Clinical trial NCT01435759: SPD489 in Combination With an Antidepressant in the Treatment of Adults With Major Depressive Disorder
Official title: A Phase 2, Multicenter, Double- Blind, Parallel-group, Randomized, Placebo-controlled, Forced-dose Titration, Dose-ranging 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Major Depressive Disorder
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2011-09-19
Enrollment: 1197
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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. 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 SPD489 help patients with depression who are also 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?


Eligibility criteria: Inclusion Criteria

1. Subject is able to provide written, personally signed and dated informed consent to participate in the study before completing any study-related procedures.
2. Subject is between 18-65 years of age.
3. Subject has a primary diagnosis of non-psychotic MDD.
4. Subject has a MADRS total score 24
5. Subject is willing and has an understanding and ability to fully comply with study procedures and restrictions defined in this protocol.
6. Subject, who is female, must have a negative serum beta human chorionic gonadotropin (HCG) pregnancy test and a negative urine pregnancy test and agrees to comply with any applicable contraceptive requirements.
7. Subject is able to swallow a capsule.

Exclusion Criteria

1. Subject whose current episode of MDD has not responded to an adequate treatment regimen.
2. Subject who has a lifetime history of treatment resistant depression, defined as having not responded to adequate treatment with 2 or more treatment regimens.
3. Subject has a current comorbid psychiatric disorder that is either controlled with medications prohibited in this study or is uncontrolled and associated with significant symptoms.
4. Subject has been hospitalized (within the last 12 months) for their current MDD episode.
5. Subject has a current or lifetime history of attention-deficit/hyperactivity disorder (ADHD).
6. Subject has a first degree relative that has been diagnosed with bipolar I disorder.
7. Subject has a recent history (within the last 6 months) of suspected substance abuse or dependence disorder.
8. Subject is considered a suicide risk, has previously made a suicide attempt within the past 3 years, or is currently demonstrating active suicidal ideation.
9. Subject has a concurrent chronic or acute illness or unstable medical condition.
10. 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.
11. 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 that may place them at increased vulnerability to the sympathomimetic effects of a stimulant medication.
12. 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.
13. Subject has a known family history of sudden cardiac death or ventricular arrhythmia.
14. Subject has glaucoma.
15. Subject has any clinically significant ECG or clinical laboratory abnormalities at the Screening Visit.
16. Subject has a history of moderate to severe hypertension.
17. Current use of any other medication (including over-the-counter \[OTC\], herbal or homeopathic preparations) that has central nervous system effects.
18. Subject has the potential to need to initiate or modify frequency of psychotherapy or to continue or initiate other treatments for depression, outside of those allowed in this protocol.
19. Subject has had electroconvulsive therapy for the current depressive episode 3 months prior to the Lead-in Baseline Visit.
20. The subject has a known or suspected intolerance or hypersensitivity to the investigational product.
21. The subject has a known or suspected intolerance or hypersensitivity to any of the possible antidepressant treatments (escitalopram oxalate or venlafaxine HCL extended release.
22. Subject has a positive urine drug result.
23. Subject has a body mass index of \<18.5 or \>40.
24. Subject is female and is pregnant or nursing.
25. Subject has participated in another clinical study involving SPD489/NRP104 or has previously used commercial lisdexamfetamine dimesylate.

