Long-term tolerability of the methylphenidate transdermal system in pediatric attention-deficit/hyperactivity disorder

A multicenter, prospective, 12-month, open-label, uncontrolled, phase III extension of four clinical trials

Robert L Findling, Sharon B. Wigal, Oscar G. Bukstein, Samuel W. Boellner, Howard B. Abikoff, John M. Turnbow, Rich Civil

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1844-1855
Number of pages12
JournalClinical Therapeutics
Volume31
Issue number8
DOIs
StatePublished - Aug 2009
Externally publishedYes

Fingerprint

Methylphenidate
Attention Deficit Disorder with Hyperactivity
Clinical Trials
Pediatrics
Ankle Fractures
Therapeutics
Vital Signs
Contusions
Syncope
Appetite
Erythema
Cough
Diagnostic and Statistical Manual of Mental Disorders
Respiratory Tract Infections
Physical Examination
Habits
Headache
Sleep
Electrocardiography
Fever

Keywords

  • attention-deficit/hyperactivity disorder
  • children
  • methylphenidate transdermal system
  • stimulants

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

Long-term tolerability of the methylphenidate transdermal system in pediatric attention-deficit/hyperactivity disorder : A multicenter, prospective, 12-month, open-label, uncontrolled, phase III extension of four clinical trials. / Findling, Robert L; Wigal, Sharon B.; Bukstein, Oscar G.; Boellner, Samuel W.; Abikoff, Howard B.; Turnbow, John M.; Civil, Rich.

In: Clinical Therapeutics, Vol. 31, No. 8, 08.2009, p. 1844-1855.

Research output: Contribution to journalArticle

@article{dcbc1cd0eea1436bbeec741b9321831b,
title = "Long-term tolerability of the methylphenidate transdermal system in pediatric attention-deficit/hyperactivity disorder: A multicenter, prospective, 12-month, open-label, uncontrolled, phase III extension of four clinical trials",
abstract = "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.",
keywords = "attention-deficit/hyperactivity disorder, children, methylphenidate transdermal system, stimulants",
author = "Findling, {Robert L} and Wigal, {Sharon B.} and Bukstein, {Oscar G.} and Boellner, {Samuel W.} and Abikoff, {Howard B.} and Turnbow, {John M.} and Rich Civil",
year = "2009",
month = "8",
doi = "10.1016/j.clinthera.2009.08.002",
language = "English (US)",
volume = "31",
pages = "1844--1855",
journal = "Clinical Therapeutics",
issn = "0149-2918",
publisher = "Excerpta Medica",
number = "8",

}

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

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

UR - http://www.scopus.com/inward/record.url?scp=72149089866&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=72149089866&partnerID=8YFLogxK

U2 - 10.1016/j.clinthera.2009.08.002

DO - 10.1016/j.clinthera.2009.08.002

M3 - Article

VL - 31

SP - 1844

EP - 1855

JO - Clinical Therapeutics

JF - Clinical Therapeutics

SN - 0149-2918

IS - 8

ER -