title: Effect of Aptensio XR (Methylphenidate HCl Extended-Release) Capsules on Sleep in Children with Attention-Deficit/Hyperactivity Disorder.
abstract: To evaluate measures of sleep (exploratory endpoints) in two pivotal studies of a multilayer bead extended-release methylphenidate (MPH-MLR) treatment of attention-deficit/hyperactivity disorder in children.
  
  
  
  Study 1 evaluated the time course of response to MPH-MLR (n = 26) patients in an analog classroom setting through four phases: screening (≤28 days), open label (OL) dose optimization (4 weeks), double-blind (DB) crossover (2 weeks; placebo vs. optimized dose), and follow-up call. Study 2 was a forced-dose parallel evaluation of MPH-MLR (n = 230) in four phases: screening (≤28 days), DB (1 week; placebo or MPH-MLR 10, 15, 20, or 40 mg/day), OL dose optimization (11 weeks), and follow-up call. Sleep was evaluated by parents using the Children's or Adolescent Sleep Habits Questionnaire (CSHQ or ASHQ) during the DB and OL phases. DB analysis: Study 1 (crossover), analysis of variance; Study 2, analysis of covariance. OL analysis: paired t-test.
  
  
  
  DB: treatments were significantly different in Study 1 only for CSHQ Sleep Onset Delay (MPH-MLR, 1.90 vs. placebo, 1.34; p = 0.0046, placebo was better), and Study 2 for CSHQ Parasomnias (treatment, p = 0.0295), but no MPH-MLR treatment was different from placebo (pairwise MPH-MLR treatment to placebo, all p ≥ 0.170). OL: CSHQ total and Bedtime Resistance, Sleep Duration, Sleep Anxiety, Night Wakings, Parasomnias, and Sleep-disordered Breathing subscales decreased (improved, Study 1) significant only for CSHQ Night Wakings (p < 0.05); in Study 2 CSHQ total and Bedtime Resistance, Sleep Duration, Night Wakings, Parasomnias, and Daytime Sleepiness, and ASHQ total, Bedtime, Sleep Behavior, and Morning Waking all significantly improved (p < 0.05).
  
  
  
  In both studies, there was minimal negative impact of MPH-MLR on sleep during the brief DB phase and none during the longer duration OL phase. Some measures of sleep improved with optimized MPH-MLR dose.
authors.affiliation: 1 Boston Children's Hospital , Harvard Medical School, Boston, Massachusetts.
authors.forename: Judith
authors.initials: J
authors.lastname: Owens
authors.affiliation: 2 Division of Child Psychiatry, British Columbia's Children's Hospital, University of British Columbia Medical Center , Vancouver, British Columbia, Canada .
authors.forename: Margaret
authors.initials: M
authors.lastname: Weiss
authors.affiliation: 3 Rhodes Pharmaceuticals L.P. , Coventry, Rhode Island.
authors.forename: Earl
authors.initials: E
authors.lastname: Nordbrock
authors.affiliation: 4 Washington University School of Medicine , St. Louis, Missouri.|5 Midwest Research Group , St. Charles, Missouri.
authors.forename: Greg
authors.initials: G
authors.lastname: Mattingly
authors.affiliation: 6 AVIDA, Inc., Newport Beach, California.
authors.forename: Sharon
authors.initials: S
authors.lastname: Wigal
authors.affiliation: 7 Division of Child and Adolescent Psychiatry, Columbia University and the New York State Psychiatric Institute , New York, New York.
authors.forename: Laurence L
authors.initials: LL
authors.lastname: Greenhill
authors.affiliation: 8 NuTec Incorporated , Boston, Massachusetts.
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Chang
authors.affiliation: 9 Center for Psychiatry and Behavioral Medicine , Inc., Las Vegas, Nevada.
authors.forename: Ann
authors.initials: A
authors.lastname: Childress
authors.affiliation: 3 Rhodes Pharmaceuticals L.P. , Coventry, Rhode Island.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Kupper
authors.affiliation: 3 Rhodes Pharmaceuticals L.P. , Coventry, Rhode Island.
authors.forename: Akwete
authors.initials: A
authors.lastname: Adjei
mesh_terms: D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy*; D002214:Capsules; D000697:Central Nervous System Stimulants / Q000008:administration & dosage*; D002648:Child; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008774:Methylphenidate / Q000008:administration & dosage*; D012890:Sleep / Q000187:drug effects*; D011795:Surveys and Questionnaires; D013997:Time Factors
chemical_list: D002214:Capsules; D000697:Central Nervous System Stimulants; D003692:Delayed-Action Preparations; D008774:Methylphenidate
keywords: ASHQ; CSHQ; MPH-MLR; extended-release methylphenidate; sleep