The prodrug lisdexamfetamine, which is metabolized to d-amphetamine, showed efficacy for up to 12 hours in children with attention deficit hyperactivity disorder who were taught in a laboratory classroom setting, according to an article in the November 1 issue of Biological Psychiatry.

The phase II study was a double-blind, placebo- and active-controlled crossover analog design study in 52 children age 6 to 12 years: Active treatments were lisdexamfetamine (30 mg, 50 mg, or 70 mg) or Adderall XR/ extended-release mixed amphetamine salts (10 mg, 20 mg, or 30 mg).

"This newly published research shows that lisdexamfetamine provided a consistent time to maximum plasma concentration from patient to patient," said Ann S. Childress, MD, President of the Center for Psychiatry and Behavioral Medicine, Inc. in Las Vegas, Nev. "This prodrug stimulant also demonstrated significant efficacy up to 12 hours after administration, which is something that my patients' parents are interested in as it may help to improve their family and homework time in the evening."

The primary efficacy measure was SKAMP-D and SKAMP-A (Swanson, Kotkin, Agler, M-Flynn, and Pelham rating scale deportment and attention) scores across eight classroom sessions held during a 12-hour treatment day. Comparison was between the two active arms with both compared with placebo. The SKAMP-D is a validated classroom tool used for evaluating behavioral symptoms of the disorder; higher scores reflect greater impairment.

Lisdexamfetamine significantly improved SKAMP deportment and attention scores from baseline, as well as clinical global impression score.

Patients taking the prodrug had significant improvement in math problems compared with placebo as assessed with the Permanent Product Measure of Performance Derived Measure (PERMP). When patients were observed over the 12-hour period, mean change in math work from first measurement was 49 for the prodrug versus 22 for mixed salts and negative 24 for placebo. The PERMP tool is an age-adjusted collection of math problems that provides an objective measure of performance based on the number of attempted and completed problems.

Pharmacokinetic testing showed there was little interpatient variability in measured parameters with the prodrug, the first such formulation tested for attention deficit hyperactivity disorder. The coefficient of variance for time to maximum drug concentration for the prodrug and extended-release mixed salts was 20.34 and 43.96, respectively. The correlation, if any, between pharmacokinetics and clinical benefit has not been established.

Adverse effects were similar for the two active treatments.