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

Attention-Deficit/Hyperactivity Disorder Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01106430
• Other study ID #: SPD489-317
• Secondary ID: 2009-011745-94
• Status: Completed
• Phase: Phase 3
• Start date: June 28, 2010
• Est. completion date: July 19, 2012

Study information

• Verified date: May 2021
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 267
• Est. completion date: July 19, 2012
• Est. primary completion date: July 19, 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 17 Years

Eligibility

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.

Related Conditions & MeSH terms

• Attention Deficit Disorder with Hyperactivity
• Attention-Deficit/Hyperactivity Disorder
• Hyperkinesis

Intervention

Drug:
• Lisdexamfetamine Dimesylate
Oral 30, 50, or 70mg once-daily for 9 weeks
• Atomoxetine Hydrochloride
Oral 10mg to 100mg once-daily for 9 weeks

Locations

Country	Name	City	State
Belgium	ZiekenhuisNetwerk Antwerpen	Hoboken	Antwerpen
Belgium	Universitair Ziekenhuis Gasthuisberg	Leuven	Flemish Brabant
Canada	Child and Adolescent Centre	Edmonton	Alberta
Canada	Centre for Anxiety Attention Deficit and Trauma	Hamilton	Ontario
Canada	AK Karan Holdings, Ltd.	Oakville	Ontario
Canada	University of Saskatchewan	Saskatoon	Saskatchewan
Canada	The Kids Clinic	Whitby	Ontario
Germany	Schwerpunktpraxis für Entwicklung und Lernen	Bamberg	Bayern
Germany	Klinikum Frankfurt/Oder	Frankfurt/Oder	Brandenburg
Germany	Albert-Ludwigs-Universitat Freiburg	Freiburg	Baden-Wuerttemberg
Germany	Praxis Dr. Wolff	Hagen	Nordrhein-Westfalen
Germany	Zentralinstitut für Seelische Gesundheit Mannheim	Mannheim	Baden-wuerttemberg
Germany	Medizinisches Studienzentrum Würzburg	Wurzburg	Bayern
Hungary	Vadaskert Korhaz es Szakambulancia Gyermek es lfjusagpszichiatria	Budapest
Hungary	Bekes Megyei Kepviselotestulet Pandy Kalman Korhaza	Gyula
Hungary	Gyermek- es lfjusagpszichiatriai Szakrendeles es Gondozo	Pecs
Hungary	Szegedi Tudományegyetem Gyermek es lfjusagpszichlatrlai Osztaly	Szeged	Csongrad
Italy	Azienda Ospedaliero-Universitaria di Cagliari	Cagliari
Poland	Katedra i Klinika Psychiatarii	Bydgoszcz	Kujawsko-Pomorskie
Poland	Samodzielny Publiczny Dzieciecy Szpital Kliniczny	Warszawa	Mazowieckie
Spain	Complejo Hospitalario Universitario de Badajoz	Badajoz
Spain	Hospital Clinic i Provincial de Barcelona	Barcelona
Spain	Hospital Sant Joan de Deu	Esplugues De Llobregat	Barcelona
Spain	Hospital Son Llàtzer	Palma de Mallorca	Baleares
Spain	Hospital Universitario de Canarias	San Cristobal De La laguna	Santa Cruz De Tenerife
Spain	Hospital Marítimo, Unidad de Salud Mental Infanto-Juvenil (USMI-J	Torremolinos	Malaga
Sweden	Drottning Silvias Barnsjukhus	Goteborg
Sweden	Astrid Lindgren Children's Hospital/Karolinska University Hospital	Stockholm
United Kingdom	Basildon Hospital	Basildon	Essex
United Kingdom	Tayside Children's Hospital	Dundee	Scotland
United States	Future Search Clinical Trials	Austin	Texas
United States	Shanti Clinical Trials	Colton	California
United States	Harmonex Neuroscience Research, Inc	Dothan	Alabama
United States	Triangle Neuropsychiatry, PLLC	Durham	North Carolina
United States	Innovis Health	Fargo	North Dakota
United States	Sarkis Clinical Trials	Gainesville	Florida
United States	Cyn3rgy Research	Gresham	Oregon
United States	Amedica Research Institute, Inc.	Hialeah	Florida
United States	Red Oak Psychiatry Association, PA	Houston	Texas
United States	Eastside Therapeutic Resource	Kirkland	Washington
United States	Center for Psychiatry and Behavioral Medicine, Inc.	Las Vegas	Nevada
United States	Fidelity Clinical Research, Inc.	Lauderhill	Florida
United States	Capstone Clinical Research	Libertyville	Illinois
United States	Premier Psychiatric Research Institute, LLC	Lincoln	Nebraska
United States	Clinical Study Centers, LLC	Little Rock	Arkansas
United States	Western Clinical Investigations	Lubbock	Texas
United States	Baber Psychiatric Associates	Naperville	Illinois
United States	Louisianna Research Associates	New Orleans	Louisiana
United States	IPS Research Company	Oklahoma City	Oklahoma
United States	Clinical Neuroscience Solutions, INC	Orlando	Florida
United States	Four Rivers Clinical Research, Inc	Paducah	Kentucky
United States	CRI Worldwide, LLC Kirkbride Division	Philadelphia	Pennsylvania
United States	Rochester Center for Behavioral Medicine	Rochester Hills	Michigan
United States	Office of Marc Hertzman, MD, PC	Rockville	Maryland
United States	Northwest Behavioral Research Center	Roswell	Georgia
United States	Midwest Research Group/Saint Charles Psychiatric Associates	Saint Charles	Missouri
United States	Lifetree Clinical Research	Salt Lake City	Utah
United States	Cerebral Research, LLC	San Antonio	Texas
United States	Psychiatric Centers at San Diego Feighner Research	San Diego	California
United States	Richmond Behavioral Associates	Staten Island	New York
United States	Clinco	Terre Haute	Indiana
United States	Children's Specialized Hospital	Toms River	New Jersey
United States	Heartland Research Associates, LLC	Wichita	Kansas
United States	Elite Clinical Trials, Inc.	Wildomar	California

Sponsors (1)

Lead Sponsor	Collaborator
Shire

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  Germany,  Hungary,  Italy,  Poland,  Spain,  Sweden,  United Kingdom, 

References & Publications (1)

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 hea — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
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.	9 weeks
Secondary	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