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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Shire
ClinicalTrials.gov Identifier:
NCT01106430
First received: April 14, 2010
Last updated: June 6, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Attention-Deficit/Hyperactivity Disorder
Drug: Lisdexamfetamine Dimesylate
Drug: Atomoxetine Hydrochloride
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Shire:

Primary Outcome Measures:
  • Time to First Response [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
    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).


Secondary Outcome Measures:
  • Percent of Participants With Improvement on Clinical Global Impression-Improvement (CGI-I) Scores - Last Observation Carried Forward (LOCF) [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Attention Deficit Hyperactivity Disorder Rating Scale-Fourth Edition (ADHD-RS-IV) Total Score at 9 Weeks - LOCF [ Time Frame: Baseline and 9 weeks ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in the Weiss Functional Impairment Rating Scale - Parent Report (WFIRS-P) Global Score at Up to 9 Weeks [ Time Frame: Baseline and up to 9 weeks ] [ Designated as safety issue: No ]
    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.

  • Health Utilities Index-2 (HUI-2) Scores at Up to 9 Weeks [ Time Frame: up to 9 weeks ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Brief Psychiatric Rating Scale for Children (BPRS-C) Total Score at Up to 9 Weeks [ Time Frame: Baseline and up to 9 weeks ] [ Designated as safety issue: Yes ]
    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.

  • Columbia-Suicide Severity Rating Scale (C-SSRS) [ Time Frame: 9 weeks ] [ Designated as safety issue: Yes ]
    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.

  • Udvalg for Kliniske Undersogelser Side Effect Rating Scale - Clinician (UKU-SERS-Clin) With Side Effects Scores >=1 [ Time Frame: 9 weeks ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 267
Study Start Date: June 2010
Study Completion Date: September 2012
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Lisdexamfetamine Dimesylate Drug: Lisdexamfetamine Dimesylate
Oral 30, 50, or 70mg once-daily for 9 weeks
Other Name: Vyvanse
Active Comparator: Atomoxetine Hydrochloride Drug: Atomoxetine Hydrochloride
Oral 10mg to 100mg once-daily for 9 weeks
Other Name: Strattera

  Eligibility

Ages Eligible for Study:   6 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01106430

  Show 64 Study Locations
Sponsors and Collaborators
Shire
Investigators
Principal Investigator: Ralf W Dittmann, MD, PhD Dept of Child and Adolescent Psychiatry and Psychotherapy, Central Inst of Mental Health
  More Information

No publications provided by Shire

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT01106430     History of Changes
Other Study ID Numbers: SPD489-317, 2009-011745-94
Study First Received: April 14, 2010
Results First Received: May 3, 2013
Last Updated: June 6, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
Canada: Ethics Review Committee
Belgium: Federal Agency for Medicinal Products and Health Products
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Ministry of Health
Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
The Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Spain: Spanish Agency of Medicines
Sweden: Medical Products Agency
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Shire:
ADHD

Additional relevant MeSH terms:
Attention Deficit Disorder with Hyperactivity
Hyperkinesis
Disease
Attention Deficit and Disruptive Behavior Disorders
Mental Disorders Diagnosed in Childhood
Mental Disorders
Dyskinesias
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Pathologic Processes
Methylphenidate
Dextroamphetamine
Atomoxetine
Central Nervous System Stimulants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Dopamine Uptake Inhibitors
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Uptake Inhibitors
Adrenergic Uptake Inhibitors
Adrenergic Agents

ClinicalTrials.gov processed this record on October 16, 2014