Patients were required to discontinue any psychoactive medication for a 7-day washout period prior to baseline (visit 0). At baseline, patients were randomized (1:1) to receive a once-daily, morning dose (at 07:00 ± 2 h) of LDX or ATX for a 9-week, double-blind evaluation period (Fig. 1) with weekly, on-site efficacy, tolerability and safety assessments. Dosing began on the morning after the baseline visit and continued for 9 weeks, starting with a 4-week, stepwise, dose-optimization stage. Randomization of patients was stratified by country, and an automated interactive response system was used to generate the random (concealed) allocation sequence and assign participants to study treatments; patients, caregivers and investigators were blinded to the treatment allocation. All study drugs were over-encapsulated so they appeared identical.

Study design. Visit window ±2 days throughout the evaluation period. Visit window +2 days for safety follow-up visit. ATX atomoxetine, ET early termination, LDX lisdexamfetamine dimesylate, V visit

The dose-optimization phase involved adjustment of the dose until an ‘acceptable’ response was achieved [defined as a reduction of at least 30 % from baseline in the ADHD-RS-IV total score and a Clinical Global Impressions-Improvement (CGI-I) score of 1 or 2 with tolerable side effects]. Only one dose reduction was permitted during the optimization phase and, following dose reduction, further increases were not allowed. Dose adjustments were not permitted beyond visit 3, and patients who were unable to tolerate the study drug were withdrawn from the study.
LDX was provided in a single capsule of 30, 50 or 70 mg, with patients initially receiving a 30-mg dose. ATX was available in 10-, 18-, 25-, 40- and 60-mg capsules. All patients in the ATX group who weighed less than 70 kg were started on a daily dose of approximately 0.5 mg/kg body weight, the final target daily dose being 1.2 mg/kg, with a maximum permitted daily dose of 1.4 mg/kg. Patients who weighed 70 kg or more initially received 40 mg and, if required, were titrated to 80 mg and then to 100 mg daily. Some patients treated with ATX would need two capsules to achieve the required dose (e.g. 80 and 100 mg were achieved using two capsules). Therefore, all patients weighing more than 64.5 kg who were titrated to a higher dose were instructed to take two capsules (the second capsule could be either active drug or placebo, as appropriate) to maintain the double-blind study design.