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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Shire
ClinicalTrials.gov Identifier:
NCT01436149
First received: September 15, 2011
Last updated: November 10, 2014
Last verified: November 2014
  Purpose

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?

Condition Intervention Phase
Major Depressive Disorder
Drug: SPD489 (Lisdexamfetamine dimesylate )
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Shire:

Primary Outcome Measures:
  • Mean Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at up to 8 Weeks [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    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:
  • Change From Baseline in Sheehan Disability Scale (SDS) Total Score at up to 8 Weeks [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants Achieving a 25% Response on the MADRS [ Time Frame: up to 8 weeks ] [ Designated as safety issue: No ]
    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).

  • Percentage of Participants Achieving a 50% Response on the MADRS [ Time Frame: up to 8 weeks ] [ Designated as safety issue: No ]
    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).

  • Percentage of Participants Achieving Remission on the MADRS [ Time Frame: up to 8 weeks ] [ Designated as safety issue: No ]
    MADRS remission was defined as a MADRS total score of ≤10. A comparison was performed at Visit 14/ET (Week 16/ET).

  • Mean Change From Baseline Over Time in MADRS Total Score [ Time Frame: Baseline and up to 8 weeks ] [ Designated as safety issue: No ]
    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.

  • Mean Change From Baseline in the Quick Inventory of Depressive Symptomatology - Self Report (QIDS SR) [ Time Frame: up to 8 weeks ] [ Designated as safety issue: No ]
    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.

  • Mean Change From Baseline in the Short Form-12 Health Survey V2 (SF-12V2) [ Time Frame: up to 8 weeks ] [ Designated as safety issue: No ]
    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.

  • Mean Change From Baseline in the Quality of Life Enjoyment Satisfaction Questionnaire Short Form (Q-LES-Q-SF) [ Time Frame: up to 8 weeks ] [ Designated as safety issue: No ]
    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.

  • Clinical Global Impressions - Global Improvement (CGI-I) [ Time Frame: up to 8 weeks ] [ Designated as safety issue: No ]
    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.

  • Columbia Suicide Severity Rating Scale (C-SSRS) [ Time Frame: up to 8 weeks ] [ Designated as safety issue: Yes ]
    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.

  • Amphetamine Cessation Symptom Assessment (ACSA) [ Time Frame: up to 8 weeks ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 1262
Study Start Date: October 2011
Study Completion Date: December 2013
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01436149

