Tu1113 Dexlansoprazole Modified-Release Orally-Disintegrating Tablet -The Bioavailability of Alternate Dosing Options

Abstract

Introduction: The proton pump inhibitor dexlansoprazole (DEX) is a modified release (MR) formulation consisting of 2 types of granules within a single capsule. DEX delayed-release capsules are approved for use in adults for treatment of heartburn associated with symptomatic nonerosive gastroesophageal reflux disease, healing of erosive esophagitis (EE), and maintenance of healed EE and relief of heartburn. Because some patients are unable or unwilling to swallow capsules, a DEX MR orally-disintegrating (OD) tablet has been developed. DEX MR OD contains 2 types of granules that release drug in a pH-dependent manner in order to extend DEX plasma concentrations. Objective: To assess the bioavailability (BA) of DEX MR OD 30 mg tablet swallowed intact with water or mixed with water and administered via nasogastric (NG) tube or oral syringe compared to administration of DEX MR OD 30 mg on the tongue, allowed to disintegrate, and swallowed without water. Methods: This was a phase 1, randomized, single-dose, 4-period crossover study. Qualified healthy subjects 18-55 years old received a single oral dose of 30 mg DEX MR OD as an intact tablet administered on the tongue, swallowed intact, or mixed with water and administered via oral syringe or NG tube. Each study period was followed by a 5-day washout. Blood samples for determination of plasma pharmacokinetics were collected for 24 hours post-dose in each period. Analyses of variance models were performed, and bioequivalence (BE) between an administration option and DEX MR OD administered on the tongue without water was declared if 90% confidence intervals (CIs) of central value ratios between 2 regimens for maximum plasma concentration (Cmax) and area under the curve (AUC) mean ratios were contained within the BE limits of 0.80-1.25. Safety was assessed via physical examination (PE), clinical laboratory evaluation, vital sign assessment, electrocardiograms (ECG), and adverse event reports (AE). Results: Seventy-seven subjects (mean age 38±9.8 years) were enrolled. The 90% CIs for the BA of DEX MR OD 30 mg administered via oral syringe or NG tube, or swallowed intact, relative to that from administration of DEX MR OD on the tongue without water, for Cmax and AUCs were within the BE range of 0.80-1.25 (TABLE). All 4 regimens were well tolerated. AEs were mild in intensity and were considered not related to study drug. Percentages of subjects experiencing AEs were comparable across the 4 regimens. There were no clinically important findings noted in the PE, safety clinical laboratory, vital sign, or ECG reports. Conclusions: DEX MR OD 30 mg administered as an aqueous mixture via an oral syringe or an NG tube, or as an intact tablet swallowed with water was each BE to the administration of the DEX MR OD 30 mg on the tongue without water. Single oral doses of DEX MR OD tablets were well tolerated in this study. Table. BE Assessment of Administration Routes for DEX MR OD Tablets