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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.

Abstract

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.

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  • Authors+Show Affiliations

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    AVIDA, Inc., 1600 Dove St, Suite 305, Newport Beach, CA, USA, drsharon@avidainc.com.

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    Source

    CNS drugs 29:4 2015 Apr pg 331-40

    MeSH

    Adolescent
    Attention Deficit Disorder with Hyperactivity
    Capsules
    Central Nervous System Stimulants
    Child
    Delayed-Action Preparations
    Double-Blind Method
    Female
    Follow-Up Studies
    Humans
    Male
    Methylphenidate
    Psychiatric Status Rating Scales
    Treatment Outcome

    Pub Type(s)

    Clinical Trial, Phase III
    Journal Article
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    25877989

    Citation

    Wigal, Sharon B., et al. "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." CNS Drugs, vol. 29, no. 4, 2015, pp. 331-40.
    Wigal SB, Nordbrock E, Adjei AL, et al. 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. CNS Drugs. 2015;29(4):331-40.
    Wigal, S. B., Nordbrock, E., Adjei, A. L., Childress, A., Kupper, R. J., & Greenhill, L. (2015). 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. CNS Drugs, 29(4), pp. 331-40. doi:10.1007/s40263-015-0241-3.
    Wigal SB, et al. 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. CNS Drugs. 2015;29(4):331-40. PubMed PMID: 25877989.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - 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. AU - Wigal,Sharon B, AU - Nordbrock,Earl, AU - Adjei,Akwete L, AU - Childress,Ann, AU - Kupper,Robert J, AU - Greenhill,Laurence, PY - 2015/4/17/entrez PY - 2015/4/17/pubmed PY - 2016/6/14/medline SP - 331 EP - 40 JF - CNS drugs JO - CNS Drugs VL - 29 IS - 4 N2 - 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. SN - 1179-1934 UR - https://www.unboundmedicine.com/medline/citation/25877989/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_ L2 - https://dx.doi.org/10.1007/s40263-015-0241-3 DB - PRIME DP - Unbound Medicine ER -