Discussion
TEAEs, decreased appetite, insomnia, ADHD, irritability
UPPER RESPIRATORY TRACT INFECTION, NASOPHARYNGITIS, CARDIOVASCULAR MORBIDITY
This 1-year DO, open-label safety study to evaluate the long-term safety and tolerability of SDX/d-MPH is the second phase 3 clinical trial with SDX/d-MPH to be completed in children aged 6–12 years with ADHD, after the pivotal, short-term DB, laboratory classroom study (Kollins et al, This 1-year study showed that SDX/d-MPH was safe and well tolerated. The most common TEAEs were decreased appetite, irritability, decreased weight, insomnia, upper respiratory tract infection, and nasopharyngitis. There were no new or unexpected TEAEs compared with those of the pivotal study that could potentially be attributed to SDX/d-MPH. Because MPH products are associated with increased blood pressure and heart rate, which are risk factors for cardiovascular morbidity (Hennissen et al, ECGs did not show prolongation of QT interval. No subjects discontinued treatment because of increased blood pressure or heart rate. Overall effects of SDX/d-MPH on reductions in body weight and height were consistent with those observed with other MPH products (Faraone and Giefer, In the treatment phase, 60% of subjects reported ≥1 AE, and 2.5% of subjects discontinued treatment. Placed into context with other MPH products for ADHD, the percentages of AEs with SDX-d-MPH were equivalent or fewer than those reported with other treatments. In general, there were fewer study discontinuations due to AEs with SDX/d-MPH than with those reported in other MPH studies.In a comprehensive 2018 systematic review of AEs associated with MPH, much higher rates of AEs were found compared with those in the present study. In 177 noncomparative studies in children and adolescents (aged 3–20 years) involving 2,207,751 subjects with ADHD, the incidence of non-serious AEs was 51.2% (range, 41.2%–61.1%), with SAEs ranging from 0.7% to 2.0% (Storebø et al, In a 1-year study of the osmotic-release oral system (OROS) formulation of MPH in children aged 6–13 years with ADHD, 344 of 407 subjects (84.5%) reported ≥1 AE, and 6.9% of subjects discontinued the medication because of an AE (Wilens et al, In a 1-year study of an MPH multilayer release (MPH-MLR) extended-release formulation in children aged 4–6 years with ADHD, 65 of 89 subjects (73%) experienced TEAEs, and 11.2% discontinued treatment because of an AE (Childress et al, In this study, efficacy was assessed by ADHD-RS-5 and CGI-S scores. SDX/d-MPH treatment produced a noticeable improvement in ADHD-RS-5 and CGI-S scores within 1 month of starting treatment, and continued effectiveness was seen during the 1-year treatment period, as shown by sustained low ADHD-RS-5 and CGI-S scores from baseline.Limitations of this study include the open-label nature of the study design and the lack of placebo or a comparator product. There may also be a selection bias during the course of the 12-month treatment duration. Subjects who experienced lack of efficacy did discontinue from the study; therefore, efficacy assessments at latter time points may be affected in part by this selection bias. No conclusions can be made regarding additional or further long-term efficacy.