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: Antidepressant + SPD489 (Lisdexamfetamine dimesylate )
Drug: Antidepressant + Placebo

Registration Number: NCT01436162

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: 1105

Inclusion Criteria

Not provided

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, defined as having not responded to adequate treatment with 2 or more treatment regimens.
Subject has a current co-morbid psychiatric disorder that is either controlled with medications prohibited in this study or is uncontrolled and associated with significant symptoms.
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, 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 any clinically significant ECG or clinical laboratory abnormalities.
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 the potential need to initiate or modify frequency of psychotherapy or to continue or initiate other treatments for depression, outside of those allowed in this protocol.
Subject has had electroconvulsive therapy (ECT) for the current depressive episode 3 months prior to the Lead-in Baseline Visit.
The subject has a known or suspected intolerance or hypersensitivity to the investigational product.
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	Antidepressant + SPD489 (Lisdexamfetamine dimesylate )	-
Antidepressant + Placebo	Antidepressant + Placebo	-

Primary Outcome Measures

Name	Time	Method
Mean Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at 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
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 the Lead-in Baseline, Visit 2).
Mean Change From Baseline in Sheehan Disability Scale (SDS) Total Score at 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.
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 the Lead-in Baseline, Visit 2).
Percent of Participants Achieving Remission on the MADRS	Up to 8 weeks	MADRS remission was defined as a MADRS total score of ≤10.
Mean Change From Baseline Over Time in MADRS Total Score	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 Abbreviated Brief Assessment of Cognition Affective Disorders (ABAC-A) Composite T-Scores	up to 8 weeks	The ABAC-A is a rater-administered series of activities designed to be sensitive to the critical cognitive deficits in affective disorders and schizophrenia. There are 6 subtests of the ABAC-A: List Learning (verbal memory); Digit Sequencing Task (working memory); Token Motor Task (motor speed); Verbal Fluency; Symbol Coding (attention and processing speed); and Tower of London Test (executive functions). The ABAC-A Composite T-score change from Augmentation Baseline Visit (Visit 8; Week 8) at Visit 14/Early Termination (ET) (Week 16/ET) was analyzed.
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.
Mean Change in Sexual Functioning Questionnaire - 14 Item Scale (CSFQ-14) Total Score Male	Up to 8 weeks	The CSFQ-14 is a short-form interview/questionnaire that measures illness- and medication-related changes in sexual functioning. A 5-point Likert scale is used ranging from 1 (never) to 5 (always). The CSFQ-14 total score can range from 14 to 70, with lower scores being associated with worsened sexual functioning.
Mean Change in Sexual Functioning Questionnaire - 14 Item Scale (CSFQ-14) Total Score Female	Up to 8 weeks	The CSFQ-14 is a short-form interview/questionnaire that measures illness- and medication-related changes in sexual functioning. A 5-point Likert scale is used ranging from 1 (never) to 5 (always). The CSFQ-14 total score can range from 14 to 70, with lower scores being associated with worsened sexual functioning.
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.
