n=62 Participants Subjects with residual depressive symptoms after the 8-week lead-in period with antidepressant were randomly assigned to receive augmentation therapy (placebo). At augmentation baseline, randomization was stratified by Non-remitters and remitters. Non-remitters were defined as subjects who had an MADRS total score of greater than 10 at augmentation baseline. Subjects received antidepressant (escitalopram @ 20 mg/day) + placebo for 6 weeks.
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	0 Percent of participants
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	14.5 Percent of participants
Assessment in Non-Remitters of Clinical Global Impression-Severity of Illness (CGI-S) at Week 6 Borderline mentally ill	31.7 Percent of participants	24.2 Percent of participants
Assessment in Non-Remitters of Clinical Global Impression-Severity of Illness (CGI-S) at Week 6 Mildly ill	30.2 Percent of participants	22.6 Percent of participants
Assessment in Non-Remitters of Clinical Global Impression-Severity of Illness (CGI-S) at Week 6 Moderately ill	9.5 Percent of participants	29.0 Percent of participants
Assessment in Non-Remitters of Clinical Global Impression-Severity of Illness (CGI-S) at Week 6 Markedly ill	1.6 Percent of participants	9.7 Percent of participants
Assessment in Non-Remitters of Clinical Global Impression-Severity of Illness (CGI-S) at Week 6 Severely ill	0 Percent of participants	0 Percent of participants

SECONDARY outcome

Timeframe: Augmentation Baseline and 6 weeks

Population: Primary Efficacy Analysis Set

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.

Outcome measures

Measure	Antidepressant + SPD489 (Non-remitters) n=62 Participants Subjects with residual depressive symptoms after the 8-week lead-in period with antidepressant were randomly assigned to receive augmentation therapy (SPD489). At augmentation baseline, randomization was stratified by Non-remitters and remitters. Non-remitters were defined as subjects who had an MADRS total score of greater than 10 at augmentation baseline. Subjects received antidepressant (escitalopram @ 20 mg/day) + an optimal dose of SPD489 (either 20, 30, or 50 mg/day) for 6 weeks.	Antidepressant + Placebo (Non-remitters) n=60 Participants Subjects with residual depressive symptoms after the 8-week lead-in period with antidepressant were randomly assigned to receive augmentation therapy (placebo). At augmentation baseline, randomization was stratified by Non-remitters and remitters. Non-remitters were defined as subjects who had an MADRS total score of greater than 10 at augmentation baseline. Subjects received antidepressant (escitalopram @ 20 mg/day) + placebo for 6 weeks.
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	-1.7 Units on a scale Standard Error 1.04
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	-1.7 Units on a scale Standard Error 0.99
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	-1.5 Units on a scale Standard Error 1.06

SECONDARY outcome

Timeframe: Augmentation Baseline and 6 weeks

Population: Primary Efficacy Analysis Set

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.

Outcome measures

Measure	Antidepressant + SPD489 (Non-remitters) n=63 Participants Subjects with residual depressive symptoms after the 8-week lead-in period with antidepressant were randomly assigned to receive augmentation therapy (SPD489). At augmentation baseline, randomization was stratified by Non-remitters and remitters. Non-remitters were defined as subjects who had an MADRS total score of greater than 10 at augmentation baseline. Subjects received antidepressant (escitalopram @ 20 mg/day) + an optimal dose of SPD489 (either 20, 30, or 50 mg/day) for 6 weeks.	Antidepressant + Placebo (Non-remitters) n=62 Participants Subjects with residual depressive symptoms after the 8-week lead-in period with antidepressant were randomly assigned to receive augmentation therapy (placebo). At augmentation baseline, randomization was stratified by Non-remitters and remitters. Non-remitters were defined as subjects who had an MADRS total score of greater than 10 at augmentation baseline. Subjects received antidepressant (escitalopram @ 20 mg/day) + placebo for 6 weeks.
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	-2.3 Units on a scale Standard Error 1.26

SECONDARY outcome

Timeframe: Augmentation Baseline and 6 weeks

Population: Primary Efficacy Analysis Set

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.

