Efficacy and Safety Study of SPD489 in Combination With an Antidepressant in the Treatment of Adults With Major Depressive Disorder

The SPD489-322 Phase 3, Multicenter, Randomized, Double-blind, Parallel-group, Placebo-controlled, Flexible Dose Titration, Efficacy and Safety Study of SPD489 in Combination With an Antidepressant in the Treatment of Adults With Major Depressive Disorder With Inadequate Response to Prospective Treatment With an Antidepressant

This study will examine SPD489 in subjects aged 18-65 with major depressive disorder (MDD) who are taking certain types of antidepressants but continue to have residual depression symptoms. Eligible patients will remain on their antidepressant but will be randomized to either receive supplemental SPD489 or placebo (i.e. sugar pill). The purpose of this study is to help answer the following questions:

• How safe is SPD489 for the supplemental treatment of depression and what are the side effects that might be related to it?
• Can supplemental SPD489 help patients who still have residual depression symptoms while taking an antidepressant?
• How much SPD489 should be given to patients with depression who are also taking an antidepressant?
• How does SPD489 compare to placebo in depressed patients who are also taking an antidepressant?

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 1262
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G3K 2P8
    • ALPHA Recherche Clinique
  • British Columbia
    • Penticton, British Columbia, Canada, V2A 4M4
      • Dr. Alexander McIntyre Inc
    • Vancouver, British Columbia, Canada, V6Z 2L4
      • Dr. D. McIntosh & Dr. K. Kjernisted Clinical Research Inc.
  • Ontario
    • Brampton, Ontario, Canada, L6T 0G1
      • Aggarwal & Associates Ltd.
    • Burlington, Ontario, Canada, L7R 4E2
      • Depression, Mood Disorders and Schizophrenia Treatment Centre
    • Chatham, Ontario, Canada, N7M 5L9
      • Chatham-Kent Clinical Trials Research Center
    • London, Ontario, Canada, N6A 4H1
      • Regional Mental Health Care
    • Mississauga, Ontario, Canada, L5M 4N4
      • Anxiety and Mood Disorder Center
    • Mississauga, Ontario, Canada, L5M 4N4
      • Medical Research Associates
    • Oakville, Ontario, Canada, L6J0B2
      • A.K. Karan Holdings
    • Parry Sound, Ontario, Canada, P2A 3A4
      • International Sleep Clinic, West Parry Sound Health Centre
    • Toronto, Ontario, Canada, M4W 2N4
      • START Clinic for Mood and Anxiety Disorders
    • Toronto, Ontario, Canada, M5T2S8
      • Univ Health Network, Toronto Western Hospital
    • Toronto, Ontario, Canada, M6J 3S3
      • Sleep & Alertness Clinic (Sleep & Alertness Research, Inc.)
    • Toronto, Ontario, Canada, M9W 4L6
      • Manna Research
    • Windsor, Ontario, Canada, N9C 3Z4
      • Windsor Regional Hospital-Tayfour Campus
  • Quebec
    • Gatineau, Quebec, Canada, J8A1K7
      • Pierre-Janet Hospital
    • Montreal, Quebec, Canada, H1N 3M5
      • l'Hopital Louis H. Lafontaine
    • Pointe-Claire, Quebec, Canada, H9R 4S3
      • Kells Medical Research Group Inc.
    • Sherbrooke, Quebec, Canada, J1H 4J6
      • Q&T Research Sherbrooke
• Croatia
  • Zagreb, Croatia, 10 000
    • Poliklinika Neuron
  • Zagreb, Croatia, 10090
    • Psychiatric Clinic Vrapoe
• Mexico
  • Leon Guanajuato, Mexico, 37000
    • Hospital Aranda de La Parra
  • Nuevo Leon, Mexico, 64710
    • Instituto de Infromacion e Investigación en Salud Mental (INFOSAME)
  • San Luis Potosi, Mexico, 78200
    • Consultorio Especializado en Psiquiatria Infantil y Adolescentes
  • Sinaloa, Mexico, 82126
    • B & B Investigaciones Medicas S.C.
  • Nuevo Leon
    • Monterrey, Nuevo Leon, Mexico, 647-10
      • Centro Regiomontano de Investigacion S.C. (CRI)
• Puerto Rico
  • San Juan, Puerto Rico, 00918
    • INSPIRA Clinical Research
  • San Juan, Puerto Rico, 00907
    • Dharma Institute & Research Center
• Spain
  • Barcelona, Spain, 08025
    • Hospital de la Santa Creo l Sant Pau
  • Barcelona, Spain, 08907
    • Hospital Universitari de Bellvitge, Servicio de Psiquiatria
  • Madrid, Spain, 28031
    • Hospital Universitario Infanta Leonor
  • Madrid, Spain, 28922
    • Hospital Fundación de Alcorcón
  • Madrid, Spain
    • Hospital Universitario de Henares
  • Oviedo, Spain, 33011
    • Centro de Salud Mental Il la Corredoria
  • Salamanca, Spain, 37003
    • Centro Salud Alamedilla Unidad de Salud Mental
  • Zamora, Spain, 49021
    • Complejo hospitalario de Zamora
  • Zaragoza, Spain, 50009
    • Hospital Clinico Universitario Lozano Blesa
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35216
      • Birmingham Research Group
  • California
    • Carson, California, United States, 90746
      • AV Institue, Inc.
