Effectiveness of Vyvanse Compared to Concerta in Adolescents With Attention-deficit/Hyperactivity Disorder

A Phase 4, Randomized, Double-blind, Multicenter, Parallel-group, Active-controlled, Forced-dose Titration, Safety and Efficacy Study of SPD489 (VYVANSE®) Compared With OROS-MPH (CONCERTA®) With a Placebo Reference Arm, in Adolescents Aged 13-17 Years With Attention-deficit/Hyperactivity Disorder (ADHD)

The purpose of this study is to determine effectiveness of Vyvanse compared to Concerta in adolescents with Attention-deficit/Hyperactivity Disorder (ADHD).

Study Overview

• Status: Completed
• Conditions: Attention-deficit/Hyperactivity Disorder
• Intervention / Treatment: Drug: Lisdexamfetamine dimesylate; Drug: Methylphenidate Hydrochloride; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 549
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Nova Scotia
    • Kentville, Nova Scotia, Canada, B4N 4K9
      • True North Clinical Research
  • Ontario
    • Whitby, Ontario, Canada, L1N 2L1
      • The Kids Clinic
• Germany
  • Bamberg, Germany, 96047
    • Schwerpunktpraxis für Entwicklung und Lernen
  • Frankfurt, Germany, 15236
    • Klinik Fur Kinder- und Jugendpsychiatrie, Psychosomatik und Psychotherapie
  • Freiburg, Germany, 79104
    • Universitätsklinikum Freiburg
  • Hamburg, Germany, 22415
    • Kinderarztpraxis Dr. Kaiser und Dr. MarineBe
  • Mannheim, Germany, 68159
    • Zentralinstitut für Seelische Gesundheit
  • Wurzburg, Germany, 97070
    • Medizinisches Studienzentrum Würzburg
• Hungary
  • Budapest, Hungary, H-1021
    • Vadaskert Gyermekpszichiatriai Korhaz es Szakambulancia
  • Gyula, Hungary, H-5700
    • Békés Megyei Pándy Kálmán Kórház
  • Pecs, Hungary, H-7632
    • Pecsi Megyei Jogu varos Egyesitett Egeszsegugyi Intezmenyek
  • Szeged, Hungary, H-6725
    • Szegedi Tudomanyegyetem
• Sweden
  • Goteborg, Sweden, 411 19
    • Gillbergcentrum
  • Spanga, Sweden, 163 74
    • PRIMA Barn-och Vuxenpsykiatri Jarva
• United States
  • Alabama
    • Dothan, Alabama, United States, 36303
      • Harmonex Neuroscience Research, Inc.
  • Arizona
    • Tucson, Arizona, United States, 85719
      • Center for Advanced Improvement
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
      • Clinical Study Centers, LLC
  • California
    • Colton, California, United States, 92324
      • Shanti Clinical Trials
    • Imperial, California, United States, 92251
      • Sun Valley Research Center
    • National City, California, United States, 91950
      • Synergy Clinical Research Center
    • Oceanside, California, United States, 92054
      • Pacific Sleep Medicine, A Medical Corporation
    • Orange, California, United States, 92868
      • Neuropsychiatric Research Center for Orange County
    • Rolling Hills Estates, California, United States, 90274
      • Peninsula Research Associates
    • San Diego, California, United States, 92108
      • PCSD - Feighner Research
    • San Francisco, California, United States, 94143
      • University of California, San Francisco
    • Spring Valley, California, United States, 91978
      • Encompass Clinical Research
    • Wildomar, California, United States, 92595
      • Elite Clinical Trials
  • Colorado
    • Centennial, Colorado, United States, 80112
      • IMMUNOe International Research Center
    • Colorado Springs, Colorado, United States, 80910
      • MCB Clinical Research Centers, LLC
  • Connecticut
    • New London, Connecticut, United States, 06320
      • Coastal Connecticut Research, LLC
  • Florida
    • Bradenton, Florida, United States, 34201
      • Florida Clinical Research Center, LLC
    • Hialeah, Florida, United States, 33013
      • Amedica Research Institute, Inc
    • Jacksonville, Florida, United States, 32256
      • Clinical Neuroscience Solutions, Inc
    • Lake City, Florida, United States, 32055
      • Sarkis Clinical Trials
    • Maitland, Florida, United States, 32751
      • Florida Clinical Research Center, LLC
    • Miami, Florida, United States, 33169
      • Prevention & Strengthening Solutions, Inc.
    • North Miami, Florida, United States, 33161
      • Scientific Clinical Research, Inc.
    • Orange City, Florida, United States, 32763
      • Medical Research Group of Central Florida
    • Orlando, Florida, United States, 32806
      • Compass Research, LLC
    • Orlando, Florida, United States, 32806
      • Clinical Neuroscience Solutions, Inc.
    • South Miami, Florida, United States, 33143
      • Miami Research Associates
    • Tampa, Florida, United States, 33613
      • Stedman Clinical Trials
  • Georgia
    • Atlanta, Georgia, United States, 30328
      • Atlanta Institute of Medicine & Research, Inc
  • Illinois
    • Chicago, Illinois, United States, 60608
      • Clinical Research Center, University of Illinois at Chicago
    • Libertyville, Illinois, United States, 60048
      • Capstone Clinical Research
    • Naperville, Illinois, United States, 60563
      • Baber Research Group
  • Indiana
    • Newburgh, Indiana, United States, 47630
      • Pedia Research, LLC
  • Kansas
    • Overland Park, Kansas, United States, 66211
      • Psychiatric Associates
  • Kentucky
