Randomized, Double-blind Safety and Efficacy Study of Lisdexamfetamine Dimesylate (LDX) in Children and Adolescents Aged 6-17 - Full Text View

Purpose

The main aim of this study is to see if giving LDX to children and adolescents aged 6-17 years with ADHD decreases symptoms of ADHD.

Condition	Intervention	Phase
ADHD	Drug: Lisdexamfetamine Dimesylate (LDX) Drug: Methylphenidate Hydrochloride Drug: Placebo	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	A Phase III, Randomised, Double-Blind, Multicentre, Parallel-Group, Placebo- and Active-Controlled, Dose-Optimisation Safety and Efficacy Study of Lisdexamfetamine Dimesylate (LDX) in Children and Adolescents Aged 6-17 With Attention-Deficit/Hyperactivity Disorder (ADHD)

Resource links provided by NLM:

MedlinePlus related topics: Attention Deficit Hyperactivity Disorder

Drug Information available for: Methylphenidate Methylphenidate hydrochloride Lisdexamfetamine Lisdexamfetamine dimesylate

U.S. FDA Resources

Further study details as provided by Shire Development LLC:

Primary Outcome Measures:

Change From Baseline in Attention Deficit Hyperactivity Disorder Rating Scale-fourth Edition (ADHD-RS-IV) Total Score at up to 7 Weeks [ Time Frame: Baseline and up to 7 weeks ] [ Designated as safety issue: No ]
The ADHD-RS-IV consists of 18 items scored on a 4-point scale ranging 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.

Secondary Outcome Measures:

Percentage of Participants With Improvement on Clinical Global Impression-Improvement (CGI-I) Scores [ Time Frame: Up to 7 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 Conner's Parent Rating Scale - Revised (CPRS-R) Total Score at up to 7 Weeks [ Time Frame: Baseline and up to 7 weeks ] [ Designated as safety issue: No ]
The Conner's Parent rating Scale-revised short version (CPRS-R) consists of 27 questions graded on a scale from 0 (not true at all) to 3 (very much true) with a total score ranging from 0 to 81. Higher scores are indicative of increased ADHD. This scale allows parents to respond on the basis of the child's behavior and help assess ADHD and evaluate problem behavior.
Health Utilities Index-2 (HUI-2) Scores at up to 7 Weeks [ Time Frame: Baseline and up to 7 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 the Child Health and Illness Profile, Child Edition: Parent Report Form (CHIP-CE:PRF) Global T-score at up to 7 Weeks [ Time Frame: Baseline and up to 7 weeks ] [ Designated as safety issue: No ]
The CHIP-CE:PRF evaluates health-related quality of life. It is composed of 5 domains (satisfaction, comfort, resilience, avoidance, and achievement) consisting of a total of 76 items. The global score is an average of the scores for the 5 domains. The majority of items assess frequency of events using a 5-point response format. There is no range for a total score. Raw scale scores are used to generate T-scores. Higher scores indicate better health.
Change From Baseline in Weiss Functional Impairment Rating Scale - Parent Report (WFIRS-P) Global Score at up to 7 Weeks [ Time Frame: Baseline and up to 7 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.
Change From Baseline in Brief Psychiatric Rating Scale for Children (BPRS-C) Total Score at up to 7 Weeks [ Time Frame: Baseline and up to 7 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: Up to 7 weeks ] [ Designated as safety issue: Yes ]
C-SSRS is a 19-item semi-structured interview designed to capture suicide-related thoughts and behaviors.

Enrollment:	336
Study Start Date:	October 2008
Study Completion Date:	April 2011
Primary Completion Date:	April 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Lisdexamfetamine Dimesylate (LDX) Overencapsulated LDX 30, 50, or 70mg	Drug: Lisdexamfetamine Dimesylate (LDX) 30, 50 or 70mg capsule once per day (Overencapsulated) Other Name: Vyvanse™
Active Comparator: Methylphenidate Hydrochloride Overencapsulated Concerta 18, 36, or 54mg	Drug: Methylphenidate Hydrochloride 18, 36, or 54mg tablet one per day (Overencapsulated) Other Name: Concerta®, OROS MPH
Placebo Comparator: Placebo Overencapsulated Placebo	Drug: Placebo Placebo capsule once per day (Overencapsulated)

Eligibility

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

Criteria

Inclusion Criteria:

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.
Subject has blood pressure measurements within the 95th percentile for age, gender, and height at Screening and Baseline.
Subject is able to swallow a capsule.

Exclusion Criteria:

Subject has failed to respond to more than one adequate course (dose and duration) of stimulant therapy. One course must have been a long-acting formulation.
Subject has a conduct disorder. Oppositional Defiant Disorder is not exclusionary.
Subject is currently considered a suicide risk, has previously made a suicide attempt or has a prior history of, or is currently, demonstrating active suicidal ideation.
Subject has glaucoma.
Subject weighs less than 22.7kg (50lbs).
Subject is significantly overweight based on Centre for Disease Control and Prevention Body Mass Index (BMI)-for-age gender specific charts at Screening. Significantly overweight is defined as a BMI >97th percentile for this study.
Subject has a documented allergy, hypersensitivity, or intolerance to amphetamine or methylphenidate.
Subject has a documented allergy, hypersensitivity, or intolerance to any excipients in the test or reference products.
Subject has a history of seizures (other than infantile febrile seizures), a 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, advance 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 drug.
Subject has a known family history of sudden cardiac death or ventricular arrhythmia.
Subject is well controlled on their current ADHD medication with acceptable tolerability.
Subject has a pre-existing severe gastrointestinal tract narrowing (pathologic or iatrogenic).

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00763971

Show 49 Study Locations

Sponsors and Collaborators

Shire Development LLC

More Information

Additional Information:

FDA recal information This link exits the ClinicalTrials.gov site

FDA medical product safety alerts This link exits the ClinicalTrials.gov site

FDA-approved label This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Shire Development LLC
ClinicalTrials.gov Identifier:	NCT00763971 History of Changes
Other Study ID Numbers:	SPD489-325
Study First Received:	September 30, 2008
Results First Received:	February 27, 2012
Last Updated:	January 23, 2013
Health Authority:	United States: Food and Drug Administration United Kingdom: Medicines and Healthcare Products Regulatory Agency Belgium: Federal Agency for Medicinal Products and Health Products France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) Germany: Federal Institute for Drugs and Medical Devices Netherlands: The Central Committee on Research Involving Human Subjects (CCMO) Spain: Spanish Agency of Medicines Sweden: Medical Products Agency

Additional relevant MeSH terms:

Attention Deficit Disorder with Hyperactivity
Attention Deficit and Disruptive Behavior Disorders
Mental Disorders Diagnosed in Childhood
Mental Disorders
Methylphenidate
Dextroamphetamine
Dopamine Uptake Inhibitors
Dopamine Agents

Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Neurotransmitter Uptake Inhibitors
Physiological Effects of Drugs
Central Nervous System Stimulants
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on May 21, 2013