    • Irvine, California, United States, 92612
      • University of California, Irvine Child Development Center
    • Norwalk, California, United States, 90650
      • South Coast Clinicals
    • Oceanside, California, United States, 92056
      • North County Clinical Research
    • Pasadena, California, United States, 91106
      • Pasadena Research Institute, LLC
    • San Diego, California, United States, 92123
      • Sharp Mesa Vista Hospital
    • San Diego, California, United States, 92108
      • Affiliated Research Institute
    • San Diego, California, United States, 92121
      • Clinical Innovations, Inc.
  • Connecticut
    • Hamden, Connecticut, United States, 06518
      • Geriatric and Adult Psychiatry, LLC
    • Middletown, Connecticut, United States, 06457
      • Middlexex Hospital Center for Behavioral Health
  • Florida
    • Coral Springs, Florida, United States, 33067
      • CNS Clinical Research Group
    • Fort Walton Beach, Florida, United States, 32547
      • Emerald Coast Mood & Memory, PA
    • Maitland, Florida, United States, 32751
      • Florida Clinical Research Center, LLC.
    • New Port Richey, Florida, United States, 34652
      • Suncoast Clinical Research
    • Orlando, Florida, United States, 32806
      • Compass Research, LLC
    • Saint Petersburg, Florida, United States, 33709
      • Meridien Research
    • Tampa, Florida, United States, 33613
      • Stedman Clinical Trials
  • Georgia
    • Smyrna, Georgia, United States, 30080
      • Carman Research
  • Illinois
    • Oak Brook, Illinois, United States, 60523
      • American Medical Research, Inc.
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • The Davis Clinic
    • Valparaiso, Indiana, United States, 46383
      • Northwest Indiana Center for Clinical Research
  • Kentucky
    • Florence, Kentucky, United States, 41042
      • MCM Clinical Research LLC
  • Maryland
    • Baltimore, Maryland, United States, 21208
      • Pharmasite Research, Inc.
    • Gaithersburg, Maryland, United States, 20877
      • Potomac Grove Clinical Research Center
    • Rockville, Maryland, United States, 20852
      • Office of Marc Hertzman, MD
  • Massachusetts
    • Watertown, Massachusetts, United States, 02472
      • Adams Clinical Trials, LLC
  • Missouri
    • Saint Charles, Missouri, United States, 63301
      • St. Charles Psychiatric Associates - Midwest Research Group
  • New York
    • Mount Kisco, New York, United States, 10549
      • Bioscience Research, LLC
    • New York, New York, United States, 10168
      • Fieve Clinical Research
    • Staten Island, New York, United States, 10312
      • Richmond Behavioral Associates
  • North Carolina
    • Durham, North Carolina, United States, 27707
      • Triangle Neuropsychiatry
    • Raleigh, North Carolina, United States, 27809
      • Rcihard H. Weisler, MD, PA & Associates
  • Ohio
    • Cincinnati, Ohio, United States, 45227
      • Community Research
    • Mason, Ohio, United States, 45040
      • Lindner Center of Hope
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • SP Research, PLLC
  • Oregon
    • Portland, Oregon, United States, 97210
      • Summit Research Network (Oregon) Inc.
  • Pennsylvania
    • Bridgeville, Pennsylvania, United States, 15107
      • Paramount Clinical Research
    • Media, Pennsylvania, United States, 19063
      • Suburban Research Associates
    • Philadelphia, Pennsylvania, United States, 19139
      • CRI Worldwide LLC
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh School of Medicine
  • Rhode Island
    • East Providence, Rhode Island, United States, 02914
      • Rhode Island Mood & Memory Research Institute
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • Clinical Neuroscience Solutions, INC.
    • Nashville, Tennessee, United States, 37203
      • Clinical Research Associates
  • Texas
    • Austin, Texas, United States, 78731
      • FutureSearch Clinical Trials, LP
  • Utah
    • Clinton, Utah, United States, 84015
      • Ericksen Research and Development
  • Washington
    • Seattle, Washington, United States, 98104
      • Summit Research Network (Seattle) Llc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subject is able to provide written, personally signed, and dated informed consent to participate in the study.
• Subject is between 18 and 65 years of age.
• Subject has a primary diagnosis of non-psychotic MDD (single or recurrent).
• Subject has a MADRS total score 24.
• Subject who is female, must have a negative serum beta human chorionic gonadotropin (HCG) pregnancy test and a negative urine pregnancy test at the and agrees to comply with any applicable contraceptive requirements of the protocol.
• Subject is able to swallow a capsule.

