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

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

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.

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: Antidepressant + SPD489 (lisdexamfetamine dimesylate); Drug: Antidepressant + placebo

• Study Type: Interventional
• Enrollment (Actual): 246
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Newport Beach, California, United States, 92660
      • Pharmacology Research Institute (Pri)
    • San Diego, California, United States, 92108
      • Affiliated Research Institute
  • Florida
    • Bradenton, Florida, United States, 34208
      • Florida Clinical Research Center, LLC
    • Fort Myers, Florida, United States, 33912
      • Gulfcoast Clinical Research Center
    • Orlando, Florida, United States, 32809
      • Clinical Neuroscience Solutions, INC.
  • Georgia
    • Atlanta, Georgia, United States, 30328
      • Atlanta Institute of Medicine & Research
    • Smyrna, Georgia, United States, 30080
      • Carman Research
  • Kansas
    • Overland Park, Kansas, United States, 66212
      • Vince & Associates Clinical Research
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University Medical Center
  • Ohio
    • Middleburg Heights, Ohio, United States, 44130
      • North Star Medical Research, LLC
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73103
      • IPS Research Company
  • Oregon
    • Portland, Oregon, United States, 97210
      • Summit Research Network
  • Texas
    • Austin, Texas, United States, 78756
      • FutureSearch Clinical Trials, LP
  • Washington
    • Bellevue, Washington, United States, 98007
      • Northwest Clinical Research Center
    • Seattle, Washington, United States, 98104
      • Summit Research Network (Seattle), LLC

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 MDD

Exclusion Criteria:

• History of non-response to multiple antidepressants

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / 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 Names: LDX, Vyvanse
PLACEBO_COMPARATOR: Placebo; Antidepressant + placebo	Drug: Antidepressant + placebo; Escitalopram oxalate (antidepressant) 20 mg/day oral + placebo oral once daily for 6 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Augmentation Baseline for Non-Remitters in Montgomery-Ǻsberg Depression Rating Scale (MADRS) Total Score at Week 6 - Last Observation Carried Forward (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.	Augmentation Baseline, 6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Augmentation Baseline for Non-Remitters in the Hamilton Depression Scale (HAM-D) Total Score at Week 6 - LOCF	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.	Augmentation Baseline, 6 weeks
Change From Augmentation Baseline for Non-Remitters in the Sheehan Disability Scale (SDS) Total Score at Week 6	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.	Augmentation Baseline, 6 weeks
Percentage of Non-Remitters With Improvement on Clinical Global Impression-Improvement (CGI-I) at Week 6 - 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.	6 weeks
Assessment in Non-Remitters of Clinical Global Impression-Severity of Illness (CGI-S) at 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)	Augmentation baseline
Assessment in Non-Remitters of Clinical Global Impression-Severity of Illness (CGI-S) at Week 6	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 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	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.	Augmentation Baseline and 6 weeks
Change From Augmentation Baseline for Non-Remitters in the Multidimensional Assessment of Fatigue (MAF) Scale Total Score at Week 6	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.	Augmentation Baseline and 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	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.	Augmentation Baseline and 6 weeks
Change From Augmentation Baseline for Remitters in MADRS Total Score at Week 6 - 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.	Augmentation Baseline and 6 weeks
Change From Augmentation Baseline for Remitters in the HAM-D Total Score at Week 6 - LOCF	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.	Augmentation Baseline and 6 weeks
Change From Augmentation Baseline for Remitters in the SDS Total Score at Week 6	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.	Augmentation Baseline and 6 weeks
Percentage of Remitters With Improvement on CGI-I at Week 6 - 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.	6 weeks
Assessment in Remitters of CGI-S at 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)	Augmentation Baseline
Assessment in Remitters of CGI-S at Week 6	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 weeks
Change From Augmentation Baseline for Remitters in the BRIEF-A Scale Total Score at Week 6	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.	Augmentation baseline and 6 weeks
Change From Augmentation Baseline for Remitters in the MAF Scale Total Score at Week 6	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.	Augmentation baseline and 6 weeks
Change From Augmentation Baseline for Remitters in the QIDS-SR Scale Total Score at Week 6	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.	Augmentation baseline and 6 weeks

Collaborators and Investigators

• Sponsor: Shire

Publications and helpful links

General Publications

• 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.

Helpful Links

• FDA Recall Information
• FDA-approved Labelling

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 30, 2009
• Primary Completion (ACTUAL): August 4, 2010
• Study Completion (ACTUAL): August 4, 2010

Study Registration Dates

• First Submitted: May 18, 2009
• First Submitted That Met QC Criteria: May 19, 2009
• First Posted (ESTIMATE): May 20, 2009

Study Record Updates

• Last Update Posted (ACTUAL): June 14, 2021
• Last Update Submitted That Met QC Criteria: June 8, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Dopamine Agents; Dopamine Uptake Inhibitors; Central Nervous System Stimulants; Lisdexamfetamine Dimesylate; Antidepressive Agents
• Other Study ID Numbers: SPD489-203