NCT00905424

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

Completed Phase 2 Results posted Last updated 14 June 2021

What this trial tests

Phase 2 trial testing Antidepressant + SPD489 (lisdexamfetamine dimesylate) in Major Depressive Disorder in 246 participants. Completed in 4 August 2010.

Timeline

30 July 2009

Primary endpoint
4 August 2010

4 August 2010

Quick facts

Lead sponsor	Shire
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	triple
Primary purpose	treatment
Enrollment	246
Start date	30 July 2009
Primary completion	4 August 2010
Estimated completion	4 August 2010
Sites	15 locations across United States

Drugs / interventions tested

• Antidepressant + SPD489 (lisdexamfetamine dimesylate) — full drug profile →
• Antidepressant + placebo — full drug profile →

Conditions studied

• Major Depressive Disorder — all drugs for Major Depressive Disorder →

Sponsor

Shire — full company profile →

Who can join

Adults 18 to 55, any sex, with Major Depressive Disorder. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Augmentation Baseline for Non-Remitters in Montgomery-Ǻsberg Depression Rating Scale (MADRS) Total Score at Week 6 - Last Observation Carried Forward (LOCF) Primary · 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.

Group	Value	95% CI
Antidepressant + SPD489 (Non-remitters)	-7.1	± 0.93
Antidepressant + Placebo (Non-remitters)	-4.9	± 0.94

Change From Augmentation Baseline for Non-Remitters in the Hamilton Depression Scale (HAM-D) Total Score at Week 6 - LOCF Secondary · 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.

Group	Value	95% CI
Antidepressant + SPD489 (Non-remitters)	-4.9	± 0.64
Antidepressant + Placebo (Non-remitters)	-4.0	± 0.65

Change From Augmentation Baseline for Non-Remitters in the Sheehan Disability Scale (SDS) Total Score at Week 6 Secondary · 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.

Group	Value	95% CI
Antidepressant + SPD489 (Non-remitters)	-3.7	± 0.73
Antidepressant + Placebo (Non-remitters)	-1.7	± 0.74

Percentage of Non-Remitters With Improvement on Clinical Global Impression-Improvement (CGI-I) at Week 6 - LOCF Secondary · 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.

Group	Value	95% CI
Antidepressant + SPD489 (Non-remitters)	60.0
Antidepressant + Placebo (Non-remitters)	45.3

Assessment in Non-Remitters of Clinical Global Impression-Severity of Illness (CGI-S) at Augmentation Baseline Secondary · 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)

Normal, not at all ill

Group	Value	95% CI
Antidepressant + SPD489 (Non-remitters)	1.5
Antidepressant + Placebo (Non-remitters)	1.6

Borderline mentally ill

Group	Value	95% CI
Antidepressant + SPD489 (Non-remitters)	20.0
Antidepressant + Placebo (Non-remitters)	12.5

Mildly ill

Group	Value	95% CI
Antidepressant + SPD489 (Non-remitters)	40.0
Antidepressant + Placebo (Non-remitters)	34.4

Moderately ill

Group	Value	95% CI
Antidepressant + SPD489 (Non-remitters)	32.3
Antidepressant + Placebo (Non-remitters)	48.4

Markedly ill

Group	Value	95% CI
Antidepressant + SPD489 (Non-remitters)	6.2
Antidepressant + Placebo (Non-remitters)	3.1

Severely ill

Group	Value	95% CI
Antidepressant + SPD489 (Non-remitters)	0
Antidepressant + Placebo (Non-remitters)	0

Among the most extremely ill

Group	Value	95% CI
Antidepressant + SPD489 (Non-remitters)	0
Antidepressant + Placebo (Non-remitters)	0

Assessment in Non-Remitters of Clinical Global Impression-Severity of Illness (CGI-S) at Week 6 Secondary · 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)

Normal, not at all ill

Group	Value	95% CI
Antidepressant + SPD489 (Non-remitters)	27.0
Antidepressant + Placebo (Non-remitters)	14.5

Borderline mentally ill

Group	Value	95% CI
Antidepressant + SPD489 (Non-remitters)	31.7
Antidepressant + Placebo (Non-remitters)	24.2

Mildly ill

Group	Value	95% CI
Antidepressant + SPD489 (Non-remitters)	30.2
Antidepressant + Placebo (Non-remitters)	22.6

Moderately ill

Group	Value	95% CI
Antidepressant + SPD489 (Non-remitters)	9.5
Antidepressant + Placebo (Non-remitters)	29.0

Markedly ill

Group	Value	95% CI
Antidepressant + SPD489 (Non-remitters)	1.6
Antidepressant + Placebo (Non-remitters)	9.7

Severely ill

Group	Value	95% CI
Antidepressant + SPD489 (Non-remitters)	0
Antidepressant + Placebo (Non-remitters)	0

Among the most extremely ill

Group	Value	95% CI
Antidepressant + SPD489 (Non-remitters)	0
Antidepressant + Placebo (Non-remitters)	0

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 Secondary · 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.

