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

Major Depressive Disorder Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01436149
• Other study ID #: SPD489-322
• Secondary ID: 2011-003018-17
• Status: Completed
• Phase: Phase 3
• Start date: October 27, 2011
• Est. completion date: December 23, 2013

Study information

• Verified date: May 2021
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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?

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1262
• Est. completion date: December 23, 2013
• Est. primary completion date: December 23, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder

Intervention

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
• Placebo
Antidepressant (either escitalopram oxalate, sertraline hydrochloride, venlafaxine hydrochloride extended release or duloxetine hydrochloride) oral, once daily + Placebo (oral, once daily) for 8 weeks

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Shire

Countries where clinical trial is conducted

United States,  Canada,  Croatia,  Mexico,  Puerto Rico,  Spain, 

References & Publications (1)

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 fr — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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