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

Abstract

Objective: 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).

Methods: 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).

Results: 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 < 0.01 and p = 0.0002, respectively). PERMP scores were not statistically significantly improved at 30 minutes postdose for AMPH EROS relative to the placebo group. PERMP scores were statistically significantly improved at 3 hours postdose for AMPH EROS relative to the placebo group (PERMP problems attempted treatment difference least-squares [LS] mean [SE] = 60.3 [12.93], p = 0.0003; PERMP problems correct treatment difference LS mean [SE] = 61.6 [13.16], p = 0.0003). AEs (>10%) during the open-label phase included upper respiratory tract infection, fatigue, upper abdominal pain, headache, decreased appetite, and affect lability.

Conclusions: AMPH EROS was effective in reducing ADHD symptoms at 30 minutes postdose as indicated by SKAMP-C score improvement, although improvements in PERMP scores at 30 minutes were not statistically significant. AEs were mild or moderate and consistent with those of other extended-release amphetamines.

Trial registration: ClinicalTrials.gov NCT03088267.

Keywords: ADHD; amphetamines; attention-deficit/hyperactivity disorder; early onset; efficacy; extended-release oral suspension.

Figures

FIG. 1.

Study design. AMPH EROS, amphetamine extended-release oral suspension; SD, study drug; DB, double-blind.

FIG. 2.

SKAMP-C scale score change from predose: double-blind treatment period (ITT population). The curves are compared using the p-value of the treatment effect. Treatment comparison was assessed using a linear model with sequence (Placebo/AMPH EROS, AMPH EROS/Placebo), period (Visit 3, Visit 4), treatment (AMPH EROS, Placebo), time point (30 minutes, 3 hours), the interaction term treatment × time point as fixed effects, and subject within sequence as a repeated effect with a compound symmetry correlation structure. AMPH EROS, amphetamine extended-release oral suspension; ITT, intent-to-treat; LS mean, least-squares mean; SE, standard error; SKAMP-C, Swanson, Kotkin, Agler, M-Flynn, Pehlan-Combined rating scale.