Safety and Tolerability of Serdexmethylphenidate/Dexmethylphenidate Capsules in Children with Attention-Deficit/Hyperactivity Disorder: A 12-Month, Open-Label Safety Study

Abstract

Objective: Serdexmethylphenidate/dexmethylphenidate (SDX/d-MPH) is approved for the treatment of patients aged ≥6 years with attention-deficit/hyperactivity disorder (ADHD). A pivotal double-blind (DB) study of children aged 6–12 years with ADHD demonstrated efficacy for ADHD with good tolerability. In this study, we assessed the safety and tolerability of daily oral SDX/d-MPH for up to 1 year in children with ADHD. Methods: This was a dose-optimized, open-label safety study with SDX/d-MPH in children aged 6–12 years with ADHD that included subjects who successfully completed the DB study (rollover) and new subjects. The study consisted of a 30-day screening phase, a dose optimization phase for new subjects only, a 360-day treatment phase, and follow-up. Adverse events (AEs) were assessed from the first day of SDX/d-MPH administration to the end of the study. During the treatment phase, ADHD Rating Scale-5 (ADHD-RS-5) and Clinical Global Impressions–Severity (CGI-S) scale assessments were used to evaluate ADHD severity. Results: Of the 282 subjects enrolled (70 rollover; 212 new), 28 discontinued treatment in the dose optimization phase and 254 entered the treatment phase. By study completion, 127 had discontinued and 155 had completed the study. The treatment-phase safety population included all enrolled subjects who received ≥1 dose of study drug and had ≥1 postdose safety assessment. Of 238 subjects assessed in the treatment-phase safety population, 143 (60.1%) had ≥1 treatment-emergent adverse events (TEAEs), and 36 (15.1%), 95 (39.9%), and 12 (5.0%) had mild, moderate, or severe TEAEs, respectively. The most common TEAEs were decreased appetite (18.5%), upper respiratory tract infection (9.7%), nasopharyngitis (8.0%), decreased weight (7.6%), and irritability (6.7%). There were no clinically meaningful trends in electrocardiograms, cardiac events, or blood pressure events, and none led to discontinuation. Two subjects had eight serious AEs that were unrelated to treatment. There were overall reductions in ADHD symptoms and severity as assessed by ADHD-RS-5 and CGI-S during the treatment phase. Conclusions: In this 1-year study, SDX/d-MPH was found to be safe and well tolerated and comparable with other methylphenidate products, with no unexpected safety findings. SDX/d-MPH also showed sustained efficacy during the 1-year treatment period. identifier: NCT03460652.

The Impact of Methylphenidate on Pubertal Maturation and Bone Age in ADHD Children and Adolescents: Results from the ADHD Drugs Use Chronic Effects (ADDUCE) Project

“…Some recent publications confirm the safety of stimulants regarding this matter of discussion. A recent analysis of Growth Velocity in ADHD Children medicated with Serdexmethylphenidate/Dexmethylphenidate for 12 months confirm that the effects of medication on height were minimal and not clinically significant (Childress et al, 2023) while our previously reported findings from the full ADDUCE prospective study found no evidence of an MPH effect on height in the medicated population compared to the No-MPH group in the long-term (24 months); only for weight velocity there was an initial slowing at 6 months in the MPH group with no group differences for BMI at any time point (Man et al, 2023).…”

Recent advances in the treatment of attention deficit hyperactivity disorder in children: A narrative review

“…13 Though stimulant, it has lower abuse potential and less severe adverse effect profile. 14,15,16 Viloxazine:Previously used as antidepressant, it is a non-stimulant drug, approved by FDA in April, 2021 for use in ADHD. 17 It acts via selectively inhibiting norepinephrine reuptake and has low abuse potential with adverse effects similar to non-stimulants.…”

Serdexmethylphenidate/dexmethylphenidate effects on sleep in children with attention-deficit/hyperactivity disorder

“…Some studies have shown beneficial effects of MPH on sleep in patients with ADHD with pre-existing sleep disturbances (6,7). Others have reported a more complicated relationship between MPH treatments and sleep in the ADHD patient population because the formulation and dose of MPH, length of treatment, measures of sleep (e.g., objective vs. subjective measures), and the patient population (e.g., inclusion of patients with sleep problems prior to treatment or those without any pre-existing sleep problems) can vary from study-tostudy (6,8) A subsequent 1-year, open-label, dose-optimized safety study of SDX/d-MPH showed that SDX/d-MPH was well tolerated with no new or unexpected safety findings and had sustained effectiveness in reducing ADHD symptoms during the 1-year treatment period in children age 6 to 12 years with ADHD (10). Of 238 participants assessed during the 12-month treatment phase of the study, the most common treatment-related AEs were decreased appetite (18.5%), upper respiratory tract infection (9.7%), nasopharyngitis (8.0%), decreased weight (7.6%), and irritability (6.7%).…”