    • Owensboro, Kentucky, United States, 42301
      • Pedia Research, LLC
  • Louisiana
    • New Orleans, Louisiana, United States, 70114
      • Louisiana Resarch Associates, Inc.
  • Maryland
    • Rockville, Maryland, United States, 20852
      • Marc Hertzman, MD, PC
  • Michigan
    • Rochester Hills, Michigan, United States, 48307
      • Rochester Center for Behavioral Medicine
    • Sterling Heights, Michigan, United States, 48314
      • Clinical Neurophysiology Services, PC
    • Troy, Michigan, United States, 48083
      • Behavioral Medical Center - Troy
  • Missouri
    • Gladstone, Missouri, United States, 64118
      • Comprehensive Psychiatric Associates
    • O'Fallon, Missouri, United States, 63368
      • Psychiatric Care & Research Center
    • Saint Charles, Missouri, United States, 63301
      • St. Charles Psychiatric Associates - Midwest Research Group
  • Nebraska
    • Lincoln, Nebraska, United States, 68526
      • Premier Psychiatric Research Institute, LLC
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center Dept Of Psychiatry
  • Nevada
    • Las Vegas, Nevada, United States, 89128
      • Center for Psychiatry & Behavioral Medicine, Inc.
  • New Jersey
    • Cherry Hill, New Jersey, United States, 08002
      • Center For Emotional Fitness
    • Mount Arlington, New Jersey, United States, 07856
      • The NeuroCognitive Institute
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • Albuquerque Neuroscience, Inc.
  • New York
    • New York, New York, United States, 10023
      • Brain Resource Center
    • New York, New York, United States, 10029
      • Mount Sinai School of Medicine/Dept of Psychiaatry
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University medical Center/ Duke ADHD Program
    • Wilmington, North Carolina, United States, 28401
      • PMG Research of Wilmington
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati College of Medicine/UCPC
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Nisonger Center
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74104
      • Tulsa Clinical Research, LLC
  • Oregon
    • Gresham, Oregon, United States, 97030
      • Cyn3rgy Research
    • Portland, Oregon, United States, 97210
      • Summit Research Network
    • Portland, Oregon, United States, 97210
      • Oregon Center for Clinical Investigations Inc
    • Salem, Oregon, United States, 97301
      • Oregon Center for Clinical Investigations, Inc
  • Pennsylvania
    • West Chester, Pennsylvania, United States, 19380
      • University Services
  • Rhode Island
    • Warwick, Rhode Island, United States, 02886
      • Omega Medical Research
  • South Carolina
    • Barnwell, South Carolina, United States, 29812
      • Rainbow Research, Inc.
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • Clinical Neuroscience Solutions, Inc.
  • Texas
    • Dallas, Texas, United States, 75231
      • FutureSearch Trials of Dallas, LP
    • Dallas, Texas, United States, 75234
      • Research Across America/Psychiatric Medical Associates
    • Houston, Texas, United States, 77090
      • Red Oak Psychiatry Associates, PA
    • Houston, Texas, United States, 77081
      • Texas Center for Drug Development, Inc.
    • Houston, Texas, United States, 77074
      • Clinical Trial Network
    • Houston, Texas, United States, 77008
      • Claghorn-Lesem Research Clinic, Ltd.
    • Houston, Texas, United States, 77007
      • Bayou City Research
    • Houston, Texas, United States, 77098
      • Houston Clinical Trials, LLC
    • Lubbock, Texas, United States, 79423
      • Westex Clinical Investigations
    • San Antonio, Texas, United States, 78229
      • Clinical Trials of Texas, Inc.
    • San Antonio, Texas, United States, 78229
      • Univ of Texas Health Science Center at San Antonio
  • Utah
    • Clinton, Utah, United States, 84015
      • Ericksen Research and Development - Westside Medical
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia Child and Family Psychiatry Clinic
  • Washington
    • Bellevue, Washington, United States, 98007
      • Northwest Clinical Research Center
    • Kirkland, Washington, United States, 98033
      • Eastside Thereapeutic Resource
    • Seattle, Washington, United States, 98104
      • Summit Research Network (Seattle), LLC
    • Spokane, Washington, United States, 99202
      • Rockwood Clinic, P.S.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years to 17 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subject must be 13-17 years of age, inclusive, at the time of consent.
• Subject must weigh more than 79.5lb.
• The parent/LAR must be available at approximately 7:00AM (±2 hours) to dispense the dose of investigational product for the study duration.
• Subject, who is a female, must have a negative serum beta human chorionic gonadotropin (β-HCG) pregnancy test and a negative urine pregnancy test and agree to comply with any applicable contraceptive requirements of the protocol.
• Subject has an ADHD-RS-IV total score ≥28.
• Subject is able to swallow a capsule.
• Subject does not have hypertension and has a resting sitting blood pressure less than or equal to 135/85mmHg.