Outcome measures

Measure	Antidepressant + SPD489 (Non-remitters) n=63 Participants Subjects with residual depressive symptoms after the 8-week lead-in period with antidepressant were randomly assigned to receive augmentation therapy (SPD489). At augmentation baseline, randomization was stratified by Non-remitters and remitters. Non-remitters were defined as subjects who had an MADRS total score of greater than 10 at augmentation baseline. Subjects received antidepressant (escitalopram @ 20 mg/day) + an optimal dose of SPD489 (either 20, 30, or 50 mg/day) for 6 weeks.	Antidepressant + Placebo (Non-remitters) n=62 Participants Subjects with residual depressive symptoms after the 8-week lead-in period with antidepressant were randomly assigned to receive augmentation therapy (placebo). At augmentation baseline, randomization was stratified by Non-remitters and remitters. Non-remitters were defined as subjects who had an MADRS total score of greater than 10 at augmentation baseline. Subjects received antidepressant (escitalopram @ 20 mg/day) + placebo for 6 weeks.
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	-1.2 Units on a scale Standard Error 0.46

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Antidepressant + SPD489 (Non-remitters) n=23 Participants Subjects with residual depressive symptoms after the 8-week lead-in period with antidepressant were randomly assigned to receive augmentation therapy (SPD489). At augmentation baseline, randomization was stratified by Non-remitters and remitters. Non-remitters were defined as subjects who had an MADRS total score of greater than 10 at augmentation baseline. Subjects received antidepressant (escitalopram @ 20 mg/day) + an optimal dose of SPD489 (either 20, 30, or 50 mg/day) for 6 weeks.	Antidepressant + Placebo (Non-remitters) n=21 Participants Subjects with residual depressive symptoms after the 8-week lead-in period with antidepressant were randomly assigned to receive augmentation therapy (placebo). At augmentation baseline, randomization was stratified by Non-remitters and remitters. Non-remitters were defined as subjects who had an MADRS total score of greater than 10 at augmentation baseline. Subjects received antidepressant (escitalopram @ 20 mg/day) + placebo for 6 weeks.
Change From Augmentation Baseline for Remitters in MADRS Total Score at Week 6 - LOCF	0.1 Units on a scale Standard Error 1.13	-1.1 Units on a scale Standard Error 1.18

SECONDARY outcome

Timeframe: Augmentation Baseline and 6 weeks

Population: FAS

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.

Outcome measures

Measure	Antidepressant + SPD489 (Non-remitters) n=23 Participants Subjects with residual depressive symptoms after the 8-week lead-in period with antidepressant were randomly assigned to receive augmentation therapy (SPD489). At augmentation baseline, randomization was stratified by Non-remitters and remitters. Non-remitters were defined as subjects who had an MADRS total score of greater than 10 at augmentation baseline. Subjects received antidepressant (escitalopram @ 20 mg/day) + an optimal dose of SPD489 (either 20, 30, or 50 mg/day) for 6 weeks.	Antidepressant + Placebo (Non-remitters) n=21 Participants Subjects with residual depressive symptoms after the 8-week lead-in period with antidepressant were randomly assigned to receive augmentation therapy (placebo). At augmentation baseline, randomization was stratified by Non-remitters and remitters. Non-remitters were defined as subjects who had an MADRS total score of greater than 10 at augmentation baseline. Subjects received antidepressant (escitalopram @ 20 mg/day) + placebo for 6 weeks.
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	-1.6 Units on a scale Standard Error 0.96

SECONDARY outcome

Timeframe: Augmentation Baseline and 6 weeks

Population: FAS

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.

Outcome measures

Measure	Antidepressant + SPD489 (Non-remitters) n=22 Participants Subjects with residual depressive symptoms after the 8-week lead-in period with antidepressant were randomly assigned to receive augmentation therapy (SPD489). At augmentation baseline, randomization was stratified by Non-remitters and remitters. Non-remitters were defined as subjects who had an MADRS total score of greater than 10 at augmentation baseline. Subjects received antidepressant (escitalopram @ 20 mg/day) + an optimal dose of SPD489 (either 20, 30, or 50 mg/day) for 6 weeks.	Antidepressant + Placebo (Non-remitters) n=21 Participants Subjects with residual depressive symptoms after the 8-week lead-in period with antidepressant were randomly assigned to receive augmentation therapy (placebo). At augmentation baseline, randomization was stratified by Non-remitters and remitters. Non-remitters were defined as subjects who had an MADRS total score of greater than 10 at augmentation baseline. Subjects received antidepressant (escitalopram @ 20 mg/day) + placebo for 6 weeks.
Change From Augmentation Baseline for Remitters in the SDS Total Score at Week 6	-1.6 Units on a scale Standard Error 0.89	-0.6 Units on a scale Standard Error 0.91

SECONDARY outcome

Timeframe: 6 weeks

Population: FAS

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.

