TAK-390MR, a Novel Dual Delayed Release Formulation of a PPI, Is Bioequivalent When Administered as Granules Sprinkled Over Applesauce or as an Intact Capsule

Abstract

Purpose: Alternative oral delivery options are useful for patients who prefer or require administration flexibility. TAK-390MR is a Dual Delayed Release™ (DDR) formulation of TAK-390, an enantiomer of lansoprazole, designed to prolong the plasma concentration-time profile of TAK-390 following oral once-daily administration. We compared the bioavailability of TAK-390MR given as granules from an intact capsule sprinkled over applesauce vs an intact capsule. Methods: In this phase 1, open-label, 2-way crossover study, 60 healthy subjects (18–55 years of age) were randomized to 2 sequence groups that determined the order in which they received a single oral dose of TAK-390MR 90 mg administered as granules from a capsule sprinkled over 1 tablespoon of applesauce or as an intact capsule with 240 mL of water after approximately a 10-hour fast. The dosing in each of the 2 study periods was separated by a ≥5 day washout interval. Blood samples were collected predose and up to 24 hours postdose in each period. Plasma concentrations were analyzed by a validated LC-MS/MS assay. Pharmacokinetic parameters were estimated using standard noncompartmental methods. Bioequivalence was assessed by point estimates and 90% CIs for the ratios of the central values for the Cmax, AUCt, and AUC∞ of TAK-390 using ANOVA. Results: A total of 50 subjects were included in the bioequivalence analysis. The mean concentration-vs-time profiles for the 2 regimens were nearly superimposable, with the characteristic 2 plasma peaks resulting from the DDR technology. The point estimates and corresponding 90% CIs for the ratios of the central values of the Cmax, AUCt, and AUC∞ of TAK-390 following administration of TAK-390MR as granules sprinkled over applesauce vs as an intact capsule were within the bioequivalency range of 0.80–1.25. TAK-390MR was well tolerated in healthy subjects in this study by either mode of administration. Conclusion: Bioequivalence was demonstrated when TAK-390MR was administered either as granules sprinkled over applesauce or as an intact capsule. This alternative mode of administration may benefit patients who prefer or require an alternate route of administration.Table: Bioavailability of TAK-390 After Administration of TAK-390MR 90 mg as Granules Sprinkled Over Applesauce Relative to an Intact Capsule