Exclusion Criteria

• Subject has a current, controlled (with medications prohibited in this study) or uncontrolled, comorbid psychiatric diagnosis with significant symptoms such as any significant comorbid Axis II disorder or significant Axis I disorder (such as post traumatic stress disorder, psychosis, bipolar illness, pervasive developmental disorder, severe obsessive compulsive disorder, depressive or anxiety disorder.
• Diagnosis of conduct disorder. Oppositional defiant disorder is not exclusionary.
• Subject is considered a suicide risk, has previously made a suicide attempt, or is currently demonstrating active suicidal ideation. Subjects with intermittent passive suicidal ideation are not necessarily excluded.
• Subject is underweight or overweight.
• Subject has a concurrent chronic or acute illness (such as severe allergic rhinitis or an infectious process requiring antibiotics), disability, or other condition. Mild, stable asthma is not exclusionary.
• Subject has a history of seizures (other than infantile febrile seizures), a chronic or current tic disorder, or a current diagnosis and/or a known family history of Tourette's Disorder.
• Subject has a 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 him/her at increased vulnerability to the sympathomimetic effects of a stimulant medication.
• Subject has a known family history of sudden cardiac death or ventricular arrhythmia.
• Subject has any clinically significant ECG or clinically significant laboratory abnormality.
• Subject has current abnormal thyroid function, defined as abnormal thyroid stimulating hormone (TSH) and thyroxine (T4). Treatment with a stable dose of thyroid medication for at least 3 months is permitted.
• Subject has a documented allergy, hypersensitivity, or intolerance to amphetamine or to any excipients in the investigational product.
• Subject has a documented allergy, hypersensitivity, or intolerance to MPH or to any excipients in the reference product.
• Subject has failed to fully respond to an adequate course(s) (dose and duration) of MPH or amphetamine therapy.
• Subject has a history of suspected substance abuse or dependence disorder (excluding nicotine). Subjects with a lifetime history of amphetamine, cocaine, or other stimulant abuse and/or dependence will be excluded.
• Subject has a positive urine drug result.
• Subject has previously participated in this study or another clinical study involving SPD489/NRP104.
• Subject has glaucoma.
• Subject is required to take or anticipates the need to take medications that have CNS effects or affect performance, such as sedating antihistamines and decongestant sympathomimetics, or are monoamine oxidase inhibitors. Stable use of bronchodilator inhalers is not exclusionary.
• Subject is female and is pregnant or lactating.
• Subject is well controlled on his/her current ADHD medication.
• Subject has a pre-existing severe gastrointestinal tract narrowing.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: Placebo; Daily oral dosing in the AM for 6 weeks
EXPERIMENTAL: Lisdexamfetamine dimesylate	Drug: Lisdexamfetamine dimesylate; Daily oral dosing in the AM ranging from 30- 70 mg. 4 week forced dose titration, 2 week dose maintenance; Other Names: SPD489, Vyvanse, LDX
ACTIVE_COMPARATOR: Methylphenidate Hydrochloride	Drug: Methylphenidate Hydrochloride; Daily oral dosing in the AM ranging from 18-72 mg. 4 week force dose titration, 2 week dose maintenance; Other Names: Concerta, OROS-MPH

