Comparison of Lisdexamfetamine Dimesylate With Atomoxetine HCl in Attention-Deficit/Hyperactivity Disorder (ADHD) Subjects With an Inadequate Response to Methylphenidate

A Phase 3b, Double-blind, Randomised, Active-controlled, Parallel Group Study to Assess the Time to Response of Lisdexamfetamine Dimesylate to Atomoxetine Hydrochloride in Children and Adolescents Aged 6-17 Years With Attention-Deficit/Hyperactivity Disorder (ADHD) Who Have Had an Inadequate Response to Methylphenidate Therapy

This study will evaluate how long it takes for ADHD symptoms to improve in subjects who are judged by the Investigator to have had an inadequate response to methylphenidate therapy. The study will also test the safety of Lisdexamfetamine Dimesylate and how well it works.

Study Overview

• Status: Completed
• Conditions: Attention-Deficit/Hyperactivity Disorder
• Intervention / Treatment: Drug: Lisdexamfetamine Dimesylate; Drug: Atomoxetine Hydrochloride

• Study Type: Interventional
• Enrollment (Actual): 267
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Antwerpen
    • Hoboken, Antwerpen, Belgium, 2660
      • ZiekenhuisNetwerk Antwerpen
  • Flemish Brabant
    • Leuven, Flemish Brabant, Belgium, 3000
      • Universitair Ziekenhuis Gasthuisberg
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6H 1P7
      • Child and Adolescent Centre
  • Ontario
    • Hamilton, Ontario, Canada, L8S 1B7
      • Centre for Anxiety Attention Deficit and Trauma
    • Oakville, Ontario, Canada, L6J 0B2
      • AK Karan Holdings, Ltd.
    • Whitby, Ontario, Canada, L1N 8M7
      • The Kids Clinic
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7N 0W8
      • University of Saskatchewan
• Germany
  • Baden-Wuerttemberg
    • Freiburg, Baden-Wuerttemberg, Germany, 79104
      • Albert-Ludwigs-Universität Freiburg
  • Baden-wuerttemberg
    • Mannheim, Baden-wuerttemberg, Germany, 68159
      • Zentralinstitut für Seelische Gesundheit Mannheim
  • Bayern
    • Bamberg, Bayern, Germany, 96047
      • Schwerpunktpraxis für Entwicklung und Lernen
    • Wurzburg, Bayern, Germany, 97070
      • Medizinisches Studienzentrum Würzburg
  • Brandenburg
    • Frankfurt/Oder, Brandenburg, Germany, 15236
      • Klinikum Frankfurt/Oder
  • Nordrhein-Westfalen
    • Hagen, Nordrhein-Westfalen, Germany, 58093
      • Praxis Dr. Wolff
• Hungary
  • Budapest, Hungary
    • Vadaskert Korhaz es Szakambulancia Gyermek es lfjusagpszichiatria
  • Gyula, Hungary, 5700
    • Bekes Megyei Kepviselotestulet Pandy Kalman Korhaza
  • Pecs, Hungary
    • Gyermek- es lfjusagpszichiatriai Szakrendeles es Gondozo
  • Csongrad
    • Szeged, Csongrad, Hungary, 6720
      • Szegedi Tudományegyetem Gyermek es lfjusagpszichlatrlai Osztaly
• Italy
  • Cagliari, Italy, 9124
    • Azienda Ospedaliero-Universitaria di Cagliari
• Poland
  • Kujawsko-Pomorskie
    • Bydgoszcz, Kujawsko-Pomorskie, Poland, 85-096
      • Katedra i Klinika Psychiatarii
  • Mazowieckie
    • Warszawa, Mazowieckie, Poland, 00-576
      • Samodzielny Publiczny Dzieciecy Szpital Kliniczny
• Spain
  • Badajoz, Spain, 6010
    • Complejo Hospitalario Universitario de Badajoz
  • Barcelona, Spain, 8036
    • Hospital Clínic i Provincial de Barcelona
  • Baleares
    • Palma de Mallorca, Baleares, Spain, 7198
      • Hospital Son Llatzer
  • Barcelona
    • Esplugues De Llobregat, Barcelona, Spain, 08950
      • Hospital Sant Joan de Deu
  • Malaga
    • Torremolinos, Malaga, Spain, 29620
      • Hospital Marítimo, Unidad de Salud Mental Infanto-Juvenil (USMI-J
  • Santa Cruz De Tenerife
    • San Cristobal De La laguna, Santa Cruz De Tenerife, Spain, 38320
      • Hospital Universitario de Canarias
• Sweden
  • Goteborg, Sweden, 411 18
    • Drottning Silvias barnsjukhus
  • Stockholm, Sweden, 141 86
    • Astrid Lindgren Children's Hospital/Karolinska University Hospital
• United Kingdom
  • Essex
    • Basildon, Essex, United Kingdom, SS16 5NL
      • Basildon Hospital
  • Scotland
    • Dundee, Scotland, United Kingdom, DD1 9SY
      • Tayside Children's Hospital
• United States
  • Alabama
    • Dothan, Alabama, United States, 36303
      • Harmonex Neuroscience Research, Inc
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Clinical Study Centers, LLC
  • California
    • Colton, California, United States, 92324
      • Shanti Clinical Trials
    • San Diego, California, United States, 92108
      • Psychiatric Centers at San Diego Feighner Research
    • Wildomar, California, United States, 92595
      • Elite Clinical Trials, Inc.
  • Florida
    • Gainesville, Florida, United States, 32607
      • Sarkis Clinical Trials
    • Hialeah, Florida, United States, 33013
      • Amedica Research Institute, Inc.
    • Lauderhill, Florida, United States, 33319
      • Fidelity Clinical Research, Inc.
    • Orlando, Florida, United States, 32806
      • Clinical Neuroscience Solutions, Inc
  • Georgia
    • Roswell, Georgia, United States, 30076
      • Northwest Behavioral Research Center
  • Illinois
    • Libertyville, Illinois, United States, 60048
      • Capstone Clinical Research
    • Naperville, Illinois, United States, 60563
      • Baber Psychiatric Associates
  • Indiana
    • Terre Haute, Indiana, United States, 47802
      • Clinco
  • Kansas
    • Wichita, Kansas, United States, 67207
      • Heartland Research Associates, LLC
  • Kentucky
    • Paducah, Kentucky, United States, 42003
      • Four Rivers Clinical Research, Inc
  • Louisiana
    • New Orleans, Louisiana, United States, 70114
      • Louisianna Research Associates
  • Maryland
    • Rockville, Maryland, United States, 20852
      • Office of Marc Hertzman, MD, PC
  • Michigan
    • Rochester Hills, Michigan, United States, 48307
      • Rochester Center for Behavioral Medicine
  • Missouri
    • Saint Charles, Missouri, United States, 63301
      • Midwest Research Group/Saint Charles Psychiatric Associates
  • Nebraska
    • Lincoln, Nebraska, United States, 68526
      • Premier Psychiatric Research Institute, LLC
  • Nevada
    • Las Vegas, Nevada, United States, 89128
      • Center for Psychiatry and Behavioral Medicine, Inc.
  • New Jersey
    • Toms River, New Jersey, United States, 08755
      • Children's Specialized Hospital
  • New York
    • Staten Island, New York, United States, 10312
      • Richmond Behavioral Associates
  • North Carolina
    • Durham, North Carolina, United States, 27707
      • Triangle Neuropsychiatry, PLLC
  • North Dakota
    • Fargo, North Dakota, United States, 58103
      • Innovis Health
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73103
      • IPS Research Company
  • Oregon
    • Gresham, Oregon, United States, 97030
      • Cyn3rgy Research
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19139
      • CRI Worldwide, LLC Kirkbride Division
  • Texas
    • Austin, Texas, United States, 78731
      • Future Search Clinical Trials
    • Houston, Texas, United States, 77090
      • Red Oak Psychiatry Association, PA
    • Lubbock, Texas, United States, 79423
      • Western Clinical Investigations
    • San Antonio, Texas, United States, 78247
      • Cerebral Research, LLC
  • Utah
    • Salt Lake City, Utah, United States, 84106
      • Lifetree Clinical Research
  • Washington
    • Kirkland, Washington, United States, 98033
      • Eastside Therapeutic Resource

