Study to Evaluate Safety & Efficacy of d-Amphetamine Transdermal System vs Placebo in Children & Adolescents With ADHD

Overview

This study will evaluate safety and efficacy of d-Amphetamine Transdermal System for the treatment of Attention Deficit Hyperactivity Disorder in children and adolescents.

Full Title of Study: “A Randomized, Double-Blind, Placebo-Controlled, Crossover, Laboratory Classroom Study to Evaluate the Safety and Efficacy of d-Amphetamine Transdermal Drug Delivery System (d-ATS) Compared to Placebo in Children and Adolescents With ADHD”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Crossover Assignment
    • Primary Purpose: Treatment
    • Masking: Triple (Participant, Care Provider, Investigator)
  • Study Primary Completion Date: March 2013

Detailed Description

The study will consist of a four-week screening period, a 3-day wash-out period (if applicable), a five-week open-label, step-wise dose optimization period and two-week double blind randomized crossover treatment period with weekly classroom assessments and a safety follow-up by telephone 7 – 10 days after last dose of study drug.

Interventions

  • Drug: d-Amphetamine Transdermal System
    • Patches will be worn for 9 hours every day. After 9 hours the patch will be removed. Every day a new patch will be applied.
  • Drug: Placebo patch
    • Patches will be worn for 9 hours every day. After 9 hours the patch will be removed. Every day a new patch will be applied.

Arms, Groups and Cohorts

  • Active Comparator: d-Amphetamine Transdermal System
    • d-Amphetamine Transdermal System
  • Placebo Comparator: Placebo patch
    • Placebo patch

Clinical Trial Outcome Measures

Primary Measures

  • Change in Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) total score
    • Time Frame: Pre-dose through all post-dose time points up to 12 hours post-dose (3 hours post-removal)
    • The SKAMP total score comprises all 13 items. The SKAMP was designed for independent observers to rate 13 items representing 2 factors of classroom behavior: attention (SKAMP-A) and deportment (SKAMP-D), as well as quality of work. Items are specific to place (classroom setting) and time (during a typical classroom period), and the scale is used to assess multiple ratings taken within a day. The SKAMP-D subscale evaluates deportment, including interacting with other children, interacting with adults, remaining quiet according to classroom rules, and staying seated according to classroom rules. The SKAMP-A subscale is a measure of attention and evaluates getting started on assignments, sticking with tasks, attending to an activity, and making activity transitions. The SKAMP quality of work subscale includes 3 items: completing assigned work, performing work accurately, and being careful and neat while writing or drawing.

Secondary Measures

  • Change in the onset of clinical effect for the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) total score
    • Time Frame: Onset of efficacy defined as the time of the first assessment time showing statistical significance between d-ATS and placebo: 2 hours post-dose
    • The SKAMP total score comprises all 13 items. The SKAMP was designed for independent observers to rate 13 items representing 2 factors of classroom behavior: attention (SKAMP-A) and deportment (SKAMP-D), as well as quality of work. Items are specific to place (classroom setting) and time (during a typical classroom period), and the scale is used to assess multiple ratings taken within a day. The SKAMP-D subscale evaluates deportment, including interacting with other children, interacting with adults, remaining quiet according to classroom rules, and staying seated according to classroom rules. The SKAMP-A subscale is a measure of attention and evaluates getting started on assignments, sticking with tasks, attending to an activity, and making activity transitions. The SKAMP quality of work subscale includes 3 items: completing assigned work, performing work accurately, and being careful and neat while writing or drawing.
  • Change in the duration of clinical effect for the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) total score
    • Time Frame: Double-blind Week 6 and Week 7: Duration of Effect from onset (2 hours) and up to 12 hours post-dose (p<0.001)
    • The SKAMP total score comprises all 13 items. The SKAMP was designed for independent observers to rate 13 items representing 2 factors of classroom behavior: attention (SKAMP-A) and deportment (SKAMP-D), as well as quality of work. Items are specific to place (classroom setting) and time (during a typical classroom period), and the scale is used to assess multiple ratings taken within a day. The SKAMP-D subscale evaluates deportment, including interacting with other children, interacting with adults, remaining quiet according to classroom rules, and staying seated according to classroom rules. The SKAMP-A subscale is a measure of attention and evaluates getting started on assignments, sticking with tasks, attending to an activity, and making activity transitions. The SKAMP quality of work subscale includes 3 items: completing assigned work, performing work accurately, and being careful and neat while writing or drawing.
  • Change in Permanent Product Measure of Performance (PERMP) scores
    • Time Frame: 1,2, 3, 4.5,6,7,9,10 and 12 hours post-dose on combined double blind period (week 6 and week 7)
    • To assess efficacy of d-ATS compared to placebo as measured by the PERMP-C (number of correct answers) and PERMP-A (number of attempted answers) score. The PERMP is an age-adjusted written math test, of 10 minutes’ duration administered at multiple time points. Subjects are given 5 pages of 80 math problems (400 total problems) and are instructed to work at their desks and to complete as many problems as possible in 10 minutes. Performance is measured as the number of problems attempted (PERMP-A) and the number of problems worked correctly (PERMP-C).
  • Change in the clinician-rated scale of ADHD symptoms based on DSM-IV-TR criteria (ADHD-RS-IV).
    • Time Frame: Combined Week 6 (visit 6) and Week 7 (visit 7) in the Double-Blind Cross-Over period
    • The ADHD-RS-IV is based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria to assess efficacy of d-ATS compared to placebo. The ADHD-RS-IV scale was developed to measure the behaviors of children with ADHD, and it consists of 18 items designed to reflect current symptomatology of ADHD based on DSM-IV criteria. Each item is scored from a range of 0 (reflecting no symptoms) to 3 (reflecting severe symptoms) with total scores ranging from 0 to 54.
  • Change in Conners Parent Rating Scale Revised Short Form (CPRS-R:S) total scores
    • Time Frame: Baseline to combined week 6 and 7
    • The CPRS-R:S evaluates problem behaviors as reported by the parent or alternative caregivers. The CPRS-R:S total score comprises 27 items and covers a subset of the subscales and items on the long parent form.
  • Change in Clinical Global Impression (CGI) scores
    • Time Frame: Improvement from Baseline to combined week 6 (visit 6) and week 7 (visit 7)
    • The CGI scale permits a global evaluation of the subject’s improvement over time. Prior to dosing (at baseline), the investigator assessed the severity of the subject’s condition using a CGI-Severity (CGI-S) Scale. During the Dose Optimization Period and the Double-Blind Treatment Period, the investigator assessed the subject’s improvement relative to symptoms prior to dosing, using the CGI-I Scale.

