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

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

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?

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: Antidepressant + SPD489 (Lisdexamfetamine dimesylate ); Drug: Antidepressant + Placebo

• Study Type: Interventional
• Enrollment (Actual): 1105
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Sint Niklaas, Belgium, 9100
    • Dr Lieven De Weirdt
• Czechia
  • Brno, Czechia, 60200
    • Saint Anne s.r.o.
  • Brno, Czechia, 615 00
    • Psychiatricka ambulance
  • Horovice, Czechia, 268 01
    • Medicana s.r.o.
  • Kutna Hora, Czechia, 284 01
    • Psychiatrie s.r.o.
  • Litomerice, Czechia, 41201
    • Bialbi s.r.o.
  • Prague 10, Czechia, 10000
    • Clintrial s.r.o.
  • Prague 5, Czechia, 15800
    • Psychiatry Trial s.r.o.
  • Prague 6, Czechia, 160 00
    • Prague Medical Services s.r.o.
  • Ricany, Czechia, 251 01
    • Ricany s.r.o.
• Estonia
  • Parnu, Estonia, 80012
    • Parnu Hospital, Psychiatric Clinic
  • Tallinn, Estonia, 10614
    • North Estonia Medical Centre Foundation Psychiatry Clinic
  • Tallinn, Estonia, 10617
    • Marienthal Psychiatry and Psychology Center
  • Tartu, Estonia, 50406
    • Jaanson & Laane Ou
  • Tartu, Estonia, 50417
    • Tartu University Hospital Psychiatric Clinic
• Finland
  • Helsinki, Finland, 00100
    • ARTES Psykiatrinen Palvelukeskus Oy
  • Kuopio, Finland, 70100
    • Satucon oy
  • Tampere, Finland, 26200
    • Satakunnan Psykiatripalveiu Oy at Mentoria Oy
  • Turku, Finland, 20100
    • Puutorin Psykiatripalvelu
• Germany
  • Achim, Germany, 28832
    • Gemeinschafstpraxis für Neurologie und Psychiatrie, Psychotherapie
  • Berlin, Germany, 10629
    • emovis GmbH
  • Berlin, Germany, 10245
    • Private Praxis Dr. Jana Thomsen
  • Berlin, Germany, 13156
    • Alexander Schulze, MD
  • Bochum, Germany, 44805
    • Private Practice Drs. Bitter/Schumann
  • Dresden, Germany, 01307
    • University Hospital Carl Gustav Carus
  • Leipzig, Germany, 04157
    • ZSL Zentrum fuer medizinische Studien in Leipzig
  • Muenchen, Germany, 80333
    • Studienzentrum Muenchen
  • Muenster, Germany, 48149
    • Universitaetsklinikum Munster
  • Nuernberg, Germany, 90419
    • Studienzentrum Klinikum Nuernberg
  • Schwerin, Germany, 19053
    • Somni Bene GmbH
  • Siegen, Germany, 57072
    • Private Practice: Eugen Schlegel
  • Westerstede, Germany, 26655
    • Studiezentrum Nord-West
  • Wuerzburg, Germany, 97070
    • Medizinisches Studienzentrum Wuerzburg
• Hungary
  • Budapest, Hungary, 1083
    • Semmelweis Univ. Dept.of Psychiatry
  • Debrecen, Hungary, H-4032
    • Debrecent Egyetem Orvos es Egeszsegtudomanyl Centrum Pszichiatrai
  • Nagykallo, Hungary, 4320
    • Santha Kalman Mentalis Egeszsegkozpont es Szakkorhaz
  • Nyiregyhaza, Hungary, H-4400
    • Josa Andras Teaching Hospital
  • Sziget, Hungary
    • Pecsi Tudomanyegyeiem Pszichiatriai es Pszichoterapias Klinika
• Poland
  • Bialystok, Poland, 15-879
    • Prywatne Gabinety Lekarskie "Promedicus"
  • Bydgoszcz, Poland, 85-156
    • Nzoz Centrum Kultury, Higieny I Zdrowia Psychicznego
  • Chelmno, Poland, 86-200
    • Zespol Opieki Zdrowotnej w Chelmnie
  • Gdansk, Poland, 80-546
    • Centrum Badan Klinicznuch Pl-House sp. z.o.o.
  • Gdansk, Poland, 80-952
    • Klinika Chorob Psychicznych i Zaburzen Nerwicowych
  • Gorlice, Poland, 38-300
    • Centrum Psychiatrii i Psychoterapli
  • Kielce, Poland, 25-317
    • NZOZ Syntonia, Poradnia Zdrowia Psychicznego
  • Lublin, Poland, 20-022
    • Osrodek Badafi Klinicznych Prof dr hab n med Meszek Szczepanski Prywatna Praktyka Lekarska
  • Zuromin, Poland, 09-300
    • Samodzielny Publiczny Zespol Zakladow Opieki Zdrowotnej w Zurominie
• Romania
  • Arad, Romania, 310022
    • Spitatul Clinic Judetean de Urgenta Arad, Clinica de Psihiatrie
  • Botosani, Romania, 710107
    • Stefi-Dent SRL
  • Bucharest, Romania, 041915
    • Spitalui Clinic de Psihiatrie "Prof. Dr. Alexandru Obregia" Sectia Clinica Psihiatrie I
  • Oradea, Romania, 410163
    • Crucea Alba
  • Targoviste, Romania, 130081
    • Lorentina 2201 SRL
  • Targu Mures, Romania, 540095
    • Spitalul Clinic Judetean Mures
• South Africa
  • Centurion, South Africa, 0046
    • Vista Clinic
  • George, South Africa, 6529
    • George Medi Clinic Extension
  • Cape Town
    • Bellville, Cape Town, South Africa, 7530
      • Cape Trial Centre
    • Bellville, Cape Town, South Africa, 7530
      • Flexivest Fourteen Research Centre
  • Gauten
    • Johannesburg, Gauten, South Africa, 2195
      • Private Practice - Gerta Brink
  • Western Cape
    • Somerset West, Western Cape, South Africa
      • Somerset West Clinical Research
• Sweden
  • Göteborg, Sweden, 41685
    • SU/ Affektiva 1
  • Lund, Sweden, 22222
    • ProbarE i Lund AB
  • Malmo, Sweden, 21153
    • Ekdahl Medical AB
  • Malmo, Sweden, 21153
