TY - JOUR
T1 - Long-term tolerability of the methylphenidate transdermal system in pediatric attention-deficit/hyperactivity disorder
T2 - A multicenter, prospective, 12-month, open-label, uncontrolled, phase III extension of four clinical trials
AU - Findling, Robert L.
AU - Wigal, Sharon B.
AU - Bukstein, Oscar G.
AU - Boellner, Samuel W.
AU - Abikoff, Howard B.
AU - Turnbow, John M.
AU - Civil, Rich
N1 - Funding Information:
Laura Miesle, PharmD, of the JB Ashtin Group, Inc., Plymouth, Michigan, provided editorial support and assisted in implementing author revisions on behalf of and with financial support from Shire Development.
Funding Information:
Dr. Findling receives or has received research support from, acted as a consultant for, and/or served on a speakers’ bureau for Abbott Laboratories, Addrenex Pharmaceuticals, AstraZeneca, Bristol-Myers Squibb, Forest Pharmaceuticals, GlaxoSmithKline, Johnson & Johnson, KemPharm, Eli Lilly, Lundbeck, Neuro-pharm, Novartis Pharmaceuticals, Organon, Otsuka Pharmaceutical, Pfizer, Sanofi-Aventis, Sepracor, Shire, Solvay Pharmaceuticals, Supernus Pharmaceuticals, Validus Pharmaceuticals, and Wyeth Pharmaceuticals. Dr. Wigal receives or has received research support from, acted as a consultant for, and/or served on a speakers’ bureau for ALZA Pharmaceuticals, Celgene, Celltech Pharmaceuticals, Cephalon, Eisai, Gliatech, Eli Lilly, Ortho-McNeil Janssen Pharmaceuticals, the National Institute of Mental Health, New River Pharmaceuticals, Novartis, Shire, Sigma-Tau Pharmaceuticals, UCB Pharma, and Next Wave Pharmaceuticals. Dr. Bukstein receives or has received research support from and/or acted as a consultant for Ortho-McNeil Pharmaceutical, Problem-Based Learning Institute, Quintiles, Routledge press, and Shire. Dr. Boellner has no financial relationships or conflicts of interest to disclose. Dr. Abikoff receives or has received research support from and/or acted as a consultant for Abbott, Celltech, Cephalon, Eli Lilly, Ortho-McNeil Pharmaceutical, Novartis, Pfizer, and Shire. Dr. Turnbow re- ceives or has received research support from, acted as a consultant for, and/or served on a speakers’ bureau for Eli Lilly, Novartis, Sanofi-Aventis, Shire, and UCB. Dr. Civil is employed by Shire Development Inc.
Funding Information:
This study was funded by Shire Development Inc., which was involved in the study design, conduct, and data analysis.
PY - 2009/8
Y1 - 2009/8
N2 - Background: Short-term treatment with the meth-ylphenidate transdermal system (MTS) has been well tolerated in several clinical trials in children with attention-deficit/hyperactivity disorder (ADHD). However, the effects of long-term use have not been systematically evaluated. Objectives: The primary objective of this study was to assess the 12-month tolerability of MTS in children with ADHD. Effectiveness was a secondary objective. Methods: This Phase III study was a multicenter, 12-month, open-label, flexible-dose extension of 4 previous trials. In those studies, children aged 6 to 12 years with a diagnosis of ADHD (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria) received MTS, osmotic-release oral system methylphenidate, or placebo. At entry into the present study, the children either continued to receive their optimal dose of MTS (10, 15, 20, or 30 mg per 9-hour patch wear time) or underwent dose titration over 4 weeks to an optimal MTS dose, which was continued for the remainder of the study. Tolerability was evaluated based on adverse events (AEs), physical examinations, vital signs, electrocardiograms, laboratory tests, the Children's Sleep Habits Questionnaire, and the occurrence of application-site reactions. Results: Of 327 enrolled subjects, 326 received treatment and 157 completed the study. The majority of enrolled subjects were male (64.8%) and white (73.7%), with a mean (SD) age of 9.2 (1.9) years. Two hundred sixty-five (81.3%) of the 326 subjects who received MTS reported AEs. AEs led to study discontinuation in 29 subjects (8.9%). The majority (98.3%) of treatment-emergent AEs were of mild or moderate severity. The most common AEs were decreased appetite (24.8%), headache (16.6%), upper respiratory tract infection (12.3%), cough (11.7%), pyrexia (10.1%), and decreased weight (10.1%). Of the 1118 AEs, 40.8% were considered possibly or probably related to study treatment. Three serious AEs (facial contusion, ankle fracture, and syncope) occurred and were considered unrelated to study treatment. Based on data collected across all study visits, application-site reactions generally consisted of mild erythema associated with mild discomfort at the patch site. Application-site reactions accounted for 22 (6.7%) study discontinuations. Conclusions: Slightly less than half (48.0%) of subjects completed this 12-month, open-label extension study of MTS. Most AEs were mild to moderate in severity and, with the exception of application-site reactions, were typical of those previously observed with methylphenidate.
