Yu-Ming Chang, MD, PhD, Eckhard Leifke, MD, Neila Smith, MD, Galen Witt, MS, Darcy J. Mulford, PhD Phathom Pharmaceuticals, Buffalo Grove, IL
Introduction: Gastroesophageal reflux disease (GERD) is a prevalent condition in which the reflux of gastric contents into the esophagus often results in unpleasant symptoms and esophageal complications. Vonoprazan, a novel, orally active potassium-competitive acid blocker (P-CAB), presents a promising treatment option for GERD and is formulated as a film-coated tablet. However, some patients may have difficulty swallowing tablets. A sprinkle capsule formulation of vonoprazan, designed to be opened and sprinkled on a small amount of soft food such as pudding or applesauce, has been developed for pediatric use and for patients incapable of swallowing tablets.
Methods: In this phase 1, single-dose, open-label, randomized, three-period, three-sequence crossover study, the bioavailability of a 20 mg vonoprazan sprinkle capsule, administered on either pudding or applesauce, relative to a 20 mg vonoprazan tablet, was determined in 27 healthy adult subjects. Plasma concentrations of vonoprazan were measured using liquid chromatography with tandem mass spectrometry. Relative bioavailability was assessed based on the maximum concentration (Cmax), area under the plasma-time curve to the last measurable concentration (AUC0-t), and AUC extrapolated to infinity (AUC0-inf) using an analysis of variance model on the natural log-transformed pharmacokinetic parameters with treatment, sequence, and period as fixed effects and subject within sequence as a random effect. Bioequivalence was assessed using confidence intervals for the ratio of geometric means (GMR).
Results: Vonoprazan 20 mg sprinkle capsule, administered with either pudding or applesauce, is bioequivalent to vonoprazan 20 mg, administered as a tablet. The endpoints of the 90% CI of the GMR of the sprinkle capsule administered with pudding or applesauce relative to the tablet for Cmax, AUC0-t, and AUC0-inf were all contained within the bioequivalence limits of 0.80 and 1.25 (Table 1). Furthermore, the geometric means from either of the sprinkle capsule regimens differed by no more than 4% from the tablet formulation for Cmax, AUC0-t, or AUC0-inf. The median time to maximum concentration (Tmax) was 2 hours for all treatments.
Discussion: Vonoprazan 20 mg sprinkle capsule, administered with pudding or applesauce, provides an alternative to the vonoprazan 20 mg tablet, and expands administration options for pediatric use and for patients unable to swallow tablets.