    • INM Psykiatrisk Mottagning
  • Stockholm, Sweden, 11486
    • Medinstructor Lippitz AB
  • Uppsala, Sweden, 75310
    • Dr. Wahlstedts mottagning
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85251
      • ResearchOne, Inc.
  • Arkansas
    • Little Rock, Arkansas, United States, 72201
      • K&S Professional Research Services, LLC
  • California
    • Costa Mesa, California, United States, 92626
      • ATP Clinical Research, Inc.
    • Downey, California, United States, 90241
      • Diligent Clinical Trials
    • Escondido, California, United States, 92025
      • Synergy Clinical Reserach Center of Escondido
    • Oakland, California, United States, 94612
      • Pacific Research Partners, LLC
    • Redlands, California, United States, 92374
      • Anderson Clinical Research
    • San Bernardino, California, United States, 92408
      • BreakThrough Clinical Trials, LLC
  • Colorado
    • Colorado Springs, Colorado, United States, 80910
      • MCB Clinical Research Centers
  • Florida
    • Bradenton, Florida, United States, 34201
      • Florida Clinical Research Center, LLC
    • North Miami, Florida, United States, 33161
      • Scientific Clinical Research, Inc.
    • Orlando, Florida, United States, 32806
      • Clinical Neuroscience Solutions, Inc.
    • Saint Petersburg, Florida, United States, 33716
      • Comprehensive NeuroScience, Inc.
    • West Palm Beach, Florida, United States, 33407
      • Janus Center For Psychiatric Research
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Atlanta Center for Medical Research
    • Atlanta, Georgia, United States, 30328
      • Atlanta Institute of Medicine & Research
  • Indiana
    • Newburgh, Indiana, United States, 47630
      • Pedia Research
  • Kansas
    • Wichita, Kansas, United States, 67207
      • Heartland Research Associates
  • Louisiana
    • Shreveport, Louisiana, United States, 71115
      • Louisiana Clinical Research, LLC
  • Missouri
    • Gladstone, Missouri, United States, 64118
      • Comprehensive Psychiatric Associates
    • Kansas City, Missouri, United States, 64114
      • The Center for Pharmaceutical Research
    • Saint Louis, Missouri, United States, 63141
      • Mercy Health Research
  • New Jersey
    • Toms River, New Jersey, United States, 08755
      • Bio Behavioral Health
  • New York
    • Brooklyn, New York, United States, 11214
      • Brooklyn Medical Institute
    • New York, New York, United States, 10023
      • Medical & Behavioral Health Research, PC
  • Ohio
    • Dayton, Ohio, United States, 45417
      • Midwest Clinical Research Center
    • Middleburg Heights, Ohio, United States, 44130
      • North Star Medical Research, LLC
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Sooner Clinical Research
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18104
      • Lehigh Center for Clinical Research
    • Philadelphia, Pennsylvania, United States, 19131
      • Belmont Center For Comprehensive Treatment
  • South Carolina
    • North Charleston, South Carolina, United States, 29406
      • Medical University South Carolina Anxiety Disorder Program
  • Tennessee
    • Franklin, Tennessee, United States, 37067
      • Psychiatric Consultants, PC
    • Memphis, Tennessee, United States, 38119
      • Research Strategies of Memphis, LLC
  • Texas
    • Dallas, Texas, United States, 75230
      • KRK Medical Research
    • Dallas, Texas, United States, 75231
      • Future Search Trials of Dallas, LP
    • San Antonio, Texas, United States, 78229
      • Clinical Trials of Texas, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Antidepressant + SPD489	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; Other Names: Vyvanse
Placebo Comparator: Antidepressant + Placebo	Drug: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
Percent of Participants Achieving Remission on the MADRS	MADRS remission was defined as a MADRS total score of ≤10.	Up to 8 weeks
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
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
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
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Shire

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): October 19, 2011
• Primary Completion (Actual): December 10, 2013
• Study Completion (Actual): December 10, 2013

Study Registration Dates

• First Submitted: September 15, 2011
• First Submitted That Met QC Criteria: September 16, 2011
• First Posted (Estimate): September 19, 2011

Study Record Updates

• Last Update Posted (Actual): June 9, 2021
• Last Update Submitted That Met QC Criteria: May 25, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Dopamine Agents; Dopamine Uptake Inhibitors; Central Nervous System Stimulants; Lisdexamfetamine Dimesylate; Antidepressive Agents
• Other Study ID Numbers: SPD489-323; 2011-003006-25 (EudraCT Number)