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subject has had an historical or current inadequate response to methylphenidate (MPH) treatment. Inadequate response includes but is not limited to the presence of some residual symptoms, with associated impairment inadequate duration of action and/or variability of symptom control, and/or Investigator feels that the subject may derive benefit from an alternative drug treatment to MPH therapy.
• Subject is a male or female aged 6-17 years inclusive at the time of consent
• Subject must meet Diagnostic and Statistical Manual of Mental Disorders, fourth edition. - Text Revision (DSM IV TR) criteria for a primary diagnosis of ADHD based on a detailed psychiatric evaluation
• Subject must have a baseline ADHD-RS-IV total score 28.

Exclusion Criteria:

• Subject has taken more than 1 MPH treatment (for example, 2 or more different MPH treatments). Examples include but are not limited to RITALIN immediate release (IR) and EQUASYM IR; MEDIKINET IR and CONCERTA; RITALIN long-acting LA and CONCERTA. Note: this does not include subjects who have taken IR MPH for dose titration on a short-term basis (for example, £4 weeks) with an adequate response
• In the Investigator's judgement, subject has failed to respond to more than 1 previous course(s) of MPH treatment. Failure to respond includes worsening of symptoms or no change/minimal improvement of symptoms.
• Subject has previously been exposed to STRATTERA or to amphetamine therapy
• Subject has previously demonstrated intolerable side effects to 1 MPH treatment which limited titration to acceptable efficacy or that required a decrease in dose resulting in unacceptable tolerability and/or efficacy
• Subject has a current, controlled (requiring a restricted medication) or uncontrolled, comorbid psychiatric diagnosis with significant symptoms such as any severe comorbid Axis II disorder or severe Axis I disorder or other symptomatic manifestations, such as agitated states, marked anxiety, or tension that, in the opinion of the examining physician, will contraindicate treatment with SPD489 or STRATTERA or confound efficacy or safety assessments.
• Subject has a conduct disorder. Oppositional Defiant Disorder is not exclusionary.

