A once-daily oral stimulant medication for treatment of attention-deficit/hyperactivity disorder (ADHD) in individuals aged 6 years or older is safe and effective after 1 year of treatment, new research shows.
Results from a phase 3, multicenter dose optimization, open-label safety study of Azstarys (KemPharm, Inc) found that most treatment-emergent adverse events (TEAEs) were mild to moderate.
“This data show that Azstarys remains safe and effective for the treatment of ADHD when given for up to a year,” lead investigator Ann Childress, MD, president of the Center for Psychiatry and Behavioral Medicine, Las Vegas, Nevada, told Medscape Medical News.
The study was published online February 20 in the Journal of Child and Adolescent Psychopharmacology.
Safety at 1 Year
The drug is a combination of extended-release serdexmethylphenidate (SDX), KemPharm’s prodrug of dexmethylphenidate (d-MPH), co-formulated with immediate-release d-MPH.
SDX is converted to d-MPH after it is absorbed in the gastrointestinal tract. The d-MPH is released gradually throughout the day, providing quick symptom control with the d-MPH and extended control with SDX.
As reported by Medscape Medical News, Azstarys was approved by the US Food and Drug Administration in 2021 on the basis of results from a laboratory classroom phase 3 trial, which showed significant improvement in ADHD symptoms compared with placebo.
For this study, the second phase 3 trial of Azstarys, investigators analyzed data from 282 children aged 6-12 years in the United States, including 70 who participated in an earlier 1-month efficacy trial.
After screening and a 3-week dose-optimization phase for new participants, patients received once-daily treatment with doses of 26.1 mg/5.2 mg, 39.2 mg/7.8 mg, or 52.3 mg/10.4 mg of SDX/d-MPH.
After 1 year of treatment, 60.1% of participants reported at least one TEAE, the majority of which were moderate. Twelve patients reported severe TEAEs. Six children (2.5%) discontinued the study due to a TEAE during the treatment phase.
Investigators also measured growth and changes in sleep with the Children’s Sleep Habits Questionnaire during the 12-month study. Sleep improved on most measures and the impact on growth was mild.
There were no life-threatening TEAEs and no deaths reported during the study.
The most common TEAEs during the treatment phase were decreased appetite, upper respiratory tract infection, nasopharyngitis, decreased weight, irritability, and increased weight.
Efficacy at 1 Year
ADHD symptoms improved considerably after 1 month of treatment, with responses continuing at 1 year.
At baseline, participants’ mean ADHD Rating Scale-5 (ADHD-RS-5) score was 41.5. After 1 month of treatment, scores averaged 16.1, a decline of -25.3 (P < .001).
The mean score stabilized in the 12-15 range for the remainder of the study. After 1 year of treatment, ADHD symptoms had decreased approximately 70% from baseline.
Investigators found similar results in clinical severity. After 1 month of treatment, the average Clinical Global Impressions–Severity (CGI-S) scale score was 2.5, a decline of -2.2 (P < .0001).
CGI-S scale scores remained in the 2.2-2.4 range for the remainder of the study.
These results, combined with the results of the original classroom trial, suggest Azstarys may offer advantages over other ADHD drugs, Childress said.
“In the laboratory classroom trial, subjects taking Azstarys completed significantly more math problems than subjects taking placebo beginning at 30 minutes and up to 13 hours after dosing,” Childress said. “No other methylphenidate extended-release product currently marketed in the United States has a 13-hour duration of effect.”
‘Reassuring Data’
Commenting on the findings for Medscape Medical News, Aditya Pawar, MD, a child and adolescent psychiatrist with the Kennedy Krieger Institute and an assistant professor of psychiatry and behavioral sciences at Johns Hopkins School of Medicine, Baltimore, Maryland, said that the study suggests the drug may be a valuable addition to ADHD treatment options for pediatric patients.
“The study provides reassuring data on the safety of stimulants in patients without significant history of cardiac events or blood pressure changes, which are usual concerns among patients and clinicians despite the evidence supporting safety, said Pawar, who was not part of the study.
“Additionally, the 1-year data on efficacy and safety of a new stimulant medication is valuable for clinicians looking for sustained relief for their patients, despite the limitations of an open-label trial,” she added.
Overall, the safety data reported here are fairly consistent with the safety profile of other methylphenidates used for treating ADHD, Pawar said.
However, she noted, the study does have some limitations, including its open-label design and lack of blinding. The research also excluded children with autism, disruptive mood dysregulation disorders, and other common comorbidities of ADHD, which may limit the generalizability of the results.
“These comorbidities often require stimulants as a part of treatment, and yet have a higher risk of side effects,” Pawar said. “Future studies with a broader population may be needed to better understand treatment effectiveness and potential risks.”
The study was funded by KemPharm, Inc. Childress serves as consultant for Aardvark, Arbor, Attentive, Cingulate, Ironshore, Neos Therapeutics, Neurocentria, Otsuka, Purdue, Rhodes, Sunovion, Tris Pharma, KemPharm, Supernus, Jazz, Corium, Tulex, and Lumos. Full disclosures are reported in the original article.
J Child Adolesc Psychopharmacol. Published online February 20, 2023. Full text
Kelli Whitlock Burton is a reporter for Medscape Medical News covering psychiatry and neurology.
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