Outcome measures

Measure	Antidepressant + SPD489 (Non-remitters) n=23 Participants Subjects with residual depressive symptoms after the 8-week lead-in period with antidepressant were randomly assigned to receive augmentation therapy (SPD489). At augmentation baseline, randomization was stratified by Non-remitters and remitters. Non-remitters were defined as subjects who had an MADRS total score of greater than 10 at augmentation baseline. Subjects received antidepressant (escitalopram @ 20 mg/day) + an optimal dose of SPD489 (either 20, 30, or 50 mg/day) for 6 weeks.	Antidepressant + Placebo (Non-remitters) n=21 Participants Subjects with residual depressive symptoms after the 8-week lead-in period with antidepressant were randomly assigned to receive augmentation therapy (placebo). At augmentation baseline, randomization was stratified by Non-remitters and remitters. Non-remitters were defined as subjects who had an MADRS total score of greater than 10 at augmentation baseline. Subjects received antidepressant (escitalopram @ 20 mg/day) + placebo for 6 weeks.
Percentage of Remitters With Improvement on CGI-I at Week 6 - LOCF	65.2 Percent of participants	52.4 Percent of participants

SECONDARY outcome

Timeframe: Augmentation Baseline

Population: FAS

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)

Outcome measures

Measure	Antidepressant + SPD489 (Non-remitters) n=23 Participants Subjects with residual depressive symptoms after the 8-week lead-in period with antidepressant were randomly assigned to receive augmentation therapy (SPD489). At augmentation baseline, randomization was stratified by Non-remitters and remitters. Non-remitters were defined as subjects who had an MADRS total score of greater than 10 at augmentation baseline. Subjects received antidepressant (escitalopram @ 20 mg/day) + an optimal dose of SPD489 (either 20, 30, or 50 mg/day) for 6 weeks.	Antidepressant + Placebo (Non-remitters) n=21 Participants Subjects with residual depressive symptoms after the 8-week lead-in period with antidepressant were randomly assigned to receive augmentation therapy (placebo). At augmentation baseline, randomization was stratified by Non-remitters and remitters. Non-remitters were defined as subjects who had an MADRS total score of greater than 10 at augmentation baseline. Subjects received antidepressant (escitalopram @ 20 mg/day) + placebo for 6 weeks.
Assessment in Remitters of CGI-S at Augmentation Baseline Normal, not at all ill	26.1 Percent of participants	23.8 Percent of participants
Assessment in Remitters of CGI-S at Augmentation Baseline Borderline mentally ill	47.8 Percent of participants	71.4 Percent of participants
Assessment in Remitters of CGI-S at Augmentation Baseline Mildly ill	21.7 Percent of participants	4.8 Percent of participants
Assessment in Remitters of CGI-S at Augmentation Baseline Moderately ill	4.3 Percent of participants	0 Percent of participants
Assessment in Remitters of CGI-S at Augmentation Baseline Markedly ill	0 Percent of participants	0 Percent of participants
Assessment in Remitters of CGI-S at Augmentation Baseline Severely ill	0 Percent of participants	0 Percent of participants
Assessment in Remitters of CGI-S at Augmentation Baseline Among the most extremely ill	0 Percent of participants	0 Percent of participants

SECONDARY outcome

Timeframe: 6 weeks

Population: FAS

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)

