title: A randomized placebo-controlled double-blind study evaluating the time course of response to methylphenidate hydrochloride extended-release capsules in children with attention-deficit/hyperactivity disorder.
abstract: OBJECTIVE
  The purpose of this study was to assess the time of onset and time course of efficacy over 12.0 hours of extended-release multilayer bead formulation of methylphenidate (MPH-MLR) compared with placebo in children 6-12 years of age with attention-deficit/hyperactivity disorder (ADHD) in a laboratory school setting.
  
  
  METHODS
  This randomized double-blind placebo-controlled study included children 6-12 years of age with ADHD. Enrolled children went through four study phases: 1) Screening period (≤4 weeks) and a 2 day medication washout period; 2) open-label period with dose initiation of MPH-MLR 15 mg daily and individual dose optimization treatment period (2-4 weeks); 3) double-blind crossover period in which participants were randomized to sequences (1 week each) of placebo and the optimized MPH-MLR dose given daily; and 4) follow-up safety call. Analog classroom time course evaluations were performed at the end of each double-blind week. The primary efficacy end-point was the mean of the on-treatment/postdose Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP)-Total scores over time points collected 1.0-12.0 hours after dosing. End-points were evaluated using a mixed-effects analysis of covariance.
  
  
  RESULTS
  The evaluable population included 20 participants. The least-squares mean postdose SKAMP-Total score was higher for placebo than for MPH-MLR (2.18 vs. 1.32, respectively; p=0.0001), indicating fewer symptoms with MPH-MLR therapy than with placebo. No difference in SKAMP-Total score between participants who received sequence 1 or sequence 2 was noted. From each of hours 1.0-12.0, least-squares mean SKAMP-Total score was significantly lower for those receiving MPH-MLR than for those receiving placebo (p≤0.0261). Neither serious adverse events nor new or unexpected safety findings were noted during the study.
  
  
  CONCLUSIONS
  MPH-MLR showed a significant decrease in SKAMP scores compared with placebo in children with ADHD 6-12 years of age, indicating a decrease in ADHD symptoms. The estimated onset was observed within 1.0 hour, and duration was measured to 12.0 hours postdose.
  
  
  BACKGROUND
  ClinicalTrials.gov Identifier: NCT01269463.
authors.affiliation: 1 AVIDA Inc. , Newport Beach, California.
authors.forename: Sharon B
authors.initials: SB
authors.lastname: Wigal
authors.forename: Laurence L
authors.initials: LL
authors.lastname: Greenhill
authors.forename: Earl
authors.initials: E
authors.lastname: Nordbrock
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Connor
authors.forename: Scott H
authors.initials: SH
authors.lastname: Kollins
authors.forename: Akwete
authors.initials: A
authors.lastname: Adjei
authors.forename: Ann
authors.initials: A
authors.lastname: Childress
authors.forename: Annamarie
authors.initials: A
authors.lastname: Stehli
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Kupper
mesh_terms: D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy*; D002214:Capsules; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008774:Methylphenidate / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011569:Psychiatric Status Rating Scales; D013997:Time Factors
chemical_list: D002214:Capsules; D000697:Central Nervous System Stimulants; D003692:Delayed-Action Preparations; D008774:Methylphenidate