Comparator pH study to evaluate the single-dose pharmacodynamics of dual delayed-release dexlansoprazole 60 mg and delayed-release esomeprazole 40 mg

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.

Keywords: TAK-390MR; esomeprazole; intragastric pH; pharmacokinetics; proton pump inhibitor; single dose.

Figure 1

Mean intragastric pH from 0 to 24 hours postdose after single oral doses of dexlansoprazole modified-release 60 mg (n = 43) and esomeprazole 40 mg (n = 44) delayed-release capsules.

Figure 2

Mean percentage of time with intragastric pH > 4.0 at 0–24 hours, 0–12 hours, and >12–24 hours after single oral doses of dexlansoprazole modified-release 60 mg and esomeprazole 40 mg delayed-release capsules (n = 43). Only subjects who had valid pharmacodynamic parameters estimated for both periods were included in the pharmacodynamic analyses for that parameter. Notes: *P ≤ 0.05; **P < 0.01; ***P < 0.001.

Figure 3

Mean intragastric pH at 0–24 hours, 0–12 hours, and >12–24 hours after single oral doses of dexlansoprazole modified-release 60 mg and esomeprazole 40 mg delayed-release capsules (n = 43). Only subjects who had valid pharmacodynamic parameters estimated for both periods were included in the pharmacodynamic analyses for that parameter. Notes: *P ≤ 0.05; **P < 0.01; ***P < 0.001.

Figure 4

Mean plasma concentration-time curves of dexlansoprazole and esomeprazole after single oral doses of dexlansoprazole modified-release 60 mg (n = 43) and esomeprazole 40 mg (n = 44) delayed-release capsules in healthy subjects, linear scale.