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 SPD489-323 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01436162
• Other study ID #: SPD489-323
• Secondary ID: 2011-003006-25
• Status: Completed
• Phase: Phase 3
• Start date: October 19, 2011
• Est. completion date: December 10, 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: 1105
• Est. completion date: December 10, 2013
• Est. primary completion date: December 10, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• Antidepressant + 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
• Antidepressant + 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
Belgium	Dr Lieven De Weirdt	Sint Niklaas
Czechia	Psychiatricka ambulance	Brno
Czechia	Saint Anne s.r.o.	Brno
Czechia	Medicana s.r.o.	Horovice
Czechia	Psychiatrie s.r.o.	Kutna Hora
Czechia	Bialbi s.r.o.	Litomerice
Czechia	Clintrial s.r.o.	Prague 10
Czechia	Psychiatry Trial s.r.o.	Prague 5
Czechia	Prague Medical Services s.r.o.	Prague 6
Czechia	Ricany s.r.o.	Ricany
Estonia	Parnu Hospital, Psychiatric Clinic	Parnu
Estonia	Marienthal Psychiatry and Psychology Center	Tallinn
Estonia	North Estonia Medical Centre Foundation Psychiatry Clinic	Tallinn
Estonia	Jaanson & Laane OU	Tartu
Estonia	Tartu University Hospital Psychiatric Clinic	Tartu
Finland	ARTES Psykiatrinen Palvelukeskus Oy	Helsinki
Finland	Satucon Oy	Kuopio
Finland	Satakunnan Psykiatripalveiu Oy at Mentoria Oy	Tampere
Finland	Puutorin Psykiatripalvelu	Turku
Germany	Gemeinschafstpraxis für Neurologie und Psychiatrie, Psychotherapie	Achim
Germany	Alexander Schulze, MD	Berlin
Germany	emovis GmbH	Berlin
Germany	Private Praxis Dr. Jana Thomsen	Berlin
Germany	Private Practice Drs. Bitter/Schumann	Bochum
Germany	University Hospital Carl Gustav Carus	Dresden
Germany	ZSL Zentrum fuer medizinische Studien in Leipzig	Leipzig
Germany	Studienzentrum Muenchen	Muenchen
Germany	Universitaetsklinikum Munster	Muenster
Germany	Studienzentrum Klinikum Nuernberg	Nuernberg
Germany	Somni bene GmbH	Schwerin
Germany	Private Practice: Eugen Schlegel	Siegen
Germany	Studiezentrum Nord-West	Westerstede
Germany	Medizinisches Studienzentrum Wuerzburg	Wuerzburg
Hungary	Semmelweis Univ. Dept.of Psychiatry	Budapest
Hungary	Debrecent Egyetem Orvos es Egeszsegtudomanyl Centrum Pszichiatrai	Debrecen
Hungary	Santha Kalman Mentalis Egeszsegkozpont es Szakkorhaz	Nagykallo
Hungary	Josa Andras Teaching Hospital	Nyiregyhaza
Hungary	Pecsi Tudomanyegyeiem Pszichiatriai es Pszichoterapias Klinika	Sziget
Poland	Prywatne Gabinety Lekarskie "Promedicus"	Bialystok
Poland	NZOZ Centrum Kultury, Higieny i Zdrowia Psychicznego	Bydgoszcz
Poland	Zespol Opieki Zdrowotnej w Chelmnie	Chelmno
Poland	Centrum Badan Klinicznuch Pl-House sp. z.o.o.	Gdansk
Poland	Klinika Chorob Psychicznych i Zaburzen Nerwicowych	Gdansk
Poland	Centrum Psychiatrii i Psychoterapli	Gorlice
Poland	NZOZ Syntonia, Poradnia Zdrowia Psychicznego	Kielce
Poland	Osrodek Badafi Klinicznych Prof dr hab n med Meszek Szczepanski Prywatna Praktyka Lekarska	Lublin
Poland	Samodzielny Publiczny Zespol Zakladow Opieki Zdrowotnej w Zurominie	Zuromin
Romania	Spitatul Clinic Judetean de Urgenta Arad, Clinica de Psihiatrie	Arad
Romania	Stefi-Dent SRL	Botosani
Romania	Spitalui Clinic de Psihiatrie "Prof. Dr. Alexandru Obregia" Sectia Clinica Psihiatrie I	Bucharest
Romania	Crucea Alba	Oradea
Romania	Lorentina 2201 SRL	Targoviste
Romania	Spitalul Clinic Judetean Mures	Targu Mures
South Africa	Cape Trial Centre	Bellville	Cape Town
South Africa	Flexivest Fourteen Research Centre	Bellville	Cape Town
South Africa	Vista Clinic	Centurion
South Africa	George Medi Clinic Extension	George
South Africa	Private Practice - Gerta Brink	Johannesburg	Gauten
South Africa	Somerset West Clinical Research	Somerset West	Western Cape
Sweden	SU/ Affektiva 1	Göteborg
Sweden	ProbarE i Lund AB	Lund
Sweden	Ekdahl Medical AB	Malmo
Sweden	INM Psykiatrisk Mottagning	Malmo
Sweden	Medinstructor Lippitz AB	Stockholm
Sweden	Dr. Wahlstedts mottagning	Uppsala
United States	Lehigh Center for Clinical Research	Allentown	Pennsylvania
United States	Atlanta Center for Medical Research	Atlanta	Georgia
United States	Atlanta Institute of Medicine & Research	Atlanta	Georgia
United States	Florida Clinical Research Center, LLC	Bradenton	Florida
United States	Brooklyn Medical Institute	Brooklyn	New York
United States	MCB Clinical Research Centers	Colorado Springs	Colorado
United States	ATP Clinical Research, Inc.	Costa Mesa	California
United States	Future Search Trials of Dallas, LP	Dallas	Texas
United States	KRK Medical Research	Dallas	Texas
United States	Midwest Clinical Research Center	Dayton	Ohio
United States	Diligent Clinical Trials	Downey	California
United States	Synergy Clinical Reserach Center of Escondido	Escondido	California
United States	Psychiatric Consultants, PC	Franklin	Tennessee
United States	Comprehensive Psychiatric Associates	Gladstone	Missouri
United States	The Center for Pharmaceutical Research	Kansas City	Missouri
United States	K&S Professional Research Services, LLC	Little Rock	Arkansas
United States	Research Strategies of Memphis, LLC	Memphis	Tennessee
United States	North Star Medical Research, LLC	Middleburg Heights	Ohio
United States	Medical & Behavioral Health Research, PC	New York	New York
United States	Pedia Research	Newburgh	Indiana
United States	Medical University South Carolina Anxiety Disorder Program	North Charleston	South Carolina
United States	Scientific Clinical Research, Inc.	North Miami	Florida
United States	Pacific Research Partners, LLC	Oakland	California
United States	Sooner Clinical Research	Oklahoma City	Oklahoma
United States	Clinical Neuroscience Solutions, Inc.	Orlando	Florida
United States	Belmont Center for Comprehensive Treatment	Philadelphia	Pennsylvania
United States	Anderson Clinical Research	Redlands	California
United States	Mercy Health Research	Saint Louis	Missouri
United States	Comprehensive NeuroScience, Inc.	Saint Petersburg	Florida
United States	Clinical Trials of Texas, Inc.	San Antonio	Texas
United States	BreakThrough Clinical Trials, LLC	San Bernardino	California
United States	ResearchOne, Inc.	Scottsdale	Arizona
United States	Louisiana Clinical Research, LLC	Shreveport	Louisiana
United States	Bio Behavioral Health	Toms River	New Jersey
United States	Janus Center for Psychiatric Research	West Palm Beach	Florida
United States	Heartland Research Associates	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Shire

