SPD489 in Combination With an Antidepressant in the Treatment of Adults With Major Depressive Disorder

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

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?

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: Antidepressant + SPD489 (Lisdexamfetamine dimesylate) 10 mg; Drug: Antidepressant + SPD489 (Lisdexamfetamine dimesylate) 30 mg; Drug: Antidepressant + SPD489 (Lisdexamfetamine dimesylate) 50 mg; Drug: Antidepressant + SPD489 (Lisdexamfetamine dimesylate) 70 mg; Drug: Antidepressant + Placebo

• Study Type: Interventional
• Enrollment (Actual): 1197
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1405BOA
    • Instituto Nacional de Psicopatologia
  • Buenos Aires, Argentina
    • Cervino
  • Caba, Argentina, 1417
    • Centro Medico de Medicina Familiar Mind Out Research
  • Caba, Argentina, C1012AAU
    • BA Psychiatric Research Center
  • Cordoba, Argentina
    • Instituto Medico SAMIC
• Australia
  • Elizabeth Vale, Australia, 5112
    • Lyell McEwin Hospital, Mental Health Clinical Trials Unit
  • Victoria
    • Frankston, Victoria, Australia, 3199
      • Peninsula Health Mental Health Services
    • Malvern, Victoria, Australia, 3144
      • Neurotherapy Victoria
    • Melbourne, Victoria, Australia, 3004
      • The Alfred, Monash Alfred Psychiatry Research Centre
    • Richmond, Victoria, Australia, 3121
      • The Melbourne Clinic
• Chile
  • Il Region
    • Antofagasta, Il Region, Chile, 1270244
      • Psocomed Estudios Medicos
  • Santiago
    • Las Condes, Santiago, Chile, 7560356
      • Especialidades Medicas L Y S
    • Las Condes, Santiago, Chile, 7580307
      • Centro de Estudios y Tratemiento de Enfermedades Psiquiatricas
    • Providencia, Santiago, Chile, 7500710
      • BioMedica Research Group
    • Providencia, Santiago, Chile, 7510186
      • Centro de Estudios Clinicos
    • San Bernardo, Santiago, Chile, 8053095
      • Unidad de Salud Mental y Psiquietriea Hospital y CRS El Pino
    • San Miguel, Santiago, Chile, 890085
      • Hospital Barros Luco Trudsau
• United Kingdom
  • Derby, United Kingdom, DE22 3NE
    • Radbourne Unit
  • Horsham, United Kingdom, RH12 1RJ
    • ADHD Mental Health Research Unit
  • Newcastle upon Tyne, United Kingdom, NE4 5PL
    • Newcastle University, Wolfson Research Centre
  • Nottingham, United Kingdom, NG2 7PG
    • Rushcliffe Mental Health Team
  • Warrington Cheshire
    • Winwick, Warrington Cheshire, United Kingdom, WA2 8WA
      • Hollins Park Hospital
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72223
      • Arkansas Psychiatric Clinic Clinical Research Trials
  • California
    • Anaheim, California, United States, 92804
      • South Coast Clinical Trials
    • Chino, California, United States, 91710
      • Catalina Research Institute, LLC
    • Colton, California, United States, 92324
      • Shanti Clinical Trials
    • Costa Mesa, California, United States, 92626
      • Clinical Innovation, Inc.
    • Garden Grove, California, United States, 92845
      • Collaborative Neuroscience Network, Inc.
    • Irvine, California, United States, 92618
      • Irvine Center for Clinical Research
    • La Habra, California, United States, 90631
      • Omega Clinical Trials
    • Los Angeles, California, United States, 90024
      • Provate Practice of Andrew Leuchter, MD
    • San Diego, California, United States, 92108
      • PCSD - Feighner Research
    • San Diego, California, United States, 92123
      • Artemis Institute for Clinical Research
    • Santa Ana, California, United States, 92701
      • Neuropsychiatric Research Center of Orange County
    • Sherman Oaks, California, United States, 91403
      • California Neuroscience Research Medical Group, Inc.
  • Colorado
    • Denver, Colorado, United States, 80209
      • Western Affiliated Research Institute
  • Connecticut
    • Cromwell, Connecticut, United States, 06416
      • Connecticut Clinical Research
    • Hartford, Connecticut, United States, 06106
      • Institute of Living
    • New Britain, Connecticut, United States, 06050
      • The Hospital of Central Connecticut, Psychiatry & Behavioral Health Research
  • Florida
    • Fort Myers, Florida, United States, 33912
      • Gulfcoast Clinical Research Center
    • Gainesville, Florida, United States, 32607
      • Sarkis Clinical Trials
    • Jacksonville, Florida, United States, 32216
      • Clinical Neuroscience Solutions, Inc.
    • Jacksonville, Florida, United States, 32256
      • Private Practice - Amit Vijapura MD
    • Lake City, Florida, United States, 32025
      • Psychiatric Associates
    • Miramar, Florida, United States, 33027
      • Comprehensive NeuroScience, Inc.
    • North Miami, Florida, United States, 33161
      • Fideltiy Clinical Research, Inc.
    • Orlando, Florida, United States, 32839
      • Ali A. Kashfi, MD, PA
    • Winter Haven, Florida, United States, 33880
      • Clinical Research of Central Florida
    • Winter Park, Florida, United States, 32789
      • Kolin Research Group
  • Georgia
    • Smyrna, Georgia, United States, 30080
      • Institute For Behavioral Medicine, Llc
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Treatment Research Center, Rush University Medical Center
    • Hoffman Estates, Illinois, United States, 60169
      • Alexian Brothers Center for Psychiatric Research
    • Skokie, Illinois, United States, 60076
      • Psychiatric Medicine Associates, LLC
    • Vernon Hills, Illinois, United States, 60061
      • Sleep and Behavior Medicine Institute
  • Kansas
    • Prairie Village, Kansas, United States, 66206
      • Clinical Trials Technology, Inc.
  • Kentucky
    • Owensboro, Kentucky, United States, 42301
      • Pedia Research, LLC
  • Missouri
    • O'Fallon, Missouri, United States, 63368
      • Psyichatric Care and Research Center
    • Saint Louis, Missouri, United States, 63109
      • Mid-America Clinical Research, LLC
  • Nebraska
    • Lincoln, Nebraska, United States, 68526
      • Premier Psychiatric Research Institute, LLC.
  • Nevada
    • Las Vegas, Nevada, United States, 89119
      • Clinical Research Consortium
  • New Jersey
    • Cherry Hill, New Jersey, United States, 08002
      • Center for Emotional Fitness
    • Willingboro, New Jersey, United States, 08046
      • CRI Worldwide LLC
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • Albuquerque Neuroscience, Inc.
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center
    • New York, New York, United States, 10010
      • Clinlabs, Inc.
    • New York, New York, United States, 11029
      • Mount Sinai School of Medicine
    • West Seneca, New York, United States, 14224
      • Private Practice - Daniel I. Rifkin MD PC
  • North Carolina
    • Hickory, North Carolina, United States, 28601
      • Clinical Trials of America, Inc.
  • Ohio
    • Beachwood, Ohio, United States, 44122
      • North Coast Clinical Trials, Inc.
    • Columbus, Ohio, United States, 43210
      • Ohio State University, Dept. of Psychiatry
    • Toledo, Ohio, United States, 43623
      • Neurology & Neuroscience Center Of Ohio
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73103
      • IPS Research Company
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
    • West Chester, Pennsylvania, United States, 19380
      • University Services
  • Texas
    • Dallas, Texas, United States, 75243
      • Pillar Clinical Research, LLC
    • Friendswood, Texas, United States, 77546
      • Bay Area Clinical Services
    • Houston, Texas, United States, 77098
      • Houston Clinical Trials, LLC
    • Wharton, Texas, United States, 77488
      • Wharton Research Center, Inc.
    • Wichita Falls, Texas, United States, 76309
      • Grayline Clinical Drug Trials
  • Virginia
    • Richmond, Virginia, United States, 23230
      • Alliance Research Group
  • Wisconsin
    • Middleton, Wisconsin, United States, 53562
      • Dean Foundation for Health, Research and Education, Inc.
    • Waukesha, Wisconsin, United States, 53188
      • Independent Psychiatric Consultants, Sc, Dba, Ipc Research

