PMID- 25877989
OWN - NLM
STAT- MEDLINE
DCOM- 20160613
LR  - 20220310
IS  - 1179-1934 (Electronic)
IS  - 1172-7047 (Print)
IS  - 1172-7047 (Linking)
VI  - 29
IP  - 4
DP  - 2015 Apr
TI  - Efficacy of Methylphenidate Hydrochloride Extended-Release Capsules (Aptensio 
      XR) in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder: A 
      Phase III, Randomized, Double-Blind Study.
PG  - 331-40
LID - 10.1007/s40263-015-0241-3 [doi]
AB  - BACKGROUND: Psychostimulants remain first-line treatment options for the 
      management of attention-deficit/hyperactivity disorder (ADHD). A multilayer 
      extended-release bead methylphenidate capsule (provisional name Aptensio XR, 
      MPH-MLR) with unique release properties is being investigated for the treatment 
      of ADHD. OBJECTIVE: The aim of this study was to assess the efficacy (primary) 
      and safety and tolerability (secondary) of MPH-MLR compared with placebo in 
      children and adolescents aged 6-18 years with ADHD. METHODS: This study was a 
      parallel, double-blind, multicenter, placebo-controlled, forced-dose, phase III 
      study in which patients were randomized to placebo or MPH-MLR 10, 15, 20, or 40 
      mg given once daily. There were four study phases: (1) 4-week screening/baseline; 
      (2) 1-week, double-blind treatment (DBP); (3) 11-week, open-label, 
      dose-optimization period; and (4) 30-day follow-up call. During the open-label 
      dose-optimization period all patients started with MPH-MLR 10 mg, unless the 
      investigator deemed it necessary to begin at a higher dose, and were titrated to 
      an optimized dose (10, 15, 20, 30, 40, 50, 60 mg; all given once daily) based on 
      response and adverse events (AEs). The primary endpoint was the change from 
      baseline to end of DBP in ADHD Rating Scale, 4th Edition (ADHD-RS-IV) total 
      score. Secondary endpoints included changes in ADHD-RS-IV subscales and Clinical 
      Global Impression-Improvement Scale (CGI-I) at the end of the DBP. The primary 
      analysis was an analysis of covariance including terms for treatment, site, and 
      baseline ADHD-RS-IV total score. RESULTS: A total of 221 patients completed the 
      DBP. The primary endpoint had a statistically significant difference among 
      treatments (p = 0.0046) and sites (p = 0.0018), and baseline covariate made a 
      significant contribution (p < 0.0001). As the MPH-MLR dose increased, the 
      ADHD-RS-IV total score improved; the 20 and 40 mg doses were statistically 
      different (p = 0.0145 and p = 0.0011, respectively) from placebo. Females 
      responded differently than did males (p = 0.0238); there was a significant 
      difference among treatments for males but not for females, partly because only 
      one-third of subjects were female and partly because some females who received 
      placebo had considerable improvement during the DBP. Similarly, the ADHD-RS-IV 
      subscales and CGI-I scores at the end of the DBP also showed more improvement as 
      the dose of MPH-MLR increased. During the open-label phase, ADHD-RS-IV total 
      scores improved (mean change from baseline -22.5) and correlated as the dose of 
      MPH-MLR increased; CGI-I scores also improved. No unexpected AEs were noted. 
      CONCLUSIONS: Dose-related improvements in ADHD-RS-IV scores that exceeded those 
      of placebo were observed in patients treated with MPH-MLR. No new safety signals 
      were noted.
FAU - Wigal, Sharon B
AU  - Wigal SB
AD  - AVIDA, Inc., 1600 Dove St, Suite 305, Newport Beach, CA, USA, 
      drsharon@avidainc.com.
FAU - Nordbrock, Earl
AU  - Nordbrock E
FAU - Adjei, Akwete L
AU  - Adjei AL
FAU - Childress, Ann
AU  - Childress A
FAU - Kupper, Robert J
AU  - Kupper RJ
FAU - Greenhill, Laurence
AU  - Greenhill L
LA  - eng
SI  - ClinicalTrials.gov/NCT01239030
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - New Zealand
TA  - CNS Drugs
JT  - CNS drugs
JID - 9431220
RN  - 0 (Capsules)
RN  - 0 (Central Nervous System Stimulants)
RN  - 0 (Delayed-Action Preparations)
RN  - 207ZZ9QZ49 (Methylphenidate)
SB  - IM
MH  - Adolescent
MH  - Attention Deficit Disorder with Hyperactivity/*drug therapy/epidemiology
MH  - Capsules
MH  - Central Nervous System Stimulants/*administration & dosage/adverse effects
MH  - Child
MH  - Delayed-Action Preparations/administration & dosage/adverse effects
MH  - Double-Blind Method
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - Male
MH  - Methylphenidate/*administration & dosage/adverse effects
MH  - Psychiatric Status Rating Scales
MH  - Treatment Outcome
PMC - PMC4425805
EDAT- 2015/04/17 06:00
MHDA- 2016/06/14 06:00
PMCR- 2015/04/16
CRDT- 2015/04/17 06:00
PHST- 2015/04/17 06:00 [entrez]
PHST- 2015/04/17 06:00 [pubmed]
PHST- 2016/06/14 06:00 [medline]
PHST- 2015/04/16 00:00 [pmc-release]
AID - 241 [pii]
AID - 10.1007/s40263-015-0241-3 [doi]
PST - ppublish
SO  - CNS Drugs. 2015 Apr;29(4):331-40. doi: 10.1007/s40263-015-0241-3.