A transdermal amphetamine therapy was effective at treating pediatric ADHD, according to a phase II trial.
In a two-part study, children with attention deficit-hyperactivity disorder (ADHD) using the dextroamphetamine transdermal system (d-ATS) saw a significant improvement in symptoms in a laboratory classroom setting, as measured by the SKAMP (Swanson, Kotkin, Agler, M-Flynn, and Pelham) total score compared with placebo (least-squares mean difference -5.87, 95% CI -6.76 to -4.97, P<0.001), reported Andrew J. Cutler, MD, of SUNY Upstate Medical University in Syracuse in New York, and colleagues.
Benefits of the transdermal system were seen as soon as 2 hours after dosing and was continuously maintained for 12 hours thereafter.
The trial met both its primary and key secondary endpoints, Cutler reported at the American Psychiatric Association (APA) virtual meeting.
Prior to dosing, children and adolescents in the treatment group had a total baseline SKAMP score of 14.9 versus 13 for placebo. By 12 hours after dosing, the treatment group had a total score of 15.7 versus 21.5 in the placebo group.
“The novel dextroamphetamine transdermal system, or d-ATS, was designed as an alternative to current oral extended release formulations of amphetamines,” Cutler explained during a virtual poster presentation.
A total of 110 children and adolescents (mean age 10.5 years) were enrolled in the trial; almost 70% of whom were male. All participants had a primary diagnosis of ADHD combined, hyperactive/impulsive subtype, or predominately inattentive subtype and all were not adequately controlled with a current ADHD medication. Young people who were already well controlled on an ADHD medication, or who were non-responders to amphetamine treatment, were excluded.
At baseline, all participants had an ADHD-RS-IV score of 90% or greater of the general population, according to age and gender (mean score 38.3).
The first part of the study was conducted as an open-label, dose-optimization period, where all participants started on a 5-mg d-ATS patch every day. Patches were placed on the hip for 9 hours on alternating sides. Over the next 5 weeks, participants’ dose was adjusted as needed at weekly clinic visits.
During this initial phase, 39% of participants achieved an optimal dose of 15 mg/9 hours, 33% achieved an optimal dose of 10 mg/9 hours, 21% achieved a dose of 20 mg/9 hours, and 7% had an optimal dose of 5 mg/9 hours.
Of note, no participants discontinued treatment during this phase due to a lack of efficacy. However, three did discontinue treatment due to adverse events (AEs), the researchers reported.
After reaching the optimal dose in the initial 5 weeks, participants then continued in a randomized, double-blind treatment period for an additional 2 weeks. During this phase, 106 participants on their optimal dose were compared with 106 participants on placebo.
Overall, 96% of patients reported experiencing a treatment-emergent AE during the dose-optimization period. While most were graded mild to moderate in severity, the most common AEs included decreased appetite (54%), headache (21%), insomnia (20%), and irritability (16%). During this phase, 25% of participants also experienced an application site reaction, most commonly pain, pruritus, burning, and erythema. But no application site reactions led to discontinuation and most resolved within a few hours, according to the researchers.
“A systemic safety profile consistent with oral amphetamines was observed,” Cutler pointed out.
“Transdermal delivery of dextroamphetamine provides potential advantages that include avoiding gastrointestinal side effects that can result with swallowed products, providing flexibility in treatment duration, providing an option for children who may not be able or willing to swallow medications, and allowing visual confirmation of treatment adherence,” he concluded.
Developer Noven Therapeutics holds the FDA approval for its methylphenidate transdermal system (Daytrana), which is the only transdermal pediatric ADHD medication currently approved.
Last Updated May 03, 2021
The study was supported by Noven Pharmaceuticals. Some co-authors are company employees.
Cutler disclosed relevant relationships with AbbVie, Acadia, Akili Interactive, Alfasigma, Alkermes, Allergan, Arbor Pharmaceuticals, Attentive, Axsome, Biohaven, Cognitive Research, Intra-Cellular Therapies, Ironshore, Janssen, KemPharm, Lundbeck, MedAvante-ProPhase, Neurocrine, Neuroscience Education Institute, Noven, Novartis, Otsuka, Purdue, Sage Therapeutics, Sunovion, Supernus, Takeda, Teva, and Tris Pharma.