Can Acid Control Be Improved with a Modified-Release Formulation of a Proton Pump Inhibitor?

Abstract

Purpose: Modified-release (MR) formulations of proton pump inhibitors (PPIs) are being investigated in attempts to improve upon the well-documented clinical efficacy of conventional formulations of PPIs by further increasing acid control. This dose-finding study assessed the pharmacodynamics of a once-daily MR formulation of esomeprazole (ESO), compared with conventional capsule formulations given twice daily (bid). Methods:Heliobacter pylori negative healthy adults were enrolled into this single-center, open, 5-way crossover study (AstraZeneca study code: D961CC00006). Subjects were randomized to standardized sequences of five 5-day ESO treatment periods (40 mg MR, 60 mg MR, 80 mg MR [given in the morning], 20 mg bid and 40 mg bid) separated by washout periods of ≥13 days. 24-h intragastric pH monitoring was performed under standardized conditions on day 5 of each treatment period. Statistical analysis comprised a mixed model ANOVA with fixed factors for period, sequence and treatment and a random factor for subject within sequence. Results: The per-protocol analysis of acid control included 39 subjects (20 males; mean age, 34 y). The results are presented in the table below. Esomeprazole was well tolerated and the safety evaluation did not raise any safety concerns. Conclusion: These results indicate that, among MR doses tested, 60 mg MR appears to be optimal for daytime, nighttime, and 24-h acid control. With the same daily dose of ESO, MR technology provided less 24-h and nighttime pH control than bid dosing.Table: Mean percentage time with intragastric pH > 4