PMID- 19808143
OWN - NLM
STAT- MEDLINE
DCOM- 20091231
LR  - 20131121
IS  - 1879-114X (Electronic)
IS  - 0149-2918 (Linking)
VI  - 31
IP  - 8
DP  - 2009 Aug
TI  - 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.
PG  - 1844-55
LID - 10.1016/j.clinthera.2009.08.002 [doi]
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. ClinicalTrials.gov identifier: 
      NCT00151957.
FAU - Findling, Robert L
AU  - Findling RL
AD  - University Hospitals Case Medical Center, Case Western Reserve University, 
      Cleveland, Ohio 44106, USA. robert.findling@UHhospitals.org
FAU - Wigal, Sharon B
AU  - Wigal SB
FAU - Bukstein, Oscar G
AU  - Bukstein OG
FAU - Boellner, Samuel W
AU  - Boellner SW
FAU - Abikoff, Howard B
AU  - Abikoff HB
FAU - Turnbow, John M
AU  - Turnbow JM
FAU - Civil, Rich
AU  - Civil R
LA  - eng
SI  - ClinicalTrials.gov/NCT00151957
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Clin Ther
JT  - Clinical therapeutics
JID - 7706726
RN  - 0 (Central Nervous System Stimulants)
RN  - 207ZZ9QZ49 (Methylphenidate)
SB  - IM
MH  - Administration, Cutaneous
MH  - Attention Deficit Disorder with Hyperactivity/*drug therapy
MH  - Central Nervous System Stimulants/administration & dosage/*adverse 
      effects/therapeutic use
MH  - Child
MH  - Dose-Response Relationship, Drug
MH  - Erythema/chemically induced
MH  - Female
MH  - Humans
MH  - Male
MH  - Methylphenidate/administration & dosage/*adverse effects/therapeutic use
MH  - Prospective Studies
MH  - Severity of Illness Index
MH  - Time Factors
EDAT- 2009/10/08 06:00
MHDA- 2010/01/01 06:00
CRDT- 2009/10/08 06:00
PHST- 2009/07/07 00:00 [accepted]
PHST- 2009/10/08 06:00 [entrez]
PHST- 2009/10/08 06:00 [pubmed]
PHST- 2010/01/01 06:00 [medline]
AID - S0149-2918(09)00266-5 [pii]
AID - 10.1016/j.clinthera.2009.08.002 [doi]
PST - ppublish
SO  - Clin Ther. 2009 Aug;31(8):1844-55. doi: 10.1016/j.clinthera.2009.08.002.