Clinical trial NCT01436162: Efficacy and Safety Study of SPD489 in Combination With an Antidepressant in the Treatment of Adults With Major Depressive Disorder
Official title: The SPD489-323 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Major Depressive Disorder
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2011-09-19
Enrollment: 1105
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. 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?


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 and 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 (B-HCG) pregnancy test and a negative urine pregnancy test and agrees to comply with any applicable contraceptive requirements of the protocol.
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 with 2 or more approved single antidepressant agents.
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 co-morbid 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.
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.
16. Subject has a history of moderate to severe hypertension.
17. Current use of any other medications (including over-the-counter \[OTC\], herbal or homeopathic preparations) that have central nervous system effects.
18. 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.
19. Subject has had electroconvulsive therapy (ECT) 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, hypersensitivity, or contraindications to their assigned antidepressant treatments (escitalopram oxalate, sertraline HCl, venlafaxine HCl extended release, or duloxetine HCl).
22. Subject has a positive urine drug result.
23. Subject has a body mass index (BMI) of \<18.5 or \>40.
24. Subject is female and is pregnant or nursing.

Primary outcomes:
measure: Mean Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at 8 Weeks
timeFrame: 8 weeks
Secondary outcomes:
measure: Mean Change From Baseline in Sheehan Disability Scale (SDS) Total Score at 8 Weeks
timeFrame: 8 weeks
measure: Percentage of Participants Achieving a 25% Response on the MADRS
timeFrame: Up to 8 weeks
measure: Percentage of Participants Achieving a 50% Response on the MADRS
timeFrame: Up to 8 weeks
measure: Percent of Participants Achieving Remission on the MADRS
timeFrame: Up to 8 weeks
measure: Mean Change From Baseline Over Time in MADRS Total Score
timeFrame: Up to 8 weeks
measure: Mean Change From Baseline in Abbreviated Brief Assessment of Cognition Affective Disorders (ABAC-A) Composite T-Scores
timeFrame: up to 8 weeks
measure: Mean Change From Baseline in the Short Form-12 Health Survey V2 (SF-12V2)
timeFrame: Up to 8 weeks
measure: Mean Change in Sexual Functioning Questionnaire - 14 Item Scale (CSFQ-14) Total Score Male
timeFrame: Up to 8 weeks
measure: Mean Change in Sexual Functioning Questionnaire - 14 Item Scale (CSFQ-14) Total Score Female
timeFrame: Up to 8 weeks
measure: Clinical Global Impressions - Global Improvement (CGI-I)
timeFrame: Up to 8 weeks
measure: Mean Change From Baseline in the Multidimensional Assessment of Fatigue (MAF) Global Fatigue Index (GFI)
timeFrame: Up to 8 weeks
measure: Columbia Suicide Severity Rating Scale (C-SSRS)
timeFrame: Up to 8 weeks
measure: Amphetamine Cessation Symptom Assessment (ACSA) - Total Aggregate Score
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: ResearchOne, Inc.
state: Arizona
city: Little Rock
country: United States
facility: K&S Professional Research Services, LLC
state: Arkansas
city: Costa Mesa
country: United States
facility: ATP Clinical Research, Inc.
state: California
city: Downey
country: United States
facility: Diligent Clinical Trials
state: California
city: Escondido
country: United States
facility: Synergy Clinical Reserach Center of Escondido
state: California
city: Oakland
country: United States
facility: Pacific Research Partners, LLC
state: California
city: Redlands
country: United States
facility: Anderson Clinical Research
state: California
city: San Bernardino
country: United States
facility: BreakThrough Clinical Trials, LLC
state: California
city: Colorado Springs
country: United States
facility: MCB Clinical Research Centers
state: Colorado
city: Bradenton
country: United States
facility: Florida Clinical Research Center, LLC
state: Florida
city: North Miami
country: United States
facility: Scientific Clinical Research, Inc.
state: Florida
city: Orlando
country: United States
facility: Clinical Neuroscience Solutions, Inc.
state: Florida
city: Saint Petersburg
country: United States
facility: Comprehensive NeuroScience, Inc.
