Efficacy measures in an open-label dose-optimization of an amphetamine extended-release oral suspension in children with attention-deficit/hyperactivity disorder

Objectives: Report the efficacy of open-label amphetamine extended-release oral suspension (AMPH EROS) for the treatment of children with ADHD. AMPH EROS has a 1-hr onset of effect and a duration of action of 13 hours and was approved by FDA for treatment of ADHD in children aged 6-17 years based on a doubleblind, placebo-controlled efficacy and safety study in children aged 6-12 years with ADHD. A significant treatment difference in change from pre-dose SKAMPcombined score was observed at the primary endpoint of 4 hours post-dose (p<0.0001) and each post-dose time point assessed (1, 2, 4, 6, 8, 10, 12, 13 hours). Data reported here are from the 5-week, open-label dose optimization period. These efficacy data support the primary endpoint result. METHODS: Males and females aged 6 to 12 years with ADHD enrolled and began open-label treatment with 2.5mg or 5 mg/day of AMPH EROS titrated in 2.5-10 mg/day increments until optimal dose (maximum 20 mg/day). Doses could be decreased for tolerability. Subjects took morning AMPH EROS for 5 weeks. Other efficacy outcomes during the open-label dose optimization phase: ADHD-RS (ADHD-Rating Scale), CGI-S (Clinical Global Impression of Severity), CGI-I (CGI-of Improvement) and CPRS (Conners' Parent Rating Scale). All subjects were assessed for safety. RESULTS: For the ITT population (n= 99): treatment with AMPH EROS was associated with a mean change in ADHD-RS-IV (baseline to end of the open-label dose optimization; week 6) of 28.2 (±9.03) (Baseline score = 41.3±7.95). 90.9% of subjects had a change from baseline to open-label week 6 of ≥50% in the ADHDRS- IV total score and were defined as responders. The CGI-S scores decreased continuously from baseline, with a high 4.8 at baseline to a low of 2.0 at open-label week 6. The percentage of subjects classified as moderately ill or greater correspondingly decreased from 97% at Baseline to 1% at open-label week 6. The decrease in the CGI-I over the study was similar to the change in CGI-S scores. CPRS for most categories decreased continuously from Baseline to open-label week 6. Mean change from baseline to open-label week 6 on the CPRS inattention T-score subscale was -25.3 (±14.38) and -24.4 (±13.87). Adverse events (>5%) reported during dose optimization were decreased appetite, insomnia, affect lability, upper abdominal pain, mood swings and headache. CONCLUSION: AMPH EROS was effective in reducing symptoms of ADHD in this open-label dose optimization. The AE profile of AMPH EROS was consistent with those of other amphetamine products.