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

Phase 3

Completed

Conditions: Major Depressive Disorder

Interventions: Drug: SPD489 (Lisdexamfetamine dimesylate )
Drug: Placebo

Registration Number: NCT01436149

Lead Sponsor: Shire

Brief Summary: 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?

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 1262

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Antidepressant + SPD489	SPD489 (Lisdexamfetamine dimesylate )	-
Antidepressant + Placebo	Placebo	-

Primary Outcome Measures

Name	Time	Method
Mean Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at up to 8 Weeks	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.

Secondary Outcome Measures

Name	Time	Method
Mean Change From Baseline in the Short Form-12 Health Survey V2 (SF-12V2)	up to 8 weeks	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.
Percentage of Participants Achieving a 25% Response on the MADRS	up to 8 weeks	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	up to 8 weeks	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	up to 8 weeks	MADRS remission was defined as a MADRS total score of ≤10. A comparison was performed at Visit 14/ET (Week 16/ET).
Change From Baseline in Sheehan Disability Scale (SDS) Total Score at up to 8 Weeks	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.
Mean Change From Baseline Over Time in MADRS Total Score	Baseline and 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.
Mean Change From Baseline in the Quick Inventory of Depressive Symptomatology - Self Report (QIDS SR)	up to 8 weeks	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 Quality of Life Enjoyment Satisfaction Questionnaire Short Form (Q-LES-Q-SF)	up to 8 weeks	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)	up to 8 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.
Columbia Suicide Severity Rating Scale (C-SSRS)	up to 8 weeks	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)	up to 8 weeks	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.

