Abstract
Background:
This paper describes a Phase 1, single-center, randomized, open-label, two-period crossover study which compared the pharmacodynamic effects of single doses of dexlansoprazole modified-release 60 mg and esomeprazole 40 mg on 24-hour intragastric pH in healthy adult subjects.
Methods:
Forty-four subjects aged 20–54 years were randomized in a 1:1 ratio to two sequence groups defining the order in which they received dexlansoprazole and esomeprazole in periods 1 and 2. Primary pharmacodynamic end points over 24 hours postdose were percentage of time with intragastric pH > 4 and mean pH, and secondary pharmacodynamic end points were percentage of time intragastric pH > 4, and mean pH at 0–12 hours, and at >12–24 hours postdose. Each drug was given after an overnight fast and one hour before breakfast. Continuous pH recording began immediately before dosing through to 24 hours postdose.
Results:
At 0–24 hours postdose, the mean percentage of time with pH > 4 for dexlansoprazole and esomeprazole was 58% and 48%, respectively; the difference was statistically significant (P = 0.003). The average of mean pH values at 0–24 hours postdose for dexlansoprazole and esomeprazole were 4.3 and 3.7, respectively; the difference was statistically significant (P < 0.001). At >12–24 hours postdose, mean percentage of time with pH > 4 and average of mean pH were greater for dexlansoprazole (60% and 4.5, respectively) compared with esomeprazole (42% and 3.5, respectively); the difference was statistically significant (P < 0.001 for both intervals). At 0–12 hours postdose, the difference in dexlansoprazole and esomeprazole values for the pharmacodynamic end points was not statistically significant.
Conclusion:
For the entire 24-hour postdose period, predominantly resulting from the >12–24-hour postdose interval, the average intragastric pH following a single dose of dexlansoprazole 60 mg was higher compared with that observed following a single dose of esomeprazole 40 mg, and the difference was statistically significant.
Acknowledgements
The authors wish to acknowledge the contribution of the Jasper Clinic Inc.
Disclosure
MK, CE, and SN are employees of Takeda Global Research & Development Center Inc, Deerfield, IL. Writing assistance was funded by Takeda Pharmaceuticals North America Inc. This study was sponsored by Takeda Global Research and Development Center Inc.