Pharmacokinetics and Safety of Vibegron 75 mg Administered as an Intact or Crushed Tablet in Healthy Adults

Abstract

Oral pharmacotherapy for overactive bladder, a condition that increases with age, includes anticholinergics and β3-adrenergic receptor agonists. Older adults, including those with dysphagia, may have difficulty swallowing tablets. In this phase 1 study in healthy adults, we assessed the pharmacokinetic profile of the β3-adrenergic receptor agonist vibegron administered as a single 75-mg dose as an intact tablet versus crushed and mixed with applesauce. Additional end points included safety (assessed by adverse events), perception of taste (assessed via questionnaire), and stability over 4 hours after crushing and mixing in applesauce (assessed by chromatography). Overall, 30 participants were randomized, and 29 were included in the pharmacokinetic analysis. Crushing a vibegron tablet and mixing with applesauce decreased vibegron maximum observed plasma concentration and area under the plasma concentration–time curve from time 0 to infinity by ≈30% and ≈10%, respectively; however, these decreases were not considered clinically significant. Treatment-emergent adverse events were reported in 16 (53.3%) participants. Approximately half of participants reported the vibegron and applesauce mixture tasted as expected; of those reporting the taste was different than expected, 50% reported the taste as bitter. The mixture was stable for 4 hours in applesauce. The results of this study showed that crushing and administering vibegron with applesauce may be an appropriate option for patients with overactive bladder and swallowing difficulties.