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: Lisdexamfetamine Dimesylate	Drug: Lisdexamfetamine Dimesylate; Oral 30, 50, or 70mg once-daily for 9 weeks; Other Names: Vyvanse
Active Comparator: Atomoxetine Hydrochloride	Drug: Atomoxetine Hydrochloride; Oral 10mg to 100mg once-daily for 9 weeks; Other Names: Strattera

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to First Response	Time to first response was defined as a Clinical Global Impression-Improvement (CGI-I) value of 1 (very much improved) or 2 (much improved) first recorded following first dose of investigational product. CGI-I consists of a 7-point scale ranging from 1 (very much improved) to 7 (very much worse).	9 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of Participants With Improvement on Clinical Global Impression-Improvement (CGI-I) Scores - Last Observation Carried Forward (LOCF)	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.	9 weeks
Change From Baseline in Attention Deficit Hyperactivity Disorder Rating Scale-Fourth Edition (ADHD-RS-IV) Total Score at 9 Weeks - LOCF	ADHD-RS-IV consists of 18 items scored on a 4-point scale from 0 (no symptoms) to 3 (severe symptoms) with total score ranging from 0 to 54. A decrease in score indicates an improvement in ADHD symptomology.	Baseline and 9 weeks
Change From Baseline in the Weiss Functional Impairment Rating Scale - Parent Report (WFIRS-P) Global Score at Up to 9 Weeks	The WFIRS-P is a 50-item scale with each item scored from 0 (never/not at all) to 3 (very often/very much). Mean scores range from 0 to 3. Higher scores indicate greater functional impairment.	Baseline and up to 9 weeks
Health Utilities Index-2 (HUI-2) Scores at Up to 9 Weeks	HUI is used to describe health status and to obtain utility scores by collecting data using one or more questionnaires in formats selected to match the specific study design criteria. Scoring ranges from 0.00 (dead) to 1.00 (perfect health). Higher scores represent better health status.	up to 9 weeks
Change From Baseline in Brief Psychiatric Rating Scale for Children (BPRS-C) Total Score at Up to 9 Weeks	The BPRS-C characterizes psychopathology. A total of 21 items are rated on a scale from 0 (not present) to 6 (extremely severe) with a total score ranging from 0 to 126. A decrease in score indicates a reduction in psychopathology.	Baseline and up to 9 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.	9 weeks
Udvalg for Kliniske Undersogelser Side Effect Rating Scale - Clinician (UKU-SERS-Clin) With Side Effects Scores >=1	UKU-SERS-Clin is composed of 48 items each of which asks about a single side effect. Each side effect is rated based on a 4-point scale ranging from 0 (no or doubtful presence) to 3 (the least favorable rating). The rating is independent of whether the symptom is regarded as related to the investigational product.	9 weeks

Collaborators and Investigators

• Sponsor: Shire

Publications and helpful links

General Publications

• Dittmann RW, Cardo E, Nagy P, Anderson CS, Bloomfield R, Caballero B, Higgins N, Hodgkins P, Lyne A, Civil R, Coghill D. Efficacy and safety of lisdexamfetamine dimesylate and atomoxetine in the treatment of attention-deficit/hyperactivity disorder: a head-to-head, randomized, double-blind, phase IIIb study. CNS Drugs. 2013 Dec;27(12):1081-92. doi: 10.1007/s40263-013-0104-8.
• Nagy P, Hage A, Coghill DR, Caballero B, Adeyi B, Anderson CS, Sikirica V, Cardo E. Functional outcomes from a head-to-head, randomized, double-blind trial of lisdexamfetamine dimesylate and atomoxetine in children and adolescents with attention-deficit/hyperactivity disorder and an inadequate response to methylphenidate. Eur Child Adolesc Psychiatry. 2016 Feb;25(2):141-9. doi: 10.1007/s00787-015-0718-0. Epub 2015 May 22.
• Dittmann RW, Cardo E, Nagy P, Anderson CS, Adeyi B, Caballero B, Hodgkins P, Civil R, Coghill DR. Treatment response and remission in a double-blind, randomized, head-to-head study of lisdexamfetamine dimesylate and atomoxetine in children and adolescents with attention-deficit hyperactivity disorder. CNS Drugs. 2014 Nov;28(11):1059-69. doi: 10.1007/s40263-014-0188-9.

Study record dates

Study Major Dates

• Study Start (Actual): June 28, 2010
• Primary Completion (Actual): July 19, 2012
• Study Completion (Actual): July 19, 2012

Study Registration Dates

• First Submitted: April 14, 2010
• First Submitted That Met QC Criteria: April 16, 2010
• First Posted (Estimate): April 19, 2010

Study Record Updates

• Last Update Posted (Actual): June 11, 2021
• Last Update Submitted That Met QC Criteria: June 1, 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; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Dopamine Agents; Dopamine Uptake Inhibitors; Central Nervous System Stimulants; Adrenergic Uptake Inhibitors; Lisdexamfetamine Dimesylate; Atomoxetine Hydrochloride
• Other Study ID Numbers: SPD489-317; 2009-011745-94 (EudraCT Number)