Early-Onset Efficacy and Safety Pilot Study of Amphetamine Extended-Release Oral Suspension in the Treatment of Children with Attention-Deficit/Hyperactivity Disorder

To determine whether amphetamine extended-release oral suspension (AMPH EROS) has an onset of effect at 30 minutes postdose in children with attention-deficit/hyperactivity disorder (ADHD). This randomized, double-blind, two-treatment, two-sequence, placebo-controlled crossover pilot study enrolled subjects aged 6-12 years with ADHD and ADHD-Rating Scale-5 scores of ≥90th percentile for sex and age. An optimized dose of 5-20 mg/day of AMPH EROS was determined during a 1-week open-label dose optimization phase based on medication history, symptom control, and tolerability. Subjects completed a practice laboratory classroom then received 1 day of double-blind active drug or placebo each in random sequence during two double-blind laboratory classroom days. Subjects completed the first double-blind laboratory classroom, returned to open-label drug for 5 days, and then crossed over on day 6 during a second double-blind laboratory classroom. Double-blind dose was fixed at AMPH EROS 15, 17.5, or 20 mg. The primary end point was change from predose in the Swanson, Kotkin, Agler, M-Flynn, Pelham-Combined (SKAMP-C) Rating Scale score at 30 minutes postdose on two double-blind days. The key secondary end points were change from predose in the SKAMP-C score at 3 hours postdose for AMPH EROS compared with placebo and change from baseline Permanent Product Measure of Performance (PERMP) scores at 30 minutes and 3 hours postdose compared with placebo. Safety assessments included vital signs and adverse events (AEs). Eighteen subjects were enrolled in the study (14 males and 4 females) with a mean age of 9 years. At both 30 minutes and 3 hours postdose, changes from baseline in SKAMP-C for AMPH EROS versus placebo were statistically significant (p 10%) during the open-label phase included upper respiratory tract infection, fatigue, upper abdominal pain, headache, decreased appetite, and affect lability. AMPH EROS was effective in reducing ADHD symptoms at 30 minutes postdose as indicated by SKAMP-C sc