PC3019: Serdexmethylphenidate/dexmethylphenidate (SDX/d-MPH) Optimized Dose Levels and Effects on Attention-deficit/hyperactivity Disorder-rating scale-5 (ADHD-RS-5) Response Rates in Children with ADHD

Background: SDX/d-MPH (Azstarys®) contains 70% SDX, a novel prodrug of d-MPH hydrochloride, and 30% d-MPH. SDX/d-MPH is approved for patients with ADHD aged ≥6 years. Efficacy and safety of SDX/d-MPH were demonstrated in a laboratory classroom study (NCT03292952) of children aged 6-12 years with ADHD. This post-hoc analysis evaluated treatment responder rates using the ADHD-RS-5 score based on optimized dose level of SDX/d-MPH.

Methods: Data were used from the 21-day dose-optimization (DO) phase of the classroom study. During the DO phase, 155 patients initiated treatment with the 39.2-/7.8-mg SDX/d-MPH dose in the first week; thereafter, patients were titrated to an optimum dose (1 of 3 available doses) based on physician assessment; 5 patients (3.2%) were down-titrated to 26.1/5.2 mg, 76 patients (49.0%) were up-titrated to 52.3/10.4 mg, and 69 patients (44.5%) remained at the 39.2-/7.8-mg optimized dose level during the following 2 weeks. The analysis involved defining a threshold value equal to or above which a patient is considered a “responder” and below which a patient is considered a “nonresponder.” Two responder variables were created with threshold values of 30% and 50% based on the percent change from baseline (day 0) to visits 3 (day 7), 4 (day 14), and 5 (day 21) in the ADHD-RS-5 score.

Results: Frequencies and percentages of patients within each threshold, by dose level, are presented for all postbaseline visits during the DO phase (Figures 1 and 2). At all 3 final optimized dose levels, nearly all patients (99.3%) had a ≥30% responder rate by visit 5 (Figure 1); 77.3% of patients had a ≥50% responder rate by visit 5 (Figure 2). Of the 5 patients optimized at the 26.1-/5.2-mg dose, ≥80% of patients across all visits had a ≥50% responder rate (Figure 2). Of the 69 patients optimized at the 39.2-/7.8-mg dose, 72.5% had a ≥50% responder rate at visit 3, and 81.2% had a ≥50% responder rate by visit 5 (Figure 2). Of 76 patients optimized to the 52.3-/10.4-mg dose, 22.4% had a ≥50% responder rate at visit 3 (initiated at the 39.2-/7.8-mg dose), and 72.4% had a ≥50% responder rate by visit 5 (Figure 2). Those patients having a suboptimal response to methylphenidate to the initial 39.2-/7.8-mg dose may need to be titrated to a higher dose or require a longer duration of treatment to achieve a ≥50% responder rate.

Conclusion: This analysis showed that responders are evident after the first week of treatment at the 26.1-/5.2-mg and 39.2-/7.8-mg final dose levels, with small increases in the proportion of responders thereafter, whereas the 52.3-/10.4-mg final dose level continued to notably increase in the proportion of responders after titration to the 52.3-/10.4-mg final dose level.