The Efficacy and Safety of Amphetamine Extended-release Oral Suspension (AMPH EROS) in Children with Attention-deficit/hyperactivity Disorder

Background: 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.

Methods: 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 (5 weeks) with an initial AMPH EROS dose of 2.5 or 5 mg once daily in the morning. The dose could be titrated every 4-7 days in increments of 2.5-10 mg until an optimal dose or the maximum dose of 20 mg/day was reached. Subjects were required to tolerate a minimal dose of 10 mg/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 4 hours postdose. The key secondary endpoint efficacy parameters were onset and duration of clinical effect. The change scores from pre-dose SKAMP-C scores at postdose time points (1, 2, 6, 8, 10, 12 and 13 hours) were used to evaluate the key secondary efficacy endpoints.

Results: 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 4 hours postdose 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.

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