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

• ClinicalTrials.gov Identifier: NCT00905424
• Recruitment Status: Completed
• First Posted: May 20, 2009
• Results First Posted: July 14, 2011
• Last Update Posted: June 14, 2021
• Sponsor: Shire
• Information provided by (Responsible Party): Takeda ( Shire )

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Major Depressive Disorder	Drug: Antidepressant + SPD489 (lisdexamfetamine dimesylate); Drug: Antidepressant + placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 246 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Multicenter, Randomized, Double-blind, Parallel-group, Placebo Controlled Exploratory Efficacy and Safety Study of SPD489 in Adults 18-55 Years With Major Depressive Disorder (MDD) as Augmentation Therapy to an Antidepressant
• Actual Study Start Date: July 30, 2009
• Actual Primary Completion Date: August 4, 2010
• Actual Study Completion Date: August 4, 2010

Arms and Interventions

Arm	Intervention/treatment
Experimental: Active; Antidepressant + SPD489	Drug: Antidepressant + SPD489 (lisdexamfetamine dimesylate); Escitalopram oxalate (antidepressant) 20 mg/day oral + 20, 30, or 50 mg SPD489 oral once daily for 6 weeks; Other Name: LDX, Vyvanse
Placebo Comparator: Placebo; Antidepressant + placebo	Drug: Antidepressant + placebo; Escitalopram oxalate (antidepressant) 20 mg/day oral + placebo oral once daily for 6 weeks

Outcome Measures

Primary Outcome Measures :

1. Change From Augmentation Baseline for Non-Remitters in Montgomery-Ǻsberg Depression Rating Scale (MADRS) Total Score at Week 6 - Last Observation Carried Forward (LOCF) [ Time Frame: 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 Outcome Measures :

1. Change From Augmentation Baseline for Non-Remitters in the Hamilton Depression Scale (HAM-D) Total Score at Week 6 - LOCF [ Time Frame: 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.
2. Change From Augmentation Baseline for Non-Remitters in the Sheehan Disability Scale (SDS) Total Score at Week 6 [ Time Frame: 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.
3. Percentage of Non-Remitters With Improvement on Clinical Global Impression-Improvement (CGI-I) at Week 6 - LOCF [ Time Frame: 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.
4. Assessment in Non-Remitters of Clinical Global Impression-Severity of Illness (CGI-S) at Augmentation Baseline [ Time Frame: 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)
5. Assessment in Non-Remitters of Clinical Global Impression-Severity of Illness (CGI-S) at Week 6 [ Time Frame: 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)
6. 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 [ Time Frame: 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.
7. Change From Augmentation Baseline for Non-Remitters in the Multidimensional Assessment of Fatigue (MAF) Scale Total Score at Week 6 [ Time Frame: 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.
8. Change From Augmentation Baseline for Non-Remitters in the Quick Inventory of Depressive Symptomatology - Self-Report (QIDS-SR) Scale Total Score at Week 6 [ Time Frame: 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.
9. Change From Augmentation Baseline for Remitters in MADRS Total Score at Week 6 - LOCF [ Time Frame: 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.
10. Change From Augmentation Baseline for Remitters in the HAM-D Total Score at Week 6 - LOCF [ Time Frame: 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.
11. Change From Augmentation Baseline for Remitters in the SDS Total Score at Week 6 [ Time Frame: 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.
12. Percentage of Remitters With Improvement on CGI-I at Week 6 - LOCF [ Time Frame: 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.
13. Assessment in Remitters of CGI-S at Augmentation Baseline [ Time Frame: 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)
14. Assessment in Remitters of CGI-S at Week 6 [ Time Frame: 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)
15. Change From Augmentation Baseline for Remitters in the BRIEF-A Scale Total Score at Week 6 [ Time Frame: 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.
16. Change From Augmentation Baseline for Remitters in the MAF Scale Total Score at Week 6 [ Time Frame: 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.
17. Change From Augmentation Baseline for Remitters in the QIDS-SR Scale Total Score at Week 6 [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Adults aged 18-55 with a primary diagnosis of nonpsychotic MDD

Exclusion Criteria:

• History of non-response to multiple antidepressants

Contacts and Locations

Locations

United States, California

Pharmacology Research Institute (PRI)

Newport Beach, California, United States, 92660

Affiliated Research Institute

San Diego, California, United States, 92108

United States, Florida

Florida Clinical Research Center, LLC

Bradenton, Florida, United States, 34208

Gulfcoast Clinical Research Center

Fort Myers, Florida, United States, 33912

Clinical Neuroscience Solutions, Inc.

Orlando, Florida, United States, 32809

United States, Georgia

Atlanta Institute of Medicine & Research

Atlanta, Georgia, United States, 30328

Carman Research

Smyrna, Georgia, United States, 30080

United States, Kansas

Vince & Associates Clinical Research

Overland Park, Kansas, United States, 66212

United States, North Carolina

Duke University Medical Center

Durham, North Carolina, United States, 27705

United States, Ohio

North Star Medical Research, LLC

Middleburg Heights, Ohio, United States, 44130

United States, Oklahoma

IPS Research Company

Oklahoma City, Oklahoma, United States, 73103

United States, Oregon

Summit Research Network

Portland, Oregon, United States, 97210

United States, Texas

FutureSearch Clinical Trials, LP

Austin, Texas, United States, 78756

United States, Washington

Northwest Clinical Research Center

Bellevue, Washington, United States, 98007

Summit Research Network (Seattle), LLC

Seattle, Washington, United States, 98104

Sponsors and Collaborators

Shire

Investigators

• Study Director: Study Director; Takeda

More Information

Additional Information:

FDA Recall Information 

FDA-approved Labelling 

Publications of Results:

Trivedi MH, Cutler AJ, Richards C, Lasser R, Geibel BB, Gao J, Sambunaris A, Patkar AA. 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. J Clin Psychiatry. 2013 Aug;74(8):802-9. doi: 10.4088/JCP.13m08360.

• Responsible Party: Shire
• ClinicalTrials.gov Identifier: NCT00905424
• Other Study ID Numbers: SPD489-203
• First Posted: May 20, 2009
• Results First Posted: July 14, 2011
• Last Update Posted: June 14, 2021
• Last Verified: June 2021

Additional relevant MeSH terms:

Depressive Disorder; Depression; Depressive Disorder, Major; Mood Disorders; Mental Disorders; Behavioral Symptoms; Lisdexamfetamine Dimesylate; Antidepressive Agents; Psychotropic Drugs; Central Nervous System Stimulants; Physiological Effects of Drugs; Dopamine Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Dopamine Agents; Neurotransmitter Agents