PMID- 32125903 OWN - NLM STAT- MEDLINE DCOM- 20210610 LR - 20210610 IS - 1557-8992 (Electronic) IS - 1044-5463 (Print) IS - 1044-5463 (Linking) VI - 30 IP - 2 DP - 2020 Mar TI - Randomized, Double-Blind, Placebo-Controlled, Flexible-Dose Titration Study of Methylphenidate Hydrochloride Extended-Release Capsules (Aptensio XR) in Preschool Children with Attention-Deficit/Hyperactivity Disorder. PG - 58-68 LID - 10.1089/cap.2019.0085 [doi] AB - Objectives: To assess the efficacy and safety of a methylphenidate hydrochloride extended-release capsule (MPH-MLR) formulation in treating attention-deficit/hyperactivity disorder (ADHD) in preschool children. Methods: Children aged 4 to <6 years with qualifying ADHD Rating Scale Fourth Edition (ADHD-RS-IV) Preschool Version scores (>/=90th percentile for age/gender) participated in four behavior management training (BMT) sessions or immediately entered (based on investigator assessment of symptom severity or previous participation) into a 6-week, open-label, flexible MPH-MLR dose optimization phase. After BMT, children with <30% improvement in ADHD-RS-IV score and >/=3 score on the Clinical Global Impression-Improvement (CGI-I) scale also entered the open-label period. All children began the open-label period with MPH-MLR 10 mg once daily; weekly adjustments permitted once-daily maximum of up to 40 mg. Children with >/=30% improvement in ADHD-RS-IV total score and a CGI-I score of 1-2 at open-label completion were randomized to their optimized dose of MPH-MLR or placebo for 2 weeks (double blind [DB]). Safety measures included adverse events (AEs), vital signs, and electrocardiograms. Results: Open-label enrollment was 119 children. Mean (SD) ADHD-RS-IV total scores at open-label start and open-label end was 40.8 (10.4) and 19.5 (11.1), respectively. Ninety children were enrolled in the DB phase. Mean (SD) ADHD-RS-IV total scores for the MPH-MLR and placebo group were similar at DB beginning and was 25.8 (14.6) and 34.9 (14.1), respectively, at DB end. Mean change from baseline in ADHD-RS-IV total score during DB was significantly greater in children randomized to placebo compared with MPH-MLR; least squares mean change difference from baseline was -11.2, p = 0.002. During open-label dosing, the most common AEs (>/=10%) were decreased appetite, decreased weight, insomnia, hypertension, emotional disorder, and affect lability. Conclusion: Results demonstrate MPH-MLR efficacy in preschool children and a safety profile consistent with known AEs of methylphenidate when used for ADHD. FAU - Childress, Ann C AU - Childress AC AD - Center for Psychiatry and Behavioral Medicine, Inc., Las Vegas, Nevada. FAU - Kollins, Scott H AU - Kollins SH AD - Department of Psychiatry and Behavioral Sciences, Duke University, Durham, North Carolina. FAU - Foehl, Henry C AU - Foehl HC AD - Foehl Statistics & Analytics LLC, Glenmoore, Pennsylvania. FAU - Newcorn, Jeffrey H AU - Newcorn JH AD - Icahn School of Medicine at Mount Sinai, New York, New York. FAU - Mattingly, Greg AU - Mattingly G AD - Washington University School of Medicine, Midwest Research Group, St. Louis, Missouri. FAU - Kupper, Robert J AU - Kupper RJ AD - Rhodes Pharmaceuticals L.P., Coventry, Rhode Island. FAU - Adjei, Akwete L AU - Adjei AL AD - Rhodes Pharmaceuticals L.P., Coventry, Rhode Island. LA - eng PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20191203 PL - United States TA - J Child Adolesc Psychopharmacol JT - Journal of child and adolescent psychopharmacology JID - 9105358 RN - 0 (Central Nervous System Stimulants) RN - 0 (Delayed-Action Preparations) RN - 207ZZ9QZ49 (Methylphenidate) SB - IM MH - Attention Deficit Disorder with Hyperactivity/*drug therapy MH - Behavior Therapy MH - Central Nervous System Stimulants/*administration & dosage/adverse effects MH - Child, Preschool MH - Delayed-Action Preparations MH - Dose-Response Relationship, Drug MH - Double-Blind Method MH - Female MH - Humans MH - Male MH - Methylphenidate/*administration & dosage/adverse effects MH - Treatment Outcome PMC - PMC7047252 OTO - NOTNLM OT - ADHD OT - MPH-MLR OT - methylphenidate extended-release OT - preschool COIS- A.C.C.: research support from AEVI, Akili, Alcobra, Arbor, Forest Research Institute, Ironshore, KemPharm, Lilly USA, Lundbeck, Neos, Neurovance, Noven, Otsuka, Pearson, Pfizer, Purdue, Rhodes Pharmaceuticals L.P., Shire, Sunovion, Supernus, and Tris; consultant and/or advisory board member for and honoraria from AEVI, Akili, Arbor, Ironshore, KemPharm, Neos, Neurovance, NLS, Noven, Pfizer, Purdue, Rhodes Pharmaceuticals L.P., Shire, Sunovion, Supernus, and Tris; payment for lectures from Arbor, Neos, Pfizer, Shire, and Tris; and writing assistance on projects from Arbor, Ironshore, Neos, Pfizer, Purdue, Rhodes Pharmaceuticals L.P., Shire, Sunovion, and Tris. S.H.K.: research support and/or consulting fees from the following: Akili, Alcobra, Bose, Ironshore, Jazz, KemPharm, Medgenics, NLS, Purdue Canada, Rhodes Pharmaceuticals L.P., Shire, SK Life Science, and Sunovion. H.C.F.: consultant for Rhodes Pharmaceuticals L.P. J.H.N.: consultant/advisory board for Akili, Alcobra, Arbor, Cingulate, Enzymotec, Ironshore, KenPharm, Lundbeck, Medici, NLS, Pfizer, Rhodes, Shire, Sunovion, and Supernus; research support from Enzymotec, Otsuka, Shire, Supernus; honoraria for disease state lectures from Shire. G.M.: researcher for Akili, Alcobra, Alkermes, Allergan, Axsome, Boehringer, Forum, Genentech, Janssen, Lundbeck, Medgenics, NLS Pharma, Otsuka, Reckitt Benckiser, Roche, Sage, Shire, Sunovion, Supernus, Takeda, Taisho, and Teva; consultant for Alkermes, Allergan, Ironshore, Janssen, Lundbeck, Merck, Otsuka, Neos, NLS Pharma, Purdue, Rhodes Pharmaceuticals L.P., Shire, Sunovion, Takeda, Teva, and Vanda; speaker for Alkermes, Allergan, Janssen, Lundbeck, Merck, Otsuka, Neos, Shire, Sunovion, Takeda, and Teva. A.L.A. and R.J.K.: employees of Rhodes Pharmaceuticals L.P. EDAT- 2020/03/04 06:00 MHDA- 2021/06/11 06:00 PMCR- 2020/02/28 CRDT- 2020/03/04 06:00 PHST- 2020/03/04 06:00 [entrez] PHST- 2020/03/04 06:00 [pubmed] PHST- 2021/06/11 06:00 [medline] PHST- 2020/02/28 00:00 [pmc-release] AID - 10.1089/cap.2019.0085 [pii] AID - 10.1089/cap.2019.0085 [doi] PST - ppublish SO - J Child Adolesc Psychopharmacol. 2020 Mar;30(2):58-68. doi: 10.1089/cap.2019.0085. Epub 2019 Dec 3.