SEATTLE – A novel formulation of methylphenidate could provide morning relief to pediatric patients with attention-deficit/hyperactivity disorder, according to results of a pivotal phase 3 classroom trial.
In the study, delayed release/extended release methylphenidate (DR/ER MPH), when taken the night before, improved ADHD symptoms throughout a 12-hour laboratory classroom period – including in the late afternoons and early mornings.
The formulation, also known as Jornay PM, received Food and Drug Administration approval for ADHD in August for patients aged 6 and older. “For kids who have a horrendous time in the morning, getting up out of bed, and getting ready for school, they get up and they’re ready to rock and roll. [The drug] makes the mornings go better,” Ann Childress, MD, said in an interview at the annual meeting of the American Academy of Child and Adolescent Psychiatry.
In a previous phase 3 trial, DR/ER MPH proved beneficial in late afternoon and early morning symptoms in a naturalistic sample over a 3- week treatment course (J Child Adolesc Pharmacol. 2017 Aug 1;27[6]:474-82). The current work sought to show its value in a classroom setting. And in yet another earlier survey, 77% of parents rated early morning functional impairment in children with ADHD as moderate to severe (J Child Adolesc Pharmacol. 2017 Oct 1;27[8]:715-22).
“,” said Dr. Childress, president of the Center for Psychiatry and Behavioral Medicine in Las Vegas.
In the current study, presented by Dr. Childress at the meeting, 117 children aged 6-12 years with ADHD and morning behavioral problems, after a 5-day washout period, were started on an evening DR/ER MPH dose of 20 mg or 40 mg. They were then seen for up to 4 more weeks, and doses optimized (maximum 100 mg/day).
Adjustments also were made in the evening dose schedule to determine an optimal dosing time, which had to range from 6:30 pm to 9:30 pm, at least 1 hour after dinner. Clinicians optimized the dose and timing to achieve maximum symptom control throughout the day (minimum 30% improvement in total symptom score from baseline), while remaining safe and well-tolerated.The participants were then randomized to maintain the current drug dose, or to switch to placebo for 1 week. The primary endpoint was the average of all post-dose SKAMP-CS (Swanson, Kotkin, Agler, M-Flynn, and Pelham combined scale) measurements, as recorded by a trained, independent observer during the 12-hour period on the last classroom day.
There was a significant improvement in the primary measure, with the treatment group averaging 14.8 on the SKAMP-CS, compared with 20.7 for the placebo group (P less than .001). The improved outcomes were steady throughout the day, failing to achieve statistical significance at 8 a.m., but achieving significance in measurements taken at 9 a.m.,10 a.m., 12 p.m., 2 pm, 4 p.m., 6 p.m., and 7 p.m.
The formulation also achieved significant difference in morning and late afternoon measurements of the Parent Rating of Evening and Morning Behavior Scale, Revised (PREMB-R AM and PREMB-R PM). The treatment group scored a mean of 0.9 on PREMB-R AM, compared with 2.7 for placebo (P less than .001), and 6.1 vs. 9.3 in the PREMB-R PM scale (P = .003).
Most treatment emergent adverse events were considered mild or moderate, and occurred in 36.9% of the treatment group and 40.7% of placebo subjects.
The study was funded by Ironshore Pharmaceuticals, which said in a press statement that it plans to launch the drug early next year. In addition to Ironshore, Dr. Childress has served on the advisory board for, consulted for, or received research support from Aevi Genomic Medicine, Akili Interactive, Alcobra, Arbor Pharmaceuticals, Eli Lilly, Forest Laboratories, Lundbeck, KemPharm, Neos Therapeutics, Noven Pharmaceuticals, Otsuka America Pharmaceutical, Pearson, Pfizer, Purdue Pharma, Rhodes Pharmaceuticals, Shire, Sunovion, and Tris Pharma.