NCT00985725 is a Phase 2 clinical trial of SPD489 (Lisdexamfetamine dimesylate) in Major Depressive Disorder, sponsored by Shire.

Who is sponsoring NCT00985725?

NCT00985725 is sponsored by Shire.

What drugs are being tested in NCT00985725?

Interventions in NCT00985725: SPD489 (Lisdexamfetamine dimesylate), Matching placebo.

What condition does NCT00985725 study?

NCT00985725 studies Major Depressive Disorder.

Is NCT00985725 still recruiting?

NCT00985725 is currently completed. Last updated 8 June 2021.

Are results published for NCT00985725?

Yes — primary outcome results have been posted to ClinicalTrials.gov. See the outcomes section above for details.

Last reviewed 2021-06-08 · How we verify

NCT00985725

Name: Drug Landscape Pharmaceutical Database
Creator: Drug Landscape
Published: 2026-01-01
License: https://creativecommons.org/licenses/by/4.0/

SPD489 in Adults With Persistent Executive Function Impairments (EFI) and Partial or Full Remission of Recurrent Major Depressive Disorder

Completed Phase 2 Results posted Last updated 8 June 2021

What this trial tests

Phase 2 trial testing SPD489 (Lisdexamfetamine dimesylate) in Major Depressive Disorder in 143 participants. Completed in 18 April 2011.

Timeline

29 October 2009

Primary endpoint
18 April 2011

18 April 2011

Quick facts

Lead sponsor	Shire
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	triple
Primary purpose	treatment
Enrollment	143
Start date	29 October 2009
Primary completion	18 April 2011
Estimated completion	18 April 2011
Sites	33 locations across United States

Drugs / interventions tested

SPD489 (Lisdexamfetamine dimesylate) — full drug profile →
Matching 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 Baseline in Behavior Rating Inventory of Executive Function - Adult Version Global Executive Composite T-score (BRIEF-A GEC T) at Week 9, Last Observation Carried Forward (LOCF) Primary · Baseline and week 9

BRIEF-A Global Executive Composite assesses behavioral aspects of executive function. Items are rated 1 (never), 2 (sometimes), and 3 (often). There is no range for a total score. Raw scale scores are used to generate T-scores. A reduction in score indicates less impairment.

Group	Value	95% CI
Lisdexamfetamine Dimesylate (LDX)	-21.2	± 1.67
Placebo	-13.2	± 1.66

Change From Baseline in Montgomery-Ǻsberg Depression Rating Scale (MADRS) Total Score at Week 9 - (LOCF) Secondary · Baseline and week 9

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
Lisdexamfetamine Dimesylate (LDX)	-5.0	± 0.66
Placebo	-3.1	± 0.66

Change From Baseline in BRIEF-A T-scores at Week 9, LOCF Secondary · Baseline and week 9

BRIEF-A is a validated 75-item questionnaire. Items are rated 1 (never), 2 (sometimes), and 3 (often). There is no range for a total score. Raw scale scores are used to generate T-scores. A reduction in score indicates less impairment.

Behavioral recognition index

Group	Value	95% CI
Lisdexamfetamine Dimesylate (LDX)	-17.4	± 1.51
Placebo	-12.3	± 1.50

Inhibit subscale

Group	Value	95% CI
Lisdexamfetamine Dimesylate (LDX)	-13.5	± 1.26
Placebo	-9.3	± 1.25

Shift subscale

Group	Value	95% CI
Lisdexamfetamine Dimesylate (LDX)	-16.2	± 1.51
Placebo	-10.6	± 1.50

Emotional control subscale

Group	Value	95% CI
Lisdexamfetamine Dimesylate (LDX)	-13.8	± 1.48
Placebo	-10.1	± 1.47

Self-monitor subscale

Group	Value	95% CI
Lisdexamfetamine Dimesylate (LDX)	-13.8	± 1.36
Placebo	-10.7	± 1.35

Metacognition index

Group	Value	95% CI
Lisdexamfetamine Dimesylate (LDX)	-21.1	± 1.67
Placebo	-12.2	± 1.66

Initiate subscale

Group	Value	95% CI
Lisdexamfetamine Dimesylate (LDX)	-19.4	± 1.57
Placebo	-10.8	± 1.56