Outcome measures

Measure	Antidepressant + SPD489 (Non-remitters) n=22 Participants Subjects with residual depressive symptoms after the 8-week lead-in period with antidepressant were randomly assigned to receive augmentation therapy (SPD489). At augmentation baseline, randomization was stratified by Non-remitters and remitters. Non-remitters were defined as subjects who had an MADRS total score of greater than 10 at augmentation baseline. Subjects received antidepressant (escitalopram @ 20 mg/day) + an optimal dose of SPD489 (either 20, 30, or 50 mg/day) for 6 weeks.	Antidepressant + Placebo (Non-remitters) n=21 Participants Subjects with residual depressive symptoms after the 8-week lead-in period with antidepressant were randomly assigned to receive augmentation therapy (placebo). At augmentation baseline, randomization was stratified by Non-remitters and remitters. Non-remitters were defined as subjects who had an MADRS total score of greater than 10 at augmentation baseline. Subjects received antidepressant (escitalopram @ 20 mg/day) + placebo for 6 weeks.
Assessment in Remitters of CGI-S at Week 6 Among the most extremely ill	0 Percent of participants	0 Percent of participants
Assessment in Remitters of CGI-S at Week 6 Normal, not at all ill	50.0 Percent of participants	61.9 Percent of participants
Assessment in Remitters of CGI-S at Week 6 Borderline mentally ill	36.4 Percent of participants	23.8 Percent of participants
Assessment in Remitters of CGI-S at Week 6 Mildly ill	13.6 Percent of participants	9.5 Percent of participants
Assessment in Remitters of CGI-S at Week 6 Moderately ill	0 Percent of participants	4.8 Percent of participants
Assessment in Remitters of CGI-S at Week 6 Markedly ill	0 Percent of participants	0 Percent of participants
Assessment in Remitters of CGI-S at Week 6 Severely ill	0 Percent of participants	0 Percent of participants

SECONDARY outcome

Timeframe: Augmentation baseline and 6 weeks

Population: FAS

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.

Outcome measures

Measure	Antidepressant + SPD489 (Non-remitters) n=21 Participants Subjects with residual depressive symptoms after the 8-week lead-in period with antidepressant were randomly assigned to receive augmentation therapy (SPD489). At augmentation baseline, randomization was stratified by Non-remitters and remitters. Non-remitters were defined as subjects who had an MADRS total score of greater than 10 at augmentation baseline. Subjects received antidepressant (escitalopram @ 20 mg/day) + an optimal dose of SPD489 (either 20, 30, or 50 mg/day) for 6 weeks.	Antidepressant + Placebo (Non-remitters) n=21 Participants Subjects with residual depressive symptoms after the 8-week lead-in period with antidepressant were randomly assigned to receive augmentation therapy (placebo). At augmentation baseline, randomization was stratified by Non-remitters and remitters. Non-remitters were defined as subjects who had an MADRS total score of greater than 10 at augmentation baseline. Subjects received antidepressant (escitalopram @ 20 mg/day) + placebo for 6 weeks.
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	-2.7 Units on a scale Standard Error 1.21
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	-1.5 Units on a scale Standard Error 1.37
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	-3.4 Units on a scale Standard Error 1.24

SECONDARY outcome

Timeframe: Augmentation baseline and 6 weeks

Population: FAS

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.

Outcome measures

Measure	Antidepressant + SPD489 (Non-remitters) n=22 Participants Subjects with residual depressive symptoms after the 8-week lead-in period with antidepressant were randomly assigned to receive augmentation therapy (SPD489). At augmentation baseline, randomization was stratified by Non-remitters and remitters. Non-remitters were defined as subjects who had an MADRS total score of greater than 10 at augmentation baseline. Subjects received antidepressant (escitalopram @ 20 mg/day) + an optimal dose of SPD489 (either 20, 30, or 50 mg/day) for 6 weeks.	Antidepressant + Placebo (Non-remitters) n=21 Participants Subjects with residual depressive symptoms after the 8-week lead-in period with antidepressant were randomly assigned to receive augmentation therapy (placebo). At augmentation baseline, randomization was stratified by Non-remitters and remitters. Non-remitters were defined as subjects who had an MADRS total score of greater than 10 at augmentation baseline. Subjects received antidepressant (escitalopram @ 20 mg/day) + placebo for 6 weeks.
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	-0.2 Units on a scale Standard Error 1.81

SECONDARY outcome

Timeframe: Augmentation baseline and 6 weeks

Population: FAS

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.

