This was a randomized, open-label, two-period, fixed-sequence crossover study (Figure S1 ). Based on the exploratory and descriptive characteristics of the study aim, the calculation of study power was not considered to determine the sample size. The enrolled subjects were randomly assigned to the aspirin group or the fexuprazan group at a ratio of 1:1. For the aspirin group, a single oral dose of aspirin 500 mg was administered alone in the first period and then in combination with fexuprazan 80 mg after 4 days of pretreatment with once-daily doses of fexuprazan 80 mg in the second period, and there was a 10-day washout period between each period. For the fexuprazan group, once-daily doses of fexuprazan 80 mg were administered alone for 5 days in the first period and then in combination with aspirin 500 mg for 5 days in the second period. The subjects received their respective treatment with 150 mL of water after overnight fasting.
For the aspirin group, serial blood samples were collected at predose, 1.5, 4, 6, 8, 10, 12, 24, and 48 h after aspirin dosing for the PD analysis and at predose, 0.17, 0.33, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, and 48 h after aspirin dosing for the PK analysis. For the PD evaluation of aspirin, 16.2 mL of blood was taken in a citrate tube and then analyzed by both arachidonic acid-induced and collagen-induced platelet aggregation assays. For the PK evaluation of aspirin and its metabolite, salicylic acid, 10 mL of blood was taken in a sodium fluoride and potassium oxalate tube at each sampling point and subsequently centrifuged at 3000 rpm for 10 min at 4 °C, and 1.0 mL of supernatant was transferred to Eppendorf tubes and stored at −70 °C until analysis. For the fexuprazan group, serial blood samples for PK analysis were collected at predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, and 48 h after the 5th dose of fexuprazan (i.e., the last dose) and at predose before the 3rd and 4th doses of fexuprazan. For PK evaluation of fexuprazan and its metabolite, M14, 6 mL of blood was taken in a sodium heparin tube for each sampling point and subsequently centrifuged at 3000 rpm for 10 min at 4 °C, and 1.0 mL of supernatant was transferred to Eppendorf tubes and stored at −70 °C until analysis.
For the aspirin group, serial blood samples were collected at predose, 1.5, 4, 6, 8, 10, 12, 24, and 48 h after aspirin dosing for the PD analysis and at predose, 0.17, 0.33, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, and 48 h after aspirin dosing for the PK analysis. For the PD evaluation of aspirin, 16.2 mL of blood was taken in a citrate tube and then analyzed by both arachidonic acid-induced and collagen-induced platelet aggregation assays. For the PK evaluation of aspirin and its metabolite, salicylic acid, 10 mL of blood was taken in a sodium fluoride and potassium oxalate tube at each sampling point and subsequently centrifuged at 3000 rpm for 10 min at 4 °C, and 1.0 mL of supernatant was transferred to Eppendorf tubes and stored at −70 °C until analysis. For the fexuprazan group, serial blood samples for PK analysis were collected at predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, and 48 h after the 5th dose of fexuprazan (i.e., the last dose) and at predose before the 3rd and 4th doses of fexuprazan. For PK evaluation of fexuprazan and its metabolite, M14, 6 mL of blood was taken in a sodium heparin tube for each sampling point and subsequently centrifuged at 3000 rpm for 10 min at 4 °C, and 1.0 mL of supernatant was transferred to Eppendorf tubes and stored at −70 °C until analysis.
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