Modified-release methylphenidate () significantly improved symptoms with a treatment difference of -4.6 points on the ADHD Rating Scale-IV compared to placebo.
The study involved 221 patients aged 6 to <18 years diagnosed with ADHD.
MPH-MR demonstrated a significant reduction in ADHD symptoms as measured by the ADHD-RS-IV total score compared to placebo.
Improvements in functional impairment, as assessed by the Weiss Functional Impairment Rating Scale-Parent Report, also favored MPH-MR over placebo.
The Clinical Global Impression-Improvement score was significantly better in the MPH-MR group at the end of the study.
Treatment-emergent adverse events were reported in 67.3% of patients receiving MPH-MR, mostly mild to moderate in severity.
Simplified
BACKGROUND AND OBJECTIVES: The efficacy and safety of modified-release methylphenidate () in the treatment of attention-deficit/hyperactivity disorder () have been shown in both pediatric and adult Caucasian patients. The objective of this study was to assess the efficacy and safety of MPH-MR in Chinese children and adolescents with ADHD.
METHODS: MICCA was a randomized, double-blind, placebo-controlled trial conducted at 19 sites in China from September 2018 to July 2021. The study enrolled children and adolescents aged 6 to < 18 years with a primary diagnosis of ADHD according to the Diagnostic and Statistical Manual for Mental Disorders, Fifth Edition (DSM-5). Patients were randomized 1:1 to once-daily MPH-MR (10-60 mg) or placebo. The study included an up-titration phase of up to 5 weeks and a dose maintenance phase of 4 weeks. The primary efficacy endpoint was the change in the ADHD Rating Scale-IV (ADHD-RS-IV) total score from baseline to the end of the maintenance phase (EoM). Secondary endpoints included the change from baseline to EoM in Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P) total score, and Clinical Global Impression-Improvement (CGI-I) scores at EoM. Safety assessments included treatment-emergent adverse events (TEAEs) and vital signs.
RESULTS: A total of 221 patients were randomized (MPH-MR: n = 110; placebo: n = 111). The change in the ADHD-RS-IV total score from baseline to EoM was significantly greater for MPH-MR versus placebo, with a least squares (LS) mean (95% confidence interval [CI]) treatment difference of - 4.6 (- 6.92, - 2.30) (p < 0.001). The mean (95% CI) treatment difference for the WFIRS-P total score change from baseline to EoM also significantly favored MPH-MR over placebo (- 6.46 [- 10.57, - 2.34]; p = 0.002). The CGI-I score at EoM was significantly lower in the MPH-MR group compared to the placebo group (2.2 vs 2.5; p = 0.002). Treatment-emergent adverse events were reported for 74 (67.3%) patients in the MPH-MR group and 55 (49.1%) patients in the placebo group. Most TEAEs were mild to moderate in severity. The most common TEAEs for MPH-MR were decreased appetite, nausea and upper respiratory tract infection. Treatment-emergent adverse events leading to study drug discontinuation/study withdrawal were reported in 4 (3.6%) patients in the MPH-MR group and 1 (0.9%) patient in the placebo group. No clinically relevant changes in vital signs were observed during the study.
CONCLUSIONS: Modified-release methylphenidate was superior to placebo in improving ADHD symptoms and functioning in Chinese pediatric patients with ADHD. Modified-release methylphenidate had a good safety and tolerability profile. Trial Registration http://www.chinadrugtrials.org.cn/ Identifier: CTR20180056 (registered on 21 May 2018).
Key numbers
-4.6
-RS-IV Score Reduction
Treatment difference from baseline to end of maintenance phase.
-6.46
WFIRS-P Score Change
Mean treatment difference from baseline to end of maintenance phase.
74 of 110 patients
TEAEs Reported
Percentage of patients experiencing treatment-emergent adverse events in the group.
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Declarations. Funding: This study was funded by MEDICE Arzneimittel Pütter GmbH & Co. KG. Open access publication was also funded by MEDICE Arzneimittel Pütter GmbH & Co. KG. No funding was received to assist with the preparation of this manuscript. Conflict of interest: Yi Zheng, Huaqing Liu, Xiuxia Wang and Haibo Li have no conflicts of interest to declare in relation to this work. Michaela Ruhmann, Anke Mayer and Oliver Dangel are employees of MEDICE Arzneimittel Pütter GmbH & Co. KG. Richard Ammer is managing owner of MEDICE Arzneimittel Pütter GmbH & Co. KG. Ethics approval: The study protocol, amendments and informed consent form were reviewed and/or approved by Independent Ethics Committees (ECs) according to local regulations before study initiation for each participating study site: Beijing Anding Hospital of Capital Medical University [submission acceptance no.: (2018)clinical review No.(08)], Peking University Sixth Hospital [no.: (2018)ethics review No.(21)], Children’s Hospital of Fudan University [no.: (2018)ethics review No.(192)], The second Xiangya Hospital of Central South University [no.: (2018)ethics review (drug) No.(092)], The First Hospital of Peking University [EC review no.: (2018)drug register No.(36)], Renmin Hospital of Wuhan University [approval no.: WDRY2018-Y054], Beijing Huilongguan Hospital [no.: 2018-28], Children’s Hospital of Shanxi [approval no.: IRB-YL-2018-003], Jiangxi Provincial Children’s Hospital [EC approval no.: PJ2018019], Xiangya Hospital Central South University [no.: Ethics review expedited No.(201809130)], Guangzhou Huiai Hospital [approval no.: (2018) No.(016)], The second affiliated Hospital of Shantou University Medical college [no.: (2018)ethics review No.(6)], Hunan provincial Children’s Hospital [EC approval no.: HNSETYYLL2018001], Guangzhou Women and Children’s Medical Center [no.: GCP (IEC) Approval [2018] No.10], The second affiliated Hospital of Xinxiang University [no.: 2018 ethics review (drug) No.2], The first affiliated Hospital of Jilin University [no.: 18Y164-002], The second Hospital of Hebei Medical University [project no.: 2018EC07-01-1], Children’s Hospital Capital Institute of Pediatrics [base drug (ethics) review no.: [2018]-004], The Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University [EC approval no.: drug ethics review No.(2020-041)]. The study was conducted in accordance with the Declaration of Helsinki and its later amendments, the International Council for Harmonization Guideline for Good Clinical Practice, and local regulations. Consent to participate: All parents/guardians and patients aged 8 to <18 years provided written informed consent before screening. Consent for publication: Not applicable. Availability of data and material: The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. Code availability: Not applicable. Author contributions: YZ, AM, OD and RA participated in the conception and design of the study. YZ served as principal investigator for the study. YZ, HL, XW and HL contributed to data collection. All authors contributed to interpretation of data. MR drafted the manuscript. All authors have read and approved the final submitted manuscript and agree to be accountable for the work.