Outcome measures

Measure	Antidepressant + SPD489 (Non-remitters) n=22 Participants Subjects with residual depressive symptoms after the 8-week lead-in period with antidepressant were randomly assigned to receive augmentation therapy (SPD489). At augmentation baseline, randomization was stratified by Non-remitters and remitters. Non-remitters were defined as subjects who had an MADRS total score of greater than 10 at augmentation baseline. Subjects received antidepressant (escitalopram @ 20 mg/day) + an optimal dose of SPD489 (either 20, 30, or 50 mg/day) for 6 weeks.	Antidepressant + Placebo (Non-remitters) n=21 Participants Subjects with residual depressive symptoms after the 8-week lead-in period with antidepressant were randomly assigned to receive augmentation therapy (placebo). At augmentation baseline, randomization was stratified by Non-remitters and remitters. Non-remitters were defined as subjects who had an MADRS total score of greater than 10 at augmentation baseline. Subjects received antidepressant (escitalopram @ 20 mg/day) + placebo for 6 weeks.
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	-0.4 Units on a scale Standard Error 0.58

Adverse Events

Antidepressant + SPD489

Serious events: 0 serious events

Other events: 35 other events

Deaths: 0 deaths

Antidepressant + Placebo .

Serious events: 1 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious adverse events

Measure	Antidepressant + SPD489 n=88 participants at risk 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).	Antidepressant + Placebo . n=85 participants at risk 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.
Musculoskeletal and connective tissue disorders Rhabdomyolysis	0.00% 0/88 Randomized Safety Analysis Set (RSAS) defined as all subjects who take at least 1 dose of randomized augmentation treatment and at least 1 follow-up safety assessment.	1.2% 1/85 Randomized Safety Analysis Set (RSAS) defined as all subjects who take at least 1 dose of randomized augmentation treatment and at least 1 follow-up safety assessment.

Other adverse events

Measure	Antidepressant + SPD489 n=88 participants at risk 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).	Antidepressant + Placebo . n=85 participants at risk 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.
Gastrointestinal disorders Dry mouth	11.4% 10/88 Randomized Safety Analysis Set (RSAS) defined as all subjects who take at least 1 dose of randomized augmentation treatment and at least 1 follow-up safety assessment.	0.00% 0/85 Randomized Safety Analysis Set (RSAS) defined as all subjects who take at least 1 dose of randomized augmentation treatment and at least 1 follow-up safety assessment.
Nervous system disorders Headache	11.4% 10/88 Randomized Safety Analysis Set (RSAS) defined as all subjects who take at least 1 dose of randomized augmentation treatment and at least 1 follow-up safety assessment.	4.7% 4/85 Randomized Safety Analysis Set (RSAS) defined as all subjects who take at least 1 dose of randomized augmentation treatment and at least 1 follow-up safety assessment.
Metabolism and nutrition disorders Decreased appetite	6.8% 6/88 Randomized Safety Analysis Set (RSAS) defined as all subjects who take at least 1 dose of randomized augmentation treatment and at least 1 follow-up safety assessment.	2.4% 2/85 Randomized Safety Analysis Set (RSAS) defined as all subjects who take at least 1 dose of randomized augmentation treatment and at least 1 follow-up safety assessment.
Infections and infestations Nasopharyngitis	5.7% 5/88 Randomized Safety Analysis Set (RSAS) defined as all subjects who take at least 1 dose of randomized augmentation treatment and at least 1 follow-up safety assessment.	3.5% 3/85 Randomized Safety Analysis Set (RSAS) defined as all subjects who take at least 1 dose of randomized augmentation treatment and at least 1 follow-up safety assessment.
Psychiatric disorders Insomnia	4.5% 4/88 Randomized Safety Analysis Set (RSAS) defined as all subjects who take at least 1 dose of randomized augmentation treatment and at least 1 follow-up safety assessment.	7.1% 6/85 Randomized Safety Analysis Set (RSAS) defined as all subjects who take at least 1 dose of randomized augmentation treatment and at least 1 follow-up safety assessment.

Additional Information

Study Director

Shire

Phone: +1 866 842 5335

Email: ClinicalTransparency@shire.com

Results disclosure agreements

• Principal investigator is a sponsor employee If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.
• Publication restrictions are in place

Restriction type: OTHER