Countries where clinical trial is conducted

United States,  Belgium,  Czechia,  Estonia,  Finland,  Germany,  Hungary,  Poland,  Romania,  South Africa,  Sweden, 

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 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	Mean Change From Baseline in Sheehan Disability Scale (SDS) Total Score at 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 the Lead-in Baseline, Visit 2).	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 the Lead-in Baseline, Visit 2).	Up to 8 weeks
Secondary	Percent of Participants Achieving Remission on the MADRS	MADRS remission was defined as a MADRS total score of =10.	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.	Up to 8 weeks
Secondary	Mean Change From Baseline in Abbreviated Brief Assessment of Cognition Affective Disorders (ABAC-A) Composite T-Scores	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.	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 in Sexual Functioning Questionnaire - 14 Item Scale (CSFQ-14) Total Score Male	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.	Up to 8 weeks
Secondary	Mean Change in Sexual Functioning Questionnaire - 14 Item Scale (CSFQ-14) Total Score Female	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.	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	Mean Change From Baseline in the Multidimensional Assessment of Fatigue (MAF) Global Fatigue Index (GFI)	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.	Up to 8 weeks
Secondary	Columbia Suicide Severity Rating Scale (C-SSRS)	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.	Up to 8 weeks
Secondary	Amphetamine Cessation Symptom Assessment (ACSA) - Total Aggregate Score	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.	8 weeks