A four-week trial did not show that 6.25 mg extended-release mixed amphetamine salts improved pediatric ADHD symptoms more than placebo. This negative finding concerns the tested dose and formulation, and should remain separate from positive trials using other dosing strategies.
Mattingly and colleagues randomized 89 children aged 6–12 years to SHP465 mixed amphetamine salts or placebo. Unlike a dose-optimization study, this trial tested a fixed 6.25 mg daily dose. The primary endpoint was change in the home-version ADHD Rating Scale 5 total score at week four.
The key secondary endpoint was clinician-rated global improvement. Eighty-three participants completed the study. This was a controlled human therapeutic experiment, with symptom severity and clinical improvement as the main efficacy outcomes.
The estimated primary treatment difference was 1.9 points in favor of active treatment, with a 95% confidence interval ranging from 6.8 points favoring active treatment to 3.1 points favoring placebo. The p value was 0.451. Global improvement also did not differ significantly.
Treatment-emergent adverse events occurred in 24.4% of the active-treatment safety group and 16.3% of the placebo group. These short-term observations inform tolerability, but neither tolerability nor a numerical symptom advantage establishes efficacy. Both groups improved from baseline, underscoring why the placebo comparison matters.
The authors considered the dose potentially subtherapeutic and proposed that the release profile might fail to produce sufficient exposure. That proposed explanation was not an established plasma concentration cutoff. The paper also noted that group means could conceal individual benefit, but no such possibility reverses the nonsignificant primary result.
Age range, sample size, prior stimulant exposure and four-week follow-up constrain generalization. The trial was industry funded. Its findings do not establish that all amphetamine doses are ineffective, nor that detecting amphetamine proves therapeutic benefit or impairment. They show why a positive result from a different regimen cannot be substituted for the actual outcome of a specific low-dose trial.
Read our analysis of a different SHP465 dose strategy in adults.
A Phase 3, Randomized Double-Blind Study of the Efficacy and Safety of Low-Dose SHP465 Mixed Amphetamine Salts Extended-Release in Children with Attention-Deficit/Hyperactivity Disorder. doi:10.1089/cap.2020.0005.