Evaluation of bioequivalence between a single-capsule formulation of esomeprazole 40 mg and acetylsalicylic acid 325 mg and the monotherapies given separately in healthy volunteers.
OBJECTIVE
The aim of this study was to investigate the bioequivalence of a single oral dose of esomeprazole 40 mg and acetylsalicylic acid 325 mg when formulated as a single capsule, relative to the components given as separate monotherapies.


METHODS
This was an open, randomized, single-center, single-dose, 2-stage group sequential design, 2-way crossover study (NCT00688428) in 49 healthy adult volunteers (29 women). In each treatment period, subjects received a single dose of esomeprazole 40 mg and ASA 325 mg formulated as a single capsule or as separate monotherapies given in combination. Treatment periods were separated by a washout period of at least 6 days. The bioequivalence of a single-capsule formulation of esomeprazole 40 mg and ASA 325 mg relative to the monotherapies given individually was assessed by the geometric mean ratios of the area under the plasma concentration-time curve (AUC) and observed maximum plasma concentration (Cmax). If the 94% confidence interval (CI) of the geometric mean ratios of AUC and Cmax were within 0.80 - 1.25, bioequivalence would be established. A 94% CI was used to compensate for the multiple analyses of the study design, and to assure that the actual overall confidence level was 90%.


RESULTS
The geometric mean ratios of the AUC for esomeprazole 40 mg and ASA 325 mg when administered in the single capsule formulation, relative to the monotherapies were 0.97 (94% CI, 0.90 - 1.04) and 1.04 (94% CI, 1.00 - 1.08). The corresponding mean geometric ratios for Cmax were 0.99 (94% CI, 0.90 - 1.09) and 1.02 (94% CI, 0.92 - 1.13).


CONCLUSIONS
Treatment with esomeprazole 40 mg and ASA 325 mg formulated as a single capsule is bioequivalent to the separate monotherapies of esomeprazole 40 mg and ASA 325 mg when given in combination as separately-administered drugs in healthy adult subjects.
AstraZeneca R&D, Mölndal, Sweden. Mohammad.Niazi@astrazeneca.com
M
M
Niazi
T
T
Andersson
E
E
Nauclér
J
J
Næsdal
D000328:Adult; D001241:Aspirin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002214:Capsules; D018592:Cross-Over Studies; D004338:Drug Combinations; D064098:Esomeprazole / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008297:Male; D013810:Therapeutic Equivalency
D002214:Capsules; D004338:Drug Combinations; D064098:Esomeprazole; D001241:Aspirin