Working memory subscale

Group	Value	95% CI
Lisdexamfetamine Dimesylate (LDX)	-20.1	± 1.65
Placebo	-11.0	± 1.64

Change From Baseline in Central Nervous System Vital Signs Computerized Cognitive Testing Battery Neurocognitive Domain and Index Scores at up to 9 Weeks/Endpoint Secondary · Baseline and up to 9 weeks/Endpoint

This measures the speed and accuracy of basic mental functions. Scores are normalized from raw scores and present an age matched score relative to other people in a normative sample. Scores are normalized with a mean of 100 and standard deviation of 15. Scores \< 70 indicate likely deficit and impairment, and scores \> 110 indicate high function and capacity. Higher scores are better.

Complex information speed processing index

Group	Value	95% CI
Lisdexamfetamine Dimesylate (LDX)	8.7	± 10.13
Placebo	3.7	± 9.02

Executive function index

Group	Value	95% CI
Lisdexamfetamine Dimesylate (LDX)	11.0	± 14.80
Placebo	6.0	± 14.43

Neurocognitive index

Group	Value	95% CI
Lisdexamfetamine Dimesylate (LDX)	11.5	± 17.14
Placebo	2.5	± 13.74

Percent of Participants With Clinical Global Impression - Severity of Illness (CGI-S) at Baseline Secondary · 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
Lisdexamfetamine Dimesylate (LDX)	0.0
Placebo	2.8

Borderline mentally ill

Group	Value	95% CI
Lisdexamfetamine Dimesylate (LDX)	7.0
Placebo	8.3

Mildly ill

Group	Value	95% CI
Lisdexamfetamine Dimesylate (LDX)	42.3
Placebo	36.1

Moderately ill

Group	Value	95% CI
Lisdexamfetamine Dimesylate (LDX)	45.1
Placebo	48.6

Markedly ill

Group	Value	95% CI
Lisdexamfetamine Dimesylate (LDX)	4.2
Placebo	4.2

Severely ill

Group	Value	95% CI
Lisdexamfetamine Dimesylate (LDX)	1.4
Placebo	0.0

Among the most extremely ill

Group	Value	95% CI
Lisdexamfetamine Dimesylate (LDX)	0.0
Placebo	0.0

Percent of Participants With CGI-S at up to 9 Weeks/Endpoint Secondary · Up to 9 weeks/Endpoint

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
Lisdexamfetamine Dimesylate (LDX)	21.7
Placebo	15.9

Borderline mentally ill

Group	Value	95% CI
Lisdexamfetamine Dimesylate (LDX)	40.6
Placebo	23.2

Mildly ill

Group	Value	95% CI
Lisdexamfetamine Dimesylate (LDX)	20.3
Placebo	24.6

Moderately ill

Group	Value	95% CI
Lisdexamfetamine Dimesylate (LDX)	14.5
Placebo	34.8

Markedly ill

Group	Value	95% CI
Lisdexamfetamine Dimesylate (LDX)	2.9
Placebo	1.4

Severely ill

Group	Value	95% CI
Lisdexamfetamine Dimesylate (LDX)	0.0
Placebo	0.0

Among the most extremely ill

Group	Value	95% CI
Lisdexamfetamine Dimesylate (LDX)	0.0
Placebo	0.0

Percentage of Participants With Improvement on Clinical Global Impression-Improvement (CGI-I) at Week 9, LOCF Secondary · Week 9

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
Lisdexamfetamine Dimesylate (LDX)	60.6
Placebo	38.9

Change From Baseline in Endicott Work Productivity Scale (EWPS) Total Score at up to 9 Weeks/Endpoint Secondary · Baseline and up to 9 weeks/Endpoint

The EWPS quantifies work performance, productivity attitudes and behaviors assessing 25 items on a scale ranging from 0 (high performance) to 4 (lowest performance). Scores range from 0 to 100 with 100 representing lowest productivity.

Group	Value	95% CI
Lisdexamfetamine Dimesylate (LDX)	-20.4	± 2.24
Placebo	-15.9	± 2.32

Change From Baseline in Changes in Sexual Functioning Questionnaire (CSFQ-14) Total Scores for Males at Week 9, LOCF Secondary · Baseline and week 9

This is a 14 item self-report tool that evaluates sexual functioning. Each item is scored on a 5-point Likert scale ranging from 1 (never) to 5 (always) with total scores ranging from 14 to 70. Higher scores reflect better sexual functioning.

