The Food and Drug Administration (FDA) has approved Azstarys™ (serdexmethylphenidate and dexmethylphenidate) capsules for the treatment of attention deficit hyperactivity disorder (ADHD) in patients 6 years of age and older.
Azstarys consists of serdexmethylphenidate, a prodrug of dexmethylphenidate, co-formulated with immediate-release dexmethylphenidate. Each capsule of Azstarys contains a fixed molar ratio of 70% serdexmethylphenidate and 30% dexmethylphenidate. Treatment is administered once daily in the morning and may be taken either whole or the contents of the capsule may be opened and mixed with water or applesauce.
The approval was based on data from a randomized, double-blind, placebo-controlled, analog classroom study (ClinicalTrials.gov: NCT03292952), which included 150 patients 6 to 12 years of age with ADHD. At the end of an open-label dose-optimization period, patients were randomly assigned 1:1 to receive either Azstarys (mean dose of 45.6mg/9mg) or placebo.
The primary efficacy end point was the mean change from baseline (pre-dose at randomization visit) of the SKAMP-Combined scores, a validated 13-item teacher-rated scale that assesses manifestations of ADHD in a classroom setting, averaged across the test day (not including baseline score), with assessments conducted at 0.5, 1, 2, 4, 8, 10, 12, and 13 hours post-dose.
Results showed the mean change from baseline in SKAMP-Combined scores was statistically significantly lower (indicating improvement) with Azstarys compared with placebo (placebo-subtracted difference: -5.4; 95% CI, -7.1, -3.7).
The efficacy of Azstarys 52.3mg/10.4mg in adults and pediatric patients 13 to 17 years of age was established by pharmacokinetic bridging between Azstarys and dexmethylphenidate hydrochloride extended-release capsules.
The safety profile of Azstarys is based on accumulated data from other methylphenidate products; the most common adverse reactions include decreased appetite, insomnia, nausea, vomiting, dyspepsia, abdominal pain, decreased weight, anxiety, dizziness, irritability, affect lability, tachycardia, and increased blood pressure.
Azstarys, a Schedule II controlled substance, should not be substituted for other methylphenidate products on a milligram-per-milligram basis because these products have different pharmacokinetic profiles and may have different methylphenidate base composition.
Azstarys is supplied in 3 capsule strengths (serdexmethylphenidate/ dexmethylphenidate): 26.1mg/5.2mg, 39.2mg/7.8mg, and 52.3mg/10.4mg. The product is expected to be available in the second half of 2021.
- KemPharm announces FDA approval of Azstarys™ (serdexmethylphenidate and dexmethylphenidate capsules, for oral use, CII), a new once-daily treatment for ADHD. [press release]. Celebration, FL: KemPharm, Inc.; March 2, 2021.
2. Azstarys™ [package insert]. Grand Rapids, MI: Corium, Inc.; 2021.