Positive study results for methylphenidate transdermal system
(24 October 2005: VIDYYA MEDICAL NEWS SERVICE) -- Shire announced at a major medical meeting in Toronto, Canada, that its investigational methylphenidate transdermal system (MTS) demonstrated statistically significant reductions in the symptoms of Attention-Deficit/Hyperactivity Disorder (ADHD) and was generally well tolerated in patients aged 6 to 12 in two clinical trials.
"Children with ADHD must cope with symptoms throughout the day and in a variety of environments, such as in the classroom, during after-school activities, or while at home," explained Sharon Wigal, Ph.D., associate clinical professor of Pediatrics at the University of California, Irvine Child Development Center. "While oral methylphenidate has long been a first-line treatment for patients with ADHD symptoms, if approved, this transdermal patch formulation would provide health care professionals and parents the first and only non-oral medication for children with the disorder."
The MTS patch was developed by Noven Pharmaceuticals, Inc. and combines the active ingredient of methylphenidate with Noven's patented DOT Matrixä transdermal technology. This transdermal delivery system was designed to provide continuous medication release throughout the day. The transdermal system releases medication that passes through the skin and directly into the blood stream. The patch is water-resistant.
Data from phase II and phase III clinical trials presented Thursday and Friday in Toronto demonstrated statistically significant improvements in the primary and secondary endpoints analyzed for children treated with MTS compared to children treated with placebo.
The phase II analog classroom study included 79 children with ADHD. The patch was worn for nine hours, and efficacy was assessed throughout the day for twelve hours. MTS demonstrated statistically significant improvement over placebo on the measures tested. Behavior, which was measured using the Swanson, Kotkin, Agler, M-Flynn, and Pelham –Deportment (SKAMP-D) scale, was improved with MTS overall (mean score 3.2 for MTS versus 8.0 for placebo) and at all time points throughout the day (P < 0.001). Children taking MTS also completed more math problems correctly on the Permanent Product Measure of Performance (PERMP) scale than did those taking placebo (110 versus 81, respectively).
In the phase III naturalistic trial with 270 participants, investigators found that MTS worn for nine hours reduced the children's overall symptoms of ADHD, compared to a placebo (P < 0.0001), as measured by scores on the ADHD Rating Scale (ADHD-RS). By the study's end, mean ADHD-RS scores declined –24.2 points (56%) from baseline for children treated with MTS versus a decline of –9.9 (24%) for those treated with placebo (P < 0.0001). ADHD-RS assesses 18 individual symptoms of ADHD as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, a publication of the American Psychiatric Association.
In both studies, MTS was generally well tolerated during both the dose optimization and double-blind phases. Adverse events typically were mild to moderate, resolved with continued therapy and were consistent with known effects of methylphenidate. The most common adverse events reported by patients who received MTS in clinical trials were: nausea, vomiting, nasopharyngitis, weight decreased, anorexia, decreased appetite, affect lability, insomnia, tic, and nasal congestion.
Shire and Noven provided funds for both studies.
Noven and Shire are seeking approval for MTS and the application is currently under review by the FDA. The trade name DAYTRANATM has been proposed to the FDA and is currently under review.
Return to Vidyya Medical News Service for 24 October 2005