Group	Value	95% CI
Lisdexamfetamine Dimesylate (LDX)	2.5	± 4.61
Placebo	2.4	± 5.34

Change From Baseline in CSFQ-14 Total Scores for Females at Week 9, LOCF Secondary · Baseline and week 9

Group	Value	95% CI
Lisdexamfetamine Dimesylate (LDX)	2.7	± 8.47
Placebo	1.6	± 5.60

Change From Baseline in Short Form-12 Health Survey (SF-12) Scale Total Scores at Week 9 Secondary · Baseline and week 9

The SF-12 is a 12-item self-report questionnaire that is a subset of the SF-36 Health Survey. The survey captures physical and mental health. Each of the 12 items is scored using various scales with a total score ranging from 0 (lowest level of health) to 100 (highest level of health).

Aggregate physical

Group	Value	95% CI
Lisdexamfetamine Dimesylate (LDX)	-0.10	± 0.461
Placebo	-0.23	± 0.473

Aggregate mental

Group	Value	95% CI
Lisdexamfetamine Dimesylate (LDX)	0.69	± 0.987
Placebo	0.63	± 0.807

Change From Baseline in Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) Total Scores at up to 9 Weeks/Endpoint Secondary · Baseline and up to 9 weeks/Endpoint

The Q-LES-Q is a 93-item self-report questionnaire on quality of life and health. Each item is rated on a 5-point scale from 1 (very poor) to 5 (very good) with a total score ranging from 93 to 465. Higher scores indicate greater satisfaction.

Physical health activities

Group	Value	95% CI
Lisdexamfetamine Dimesylate (LDX)	17.9	± 20.03
Placebo	8.2	± 16.82

Overall life satisfaction

Group	Value	95% CI
Lisdexamfetamine Dimesylate (LDX)	12.1	± 25.37
Placebo	9.1	± 22.27

Adverse events — posted to ClinicalTrials.gov

Reporting threshold: 2%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Lisdexamfetamine Dimesylate (LDX)

Serious: 2/71 (3%)

Deaths: —

Placebo

Serious: 4/72 (6%)

Deaths: —

Serious adverse events (6 terms)

Reaction	System	Lisdexamfetamine Dimesylat…	Placebo
Loss of consciousness	Nervous system disorders	—	—
Suicidal ideation	Psychiatric disorders	—	—
Gastroenteritis	Infections and infestations	—	—
Rhabdomyolysis	Musculoskeletal and connective tissue disorders	—	—
Salmonellosis	Infections and infestations	—	—
Pelvic inflammatory disease	Infections and infestations	—	—

Other adverse events (36 terms — click to expand)

Reaction	System	Lisdexamfetamine Dimesylat…	Placebo
Decreased appetite	Investigations	—	—
Headache	Nervous system disorders	—	—
Dry mouth	Gastrointestinal disorders	—	—
Insomnia	Psychiatric disorders	—	—
Irritability	General disorders	—	—
Urinary tract infection	Infections and infestations	—	—
Upper respiratory tract infection	Infections and infestations	—	—
Anxiety	Psychiatric disorders	—	—
Nausea	Gastrointestinal disorders	—	—
Diarrhea	Gastrointestinal disorders	—	—
Fatigue	General disorders	—	—
Sinusitis	Infections and infestations	—	—
Somnolence	Nervous system disorders	—	—
Hyperhidrosis	Skin and subcutaneous tissue disorders	—	—
Gastroesophageal reflux disease	Gastrointestinal disorders	—	—
Heart rate increased	Investigations	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—
Dizziness	Nervous system disorders	—	—
Rash	Skin and subcutaneous tissue disorders	—	—
Hyperacusis	Ear and labyrinth disorders	—	—
Abdominal pain	Gastrointestinal disorders	—	—
Constipation	Gastrointestinal disorders	—	—
Vomiting	Gastrointestinal disorders	—	—
Feeling jittery	General disorders	—	—
Nasopharyngitis	Infections and infestations	—	—
Viral infection	Infections and infestations	—	—
Blood pressure increased	Investigations	—	—
Weight decreased	Investigations	—	—
Anorexia	Metabolism and nutrition disorders	—	—
Memory impairment	Nervous system disorders	—	—
Tremor	Nervous system disorders	—	—
Abnormal dreams	Psychiatric disorders	—	—
Agitation	Psychiatric disorders	—	—
Nervousness	Psychiatric disorders	—	—
Sinus congestion	Respiratory, thoracic and mediastinal disorders	—	—
Uticaria	Skin and subcutaneous tissue disorders	—	—

Most-reported serious reactions: Loss of consciousness, Suicidal ideation, Gastroenteritis, Rhabdomyolysis, Salmonellosis, Pelvic inflammatory disease.

