Characteristics of ADHD symptom response/remission in a clinical trial of methylphenidate extended release

Clinical trials in attention-deficit/hyperactivity disorder (ADHD) have typically measured outcome using clinician ratings on the Attention-Deficit/Hyperactivity Disorder Rating Scale, Fourth Edition (ADHD-RS-IV) and the Clinical Global Impression-Improvement (CGI-I) scale. Remission has been defined as an endpoint score of less than or equal to 18 on the ADHD-RS-IV (or a mean score of 1). Responders have been defined as patients who achieve a CGI-I score of much or very much improved (1 or 2). There is a lack of agreement in the literature on what percent change in symptoms on the ADHD-RS-IV should be used to define improvement or remission. This study uses data from a clinical trial of a methylphenidate extended release (MPH-MLR; Aptensio XR®) phase III clinical trial to attempt to determine the percent change of symptoms that best corresponds with improvement and remission. Symptom remission at endpoint (ADHD-RS-IV total score ≤18) was most closely aligned with a ≥46% reduction in ADHD-RS-IV total score. Clinical improvement was most closely aligned with a ≥40% reduction in ADHD-RS-IV total score. The three different measures of outcome were strongly aligned during double blind and open label treatment, and were independent of subtype status. Our data suggest that at least 40% improvement in symptoms is needed to achieve a robust response at endpoint

Serdexmethylphenidate/dexmethylphenidate effects on sleep in children with attention-deficit/hyperactivity disorder

IntroductionSleep-related problems are common in children with attention-deficit/hyperactivity disorder (ADHD). Sleep disorders are also side effects of all stimulant ADHD medications. Serdexmethylphenidate/dexmethylphenidate (SDX/d-MPH) is a once-daily treatment approved for patients age 6 years and older with ADHD. In this analysis, sleep behavior was assessed during SDX/d-MPH treatment in children with ADHD.MethodsIn a 12-month, dose-optimized, open-label safety study in 6- to 12-year-old participants (NCT03460652), a secondary endpoint was assessment of sleep behavior based on the Children’s Sleep Habits Questionnaire (CSHQ) consisting of 8 sleep domains (bedtime resistance, sleep onset delay, sleep duration, sleep anxiety, night wakings, parasomnias, sleep-disordered breathing, and daytime sleepiness). This post hoc analysis examined the individual sleep domains in the 12-month safety study.ResultsOf 282 participants enrolled, 238 were included in the sleep analysis. At baseline, mean (SD) CSHQ total sleep disturbance score was 53.4 (5.9). After 1 month of treatment, the mean (SD) CSHQ total score significantly decreased to 50.5 (5.4); least-squares mean change from baseline was −2.9 (95% CI: −3.5 to −2.4; p < 0.0001) and remained decreased up to 12 months. Mean sleep-score improvements from baseline to 12 months were statistically significant (p < 0.0001) for 5 of 8 sleep domains, including bedtime resistance, sleep anxiety, night wakings, parasomnias, and daytime sleepiness. Parasomnias and daytime sleepiness sleep domains showed the greatest mean improvement from baseline to 12 months. Sleep onset delay and sleep duration scores increased from baseline to 12 months. No statistically significant worsening occurred from baseline in sleep duration and sleep-disordered breathing domains; however, worsening of sleep onset delay was statistically significant.ConclusionIn this analysis of children taking SDX/d-MPH for ADHD, sleep problems did not worsen based on the mean CSHQ total sleep disturbance score. Statistically significant improvements in most CSHQ sleep domains were observed after 1 month and lasted for up to 12 months of treatment

Analysis of individual items on the attention-deficit/hyperactivity disorder symptom rating scale in children and adults: the effects of age and sex in pivotal trials of lisdexamfetamine dimesylate

Attention-deficit/hyperactivity disorder (ADHD) symptom presentation across age and sex has not been fully elucidated. The present post hoc analyses qualitatively explored the baseline levels of ADHD symptomatology across subgroups in two clinical trials of children and adults with ADHD to elucidate differences in participant presentation. The response to treatment was examined to determine patterns of response among items of the ADHD Rating Scale IV

Advances in Sample Preparation at the National Ocean Sciences Accelerator Mass Spectrometry Facility (NOSAMS): Investigation of Carbonate Secondary Standards

The development of robust sample preparation techniques for ocean science research has been a hallmark of NOSAMS since its inception. Improvements to our standard methods include reducing the minimum size of the samples we can analyze, building modular graphite reactors of different sizes that we can swap in and out depending on our sample stream, and modifying our carbonate acidification methods to improve handling of the smaller samples we now receive. A relatively new instrument, the Ramped PyrOx, which allows the separation of organic matter into thermal fractions, has attracted much interest as a research and development tool. We will also discuss our progress on incorporating a Picarro isotope analyzer into our sample preparation options

A 13-hour laboratory school study of lisdexamfetamine dimesylate in school-aged children with attention-deficit/hyperactivity disorder

BackgroundLisdexamfetamine dimesylate (LDX) is indicated for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children 6 to 12 years of age and in adults. In a previous laboratory school study, LDX demonstrated efficacy 2 hours postdose with duration of efficacy through 12 hours. The current study further characterizes the time course of effect of LDX.MethodsChildren aged 6 to 12 years with ADHD were enrolled in a laboratory school study. The multicenter study consisted of open-label, dose-optimization of LDX (30, 50, 70 mg/d, 4 weeks) followed by a randomized, placebo-controlled, 2-way crossover phase (1 week each). Efficacy measures included the SKAMP (deportment [primary] and attention [secondary]) and PERMP (attempted/correct) scales (secondary) measured at predose and at 1.5, 2.5, 5, 7.5, 10, 12, and 13 hours postdose. Safety measures included treatment-emergent adverse events (AEs), physical examination, vital signs, and ECGs.ResultsA total of 117 subjects were randomized and 111 completed the study. Compared with placebo, LDX demonstrated significantly greater efficacy at each postdose time point (1.5 hours to 13.0 hours), as measured by SKAMP deportment and attention scales and PERMP (P < .005). The most common treatment-emergent AEs during dose optimization were decreased appetite (47%), insomnia (27%), headache (17%), irritability (16%), upper abdominal pain (16%), and affect lability (10%), which were less frequent in the crossover phase (6%, 4%, 5%, 1%, 2%, and 0% respectively).ConclusionIn school-aged children (6 to 12 years) with ADHD, efficacy of LDX was maintained from the first time point (1.5 hours) up to the last time point assessed (13.0 hours). LDX was generally well tolerated, resulting in typical stimulant AEs.Trial registrationOfficial Title: A Phase IIIb, Randomized, Double-Blind, Multi-Center, Placebo-Controlled, Dose-Optimization, Cross-Over, Analog Classroom Study to Assess the Time of Onset of Vyvanse (Lisdexamfetamine Dimesylate) in Pediatric Subjects Aged 6-12 With Attention-Deficit/Hyperactivity Disorder. ClinicalTrials.gov Identifier: NCT00500149 http://clinicaltrials.gov/ct2/show/NCT00500149