Primary outcomes:
measure: Change in Montgomery-Ǻsberg Depression Rating Scale (MADRS) Total Score From Augmentation Baseline (Week 8) to Week 16 (Double-blind Phase, Dose Response Evaluable Set)
timeFrame: Augmentation Baseline (Week 8) to Week 16
Secondary outcomes:
measure: Change in Average Systolic Blood Pressure From Augmentation Baseline (Week 8) to Week 16
timeFrame: From Augmentation Baseline (Week 8) to Week 16
measure: Change in Average Diastolic Blood Pressure From Augmentation Baseline (Week 8) to Week 16
timeFrame: From Augmentation Baseline (Week 8) to Week 16
measure: Change in Average Pulse Rate From Augmentation Baseline (Week 8) to Week 16
timeFrame: From Augmentation Baseline (Week 8) to Week 16
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Arkansas Psychiatric Clinic Clinical Research Trials
state: Arkansas
city: Anaheim
country: United States
facility: South Coast Clinical Trials
state: California
city: Chino
country: United States
facility: Catalina Research Institute, LLC
state: California
city: Colton
country: United States
facility: Shanti Clinical Trials
state: California
city: Costa Mesa
country: United States
facility: Clinical Innovation, Inc.
state: California
city: Garden Grove
country: United States
facility: Collaborative Neuroscience Network, Inc.
state: California
city: Irvine
country: United States
facility: Irvine Center for Clinical Research
state: California
city: La Habra
country: United States
facility: Omega Clinical Trials
state: California
city: Los Angeles
country: United States
facility: Provate Practice of Andrew Leuchter, MD
state: California
city: San Diego
country: United States
facility: PCSD - Feighner Research
state: California
city: San Diego
country: United States
facility: Artemis Institute for Clinical Research
state: California
city: Santa Ana
country: United States
facility: Neuropsychiatric Research Center of Orange County
state: California
city: Sherman Oaks
country: United States
facility: California Neuroscience Research Medical Group, Inc.
state: California
city: Denver
country: United States
facility: Western Affiliated Research Institute
state: Colorado
city: Cromwell
country: United States
facility: Connecticut Clinical Research
state: Connecticut
city: Hartford
country: United States
facility: Institute of Living
state: Connecticut
city: New Britain
country: United States
facility: The Hospital of Central Connecticut, Psychiatry & Behavioral Health Research
state: Connecticut
city: Fort Myers
country: United States
facility: Gulfcoast Clinical Research Center
state: Florida
city: Gainesville
country: United States
facility: Sarkis Clinical Trials
state: Florida
city: Jacksonville
country: United States
facility: Clinical Neuroscience Solutions, Inc.
state: Florida
city: Jacksonville
country: United States
facility: Private Practice - Amit Vijapura MD
state: Florida
city: Lake City
country: United States
facility: Psychiatric Associates
state: Florida
city: Miramar
country: United States
facility: Comprehensive Neuroscience, Inc.
state: Florida
city: North Miami
country: United States
facility: Fideltiy Clinical Research, Inc.
state: Florida
city: Orlando
country: United States
facility: Ali A. Kashfi, MD, PA
state: Florida
city: Winter Haven
country: United States
facility: Clinical Research of Central Florida
state: Florida
city: Winter Park
country: United States
facility: Kolin Research Group
state: Florida
city: Smyrna
country: United States
facility: Institute for Behavioral Medicine, LLC
state: Georgia
city: Chicago
country: United States
facility: Treatment Research Center, Rush University Medical Center
state: Illinois
city: Hoffman Estates
country: United States
facility: Alexian Brothers Center for Psychiatric Research
state: Illinois
city: Skokie
country: United States
facility: Psychiatric Medicine Associates, LLC
state: Illinois
city: Vernon Hills
country: United States
facility: Sleep and Behavior Medicine Institute
state: Illinois
city: Prairie Village
country: United States
facility: Clinical Trials Technology, Inc.
state: Kansas
city: Owensboro
country: United States
facility: Pedia Research, LLC
state: Kentucky
city: O'Fallon
country: United States
facility: Psyichatric Care and Research Center
state: Missouri
city: Saint Louis
country: United States
facility: Mid-America Clinical Research, LLC
state: Missouri
city: Lincoln
country: United States
facility: Premier Psychiatric Research Institute, LLC.
state: Nebraska