AB - Background: Short-term treatment with the meth-ylphenidate transdermal system (MTS) has been well tolerated in several clinical trials in children with attention-deficit/hyperactivity disorder (ADHD). However, the effects of long-term use have not been systematically evaluated. Objectives: The primary objective of this study was to assess the 12-month tolerability of MTS in children with ADHD. Effectiveness was a secondary objective. Methods: This Phase III study was a multicenter, 12-month, open-label, flexible-dose extension of 4 previous trials. In those studies, children aged 6 to 12 years with a diagnosis of ADHD (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria) received MTS, osmotic-release oral system methylphenidate, or placebo. At entry into the present study, the children either continued to receive their optimal dose of MTS (10, 15, 20, or 30 mg per 9-hour patch wear time) or underwent dose titration over 4 weeks to an optimal MTS dose, which was continued for the remainder of the study. Tolerability was evaluated based on adverse events (AEs), physical examinations, vital signs, electrocardiograms, laboratory tests, the Children's Sleep Habits Questionnaire, and the occurrence of application-site reactions. Results: Of 327 enrolled subjects, 326 received treatment and 157 completed the study. The majority of enrolled subjects were male (64.8%) and white (73.7%), with a mean (SD) age of 9.2 (1.9) years. Two hundred sixty-five (81.3%) of the 326 subjects who received MTS reported AEs. AEs led to study discontinuation in 29 subjects (8.9%). The majority (98.3%) of treatment-emergent AEs were of mild or moderate severity. The most common AEs were decreased appetite (24.8%), headache (16.6%), upper respiratory tract infection (12.3%), cough (11.7%), pyrexia (10.1%), and decreased weight (10.1%). Of the 1118 AEs, 40.8% were considered possibly or probably related to study treatment. Three serious AEs (facial contusion, ankle fracture, and syncope) occurred and were considered unrelated to study treatment. Based on data collected across all study visits, application-site reactions generally consisted of mild erythema associated with mild discomfort at the patch site. Application-site reactions accounted for 22 (6.7%) study discontinuations. Conclusions: Slightly less than half (48.0%) of subjects completed this 12-month, open-label extension study of MTS. Most AEs were mild to moderate in severity and, with the exception of application-site reactions, were typical of those previously observed with methylphenidate.
KW - attention-deficit/hyperactivity disorder
KW - children
KW - methylphenidate transdermal system
KW - stimulants
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U2 - 10.1016/j.clinthera.2009.08.002
DO - 10.1016/j.clinthera.2009.08.002
M3 - Article
C2 - 19808143
AN - SCOPUS:72149089866
VL - 31
SP - 1844
EP - 1855
JO - Clinical Therapeutics
JF - Clinical Therapeutics
SN - 0149-2918
IS - 8
ER -