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Attention-Deficit/Hyperactivity Disorder Rating Scale, Fourth Edition (ADHD-RS-IV) Total Score at Week 6	The ADHD-RS-IV was developed to measure the behaviors of children with ADHD and is commonly used in clinical studies of ADHD. The ADHD-RS-IV consisted of 18 items designed to reflect current symptomatology of ADHD based on Diagnostic and Statistical Manual of Mental Disorders, 4th Edition-Text Revision (DSM-IV-TR) criteria. Each item was scored on a 4-point scale ranging from 0 (reflecting no symptoms) to 3 (reflecting severe symptoms) with total scores ranging from 0-54, Higher score = more severe symptoms.	Baseline, Week 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With an Improvement on Clinical Global Impression - Global Improvement (CGI-I) at Week 6	The Clinical Global Impressions Scale permits a global evaluation of the participant's severity of illness and improvement over time. The scale included a severity of illness item and a global improvement item. The investigator performed the CGI-I to rate the improvement of a participant's ADHD symptoms based on a 7-point scale (1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; or 7=very much worse.). Percentage of participants with an improved measurement (response of very much improved and much improved) is reported.	Week 6

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs	An adverse event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered as a pharmaceutical product that did not necessarily have a causal relationship with this treatment. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs were events between first dose of double-blind investigational product and up to 3 days after last dose that were absent before treatment or that worsened relative to pretreatment state.	Baseline up to 3 days after last dose (last dose at Week 6)
Change From Baseline in Blood Pressure at Week 6		Baseline, Week 6
Change From Baseline in Pulse Rate at Week 6		Baseline, Week 6

Collaborators and Investigators

• Sponsor: Shire

Publications and helpful links

General Publications

• Newcorn JH, Nagy P, Childress AC, Frick G, Yan B, Pliszka S. Randomized, Double-Blind, Placebo-Controlled Acute Comparator Trials of Lisdexamfetamine and Extended-Release Methylphenidate in Adolescents With Attention-Deficit/Hyperactivity Disorder. CNS Drugs. 2017 Nov;31(11):999-1014. doi: 10.1007/s40263-017-0468-2.

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 3, 2012
• Primary Completion (ACTUAL): May 22, 2014
• Study Completion (ACTUAL): May 22, 2014

Study Registration Dates

• First Submitted: March 6, 2012
• First Submitted That Met QC Criteria: March 9, 2012
• First Posted (ESTIMATE): March 13, 2012

Study Record Updates

• Last Update Posted (ACTUAL): June 10, 2021
• Last Update Submitted That Met QC Criteria: May 29, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: ADHD
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Dyskinesias; Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Attention Deficit Disorder with Hyperactivity; Hyperkinesis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Dopamine Agents; Dopamine Uptake Inhibitors; Central Nervous System Stimulants; Methylphenidate; Lisdexamfetamine Dimesylate
• Other Study ID Numbers: SPD489-406; 2011-005452-34 (EUDRACT_NUMBER)