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 18-65 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Antidepressant + SPD489 10 mg	Drug: Antidepressant + SPD489 (Lisdexamfetamine dimesylate) 10 mg; Antidepressant + SPD489 oral, 10 mg, once daily for 8 weeks; Other Names: Vyvanse
EXPERIMENTAL: Antidepressant + SPD489 30 mg	Drug: Antidepressant + SPD489 (Lisdexamfetamine dimesylate) 30 mg; Antidepressant + SPD489 oral, 30 mg, once daily for 8 weeks; Other Names: Vyvanse
EXPERIMENTAL: Antidepressant + SPD489 50 mg	Drug: Antidepressant + SPD489 (Lisdexamfetamine dimesylate) 50 mg; Antidepressant + SPD489 oral, 50 mg, once daily for 8 weeks; Other Names: Vyvanse
EXPERIMENTAL: Antidepressant + SPD489 70 mg	Drug: Antidepressant + SPD489 (Lisdexamfetamine dimesylate) 70 mg; Antidepressant + SPD489 oral, 70 mg, once daily for 8 weeks; Other Names: Vyvanse
PLACEBO_COMPARATOR: Antidepressant + Placebo	Drug: Antidepressant + Placebo; oral, once daily for 8 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	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. CHange in MADRS total score in Augmentsion Baseline to Week 16.	Augmentation Baseline (Week 8) to Week 16

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in Average Systolic Blood Pressure From Augmentation Baseline (Week 8) to Week 16	From Augmentation Baseline (Week 8) to Week 16
Change in Average Diastolic Blood Pressure From Augmentation Baseline (Week 8) to Week 16	From Augmentation Baseline (Week 8) to Week 16
Change in Average Pulse Rate From Augmentation Baseline (Week 8) to Week 16	From Augmentation Baseline (Week 8) to Week 16

Collaborators and Investigators

• Sponsor: Shire

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 31, 2011
• Primary Completion (ACTUAL): January 17, 2014
• Study Completion (ACTUAL): January 17, 2014

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: SPD489-209; 2011-003615-28 (EUDRACT_NUMBER)