Mean Change From Baseline in the Multidimensional Assessment of Fatigue (MAF) Global Fatigue Index (GFI)	Up to 8 weeks	MAF contains 16 items scored on a scale from 1 (not at all) to 10 (a great deal). Answers are converted to a Global Fatigue Index with total scores ranging from 1 (no fatigue) to 50 (severe fatigue). Lower scores indicate less fatigue.
Columbia Suicide Severity Rating Scale (C-SSRS)	Up to 8 weeks	C-SSRS is a semi-structured interview that captures the occurence, 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 behaviour occurred. The assessment is done by the nature of the responses, not by a numbered scale.
Amphetamine Cessation Symptom Assessment (ACSA) - Total Aggregate Score	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 (101): Atlanta Institute of Medicine & Research
🇺🇸
Atlanta, Georgia, United States
Medical University South Carolina Anxiety Disorder Program
🇺🇸
North Charleston, South Carolina, United States
Sooner Clinical Research
🇺🇸
Oklahoma City, Oklahoma, United States
Cape Trial Centre
🇿🇦
Bellville, Cape Town, South Africa
Vista Clinic
🇿🇦
Centurion, South Africa
Atlanta Center for Medical Research
🇺🇸
Atlanta, Georgia, United States
Clinical Trials of Texas, Inc.
🇺🇸
San Antonio, Texas, United States
Bio Behavioral Health
🇺🇸
Toms River, New Jersey, United States
Centrum Badan Klinicznuch Pl-House sp. z.o.o.
🇵🇱
Gdansk, Poland
Janus Center for Psychiatric Research
🇺🇸
West Palm Beach, Florida, United States
Flexivest Fourteen Research Centre
🇿🇦
Bellville, Cape Town, South Africa
Bialbi s.r.o.
🇨🇿
Litomerice, Czechia
Saint Anne s.r.o.
🇨🇿
Brno, Czechia
ResearchOne, Inc.
🇺🇸
Scottsdale, Arizona, United States
K&S Professional Research Services, LLC
🇺🇸
Little Rock, Arkansas, United States
Diligent Clinical Trials
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Downey, California, United States
Heartland Research Associates
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Wichita, Kansas, United States
Louisiana Clinical Research, LLC
🇺🇸
Shreveport, Louisiana, United States
The Center for Pharmaceutical Research
🇺🇸
Kansas City, Missouri, United States
Mercy Health Research
🇺🇸
Saint Louis, Missouri, United States
Future Search Trials of Dallas, LP
🇺🇸
Dallas, Texas, United States
Psychiatric Consultants, PC
🇺🇸
Franklin, Tennessee, United States
Jaanson & Laane OU
🇪🇪
Tartu, Estonia
Private Practice Drs. Bitter/Schumann
🇩🇪
Bochum, Germany
Psychiatricka ambulance
🇨🇿
Brno, Czechia
Medical & Behavioral Health Research, PC
🇺🇸
New York, New York, United States
Clintrial s.r.o.
🇨🇿
Prague 10, Czechia
KRK Medical Research
🇺🇸
Dallas, Texas, United States
North Estonia Medical Centre Foundation Psychiatry Clinic
🇪🇪
Tallinn, Estonia
North Star Medical Research, LLC
🇺🇸
Middleburg Heights, Ohio, United States
Satakunnan Psykiatripalveiu Oy at Mentoria Oy
🇫🇮
Tampere, Finland
Spitalul Clinic Judetean Mures
🇷🇴
Targu Mures, Romania
Semmelweis Univ. Dept.of Psychiatry
🇭🇺
Budapest, Hungary
Pecsi Tudomanyegyeiem Pszichiatriai es Pszichoterapias Klinika
🇭🇺
Sziget, Hungary
Studiezentrum Nord-West
🇩🇪
Westerstede, Germany
Prywatne Gabinety Lekarskie "Promedicus"
🇵🇱
Bialystok, Poland
Centrum Psychiatrii i Psychoterapli
🇵🇱
Gorlice, Poland
Stefi-Dent SRL
🇷🇴
Botosani, Romania
ZSL Zentrum fuer medizinische Studien in Leipzig
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Leipzig, Germany
Somni bene GmbH
🇩🇪
Schwerin, Germany
Santha Kalman Mentalis Egeszsegkozpont es Szakkorhaz
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Nagykallo, Hungary
Dr. Wahlstedts mottagning
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Uppsala, Sweden
Medinstructor Lippitz AB
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Stockholm, Sweden
Medicana s.r.o.
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Horovice, Czechia
Studienzentrum Klinikum Nuernberg
🇩🇪
Nuernberg, Germany
Zespol Opieki Zdrowotnej w Chelmnie
🇵🇱
