To determine the efficacy and safety of amphetamine extended-release oral suspension (AMPH EROS) in the treatment of attention-deficit/hyperactivity disorder (ADHD) compared with placebo in a dose-optimized, randomized, double-blind study.

The efficacy of AMPH EROS was evaluated in a laboratory classroom study conducted in 108 pediatric patients (aged 6–12 years) with ADHD. The study began with an open-label dose optimization (5weeks) with an initial AMPH EROS dose of 2.5 or 5mg once daily in the morning. The dose could be titrated every 4–7 days in increments of 2.5–10mg until an optimal dose or the maximum dose of 20mg/day was reached. Subjects were required to tolerate a minimal dose of 10mg/day. Subjects then entered a 1-week randomized, double-blind treatment phase with the individually optimized dose or placebo. At the end of the week, raters evaluated the attention and behavior of the subjects in a laboratory classroom using the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP-C) rating scale. SKAMP-C is a 13-item teacher-rated scale that assesses manifestations of ADHD in a classroom setting.

The primary efficacy endpoint was change from pre-dose in the SKAMP-C score at 4hours post dose. The key secondary endpoint efficacy parameters were onset and duration of clinical effect. The change scores from pre-dose SKAMP-C scores at post dose time points (1, 2, 6, 8, 10, 12 and 13hours) were used to evaluate the key secondary efficacy endpoints.

More boys (68.7%) than girls participated in the study. The study population was 55.6% white, most patients had inattentive or combined type ADHD presentations. The primary efficacy endpoint, the change from pre-dose SKAMP-C score at 4hours post dose was statistically significantly improved (p<0.0001) compared with placebo. Each of the secondary efficacy endpoints were also significantly improved (p<0.0001 at each time point) compared with placebo. Adverse events reported (frequency >5%) reported during the dose optimization phase were decreased appetite, insomnia, affect lability, upper abdominal pain, mood swings, and headache.

AMPH EROS was effective in reducing symptoms or ADHD from 1 to 13hours after dosing. Adverse events reported were consistent with those of other amphetamine products.

Funding Acknowledgements: This study was supported by Tris Pharma, Inc.