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

Phase 2, Multicenter, Randomized, Double-blind, Placebo-Controlled, Study to Evaluate the Efficacy, Safety, and Tolerability of SPD489 in Adults With Clinically Significant, Persistent Executive Function Impairments (EFI) and Partial or Full Remission of Recurrent Major Depressive Disorder

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).

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: SPD489 (Lisdexamfetamine dimesylate); Drug: Matching placebo

• Study Type: Interventional
• Enrollment (Actual): 143
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Imperial, California, United States, 92251
      • Sun Valley Research Center
    • Los Alamitos, California, United States, 90720
      • Pharmacology Research Center
    • Oceanside, California, United States, 92056
      • Excell Research
    • Santa Ana, California, United States, 92701
      • Neuropsychiatric Resesarch Center of Orange County
  • Connecticut
    • Cromwell, Connecticut, United States, 06416
      • Connecticut Clincal Research
  • Florida
    • Jacksonville, Florida, United States, 32216
      • Clinical Neuroscience Solutions, Inc.
    • Jacksonville, Florida, United States, 32256
      • Amit Vijapura, MD
    • North Miami, Florida, United States, 33161
      • Scientific Clinical Research, Inc.
    • Orlando, Florida, United States, 32806
      • Clinical Neuroscience Solutions, Inc.
  • Georgia
    • Atlanta, Georgia, United States, 30328
      • Atlanta Institute of Medicine & Research
    • Smyrna, Georgia, United States, 30080
      • Carman Research
  • Illinois
    • Joliet, Illinois, United States, 60435
      • Joliet Center for Clinical Research
    • Libertyville, Illinois, United States, 60048
      • Capstone Clinical Research
  • Kansas
    • Overland Park, Kansas, United States, 66211
      • Psychiatric Associates
  • Massachusetts
    • Fall River, Massachusetts, United States, 02721
      • AccelRx Research
  • Missouri
    • Saint Charles, Missouri, United States, 63301
      • St. Charles Psychiatric Associates
    • Saint Louis, Missouri, United States, 63128
      • PsychCare Consultants Research
  • Nebraska
    • Lincoln, Nebraska, United States, 68510
      • Premier Psychiatric Research Institute, LLC
  • New York
    • Staten Island, New York, United States, 10312
      • Richmond Behavioral Associates
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • North Carolina Neuropsychiatry, PA
    • Durham, North Carolina, United States, 27705
      • Duke University Medical Center
    • Raleigh, North Carolina, United States, 27609
      • Richard H. Weisler, MD, PA & Associates
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Patient Priority Clinical Sites, LLC
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18104
      • Lehigh Center for Clinical Research
    • Bridgeville, Pennsylvania, United States, 15017
      • Paramount Clinical Research
    • Media, Pennsylvania, United States, 19063
      • Suburban Research Associates
  • Texas
    • Dallas, Texas, United States, 75231
      • FutureSearch Trials of Dallas, LP
    • Houston, Texas, United States, 77090
      • Red Oak Psychiatry Associates, PA
    • Houston, Texas, United States, 77007
      • Bayou City Resesarch, LTD
    • Irving, Texas, United States, 75062
      • University Hills Clinical Research
    • Lake Jackson, Texas, United States, 77566
      • R/D Clinical Research, Inc.
    • Wharton, Texas, United States, 77488
      • Wharton Research Center
  • Washington
    • Bellevue, Washington, United States, 98007
      • Northwest Clinical Research Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Adults aged 18-55 with a primary diagnosis of nonpsychotic uni-polar depression

Exclusion Criteria:

• Current co-morbid psychiatric disorder

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Matching placebo; oral, once daily
Experimental: Active; SPD489	Drug: SPD489 (Lisdexamfetamine dimesylate); Oral, 20, 30, 40, 50, 60, and 70mg capsules, once daily; Other Names: Vyvanse

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	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.	Baseline and week 9

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of Participants With Clinical Global Impression - Severity of Illness (CGI-S) at 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)	Baseline
Change From Baseline in Montgomery-Ǻsberg Depression Rating Scale (MADRS) Total Score at Week 9 - (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.	Baseline and week 9
Change From Baseline in BRIEF-A T-scores at Week 9, LOCF	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.	Baseline and week 9
Change From Baseline in Central Nervous System Vital Signs Computerized Cognitive Testing Battery Neurocognitive Domain and Index Scores at 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.	Baseline and up to 9 weeks/Endpoint
Percent of Participants With CGI-S at 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)	Up to 9 weeks/Endpoint
Percentage of Participants With Improvement on Clinical Global Impression-Improvement (CGI-I) at Week 9, 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.	Week 9
Change From Baseline in Endicott Work Productivity Scale (EWPS) Total Score at 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.	Baseline and up to 9 weeks/Endpoint
Change From Baseline in Changes in Sexual Functioning Questionnaire (CSFQ-14) Total Scores for Males at Week 9, LOCF	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.	Baseline and week 9
Change From Baseline in CSFQ-14 Total Scores for Females at Week 9, LOCF	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.	Baseline and week 9
Change From Baseline in Short Form-12 Health Survey (SF-12) Scale Total Scores at 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).	Baseline and week 9
Change From Baseline in Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) Total Scores at 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.	Baseline and up to 9 weeks/Endpoint
Change From Baseline in Amphetamine Cessation Symptom Assessment (ACSA) Total Score at Week 11	ACSA scale has 16 symptom items rated on a scale from 0 (not at all) to 4 (extremely) with a possible total score range of 0 to 64. Higher scores indicate greater withdrawal symptom severity.	Baseline and week 11
Change From Baseline in the Generalized Anxiety Disorder 7-Item (GAD-7) Total Score at Week 9, LOCF	The GAD-7 is a 7-item self-report questionnaire for assessing anxiety severity. Each item is scored using a scale that ranges from 0 (not at all) to 3 (nearly every day) with total scores ranging from 0 to 21. Lower scores indicate a reduction in anxiety.	Baseline and week 9
Change From Baseline in Sheehan Suicidality Tracking Scale (STS) Total Score at Week 9	The STS is an 8-question clinician-rated assessment of suicidal ideation, suicidal behavior, and accidents. The items are scored on a 5-point Likert scale from 0 (not at all) to 4 (extremely) and summed to produce a total score ranging from 0 to 32. Lower scores indicate reduced suicidal tendencies.	Baseline and week 9

Collaborators and Investigators

• Sponsor: Shire

Publications and helpful links

General Publications

• Madhoo M, Keefe RS, Roth RM, Sambunaris A, Wu J, Trivedi MH, Anderson CS, Lasser R. Lisdexamfetamine dimesylate augmentation in adults with persistent executive dysfunction after partial or full remission of major depressive disorder. Neuropsychopharmacology. 2014 May;39(6):1388-98. doi: 10.1038/npp.2013.334. Epub 2013 Dec 6.

Study record dates

Study Major Dates

• Study Start (Actual): October 29, 2009
• Primary Completion (Actual): April 18, 2011
• Study Completion (Actual): April 18, 2011

Study Registration Dates

• First Submitted: September 25, 2009
• First Submitted That Met QC Criteria: September 25, 2009
• First Posted (Estimate): September 28, 2009

Study Record Updates

• Last Update Posted (Actual): June 8, 2021
• Last Update Submitted That Met QC Criteria: May 16, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Major Depressive Disorder
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Pathologic Processes; Mood Disorders; Depression; Depressive Disorder; Disease; Depressive Disorder, Major; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Dopamine Agents; Dopamine Uptake Inhibitors; Central Nervous System Stimulants; Lisdexamfetamine Dimesylate
• Other Study ID Numbers: SPD489-205