Chelmno, Poland
Psychiatrie s.r.o.
🇨🇿
Kutna Hora, Czechia
Private Practice: Eugen Schlegel
🇩🇪
Siegen, Germany
Somerset West Clinical Research
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Somerset West, Western Cape, South Africa
ProbarE i Lund AB
🇸🇪
Lund, Sweden
Private Praxis Dr. Jana Thomsen
🇩🇪
Berlin, Germany
Debrecent Egyetem Orvos es Egeszsegtudomanyl Centrum Pszichiatrai
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Debrecen, Hungary
Tartu University Hospital Psychiatric Clinic
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Tartu, Estonia
Lorentina 2201 SRL
🇷🇴
Targoviste, Romania
Ekdahl Medical AB
🇸🇪
Malmo, Sweden
Universitaetsklinikum Munster
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Muenster, Germany
Medizinisches Studienzentrum Wuerzburg
🇩🇪
Wuerzburg, Germany
Ricany s.r.o.
🇨🇿
Ricany, Czechia
MCB Clinical Research Centers
🇺🇸
Colorado Springs, Colorado, United States
ATP Clinical Research, Inc.
🇺🇸
Costa Mesa, California, United States
Synergy Clinical Reserach Center of Escondido
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Escondido, California, United States
Anderson Clinical Research
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Redlands, California, United States
Pacific Research Partners, LLC
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Oakland, California, United States
Florida Clinical Research Center, LLC
🇺🇸
Bradenton, Florida, United States
Comprehensive NeuroScience, Inc.
🇺🇸
Saint Petersburg, Florida, United States
BreakThrough Clinical Trials, LLC
🇺🇸
San Bernardino, California, United States
Clinical Neuroscience Solutions, Inc.
🇺🇸
Orlando, Florida, United States
Pedia Research
🇺🇸
Newburgh, Indiana, United States
Brooklyn Medical Institute
🇺🇸
Brooklyn, New York, United States
Comprehensive Psychiatric Associates
🇺🇸
Gladstone, Missouri, United States
Dr Lieven De Weirdt
🇧🇪
Sint Niklaas, Belgium
Psychiatry Trial s.r.o.
🇨🇿
Prague 5, Czechia
Parnu Hospital, Psychiatric Clinic
🇪🇪
Parnu, Estonia
Prague Medical Services s.r.o.
🇨🇿
Prague 6, Czechia
Studienzentrum Muenchen
🇩🇪
Muenchen, Germany
Marienthal Psychiatry and Psychology Center
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Tallinn, Estonia
Puutorin Psykiatripalvelu
🇫🇮
Turku, Finland
Satucon Oy
🇫🇮
Kuopio, Finland
ARTES Psykiatrinen Palvelukeskus Oy
🇫🇮
Helsinki, Finland
University Hospital Carl Gustav Carus
🇩🇪
Dresden, Germany
Josa Andras Teaching Hospital
🇭🇺
Nyiregyhaza, Hungary
NZOZ Centrum Kultury, Higieny i Zdrowia Psychicznego
🇵🇱
Bydgoszcz, Poland
Osrodek Badafi Klinicznych Prof dr hab n med Meszek Szczepanski Prywatna Praktyka Lekarska
🇵🇱
Lublin, Poland
NZOZ Syntonia, Poradnia Zdrowia Psychicznego
🇵🇱
Kielce, Poland
Klinika Chorob Psychicznych i Zaburzen Nerwicowych
🇵🇱
Gdansk, Poland
Spitatul Clinic Judetean de Urgenta Arad, Clinica de Psihiatrie
🇷🇴
Arad, Romania
Crucea Alba
🇷🇴
Oradea, Romania
Private Practice - Gerta Brink
🇿🇦
Johannesburg, Gauten, South Africa
George Medi Clinic Extension
🇿🇦
George, South Africa
SU/ Affektiva 1
🇸🇪
Göteborg, Sweden
INM Psykiatrisk Mottagning
🇸🇪
Malmo, Sweden
Belmont Center for Comprehensive Treatment
🇺🇸
Philadelphia, Pennsylvania, United States
Midwest Clinical Research Center
🇺🇸
Dayton, Ohio, United States
Scientific Clinical Research, Inc.
🇺🇸
North Miami, Florida, United States
Lehigh Center for Clinical Research
🇺🇸
Allentown, Pennsylvania, United States
Research Strategies of Memphis, LLC
🇺🇸
Memphis, Tennessee, United States
Gemeinschafstpraxis für Neurologie und Psychiatrie, Psychotherapie
🇩🇪
Achim, Germany
emovis GmbH
🇩🇪
Berlin, Germany
Alexander Schulze, MD
🇩🇪
Berlin, Germany
Samodzielny Publiczny Zespol Zakladow Opieki Zdrowotnej w Zurominie
🇵🇱
Zuromin, Poland
Spitalui Clinic de Psihiatrie "Prof. Dr. Alexandru Obregia" Sectia Clinica Psihiatrie I
🇷🇴
Bucharest, Romania