Trial Locations

Locations (85): Kells Medical Research Group Inc.
🇨🇦
Pointe-Claire, Quebec, Canada
Geriatric and Adult Psychiatry, LLC
🇺🇸
Hamden, Connecticut, United States
MCM Clinical Research LLC
🇺🇸
Florence, Kentucky, United States
University of California, Irvine Child Development Center
🇺🇸
Irvine, California, United States
North County Clinical Research
🇺🇸
Oceanside, California, United States
Potomac Grove Clinical Research Center
🇺🇸
Gaithersburg, Maryland, United States
Lindner Center of HOPE
🇺🇸
Mason, Ohio, United States
Pasadena Research Institute, LLC
🇺🇸
Pasadena, California, United States
Rcihard H. Weisler, MD, PA & Associates
🇺🇸
Raleigh, North Carolina, United States
Anxiety and Mood Disorder Center
🇨🇦
Mississauga, Ontario, Canada
Carman Research
🇺🇸
Smyrna, Georgia, United States
Middlexex Hospital Center for Behavioral Health
🇺🇸
Middletown, Connecticut, United States
Florida Clinical Research Center, LLC.
🇺🇸
Maitland, Florida, United States
CRI Worldwide LLC
🇺🇸
Philadelphia, Pennsylvania, United States
Emerald Coast Mood & Memory, PA
🇺🇸
Fort Walton Beach, Florida, United States
Aggarwal & Associates Ltd.
🇨🇦
Brampton, Ontario, Canada
CNS Clinical Research Group
🇺🇸
Coral Springs, Florida, United States
Psychiatric Clinic Vrapoe
🇭🇷
Zagreb, Croatia
Northwest Indiana Center for Clinical Research
🇺🇸
Valparaiso, Indiana, United States
Adams Clinical Trials, LLC
🇺🇸
Watertown, Massachusetts, United States
Fieve Clinical Research
🇺🇸
New York, New York, United States
Richmond Behavioral Associates
🇺🇸
Staten Island, New York, United States
St. Charles Psychiatric Associates - Midwest Research Group
🇺🇸
Saint Charles, Missouri, United States
Rhode Island Mood & Memory Research Institute
🇺🇸
East Providence, Rhode Island, United States
Hospital Universitario de Henares
🇪🇸
Madrid, Spain
Hospital Universitari de Bellvitge, Servicio de Psiquiatria
🇪🇸
Barcelona, Spain
INSPIRA Clinical Research
🇵🇷
San Juan, Puerto Rico
Bioscience Research, LLC
🇺🇸
Mount Kisco, New York, United States
Regional Mental Health Care
🇨🇦
London, Ontario, Canada
Dr. Alexander McIntyre Inc
🇨🇦
Penticton, British Columbia, Canada
A.K. Karan Holdings
🇨🇦
Oakville, Ontario, Canada
Q&T Research Sherbrooke
🇨🇦
Sherbrooke, Quebec, Canada
Dharma Institute & Research Center
🇵🇷
San Juan, Puerto Rico
Hospital Universitario Infanta Leonor
🇪🇸
Madrid, Spain
Centro Salud Alamedilla Unidad de Salud Mental
🇪🇸
Salamanca, Spain
Centro de Salud Mental Il la Corredoria
🇪🇸
Oviedo, Spain
Consultorio Especializado en Psiquiatria Infantil y Adolescentes
🇲🇽
San Luis Potosi, Mexico
Birmingham Research Group
🇺🇸
Birmingham, Alabama, United States
Compass Research, LLC
🇺🇸
Orlando, Florida, United States
Stedman Clinical Trials
🇺🇸
Tampa, Florida, United States
The Davis Clinic
🇺🇸
Indianapolis, Indiana, United States
Triangle Neuropsychiatry
🇺🇸
Durham, North Carolina, United States
Community Research
🇺🇸
Cincinnati, Ohio, United States
SP Research, PLLC
🇺🇸
Oklahoma City, Oklahoma, United States
Pharmasite Research, Inc.
🇺🇸
Baltimore, Maryland, United States
Office of Marc Hertzman, MD
🇺🇸
Rockville, Maryland, United States
Instituto de Infromacion e Investigación en Salud Mental (INFOSAME)
🇲🇽
Nuevo Leon, Mexico
Hospital Aranda de la Parra
🇲🇽
Leon Guanajuato, Mexico
B & B Investigaciones Medicas S.C.
🇲🇽
Sinaloa, Mexico
Dr. D. McIntosh & Dr. K. Kjernisted Clinical Research Inc.
🇨🇦
Vancouver, British Columbia, Canada
Centro Regiomontano de Investigacion S.C. (CRI)
🇲🇽
Monterrey, Nuevo Leon, Mexico
Medical Research Associates
🇨🇦
Mississauga, Ontario, Canada
Chatham-Kent Clinical Trials Research Center
🇨🇦
Chatham, Ontario, Canada
International Sleep Clinic, West Parry Sound Health Centre
🇨🇦
Parry Sound, Ontario, Canada
START Clinic for Mood and Anxiety Disorders
🇨🇦
Toronto, Ontario, Canada
Windsor Regional Hospital-Tayfour Campus
🇨🇦
Windsor, Ontario, Canada
Univ Health Network, Toronto Western Hospital
🇨🇦
Toronto, Ontario, Canada
Sleep & Alertness Clinic (Sleep & Alertness Research, Inc.)
🇨🇦
Toronto, Ontario, Canada
l'Hopital Louis H. Lafontaine
🇨🇦
Montreal, Quebec, Canada
ALPHA Recherche Clinique
🇨🇦
Quebec, Canada
AV Institue, Inc.
🇺🇸
Carson, California, United States
South Coast Clinicals
🇺🇸
Norwalk, California, United States
Suncoast Clinical Research
🇺🇸
New Port Richey, Florida, United States
Meridien Research
🇺🇸
Saint Petersburg, Florida, United States
American Medical Research, Inc.
🇺🇸
Oak Brook, Illinois, United States
Clinical Neuroscience Solutions, Inc.
🇺🇸
Memphis, Tennessee, United States
Ericksen Research and Development
🇺🇸
Clinton, Utah, United States
Poliklinika Neuron
🇭🇷
Zagreb, Croatia
Hospital de la Santa Creo l Sant Pau
🇪🇸
Barcelona, Spain
Hospital Fundacion de Alcorcon
🇪🇸
Madrid, Spain
Complejo hospitalario de Zamora
🇪🇸
Zamora, Spain
Hospital Clinico Universitario Lozano Blesa
🇪🇸
Zaragoza, Spain
Manna Research
🇨🇦
Toronto, Ontario, Canada
Pierre-Janet Hospital
🇨🇦
Gatineau, Quebec, Canada
Affiliated Research Institute
🇺🇸
San Diego, California, United States
Clinical Innovations, Inc.
🇺🇸
San Diego, California, United States
Sharp Mesa Vista Hospital
🇺🇸
San Diego, California, United States
Summit Research Network (Oregon) Inc.
🇺🇸
Portland, Oregon, United States
University of Pittsburgh School of Medicine
🇺🇸
Pittsburgh, Pennsylvania, United States
Clinical Research Associates
🇺🇸
Nashville, Tennessee, United States
FutureSearch Clinical Trials, LP
🇺🇸
Austin, Texas, United States
Summit Research Network (Seattle) LLC
🇺🇸
Seattle, Washington, United States
Paramount Clinical Research
🇺🇸
Bridgeville, Pennsylvania, United States
Suburban Research Associates
🇺🇸
Media, Pennsylvania, United States
Depression, Mood Disorders and Schizophrenia Treatment Centre
🇨🇦
Burlington, Ontario, Canada