Exclusion Criteria:

• Subject whose current episode of MDD has not responded to an adequate treatment regimen with 2 or more approved single antidepressant agents.
• Subject who has a lifetime history of treatment resistant depression.
• Subject has a current co-morbid psychiatric disorder. Excluded are: any significant Axis II disorder (including borderline personality disorder), any bipolar disorder, any current or lifetime psychosis, post traumatic stress disorder, obsessive compulsive disorder, any pervasive development disorder, anorexia nervosa and bulimia nervosa.
• Subject has been hospitalized (within the last 12 months) for their current MDD episode.
• Subject has a current or lifetime history of attention-deficit/hyperactivity disorder (ADHD).
• Subject has a first degree relative that has been diagnosed with bipolar I disorder.
• Subject has a recent history (within the last 6 months) of suspected substance abuse or dependence disorder
• Subject is considered a suicide risk in the opinion of the Investigator, has previously made a suicide attempt within the past 3 years, or is currently demonstrating active suicidal ideation.
• Subject has a concurrent chronic or acute illness or unstable medical condition.
• Subject has a history of seizures (other than infantile febrile seizures), any tic disorder, or a current diagnosis and/or a known family history of Tourette's Disorder, serious neurological disease, history of significant head trauma, dementia, cerebrovascular disease, Parkinson's disease, or intracranial lesions.
• Subject has known history of symptomatic cardiovascular disease, advanced arteriosclerosis, structural cardiac abnormality, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, or other serious cardiac problems.
• Subject has a history of thyroid disorder that has not been stabilized on thyroid medication or treatment within 3 months prior to the Screening Visit.
• Subject has a known family history of sudden cardiac death or ventricular arrhythmia.
• Subject has glaucoma.
• Subject has a history of moderate to severe hypertension.
• Current use of any other medications (including over-the-counter [OTC], herbal or homeopathic preparations) that have central nervous system effects.
• Subject has had electroconvulsive therapy (ECT) for the current depressive episode 3 months prior.
• The subject has a known or suspected intolerance, hypersensitivity, or contraindications to their assigned antidepressant treatments (escitalopram oxalate, sertraline HCl, venlafaxine HCl extended release, or duloxetine HCl).
• Subject has a positive urine drug result.
• Subject has a body mass index (BMI) of <18.5 or >40.
• Subject is female and is pregnant or nursing.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Antidepressant + SPD489	Drug: SPD489 (Lisdexamfetamine dimesylate ); Antidepressant (either escitalopram oxalate, sertraline hydrochloride, venlafaxine hydrochloride extended release or duloxetine hydrochloride) oral, once daily + SPD489 (oral, 20, 30, 50 or 70 mg, once daily) for 8 weeks; Other Names: Vyvanse
Placebo Comparator: Antidepressant + Placebo	Drug: Placebo; Antidepressant (either escitalopram oxalate, sertraline hydrochloride, venlafaxine hydrochloride extended release or duloxetine hydrochloride) oral, once daily + Placebo (oral, once daily) for 8 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at up to 8 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.	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Sheehan Disability Scale (SDS) Total Score at up to 8 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.	8 weeks
Percentage of Participants Achieving a 25% Response on the MADRS	The percentage of subjects who achieved a 25% response (i.e., ≥25% reduction in MADRS total score from Lead-in Baseline, Visit 2; Week 0). A comparison was performed at Visit 14/Early Termination (ET) (Week 16/ET).	up to 8 weeks
