NWP06, an extended-release oral suspension of methylphenidate, improved attention-deficit/hyperactivity disorder symptoms compared with placebo in a laboratory classroom study

Abstract

Objective: The purpose of this study was to determine the efficacy of NWP06, a novel extended-release (ER) liquid formulation of methylphenidate (MPH), compared with placebo in the treatment of attention-deficit/hyperactivity disorder (ADHD) in children in a laboratory school.

Methods: A total of 45 subjects ages 6-12 years were enrolled in this dose-optimized, randomized, double-blind, placebo-controlled, crossover laboratory school study. Following open-label dose optimization, subjects received 2 weeks of double-blind treatment (1 week of NWP06 and 1 week of placebo). The treatment sequence (NWP06/placebo or placebo/NWP06) was randomly assigned with the last day of each week-long treatment occurring on the laboratory school test day. Efficacy measures included Swanson, Kotkin, Agler, M-Flynn and Pelham (SKAMP) Rating Scale-Combined and Permanent Product Measure of Performance (PERMP) mathematics tests measured at pre-dose and at 0.75, 2, 4, 8, 10, and 12 hours post-dose on each laboratory classroom day. Safety assessments included physical examination, screening electrocardiogram (ECG), vital signs, clinical laboratory tests, adverse event measures, and assessment of suicidality with the Columbia Suicide Severity Rating Scale.

Results: NWP06 resulted in significant (p<0.0001) improvements in the SKAMP-Combined score at 4 hours post-dose (mean=7.12) as compared with placebo (mean=19.58) in the completers (n=39). Significant separation from placebo occurred at each time point tested (0.75, 2, 4, 8, 10, 12 hours), with onset of action of NWP06 at 45 minutes post-dose and duration of efficacy extending to 12 hours post-dose. Adverse events (AEs) and changes in vital signs following NWP06 treatment were generally mild and consistent with the known safety profile of MPH. The most common AEs in the open-label phase were decreased appetite (55.6%), upper abdominal pain (42.2%), affect lability (26.7%), initial insomnia (22.2%), insomnia (17.8%), and headache (17.8%).

Conclusions: NWP06 treatment effectively reduced symptoms of ADHD in children beginning at 45 minutes and continuing for 12 hours post-dose. NWP06 was well tolerated.

Trial registration: ClinicalTrials.gov Identifier: NCT00904670. http://www.clinicaltrials.gov/ct2/show/NCT00904670 .

Figures

FIG. 1.

NWP06 laboratory classroom trial design. a4–6 weeks open-label treatment with NWP06 for dose optimization. Study adjustments in approximately weekly intervals (visits 3, 4, 5) in 10 or 20 mg adjustments allowed. bMedication doses remain stable during double-blind phase.

FIG. 2.

Laboratory classroom Swanson, Kotkin, Agler, M-Flynn and Pelham (SKAMP)-combined scores