Comparison of the clinical efficacy of twice-daily Ritalin® and once-daily Equasym™ XL with placebo in children with Attention Deficit/Hyperactivity Disorder

Objective: To compare the efficacy and safety of two methylphenidate (MPH) formulations-once-daily modified-release MPH (EqXL, Equasym™ XL) and twice-daily immediate-release methylphenidate (MPH-IR, Ritalin®)-and placebo in children with Attention Deficit/Hyperactivity Disorder (ADHD). Methods: Children aged 6-12 years on a stable dose of MPH were randomized into a double-blind, three-arm, parallel-group, multi-center study and received 3 weeks of EqXL (20, 40, or 60 mg qd), MPH-IR (10, 20, or 30 mg bid) or placebo. Non-inferiority of EqXL to MPH-IR was assessed by the difference in the inattention/overactivity component of the overall teacher's IOWA Conners' Rating Scale on the last week of treatment (per protocol population). Safety was monitored by adverse events, laboratory parameters, vital signs, physical exam, and a Side Effect Rating Scale. Results: The lower 97.5% confidence interval bound of the difference between MPH groups fell above the non-inferiority margin (-1.5 points) not only during the last week of treatment but during all three treatment weeks. Both MPH-treatment groups experienced superior benefit when compared to placebo during all treatment weeks (P < 0.001). All treatments were well tolerated. Conclusions: EqXL given once-daily was non-inferior to MPH-IR given twice-daily. Both treatments were superior to placebo in reducing ADHD symptoms.