Percentage of Participants Achieving a 50% Response on the MADRS	The percentage of subjects who achieved a 50% response (i.e., ≥50% reduction in MADRS total score from Lead-in Baseline, Visit 2; Week 0). A comparison was performed at Visit 14/ET (Week 16/ET).	up to 8 weeks
Percentage of Participants Achieving Remission on the MADRS	MADRS remission was defined as a MADRS total score of ≤10. A comparison was performed at Visit 14/ET (Week 16/ET).	up to 8 weeks
Mean Change From Baseline Over Time in MADRS Total Score	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 up to 8 weeks
Mean Change From Baseline in the Quick Inventory of Depressive Symptomatology - Self Report (QIDS SR)	The QIDS-SR is a self-administered questionnaire designed to rate depressive symptoms. The scale contains 16 items, each scored using a 4-point scale ranging from 0 (representing the most favorable response [low amount of symptom]) to 3 (representing the least favorable response [frequent/intense symptom]). The total score could range from 0 (no depression) to 27 (very severe depression). Higher scores represent more severe depressive symptoms.	up to 8 weeks
Mean Change From Baseline in the Short Form-12 Health Survey V2 (SF-12V2)	Total score ranges from 0 (lowest level of health) - 100 (highest level of health) on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability (i.e. a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability). Higher scores are associated with better quality of life.	up to 8 weeks
Mean Change From Baseline in the Quality of Life Enjoyment Satisfaction Questionnaire Short Form (Q-LES-Q-SF)	The short form is a 16-item self-report questionnaire which evaluates general subject satisfaction with health, mood, relationships, functioning in daily life, and the treatment being taken. Overall level of satisfaction is evaluated on a 5-point scale from 1 (very poor) to 5 (very good). The total score ranges from 14-70 (last two items on the form are not included in the total score). A higher score indicates a better quality of life.	up to 8 weeks
Clinical Global Impressions - Global Improvement (CGI-I)	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.	up to 8 weeks
Columbia Suicide Severity Rating Scale (C-SSRS)	C-SSRS is a semi-structured interview that captures the occurrence, severity, and frequency of suicide-related thoughts and behaviors during the assessment period. The interview includes definitions and suggested questions to solicit the type of information needed to determine if a suicide-related thought or behavior occurred. The assessment is done by the nature of the responses, not by a numbered scale.	up to 8 weeks
Amphetamine Cessation Symptom Assessment (ACSA)	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.	up to 8 weeks

Collaborators and Investigators

• Sponsor: Shire

Publications and helpful links

General Publications

• Richards C, McIntyre RS, Weisler R, Sambunaris A, Brawman-Mintzer O, Gao J, Geibel B, Dauphin M, Madhoo M. Lisdexamfetamine dimesylate augmentation for adults with major depressive disorder and inadequate response to antidepressant monotherapy: Results from 2 phase 3, multicenter, randomized, double-blind, placebo-controlled studies. J Affect Disord. 2016 Dec;206:151-160. doi: 10.1016/j.jad.2016.07.006. Epub 2016 Jul 5.

Study record dates

Study Major Dates

• Study Start (Actual): October 27, 2011
• Primary Completion (Actual): December 23, 2013
• Study Completion (Actual): December 23, 2013

Study Registration Dates

• First Submitted: September 15, 2011
• First Submitted That Met QC Criteria: September 16, 2011
• First Posted (Estimate): September 19, 2011

Study Record Updates

• Last Update Posted (Actual): June 9, 2021
• Last Update Submitted That Met QC Criteria: May 25, 2021
• Last Verified: May 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; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Dopamine Agents; Dopamine Uptake Inhibitors; Central Nervous System Stimulants; Lisdexamfetamine Dimesylate
• Other Study ID Numbers: SPD489-322; 2011-003018-17 (EudraCT Number)