Double-blind, Placebo-controlled, Randomised Withdrawal, Extension, Safety and Efficacy Study of LDX in Children and Adolescents Aged 6-17

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Shire
ClinicalTrials.gov Identifier:
NCT00784654
First received: November 3, 2008
Last updated: June 3, 2014
Last verified: August 2012
  Purpose

The main aim of this study is to evaluate the long-term maintenance of efficacy of LDX after administered to children and adolescents aged 6-17 with ADHD for at least 6 months


Condition Intervention Phase
ADHD
Drug: Lisdexamfetamine dimesylate (LDX)
Drug: Placebo
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 III, Double-blind, Placebo-controlled, Randomised Withdrawal, Multicentre, Extension, 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:


Further study details as provided by Shire:

Primary Outcome Measures:
  • Percent of Participants With Treatment Failures at up to 6 Weeks During the Randomized Withdrawal Period [ Time Frame: Up to 6 weeks ] [ Designated as safety issue: No ]
    Treatment failure defined as 50% increase (worsening) in Attention Deficit Hyperactivity Disorder Rating Scale (ADHD-RS-IV) total score and >= 2 point increase (worsening) in the Clinical Global Impression-Severity of Illness (CGI-S) score observed at any visit during the randomized withdrawal period compared to the respective scores at baseline of randomized withdrawal period.


Secondary Outcome Measures:
  • Change From Open-Label Baseline in Attention Deficit Hyperactivity Disorder Rating Scale-Fourth Edition (ADHD-RS-IV) Total Score at at Least 26 Weeks During the Open-label Period [ Time Frame: Open-label baseline and at least 26 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 Randomized Withdrawal Baseline in ADHD-RS-IV Total Score at up to 6 Weeks During the Randomized Withdrawal Period [ Time Frame: Randomized withdrawal baseline and up to 6 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.

  • Percent of Participants With Clinical Global Impression - Severity of Illness (CGI-S) at Open-label Baseline [ Time Frame: Open-label baseline ] [ Designated as safety issue: No ]
    CGI-S assesses the severity of the subject's condition on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill)

  • Percent of Participants With CGI-S at at Least 26 Weeks During the Open-label Period [ Time Frame: At least 26 weeks ] [ Designated as safety issue: No ]
    CGI-S assesses the severity of the subject's condition on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill)

  • Percent of Participants With CGI-S at Randomized Withdrawal Baseline, Last Observation Carried Forward (LOCF) [ Time Frame: Randomized withdrawal baseline ] [ Designated as safety issue: No ]
    CGI-S assesses the severity of the subject's condition on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill)

  • Percent of Participants With CGI-S at up to 6 Weeks During Randomized Withdrawal Period, LOCF [ Time Frame: up to 6 weeks ] [ Designated as safety issue: No ]
    CGI-S assesses the severity of the subject's condition on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill)

  • Percent of Participants With Improvement on Clinical Global Impression - Improvement (CGI-I) at at Least 26 Weeks During the Open-label Period [ Time Frame: at least 26 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.

  • Health Utilities Index-2 (HUI-2) Scores at at Least 26 Weeks During the Open-label Period [ Time Frame: Open-label baseline and at least 26 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.

  • HUI-2 Scores at up to 6 Weeks During the Randomized Withdrawal Period [ Time Frame: Randomized withdrawal baseline and up to 6 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 Open-label Baseline in the Child Health and Illness Profile, Child Edition: Parent Report Form (CHIP-CE:PRF) Global T-score at at Least 26 Weeks During the Open-label Period [ Time Frame: Open-label baseline and at least 26 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 Randomized Withdrawal Baseline in the CHIP-CE:PRF Global T-score at up to 6 Weeks During the Randomized Withdrawal Period [ Time Frame: Randomized withdrawal baseline and up to 6 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 Open-Label Baseline in Weiss Functional Impairment Rating Scale - Parent Report (WFIRS-P) Global Score at at Least 26 Weeks During the Open-label Period [ Time Frame: Open-label baseline and at least 26 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 Randomized Withdrawal Baseline in the WFIRS-P Global Score at up to 6 Weeks During the Randomized Withdrawal Period [ Time Frame: Randomized withdrawal baseline and up to 6 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 Open-Label Baseline in Brief Psychiatric Rating Scale for Children (BPRS-C) Total Score at at Least 26 Weeks During the Open-label Period [ Time Frame: Open-label baseline and at least 26 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.

  • Change From Randomized Withdrawal Baseline in BPRS-C Total Score at up to 6 Weeks During the Randomized Withdrawal Period [ Time Frame: Randomized withdrawal baseline and up to 6 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) During the Open-label Period [ Time Frame: at least 26 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.

  • C-SSRS During the Randomized Withdrawal Period [ Time Frame: up to 6 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.