Participating in This Clinical Trial

Inclusion Criteria

1. Gender: Male or female 2. Age: Between 6 and 17 years of age (inclusive) 3. Race: All eligible 4. Females of child-bearing potential must have agreed to practice a clinically accepted method of contraception during the study and for at least 1 month prior to study dosing and 1 month following completion of the study. Acceptable contraceptive methods included abstinence, oral contraception, surgical sterilization (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy), intrauterine device, diaphragm in addition to spermicidal foam and condom on male partner, or systemic contraception (e.g., Norplant System) 5. Must have met Diagnostic and Statistical Manual of Mental Disorders, 4th edition - Text Revision (DSM-IV-TR) criteria for a primary diagnosis of ADHD combined, hyperactive/impulsive subtype, or predominately inattentive subtype 6. The Screening and Baseline visit ADHD-RS-IV total score must have been ≥90% of the general population of children by age and gender 7. Able to wear a patch for 9 hours (for children and, if applicable, for adolescents, parent or caregiver must be present to apply and remove the patches and maintain the used and unused patches in a secure, controlled area of the home) 8. Functioning at an age-appropriate level intellectually as determined by an intelligence quotient (IQ) of ≥80 on the Wechsler Abbreviated Scale of Intelligence II™ (WASI II™) vocabulary and matrix reasoning components 9. Must have been able to complete PERMP assessment 10. Must have provided parental consent (signed ICF) and obtained written/verbal assent from the subject 11. Subject and parent(s)/ caregiver must have been willing and able to comply with all the protocol requirements and parent(s) or caregiver must be able to provide transportation for the subject to and from the analog classroom sessions Exclusion Criteria:

1. Blood pressure outside the 95th percentile for age and gender 2. Pulse of <50 (age 6 – 17), or >120 (age 6 – 12), or >125 (age 13 – 17) 3. Known non-responder to amphetamine treatment 4. Documented allergy, intolerance, or hypersensitivity to amphetamine 5. Currently taking an ADHD medication that is providing symptom control with no residual impairment at home or school and has acceptable tolerability and adherence 6. Recent history (within the past 6 months) of suspected substance abuse or dependence disorder (including nicotine) 7. History of seizures during the last 2 years (excluding infantile febrile seizures), a tic disorder (exclusive of transient tic disorder), a current diagnosis, and/or a family history of Tourette's Disorder. Mild medication-induced tics were not exclusionary 8. Any psychiatric disorder that could interfere with study participation or the safety of the subject or other participants, such as conduct disorder (CD) or oppositional defiant disorder (ODD) with a history of prominent aggressive outbursts. Children meeting CD or ODD but without prominent aggression will be allowed to enroll at the discretion of the Investigator 9. Autism or Asperger's Disorder 10. Family history (first degree relatives) of sudden cardiac death 11. Current controlled (requiring medication) or uncontrolled comorbid psychiatric conditions such as post-traumatic stress disorder, psychosis, bipolar illness, severe obsessive compulsive disorder, severe depressive or severe anxiety disorder, was considered a suicide risk, had recent (last 6 months) suicidal ideation, or any lifetime self-harm event 12. History of abnormal thyroid function 13. Has a body mass index (BMI) for age greater than 95th percentile per Centers for Disease Control BMI (for gender-specific charts) 14. 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 15. Any skin abnormality present at the potential application site (i.e., infection, rash, atrophy, excessive fragility or dryness, any cut or abrasion, or tattoo) 16. History of hypersensitivity, allergy to topical medication, preparation, or adhesive dressings 17. Concurrent chronic or significant acute illnesses (such as severe allergic rhinitis or an infectious process requiring antibiotics, unless expected to resolve or has resolved by Day 0) disability or any unstable medical condition that in the Investigator's opinion would lead to difficulty complying with the protocol requirements 18. Used any investigational drug within 30 days of the Screening visit 19. History of physical, sexual, or emotional abuse in the last year 20. Medical history of hepatitis A/B/C or HIV 21. Positive urine drug screen for drugs of abuse

Gender Eligibility: All

Minimum Age: 6 Years

Maximum Age: 17 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Noven Pharmaceuticals, Inc.
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • James Waxmonsky, MD, Principal Investigator, Not Affiliated

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