This study will evaluate safety and efficacy of d-Amphetamine Transdermal System for the treatment of Attention Deficit Hyperactivity Disorder in children and adolescents.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
110
The study was conducted in 2 parts: a 5 week, open-label, step-wise Dose Optimization Period and a 2-week, randomized, cross-over Double-Blind Treatment Period. 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.
The study was conducted in 2 parts: a 5 week, open-label, step-wise Dose Optimization Period and a 2-week, randomized, cross-over Double-Blind Treatment Period. 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.
University of California - Irvine
Irvine, California, United States
Florida International University Center for Children and Families
Miami, Florida, United States
Center for Psychiatry and Behavioral Medicine Inc.
Las Vegas, Nevada, United States
Mean Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Total Score During the Double-Blind Treatment Period
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) \& time (during a typical classroom period), \& 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, \& staying seated according to classroom rules. The SKAMP-A subscale is a measure of attention \& 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. Scores range from 0-78 with higher scores indicating worse impairment.
Time frame: Mean SKAMP Total Score of SKAMP Total Scores from 9 different time points including (1, 2, 3, 4.5, 6, 7, 9, 10, 12 hours post-dose)
Onset of Efficacy Measured by Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Total Score
Onset of efficacy defined as the time of the first assessment time showing statistical significance between d-ATS and placebo. The time point for the reported data are SKAMP scores (LS mean) from 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) \& time (during a typical classroom period), \& the scale is used to assess multiple ratings taken within a day. Scores range from 0-78 with higher scores indicating worse impairment.
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 in Double-Blind Treatment Period
Duration of Effect for d-Amphetamine and Placebo Treatment
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Duration of Effect is the difference between the End of Effect and Onset of Effect in hours, where End of Effect is the first time point after Onset of Effect at which the 50% reduction in SKAMP total score from pre-dose is not observed.
Time frame: Duration of Effect was from onset (2 hours post-dose) and up to 12 hours post-dose (p<0.001)
Permanent Product Measure of Performance (PERMP) Scores Including PREMP-C and PREMP-A From Different Timepoints Post-dose
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). The scores range from 0-800 with higher scores indicating better performance.
Time frame: 1,2, 3, 4.5,6,7,9,10 and 12 hours post-dose from double-blind treatment period
Change in the Clinician-rated Scale of ADHD Symptoms Based on DSM-IV-TR Criteria (ADHD-RS-IV).
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. Note: Week 6 is the first week of the double-blind treatment period, week 7 is the second week of the double-blind treatment period.
Time frame: Averaged from week 6 and week 7 results during the Double-Blind Cross-Over treatment period.
Conners Parent Rating Scale Revised Short Form (CPRS-R:S) Total Scores From Week 6 and Week 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. The score ranges from 0-81 calculated from summed subscales scores. Higher score is considered a worse outcome for ADHD patients. Note: Week 6 is the first week of the double-blind treatment period, week 7 is the second week of the double-blind treatment period.
Time frame: Combined analysis by treatment groups from week 6 and week 7 (averaged)
Number of Responders Evaluated by Clinical Global Impression (CGI-I) Scale by Treatments From the Double-blind Treatment Period
The CGI scale permits a global evaluation of the subject's improvement over time. 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. For CGI-I scale, the responders are defined as subjects achieving a score of 1. Very much improved or 2. Much improved or The non-responders are defined as subjects achieving a score of 3. Minimally improved on the clinician-rated CGI global improvement item or 4. No change or 5. Minimally worse or 6. Much worse or 7. Very much worse Then the number of responders are calculated by treatment arms. Note: Week 6 is the first week of the double-blind treatment period, week 7 is the second week of the double-blind treatment period.
Time frame: the double-blind treatment period