Enrollment: 276
Study Start Date: January 2009
Study Completion Date: October 2011
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Lisdexamfetamine dimesylate (LDX)
Open-label 30, 50, or 70mg
Drug: Lisdexamfetamine dimesylate (LDX)
LDX 30, 50, or 70mg capsule once per day (open-label and double-blind periods)
Other Name: Vyvanse, SPD489
Placebo Comparator: Placebo Drug: Placebo
Placebo capsule once per day (double-blind period)

  Eligibility

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

Inclusion Criteria:

  1. Subject's parent or legally authorised representative(LAR) must provide signature of informed consent, and there must be documentation of assent (if applicable) by the subject indicating that the subject is aware of the investigational nature of the study and the required procedures and restrictions in accordance with the International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) Guideline E6 and applicable regulations before completing any study-related procedures.
  2. Subject and parent/LAR are willing and able to comply with all the testing and requirements defined in this protocol, including oversight of morning dosing. Specifically, the parent/LAR must be available upon awakening, at approximately 7:00AM, to dispense the dose of test product for the duration of the study.
  3. Subject is a male or female aged 6-17 years inclusive at the time of consent for the antecedent study (SPD489-325).
  4. Subject satisfied all entry criteria for the antecedent study (SPD489-325), and completed a minimum of 4 weeks of double-blind treatment, reached Visit 4 and completed the 1-week post-treatment washout in the antecedent study (SPD489-325), without experiencing any clinically significant AEs that would preclude exposure to LDX.
  5. Subject must have a satisfactory medical assessment with no clinically significant or relevant abnormalities as determined by medical history, physical examination findings and clinical laboratory test results.
  6. Subject has blood pressure measurements within the 95th percentile for age, gender, and height.

Exclusion Criteria:

  1. Subject was terminated from SPD489-325 for non-compliance and/or experienced an SAE or AE resulting in termination from the antecedent study.
  2. 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 (such as Post Traumatic Stress Disorder, psychosis, bipolar illness, pervasive developmental disorder, severe obsessive compulsive disorder, severe depressive or severe anxiety disorder) or other symptomatic manifestations, such as agitated states, marked anxiety, or tension that, in the opinion of the examining clinician, will contraindicate treatment with LDX or confound efficacy or safety assessments. Comorbid psychiatric diagnoses will be established at the Screening Visit (Visit -1)of the antecedent study (SPD489-325)with the Screening interview of the Kiddie-SADS-Present and Lifetime-Diagnostic Interview (K-SADS-PL)and additional modules if warranted by the results of the initial interview. Participation in behavioural therapy is permitted provided the subject was receiving the therapy for at least 1 month at the time of the Baseline Visit (Visit 0) of the antecedent study (SPD489-325).
  3. Subject has a conduct disorder. Oppositional defiant disorder is not exclusionary.
  4. Subject has any concurrent chronic or acute illness or unstable medical condition that could confound the results of safety assessments, increase risk to the subject or lead to difficulty complying with the protocol.
  5. 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.
  6. Subject is female and is pregnant or lactating.
  7. Subject has glaucoma.
  8. Subject has any clinically significant ECG at Visit 8 of the antecedent study (SPD489-325) or clinically significant laboratory abnormalities at Visit 7 of the antecedent study (SPD489-325).
  9. Subject has a documented allergy, hypersensitivity, or intolerance to amphetamine.
  10. Subject has a recent history (within the past 6 months) of suspected substance abuse or dependence disorder (excluding nicotine)in accordance with the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition - Text Revision (DSM-IV-TR)criteria.
  11. Subject has a history of seizures (other than infantile febrile seizures), a tic disorder, a current diagnosis and or a known family history of Tourette's Disorder.
  12. 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 them at increased vulnerability to the sympathomimetic effects of a stimulant drug.
  13. Subject has a known family history of sudden cardiac death or ventricular arrhythmia.
  14. Subject is taking any medication that is excluded.
  15. Subject is taking other medications that have central nervous system (CNS) effects, affect performance, such as sedating antihistamines and decongestant sympathomimetics, or are monoamine oxidase inhibitors (during or within 14 days of investigational medicinal product administration). Stable use of bronchodilator inhalers is not exclusionary.
  16. Subject has a documented allergy, hypersensitivity, or intolerance to any excipients in the investigational medicinal product(s).
  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: NCT00784654

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Sponsors and Collaborators
Shire
  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: NCT00784654     History of Changes
Other Study ID Numbers: SPD489-326, 2008-000720-10
Study First Received: November 3, 2008
Results First Received: July 16, 2012
Last Updated: June 3, 2014
Health Authority: 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
Italy: The Italian Medicines Agency
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Spain: Spanish Agency of Medicines
Sweden: Medical Products Agency
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Additional relevant MeSH terms:
Attention Deficit Disorder with Hyperactivity
Attention Deficit and Disruptive Behavior Disorders
Mental Disorders Diagnosed in Childhood
Mental Disorders
Dextroamphetamine
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

ClinicalTrials.gov processed this record on October 19, 2014