Zevra Therapeutics highlighted the heart safety of serdexmethylphenidate (SDX), the main ingredient in KP1077, its potential treatment for idiopathic hypersomnia (IH), during a poster presentation at Psych Congress 2023.
The poster presentation reported on the cardiovascular effects and pharmacokinetics of the 80 mg and 200 mg dose levels of SDX, a prodrug of d-methylphenidate (d-MPH), compared to immediate-release racemic methylphenidate (Ritalin) and long-acting racemic methylphenidate (Ritalin LA) from an open-label, single-dose, four-treatment, four-period, randomized, crossover study in healthy volunteers.
The immediate-release Ritalin total dose (two 40 mg doses), the 80 mg dose of Ritalin LA, and 80 mg dose of SDX represent approximately the same amount of d-MPH, the active ingredient of interest. Results of the study demonstrate that at an SDX dose (200 mg) 2.5-fold higher than the molar-equivalent Ritalin doses (80 mg), the peak exposure to d-MPH occurred later and was lower.
In addition, both doses of SDX were generally better tolerated compared to Ritalin, and fewer subjects experienced cardiovascular adverse events after SDX compared to Ritalin. Lastly, vital signs after a single oral dose of 200 mg SDX (the highest dose tested) were comparable to Ritalin IR 80 mg and Ritalin LA 80 mg. The results demonstrate a robust safety profile for SDX, positioning it as a promising option for treating sleep disorders characterized by excessive daytime sleepiness.
“The study results affirm that SDX is safe and well-tolerated at higher doses and has no greater cardiovascular safety risk than other methylphenidate products currently being used off-label for the treatment of IH while providing higher overall exposure levels of d-MPH. These data play an important role in the development of KP1077 as we work to address the unmet needs of people living with rare sleep disorders,” says Rene Braeckman, PhD, senior vice president of clinical development at Zevra, in a release.
Zevra also is investigating KP1077 as a potential treatment for narcolepsy.