  Hide Study Locations
Locations
United States, Alabama
Birmingham Research Group
Birmingham, Alabama, United States, 35216
United States, California
AV Institue, Inc.
Carson, California, United States, 90746
University of California, Irvine Child Development Center
Irvine, California, United States, 92612
South Coast Clinicals
Norwalk, California, United States, 90650
North County Clinical Research
Oceanside, California, United States, 92056
Pasadena Research Institute, LLC
Pasadena, California, United States, 91106
Affiliated Research Institute
San Diego, California, United States, 92108
Clinical Innovations, Inc.
San Diego, California, United States, 92121
Sharp Mesa Vista Hospital
San Diego, California, United States, 92123
United States, Connecticut
Geriatric and Adult Psychiatry, LLC
Hamden, Connecticut, United States, 06518
Middlexex Hospital Center for Behavioral Health
Middletown, Connecticut, United States, 06457
United States, Florida
CNS Clinical Research Group
Coral Springs, Florida, United States, 33067
Emerald Coast Mood & Memory, PA
Fort Walton Beach, Florida, United States, 32547
Florida Clinical Research Center, LLC.
Maitland, Florida, United States, 32751
Suncoast Clinical Research
New Port Richey, Florida, United States, 34652
Compass Research, LLC
Orlando, Florida, United States, 32806
Meridien Research
St. Petersburg, Florida, United States, 33709
Stedman Clinical Trials
Tampa, Florida, United States, 33613
United States, Georgia
Carman Research
Smyrna, Georgia, United States, 30080
United States, Illinois
American Medical Research, Inc.
Oak Brook, Illinois, United States, 60523
United States, Indiana
The Davis Clinic
Indianapolis, Indiana, United States, 46260
Northwest Indiana Center for Clinical Research
Valparaiso, Indiana, United States, 46383
United States, Kentucky
MCM Clinical Research LLC
Florence, Kentucky, United States, 41042
United States, Maryland
Pharmasite Research, Inc.
Baltimore, Maryland, United States, 21208
Potomac Grove Clinical Research Center
Gaithersburg, Maryland, United States, 20877
Office of Marc Hertzman, MD
Rockville, Maryland, United States, 20852
United States, Massachusetts
Adams Clinical Trials, LLC
Watertown, Massachusetts, United States, 02472
United States, Missouri
St. Charles Psychiatric Associates - Midwest Research Group
St. Charles, Missouri, United States, 63301
United States, New York
Bioscience Research, LLC
Mt. Kisco, New York, United States, 10549
Fieve Clinical Research
New York, New York, United States, 10168
Richmond Behavioral Associates
Staten Island, New York, United States, 10312
United States, North Carolina
Triangle Neuropsychiatry
Durham, North Carolina, United States, 27707
Rcihard H. Weisler, MD, PA & Associates
Raleigh, North Carolina, United States, 27809
United States, Ohio
Community Research
Cincinatti, Ohio, United States, 45227
Lindner Center of HOPE
Mason, Ohio, United States, 45040
United States, Oklahoma
SP Research, PLLC
Oklahoma City, Oklahoma, United States, 73112
United States, Oregon
Summit Research Network (Oregon) Inc.
Portland, Oregon, United States, 97210
United States, Pennsylvania
Paramount Clinical Research
Bridgeville, Pennsylvania, United States, 15107
Suburban Research Associates
Media, Pennsylvania, United States, 19063
CRI Worldwide LLC
Philadelphia, Pennsylvania, United States, 19139
University of Pittsburgh School of Medicine
Pittsburgh, Pennsylvania, United States, 15213
United States, Rhode Island
Rhode Island Mood & Memory Research Institute
East Providence, Rhode Island, United States, 02914
United States, Tennessee
Clinical Neuroscience Solutions, Inc.
Memphis, Tennessee, United States, 38119
Clinical Research Associates
Nashville, Tennessee, United States, 37203
United States, Texas
FutureSearch Clinical Trials, LP
Austin, Texas, United States, 78731
United States, Utah
Ericksen Research and Development
Clinton, Utah, United States, 84015
United States, Washington
Summit Research Network (Seattle) LLC
Seattle, Washington, United States, 98104
Canada, British Columbia
Dr. Alexander McIntyre Inc
Penticton, British Columbia, Canada, V2A 4M4
Dr. D. McIntosh & Dr. K. Kjernisted Clinical Research Inc.
Vancouver, British Columbia, Canada, V6Z 2L4
Canada, Ontario
Aggarwal & Associates Ltd.
Brampton, Ontario, Canada, L6T 0G1
Depression, Mood Disorders and Schizophrenia Treatment Centre
Burlington, Ontario, Canada, L7R 4E2
Chatham-Kent Clinical Trials Research Center
Chatham, Ontario, Canada, N7M 5L9
Regional Mental Health Care
London, Ontario, Canada, N6A 4H1
Medical Research Associates
Mississauga, Ontario, Canada, L5M 4N4
Anxiety and Mood Disorder Center
Mississauga, Ontario, Canada, L5M 4N4
A.K. Karan Holdings
Oakville, Ontario, Canada, L6J0B2
International Sleep Clinic, West Parry Sound Health Centre
Parry Sound, Ontario, Canada, P2A 3A4
Univ Health Network, Toronto Western Hospital
Toronto, Ontario, Canada, M5T2S8
Manna Research
Toronto, Ontario, Canada, M9W 4L6
START Clinic for Mood and Anxiety Disorders
Toronto, Ontario, Canada, M4W 2N4
Sleep & Alertness Clinic (Sleep & Alertness Research, Inc.)
Toronto, Ontario, Canada, M6J 3S3
Windsor Regional Hospital-Tayfour Campus
Windsor, Ontario, Canada, N9C 3Z4
Canada, Quebec
Pierre-Janet Hospital
Gatineau, Quebec, Canada, J8A1K7
l'Hopital Louis H. Lafontaine
Montreal, Quebec, Canada, H1N 3M5
Kells Medical Research Group Inc.
Pointe-Claire, Quebec, Canada, H9R 4S3
Q&T Research Sherbrooke
Sherbrooke, Quebec, Canada, J1H 4J6
Canada
ALPHA Recherche Clinique
Quebec, Canada, G3K 2P8
Croatia
Poliklinika Neuron
Zagreb, Croatia, 10 000
Psychiatric Clinic Vrapoe
Zagreb, Croatia, 10090
Mexico
Centro Regiomontano de Investigacion S.C. (CRI)
Monterrey, Nuevo Leon, Mexico, 647-10
Hospital Aranda de la Parra
Leon Guanajuato, Mexico, 37000
Instituto de Infromacion e Investigación en Salud Mental (INFOSAME)
Nuevo Leon, Mexico, 64710
Consultorio Especializado en Psiquiatria Infantil y Adolescentes
San Luis Potosi, Mexico, 78200
B & B Investigaciones Medicas S.C.
Sinaloa, Mexico, 82126
Puerto Rico
Dharma Institute & Research Center
San Juan, Puerto Rico, 00907
INSPIRA Clinical Research
San Juan, Puerto Rico, 00918
Spain
Hospital de la Santa Creo l Sant Pau
Barcelona, Spain, 08025
Hospital Universitari de Bellvitge, Servicio de Psiquiatria
Barcelona, Spain, 08907
Hospital Fundacion de Alcorcon
Madrid, Spain, 28922
Hospital Universitario de Henares
Madrid, Spain
Hospital Universitario Infanta Leonor
Madrid, Spain, 28031
Centro de Salud Mental Il la Corredoria
Oviedo, Spain, 33011
Centro Salud Alamedilla Unidad de Salud Mental
Salamanca, Spain, 37003
Complejo hospitalario de Zamora
Zamora, Spain, 49021
Hospital Clinico Universitario Lozano Blesa
Zaragoza, Spain, 50009
Sponsors and Collaborators
Shire
Investigators
Principal Investigator: Madhukar H Trivedi, M.D. University of Texas Southwestern Medical School, Dallas, Texas 75235
  More Information

No publications provided

Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT01436149     History of Changes
Other Study ID Numbers: SPD489-322, 2011-003018-17
Study First Received: September 15, 2011
Results First Received: November 10, 2014
Last Updated: November 10, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Depression
Depressive Disorder
Depressive Disorder, Major
Disease
Behavioral Symptoms
Mental Disorders
Mood Disorders
Pathologic Processes
Antidepressive Agents
Dextroamphetamine
Central Nervous System Agents
Central Nervous System Stimulants
Dopamine Agents
Dopamine Uptake Inhibitors
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014