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Clinical Trial
. 2016 Dec;26(10):873-881.
doi: 10.1089/cap.2016.0083. Epub 2016 Oct 18.

Effect of Aptensio XR (Methylphenidate HCl Extended-Release) Capsules on Sleep in Children with Attention-Deficit/Hyperactivity Disorder

Judith Owens  1 , Margaret Weiss  2 , Earl Nordbrock  3 , Greg Mattingly  4   5 , Sharon Wigal  6 , Laurence L Greenhill  7 , Wei-Wei Chang  8 , Ann Childress  9 , Robert J Kupper  3 , Akwete Adjei  3
Affiliations
Clinical Trial

Effect of Aptensio XR (Methylphenidate HCl Extended-Release) Capsules on Sleep in Children with Attention-Deficit/Hyperactivity Disorder

Judith Owens et al. J Child Adolesc Psychopharmacol. 2016 Dec.

Abstract

Objective: 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.

Methods: 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.

Results: 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).

Conclusions: 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.

Keywords: ASHQ; CSHQ; MPH-MLR; extended-release methylphenidate; sleep.

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Conflict of interest statement

Dr. Owens is a consultant for Jazz, Pfizer, Purdue, Rhodes Pharmaceuticals L.P., Teva, and UCB, and has received research support from Jazz and UCB. Dr. Weiss is on the speakers bureau for Eli Lilly, Janssen, Purdue, and Shire, is a consultant for Purdue and Rhodes, and has received research support from Purdue. Dr. Nordbrock is a consultant for Rhodes Pharmaceuticals L.P. Dr. Mattingly is a speaker for Forest, Lundbeck, Merck, Otsuka, Shire, Sunovion, and Takeda, and has served as a consultant or performed research for Alcobra, Alkermes, Forest, Forum, Janssen, Lundbeck, Merck, Novartis, Noven, Otsuka, Pfizer, Purdue, Reckitt Benckiser, Rhodes Pharmaceuticals L.P., Shire, Sunovion, Takeda, and Vanda. Dr. Wigal is a consultant, advisory board member, and speakers bureau member for Attentiv, Eli Lilly, Ironshore, Neos, Neurovance, NextWave, Noven, NuTec, Pfizer, Purdue, Rho, Rhodes Pharmaceuticals L.P., Shionogi, Shire, Sunovion, Tris, and Vernalis, and has received grant/research support from Eli Lilly, Forest, Ironshore, the National Institutes of Health, Neurovance, NextWave, Noven, NuTec, Purdue, Rho, Rhodes Pharmaceuticals L.P., Shire, Sunovion, and Tris. Dr. Greenhill has received research support from the National Institute on Drug Abuse, the National Institutes of Health, and Shire, and is on the advisory board for BioBehavioral Diagnostics. Dr. Chang is a consultant for Rhodes Pharmaceuticals L.P. Dr. Childress has received research support from Alcobra, Arbor, Forest, Ironshore, Lilly, Lundbeck, Medgenics, Neos, Neurovance, NextWave, Noven, Otsuka, Pearson, Pfizer, Purdue, Rhodes Pharmaceuticals L.P., Shire, Sunovion, Theravance, and Tris; been a consultant for and received honoraria from Ironshore, Neos, Pfizer, Rhodes Pharmaceuticals L.P., and Shire; received travel support from Ironshore, NextWave, Pfizer, and Shire; has received writing assistance on projects from Arbor, Ironshore, Neos, NextWave, Pfizer, Rhodes Pharmaceuticals L.P., and Shire; received payment for lectures from Arbor, Pfizer, and Shire; and has been an advisory board member for Arbor, Ironshore, Neos, Neurovance, NextWave, Noven, Pfizer, and Rhodes Pharmaceuticals L.P. Drs. Kupper and Adjei are employees of Rhodes Pharmaceuticals L.P.

Figures

<b>FIG. 1.</b>
FIG. 1.
Mean plasma MPH concentration versus time following a single dose of MPH-MLR capsule or sprinkles. MPH, methylphenidate; MPH-MLR, multilayer bead extended-release methylphenidate.
See this image and copyright information in PMC

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