Data from ClinicalTrials.gov NCT00985725 adverse events section.

Sponsor's own description

To evaluate the efficacy of SPD489 for the treatment of executive function impairments (EFI) when used as an adjunct to stable, standard therapy in the setting of partial or full remission from recurrent Major Depressive Disorder (MDD) as measured by the Global Executive Composite (GEC) T-score of the Behavioral Rating Inventory of Executive Functioning - Adult Version (BRIEF-A).

Publications & conference data

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

Lisdexamfetamine dimesylate augmentation in adults with persistent executive dysfunction after partial or full remission of major depressive disorder.
Madhoo M, Keefe RS, Roth RM, Sambunaris A, et al · · 2014 · cited 41× · PMID 24309905 · DOI 10.1038/npp.2013.334
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

Verify or expand the search:

Other trials of SPD489 (Lisdexamfetamine dimesylate)

Trials testing the same drug.

NCT03260205 — Safety and Efficacy Study in Preschool Children Aged 4-5 Years With Attention-deficit/Hyperactivity Disorder (ADHD) · Phase 3 · completed
NCT01718509 — SPD489 in Adults Aged 18-55 Years With Moderate to Severe Binge Eating Disorder · Phase 3 · completed
NCT01718483 — SPD489 in Adults Aged 18-55 Years With Moderate to Severe Binge Eating Disorder · Phase 3 · completed
NCT01457339 — Assess the Safety and Pharmacokinetics of Ascending, Multiple Oral Doses of SPD489 in Adults With Schizophrenia · Phase 1 · completed
NCT00877487 — Safety and Efficacy of Vyvanse in Adults With Attention-Deficit/Hyperactivity Disorder · Phase 4 · completed

Other recruiting trials for Major Depressive Disorder

Currently open trials in the same condition.

NCT07219394 — Peer-Delivered Behavioral Activation in a CCBHC · NA · recruiting
NCT06705478 — Pramipexole Versus Escitalopram to Treat Major Depressive Disorder (MDD) and Comorbid MDD With Mild Neurocognitive Disor · Phase 2 · recruiting
NCT06749392 — An Individual-specific Synchrony Signature · NA · recruiting
NCT07316803 — Group Intervention for Romantic Relationships in Young Adults With Severe Mental Illness · NA · recruiting
NCT07242105 — Optimizing Brain Excitability in Depression · NA · recruiting

Other Shire trials

Trials by the same sponsor.

NCT05067868 — A Study of Replagal in Children and Adults With Fabry Disease in India · Phase 4 · recruiting
NCT03878953 — A Clinical Study of rhPTH(1-84) Treatment in Japanese Participants With Chronic Hypoparathyroidism · Phase 3 · withdrawn
NCT04840667 — A Study of Replagal in Treatment-naïve Adults With Fabry Disease · Phase 3 · terminated
NCT04429984 — Post Marketing Surveillance (PMS) Study for Velaglucerase Alfa (VPRIV) in India · completed
NCT04440488 — ARALAST NP Alpha-1 Lung Density Chronic Obstructive Pulmonary Disease-Emphysema (COPD-E) Study · Phase 4 · withdrawn

Verify against primary sources

ClinicalTrials.gov — authoritative US registry record
WHO ICTRP — international registry index
EU Clinical Trials Register
Sponsor press releases (Google)

Data sources for this page

Trial protocol + status: ClinicalTrials.gov NCT00985725 (US National Library of Medicine, public domain)
Publications: Europe PMC API search by NCT ID, retrieved 10 June 2026
Drug + disease cross-links: matched in real time against Drug Landscape's normalised drug + company + condition tables
Sponsor: as reported to ClinicalTrials.gov by Shire
Last refreshed: 8 June 2021

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT00985725.

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