In the 6-week, open-label phase of the CEES trial [NCT02255513], nighttime dosing of delayed- and controlled-release oral methylphenidate reduced attention-deficit/hyperactivity disorder (ADHD) symptoms in the early morning, with symptom control maintained through the day, according to a poster presented by Mary Ann A. McDonnell, PhD, Northeastern University, Boston, Massachusetts, USA. This phase of the trial, which was carried out with 43 children diagnosed with ADHD as an effort to optimize the dose of the central nervous system stimulant, was a prelude to a 1-week, double-blind, placebo-controlled phase to assess the safety and efficacy of the approach.

This trial assessed a proprietary oral delivery system, HLD200, intended to be used in the evening, with the goal of lessening early morning ADHD symptoms in children. The 43 children (20 girls; 46.5%) ranged in age from 6 to 12 years (mean, 9.7 ± 1.7 years). Most of the children were aged 8 to 10 years (n = 22; 51.2%), followed by > 10 years (n = 14; 32.6%). Most were white (n = 34; 79.1%). All had confirmed ADHD, current or prior response to methylphenidate, and no other major medical condition.

In the dose-optimization process, HLD200 at the second visit was administered to deliver the same dose of methylphenidate that a patient had previously been taking or, at the discretion of the investigator, a dose of about 1.4 mg/kg. The dosage was altered in subsequent weekly sessions until a concentration deemed satisfactory was reached at visit 8. This dosage was then carried forward in the 1-week double-blind, randomized, placebo-controlled trial.

The current data are from the initial 6-week period of dose optimization. Analyses during this time included the ADHD Rating Scale–IV (ADHD-RS-IV), Before School Function Questionnaire (BSFQ), and Daily Parent Rating of Evening and Morning Behavior–Revised (DPREMB-R).

The mean starting dose at baseline (visit 2) was 32.02 ± 17.93 mg. The subsequent dose adjustment yielded an optimal and significantly greater dose of 65.58 ± 24.81 mg (P < .0001).

The time the doses were given remained constant (9:00 pm ± 0 minutes and 8:56 pm ± 19.8 minutes; P = .18). The mean ADHD-RS-IV score decreased significantly during the dose-adjustment period, from 38.23 ± 8.90 at visit 2 to 12.51 ± 6.62 at visit 8 (P < .0001).

The mean BSFQ scores likewise decreased significantly from visit 2 (36.21 ± 13.31) to visit 8 (10.12 ± 7.25; P < .0001). DPREMB-R scores in the morning and evening also differed significantly as treatment progressed. The mean morning score at visits 2 and 8 was 4.91 ± 2.42 and 1.21 ± 1.21, respectively (P < .0001). The corresponding evening score at visits 2 and 8 was 15.14 ± 5.91 and 7.65 ± 5.68, respectively (P < .0001).

The 6-week trial was successful in establishing a dose that produced significant lessening of morning ADHD symptoms. Furthermore, symptom control was maintained through the day. Full results are forthcoming.