state: Florida
city: West Palm Beach
country: United States
facility: Janus Center for Psychiatric Research
state: Florida
city: Atlanta
country: United States
facility: Atlanta Center for Medical Research
state: Georgia
city: Atlanta
country: United States
facility: Atlanta Institute of Medicine & Research
state: Georgia
city: Newburgh
country: United States
facility: Pedia Research
state: Indiana
city: Wichita
country: United States
facility: Heartland Research Associates
state: Kansas
city: Shreveport
country: United States
facility: Louisiana Clinical Research, LLC
state: Louisiana
city: Gladstone
country: United States
facility: Comprehensive Psychiatric Associates
state: Missouri
city: Kansas City
country: United States
facility: The Center for Pharmaceutical Research
state: Missouri
city: Saint Louis
country: United States
facility: Mercy Health Research
state: Missouri
city: Toms River
country: United States
facility: Bio Behavioral Health
state: New Jersey
city: Brooklyn
country: United States
facility: Brooklyn Medical Institute
state: New York
city: New York
country: United States
facility: Medical & Behavioral Health Research, PC
state: New York
city: Dayton
country: United States
facility: Midwest Clinical Research Center
state: Ohio
city: Middleburg Heights
country: United States
facility: North Star Medical Research, LLC
state: Ohio
city: Oklahoma City
country: United States
facility: Sooner Clinical Research
state: Oklahoma
city: Allentown
country: United States
facility: Lehigh Center for Clinical Research
state: Pennsylvania
city: Philadelphia
country: United States
facility: Belmont Center for Comprehensive Treatment
state: Pennsylvania
city: North Charleston
country: United States
facility: Medical University South Carolina Anxiety Disorder Program
state: South Carolina
city: Franklin
country: United States
facility: Psychiatric Consultants, PC
state: Tennessee
city: Memphis
country: United States
facility: Research Strategies of Memphis, LLC
state: Tennessee
city: Dallas
country: United States
facility: KRK Medical Research
state: Texas
city: Dallas
country: United States
facility: Future Search Trials of Dallas, LP
state: Texas
city: San Antonio
country: United States
facility: Clinical Trials of Texas, Inc.
state: Texas
city: Sint Niklaas
country: Belgium
facility: Dr Lieven De Weirdt
city: Brno
country: Czechia
facility: Saint Anne s.r.o.
city: Brno
country: Czechia
facility: Psychiatricka ambulance
city: Horovice
country: Czechia
facility: Medicana s.r.o.
city: Kutna Hora
country: Czechia
facility: Psychiatrie s.r.o.
city: Litomerice
country: Czechia
facility: Bialbi s.r.o.
city: Prague 10
country: Czechia
facility: Clintrial s.r.o.
city: Prague 5
country: Czechia
facility: Psychiatry Trial s.r.o.
city: Prague 6
country: Czechia
facility: Prague Medical Services s.r.o.
city: Ricany
country: Czechia
facility: Ricany s.r.o.
city: Parnu
country: Estonia
facility: Parnu Hospital, Psychiatric Clinic
city: Tallinn
country: Estonia
facility: North Estonia Medical Centre Foundation Psychiatry Clinic
city: Tallinn
country: Estonia
facility: Marienthal Psychiatry and Psychology Center
city: Tartu
country: Estonia
facility: Jaanson & Laane OU
city: Tartu
country: Estonia
facility: Tartu University Hospital Psychiatric Clinic
city: Helsinki
country: Finland
facility: ARTES Psykiatrinen Palvelukeskus Oy
city: Kuopio
country: Finland
facility: Satucon Oy
city: Tampere
country: Finland
facility: Satakunnan Psykiatripalveiu Oy at Mentoria Oy
city: Turku
country: Finland
facility: Puutorin Psykiatripalvelu
city: Achim
country: Germany
facility: Gemeinschafstpraxis für Neurologie und Psychiatrie, Psychotherapie
city: Berlin
country: Germany
facility: Private Praxis Dr. Jana Thomsen
city: Berlin
country: Germany
