Shire plc announced that DAYTRANATM (methylphenidate transdermal system), the first and only non-oral medication approved for treatment of Attention Deficit Hyperactivity Disorder (ADHD) in children aged 6 to 12 years, provided significant improvement in symptom control and tolerability, according to results of a 12-month open-label study presented at the American Psychiatric Association (APA) annual meeting in San Diego.
"We documented that children with ADHD experienced effective ADHD treatment with use of DAYTRANA for 12 months, sustaining the improvements in their ability to maintain focus and concentration," said investigator Oscar Bukstein, M.D., M.P.H ,Associate Professor of Psychiatry, University of Pittsburgh School of Medicine. "More importantly, Daytrana maintained a favorable safety profile, meeting the study's primary endpoint, and demonstrating an incidence of adverse events that is consistent with previous trials and other stimulants in this class."
Shire's DAYTRANA is the first and only patch medication approved by the U.S. Food and Drug Administration (FDA) to treat the symptoms of ADHD in children aged 6 to 12 years. DAYTRANA is available in four dosage strengths – 10 mg, 15 mg, 20 mg and 30 mg – all designed for once-daily use. When worn for the recommended nine hours, efficacy has been demonstrated from the first time point measured (two hours) through the 12-hour time point. Because DAYTRANA is a patch, physicians may recommend that patients shorten the wear time if shorter duration of effect is desired or to help manage the potential for late-day side effects.
Bukstein added, "DAYTRANA's novel patch delivery system offers physicians and parents of children with ADHD a convenient, non-oral option to individualize ADHD treatment to meet their children's changing schedules."
This study was an open-label extension of four clinical trials. Those children not optimized on DAYTRANA from the previous trials entered a four-week stepwise DAYTRANA dose-optimization phase. All children then entered an 11-month DAYTRANA dose maintenance phase. DAYTRANA was applied each morning to the hip area and worn for approximately nine hours daily. During the dose-optimization phase, titration to a higher dose was permitted after a minimum of three days. Tapering to a lower dose was permitted throughout the dose optimization period and dose adjustments were also permitted during the dose maintenance period.
All of the children in this open-label, flexible-dose trial participated in one of four trials in which the children previously received DAYTRANA, OROS methylphenidate or a placebo. All of the children previously used DAYTRANA for at least a minimum of three days and a maximum of 37 months. While this study evaluated the safety and effectiveness of DAYTRANA for up to 12 months, DAYTRANA has not been studied versus placebo for longer than 7 weeks. Physicians, who prescribe DAYTRANA for long-term use, should periodically re-evaluate patients to assess the usefulness of DAYTRANA for the individual patient.
Children were diagnosed with ADHD using DSM-IV-TR® criteria. Researchers assessed safety and tolerability, through physical exams, skin evaluations, laboratory tests, and monitoring of vital signs, including ECGs throughout the study.
The ADHD-RS-IV assesses 18 individual symptoms of ADHD as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR®), a publication of the American Psychiatric Association.
Of the 327 children enrolled, 157 completed the study. Investigators used data from the intent-to-treat population (324 children) for the efficacy evaluations. Of the safety population (326 children) 7 percent withdrew due to skin irritation at the patch application site, and 9 percent withdrew due to adverse events. The highest percentage of discontinuations were due to withdrawn consent or lost to follow-up (12 percent and 11 percent, respectively).
The most commonly reported treatment-emergent adverse events reported throughout the study (≥10 percent) included decreased appetite, headache, upper respiratory tract infection, cough, pyrexia and decreased weight. Most (98 percent) adverse events were mild or moderate in severity and consistent with known effects of methylphenidate. Three serious adverse events were reported and all were considered unrelated to DAYTRANA use.
DAYTRANA Demonstrated Significant Improvements in ADHD-RS-IV, CGI-I and PGA Scores
In the study, the children experienced a significant overall mean reduction in their ADHD Rating Scale-IV (ADHD-RS-IV) total score. When the study began, the mean total score on the ADHD-RS-IV was 25.0. When using Daytrana, the mean ADHD-RS-IV total scores declined, with children averaging 15.4 at study end. The overall mean change in ADHD-RS-IV total score from study start to end was -9.3 (+/- 16.29) and was statistically significant (p<.0001). The total scores also declined significantly from study start to end on both the inattentiveness and hyperactivity/impulsivity ADHD-RS-IV subscales (P<.0001).
Investigators evaluated DAYTRANA's overall effectiveness using the Clinical Global Impressions-Improvement (CGI-I) and Parent Global Assessment (PGA) scales, both of which yielded significant ratings of improvement at study end, with 83 and 78 percent, respectively, reporting DAYTRANA "very much improved" or "much improved" the children's ADHD symptoms (P<.0001).
Approximately 7.8 percent of all school-age children, or about 4.4 million U.S. children aged 4 to 17 years, have been diagnosed with ADHD at some point in their lives, according to the U.S. Centers for Disease Control and Prevention (CDC). ADHD is one of the most common psychiatric disorders in children and adolescents. ADHD is a neurobiological psychiatric disorder that manifests as a persistent pattern of inattention and/or hyperactivity-impulsivity that is more frequent and severe than is typically observed in individuals at a comparable level of development. To be properly diagnosed with ADHD, a child needs to demonstrate at least six of nine symptoms of inattention; and/or at least six of nine symptoms of hyperactivity/impulsivity; the onset of which appears before age 7 years; that some impairment from the symptoms is present in two or more settings (e.g., at school and home); that the symptoms continue for at least six months; and that there is clinically significant impairment in social, academic or occupational functioning and the symptoms cannot be better explained by another psychiatric disorder.
Although there is no "cure" for ADHD, there are accepted treatments that specifically target its symptoms. The most common standard treatments include educational approaches, psychological or behavioral modification, and medication.