Shire reports tolerability/clinical effects results of Daytrana from study in adolescents with ADHD

November 2nd, 2009

Shire plc (LSE: SHP, NASDAQ: SHPGY), the global specialty biopharmaceutical company, today announced findings at a major medical meeting from a Phase IIIb study of the tolerability and effectiveness of Daytrana® (methylphenidate transdermal system) in adolescents aged 13 to 17 years diagnosed with Attention-Deficit/Hyperactivity Disorder (ADHD). In addition, data regarding the pharmacokinetic profile of Daytrana in children and adolescents was also presented. Daytrana, the first and only patch for the treatment of ADHD, is indicated for use in children aged 6 to 12 years with the disorder.

Alain Katic, MD, child psychiatrist at the Claghorn Research Clinic in Houston, Texas, states, "In this 6-month, open-label adolescent extension study, we found that most adverse events were generally mild to moderate in intensity. Additionally, Daytrana treatment resulted in significant improvements in ADHD Rating Scale IV mean total scores from baseline to end point."

Daytrana delivers medication directly through the skin into the bloodstream and is designed to release methylphenidate continuously while applied to the skin. Daytrana is approved by the US Food and Drug Administration (FDA) for a wear-time of nine hours; however, the patch can be removed earlier to accommodate changing schedules or to help manage late day side effects, allowing parents, working with physicians, to tailor the treatment to a child's specific needs. Daytrana is available in 10-mg, 15-mg, 20-mg, and 30-mg patches.

"As a leader in ADHD treatment, Shire is proud to offer treatment options to help meet the various needs of patients diagnosed with ADHD. Once-daily Daytrana is a transdermal alternative to oral immediate- and extended-release formulations of methylphenidate, an active ingredient that has been used to treat ADHD for over 50 years," said Michael Yasick, Senior Vice President of the ADHD Business Unit at Shire. "The short term efficacy and safety profile of Daytrana in adolescents has been previously reported and this Shire-supported study examined the tolerability and effectiveness of the medication in the adolescent population over an extended period of six months."

Long-Term Open-Label Tolerability and Effectiveness Study in Adolescents with ADHD

In this study, Daytrana participants were titrated to their optimal dose over five weeks and were then maintained on that dose for an additional five months. Participants from a previous double-blind, seven week study were able to enroll. In this seven week study, Daytrana was shown to significantly improve ADHD symptoms as rated by clinicians and parents compared with placebo. The frequency of adverse events was typical of these seen in studies of oral methylphenidate in adolescents, with the exception of dermal reactions. The long term extension study evaluated four doses of the Daytrana patch worn for nine hours at alternating hips and used for about six months. Most adverse events were mild to moderate in intensity. The most commonly reported treatment-emergent adverse events reported by 5 percent or more of participants that received Daytrana were decreased appetite (11.0 percent); headache (10.1 percent); upper respiratory tract infection (10.1 percent); nasopharyngitis (inflammation of the nasal passages and of the upper part of the pharynx) (9.2 percent); and irritability (5.5 percent). The majority (93.6 percent) of skin response scores were defined as no irritation or minimal to definite redness.

The primary effectiveness measure was the change from baseline to end point of the total mean ADHD Rating Scale IV (ADHD-RS-IV) score. The baseline was defined as the baseline from the previous double-blind study and the end point was defined as the last assessment for which a valid ADHD-RS-IV score was obtained. The ADHD-RS-IV scale contains 18 items and is based on the ADHD diagnostic criteria as defined in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision®, a publication of the American Psychiatric Association.

Daytrana demonstrated significant improvement in the overall mean (±SD) change in ADHD-RS-IV total score from antecedent study baseline to end point of this study of -23.0 (±10.77) P<.001. in addition, the average adhd-rs-iv mean total scores decreased from this study start to end from 19.8 to 13.8 (p<.001).

Pharmacokinetic Study in Children and Adolescents with ADHD

The pharmacokinetic profile of Daytrana has been previously reported for children aged 6 to 12 years; the data presented today are the first to report Daytrana pharmacokinetics that also included an adolescent population aged 13 to 17 years.

In this one-month, open-label, multiple-phase study, investigators randomized 35 children and 36 adolescents who received either Daytrana (single, multiple fixed, and multiple escalating doses, each worn for nine hours), or OROS MPH. The study's four phases were single dosing, multiple fixed dosing, dose escalation, and follow-up.

Following single and multiple fixed or escalating doses, systemic exposure was greater in children compared with adolescents, and was consistent with their lower body weights. As a result of accumulation, systemic exposure to d-MPH in children after multiple escalating doses was 1.4- to 1.6-fold higher for Daytrana compared with OROS MPH, but in adolescents was similar for the two formulations.

All treatment-emergent adverse events were of mild to moderate intensity and none led to discontinuation from the study. No deaths or serious adverse events were reported.5 Eighteen children reported at least one treatment-emergent adverse event, and the most frequently reported was decreased appetite (27.3 percent of participants receiving OROS MPH and 8.3 percent of participants receiving both escalating doses and multiple fixed doses of Daytrana). Nineteen adolescents reported at least one treatment-emergent adverse event, and the most frequently reported was headache (27.3 percent of participants receiving OROS MPH and 16.7 percent of participants receiving escalating doses of Daytrana, and none of the participants receiving multiple fixed doses of Daytrana).

This study was not designed to make comparisons between Daytrana and OROS MPH.

Source: Porter Novelli