city: Las Vegas
country: United States
facility: Clinical Research Consortium
state: Nevada
city: Cherry Hill
country: United States
facility: Center for Emotional Fitness
state: New Jersey
city: Willingboro
country: United States
facility: CRI Worldwide LLC
state: New Jersey
city: Albuquerque
country: United States
facility: Albuquerque Neuroscience, Inc.
state: New Mexico
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: New York
country: United States
facility: Clinlabs, Inc.
state: New York
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: West Seneca
country: United States
facility: Private Practice - Daniel I. Rifkin MD PC
state: New York
city: Hickory
country: United States
facility: Clinical Trials of America, Inc.
state: North Carolina
city: Beachwood
country: United States
facility: North Coast Clinical Trials, Inc.
state: Ohio
city: Columbus
country: United States
facility: Ohio State University, Dept. of Psychiatry
state: Ohio
city: Toledo
country: United States
facility: Neurology & Neuroscience Center of Ohio
state: Ohio
city: Oklahoma City
country: United States
facility: IPS Research Company
state: Oklahoma
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: West Chester
country: United States
facility: University Services
state: Pennsylvania
city: Dallas
country: United States
facility: Pillar Clinical Research, LLC
state: Texas
city: Friendswood
country: United States
facility: Bay Area Clinical Services
state: Texas
city: Houston
country: United States
facility: Houston Clinical Trials, LLC
state: Texas
city: Wharton
country: United States
facility: Wharton Research Center, Inc.
state: Texas
city: Wichita Falls
country: United States
facility: Grayline Clinical Drug Trials
state: Texas
city: Richmond
country: United States
facility: Alliance Research Group
state: Virginia
city: Middleton
country: United States
facility: Dean Foundation for Health, Research and Education, Inc.
state: Wisconsin
city: Waukesha
country: United States
facility: Independent Psychiatric Consultants, SC, dba, IPC Research
state: Wisconsin
city: Buenos Aires
country: Argentina
facility: Instituto Nacional de Psicopatologia
city: Buenos Aires
country: Argentina
facility: Cervino
city: Caba
country: Argentina
facility: Centro Medico de Medicina Familiar Mind Out Research
city: Caba
country: Argentina
facility: BA Psychiatric Research Center
city: Cordoba
country: Argentina
facility: Instituto Medico SAMIC
city: Frankston
country: Australia
facility: Peninsula Health Mental Health Services
state: Victoria
city: Malvern
country: Australia
facility: Neurotherapy Victoria
state: Victoria
city: Melbourne
country: Australia
facility: The Alfred, Monash Alfred Psychiatry Research Centre
state: Victoria
city: Richmond
country: Australia
facility: The Melbourne Clinic
state: Victoria
city: Elizabeth Vale
country: Australia
facility: Lyell McEwin Hospital, Mental Health Clinical Trials Unit
city: Antofagasta
country: Chile
facility: Psocomed Estudios Medicos
state: Il Region
city: Las Condes
country: Chile
facility: Especialidades Medicas L y S
state: Santiago
city: Las Condes
country: Chile
facility: Centro de Estudios y Tratemiento de Enfermedades Psiquiatricas
state: Santiago
city: Providencia
country: Chile
facility: Biomedica Research Group
state: Santiago
city: Providencia
country: Chile
facility: Centro de Estudios Clinicos
state: Santiago
city: San Bernardo
country: Chile
facility: Unidad de Salud Mental y Psiquietriea Hospital y CRS El Pino
state: Santiago
city: San Miguel
country: Chile
facility: Hospital Barros Luco Trudsau
state: Santiago
city: Winwick
country: United Kingdom
facility: Hollins Park Hospital
state: Warrington Cheshire
city: Derby
country: United Kingdom
facility: Radbourne Unit
city: Horsham
country: United Kingdom
facility: ADHD Mental Health Research Unit
city: Newcastle upon Tyne
country: United Kingdom
facility: Newcastle University, Wolfson Research Centre
city: Nottingham
country: United Kingdom
facility: Rushcliffe Mental Health Team
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References:
citation: Richards C, Iosifescu DV, Mago R, Sarkis E, Reynolds J, Geibel B, Dauphin M. A randomized, double-blind, placebo-controlled, dose-ranging study of lisdexamfetamine dimesylate augmentation for major depressive disorder in adults with inadequate response to antidepressant therapy. J Psychopharmacol. 2017 Sep;31(9):1190-1203. doi: 10.1177/0269881117722998. Epub 2017 Aug 31.