Efficacy and Safety of Methylphenidate HCl ER Capsules in Children and Adolescents With ADHD

A Randomized, Parallel, Double-Blind Efficacy and Safety Study of Biphentin Methylphenidate HCl Extended Release Capsules Compared to Placebo in Children and Adolescents 6 to 18 Years With Attention Deficit Hyperactivity Disorder (ADHD)

This multi-center parallel study is designed to study the efficacy and safety of fixed doses of methylphenidate extended release (ER) capsules of four dose levels compared with a placebo group in pediatric patients with Attention Deficit Hyperactivity Disorder (ADHD) who are between 6 and 18 years old.

This is a parallel, randomized, double-blind, multi-center, placebo-controlled, forced dose, phase 3 study to evaluate the safety and efficacy of Biphentin® methylphenidate hydrochloride (HCl) extended release (ER) capsules in the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in pediatric and adolescent patients aged 6 up to 18 years.

The primary objective was to assess the efficacy of Biphentin compared to placebo, in the clinic setting, as measured by the clinician-administered parent version of the ADHD-RS-IV.

Subjects who met study entry criteria were enrolled in the Double-blind Phase and were randomized to either a fixed dose of Biphentin (!0, 15, 20, or 40 mg/day) or placebo capsule taken daily in the morning for 1 week. Subjects then continued into an Open-label Phase that included dose optimization with doses starting at 10 mg and allowed up to 60 mg. The open-label period following the one double-blind fixed dose week provides additional opportunity for subjects to receive treatment with Biphentin. Extra unscheduled dose optimization visits are allowed as needed for additional dose titration visits during the open-label period.

The safety and tolerability, and efficacy assessments will be conducted throughout the study.

Biphentin® is designed to be a single daily dose alternative to separate doses of immediate release methylphenidate by providing a biphasic plasma profile. It achieves a first Cmax more similar to immediate release methylphenidate.

Inclusion Criteria:

• Males and females ages 6 up to 18
• ADHD diagnosis with ADHD Rating Scale - 4th Edition scores ≥ 90th percentile
• In need of treatment for ADHD and able to have 2-day washout from previous medication
• Females of child-bearing potential not pregnant and practice birth control
• Subject and parent/guardian willing to comply with protocol
• Signed consent and assent

Exclusion Criteria:

• Estimated Full Scale intellectual level below 80 using Wechsler Abbreviated Scale of Intelligence (WASI)
• Current primary psychiatric diagnosis of other listed disorders
• Chronic medical illnesses: seizure, hypertension, thyroid disease, cardiac, family history of sudden death, glaucoma
• Use of psychotropic central nervous system (CNS) meds having effect exceeding 14 days from screening
• Planned use of prohibited drugs
• Is pregnant or breast-feeding
• Significant ECG or laboratory abnormalities
• Experimental drug or medical device within 30 days prior to screening
• Hypersensitivity to methylphenidate
• Inability or unwillingness to comply with protocol
• Well controlled on current ADHD treatment
• Inability to take oral capsules