Global Executive Composite

Group	Value	95% CI
Antidepressant + SPD489 (Non-remitters)	-4.7	± 1.03
Antidepressant + Placebo (Non-remitters)	-1.7	± 1.04

Behavioral Regulation Index

Group	Value	95% CI
Antidepressant + SPD489 (Non-remitters)	-3.7	± 0.97
Antidepressant + Placebo (Non-remitters)	-1.7	± 0.99

Metacognition Index

Group	Value	95% CI
Antidepressant + SPD489 (Non-remitters)	-4.8	± 1.04
Antidepressant + Placebo (Non-remitters)	-1.5	± 1.06

Change From Augmentation Baseline for Non-Remitters in the Multidimensional Assessment of Fatigue (MAF) Scale Total Score at Week 6 Secondary · 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.

Group	Value	95% CI
Antidepressant + SPD489 (Non-remitters)	-5.3	± 1.25
Antidepressant + Placebo (Non-remitters)	-2.3	± 1.26

Change From Augmentation Baseline for Non-Remitters in the Quick Inventory of Depressive Symptomatology - Self-Report (QIDS-SR) Scale Total Score at Week 6 Secondary · 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.

Group	Value	95% CI
Antidepressant + SPD489 (Non-remitters)	-2.4	± 0.45
Antidepressant + Placebo (Non-remitters)	-1.2	± 0.46

Change From Augmentation Baseline for Remitters in MADRS Total Score at Week 6 - LOCF Secondary · 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.

Group	Value	95% CI
Antidepressant + SPD489 (Remitters)	0.1	± 1.13
Antidepressant + Placebo (Remitters)	-1.1	± 1.18

Change From Augmentation Baseline for Remitters in the HAM-D Total Score at Week 6 - LOCF Secondary · 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.

Group	Value	95% CI
Antidepressant + SPD489 (Remitters)	-0.8	± 0.92
Antidepressant + Placebo (Remitters)	-1.6	± 0.96

Change From Augmentation Baseline for Remitters in the SDS Total Score at Week 6 Secondary · 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.

Group	Value	95% CI
Antidepressant + SPD489 (Remitters)	-1.6	± 0.89
Antidepressant + Placebo (Remitters)	-0.6	± 0.91

Adverse events — posted to ClinicalTrials.gov

Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Antidepressant + SPD489

Serious: 0/88 (0%)

Deaths: —

Antidepressant + Placebo .

Serious: 1/85 (1%)

Deaths: —

Serious adverse events (1 terms)

Reaction	System	Antidepressant + SPD489	Antidepressant + Placebo .
Rhabdomyolysis	Musculoskeletal and connective tissue disorders	—	—

Other adverse events (5 terms — click to expand)

Reaction	System	Antidepressant + SPD489	Antidepressant + Placebo .
Dry mouth	Gastrointestinal disorders	—	—
Headache	Nervous system disorders	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—
Insomnia	Psychiatric disorders	—	—
Nasopharyngitis	Infections and infestations	—	—

Most-reported serious reactions: Rhabdomyolysis.

Data from ClinicalTrials.gov NCT00905424 adverse events section.

Sponsor's own description

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.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. A randomized controlled trial of the efficacy and safety of lisdexamfetamine dimesylate as augmentation therapy in adults with residual symptoms of major depressive disorder after treatment with escitalopram.
   Trivedi MH, Cutler AJ, Richards C, Lasser R, et al · · 2013 · cited 37× · PMID 24021497 · DOI 10.4088/jcp.13m08360
2. Update on optimal use of lisdexamfetamine in the treatment of ADHD.
   Madaan V, Kolli V, Bestha DP, Shah MJ. · · 2013 · cited 11× · PMID 23901276 · DOI 10.2147/ndt.s34092