facility: emovis GmbH
city: Berlin
country: Germany
facility: Alexander Schulze, MD
city: Bochum
country: Germany
facility: Private Practice Drs. Bitter/Schumann
city: Dresden
country: Germany
facility: University Hospital Carl Gustav Carus
city: Leipzig
country: Germany
facility: ZSL Zentrum fuer medizinische Studien in Leipzig
city: Muenchen
country: Germany
facility: Studienzentrum Muenchen
city: Muenster
country: Germany
facility: Universitaetsklinikum Munster
city: Nuernberg
country: Germany
facility: Studienzentrum Klinikum Nuernberg
city: Schwerin
country: Germany
facility: Somni bene GmbH
city: Siegen
country: Germany
facility: Private Practice: Eugen Schlegel
city: Westerstede
country: Germany
facility: Studiezentrum Nord-West
city: Wuerzburg
country: Germany
facility: Medizinisches Studienzentrum Wuerzburg
city: Budapest
country: Hungary
facility: Semmelweis Univ. Dept.of Psychiatry
city: Debrecen
country: Hungary
facility: Debrecent Egyetem Orvos es Egeszsegtudomanyl Centrum Pszichiatrai
city: Nagykallo
country: Hungary
facility: Santha Kalman Mentalis Egeszsegkozpont es Szakkorhaz
city: Nyiregyhaza
country: Hungary
facility: Josa Andras Teaching Hospital
city: Sziget
country: Hungary
facility: Pecsi Tudomanyegyeiem Pszichiatriai es Pszichoterapias Klinika
city: Bialystok
country: Poland
facility: Prywatne Gabinety Lekarskie "Promedicus"
city: Bydgoszcz
country: Poland
facility: NZOZ Centrum Kultury, Higieny i Zdrowia Psychicznego
city: Chelmno
country: Poland
facility: Zespol Opieki Zdrowotnej w Chelmnie
city: Gdansk
country: Poland
facility: Centrum Badan Klinicznuch Pl-House sp. z.o.o.
city: Gdansk
country: Poland
facility: Klinika Chorob Psychicznych i Zaburzen Nerwicowych
city: Gorlice
country: Poland
facility: Centrum Psychiatrii i Psychoterapli
city: Kielce
country: Poland
facility: NZOZ Syntonia, Poradnia Zdrowia Psychicznego
city: Lublin
country: Poland
facility: Osrodek Badafi Klinicznych Prof dr hab n med Meszek Szczepanski Prywatna Praktyka Lekarska
city: Zuromin
country: Poland
facility: Samodzielny Publiczny Zespol Zakladow Opieki Zdrowotnej w Zurominie
city: Arad
country: Romania
facility: Spitatul Clinic Judetean de Urgenta Arad, Clinica de Psihiatrie
city: Botosani
country: Romania
facility: Stefi-Dent SRL
city: Bucharest
country: Romania
facility: Spitalui Clinic de Psihiatrie "Prof. Dr. Alexandru Obregia" Sectia Clinica Psihiatrie I
city: Oradea
country: Romania
facility: Crucea Alba
city: Targoviste
country: Romania
facility: Lorentina 2201 SRL
city: Targu Mures
country: Romania
facility: Spitalul Clinic Judetean Mures
city: Bellville
country: South Africa
facility: Cape Trial Centre
state: Cape Town
city: Bellville
country: South Africa
facility: Flexivest Fourteen Research Centre
state: Cape Town
city: Johannesburg
country: South Africa
facility: Private Practice - Gerta Brink
state: Gauten
city: Somerset West
country: South Africa
facility: Somerset West Clinical Research
state: Western Cape
city: Centurion
country: South Africa
facility: Vista Clinic
city: George
country: South Africa
facility: George Medi Clinic Extension
city: Göteborg
country: Sweden
facility: SU/ Affektiva 1
city: Lund
country: Sweden
facility: ProbarE i Lund AB
city: Malmo
country: Sweden
facility: Ekdahl Medical AB
city: Malmo
country: Sweden
facility: INM Psykiatrisk Mottagning
city: Stockholm
country: Sweden
facility: Medinstructor Lippitz AB
city: Uppsala
country: Sweden
facility: Dr. Wahlstedts mottagning
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References:
citation: 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 from 2 phase 3, multicenter, randomized, double-blind, placebo-controlled studies. J Affect Disord. 2016 Dec;206:151-160. doi: 10.1016/j.jad.2016.07.006. Epub 2016 Jul 5.