Pharmacodynamics and Pharmacokinetics of a Novel, Low-Dose, Soft-Gel Capsule of Acetylsalicylic Acid in Comparison with an Oral Solution After Single-Dose Administration to Healthy Volunteers: A Phase I, Two-Way Crossover Study

Abstract

Low-dose acetylsalicylic acid (ASA; aspirin) is well-established as a platelet anti-aggregating agent for the secondary prevention of cardiovascular events. The objective of this study was to investigate the non-inferiority of a novel ASA 75 mg soft-gel capsule formulation compared with a marketed powder for oral solution in terms of reduction in serum thromboxane B2 (TXB2), a surrogate for platelet aggregation. Pharmacokinetics and tolerability of the products were also investigated. In this randomised, two-way crossover study, 46 male and female healthy subjects received a single dose of the investigational products in two periods separated by a 14-day washout. Serum TXB2 and plasma ASA were determined up to 24 h post-dose. Maximum percentage of TXB2 inhibition (I max) and area under the inhibition-time curve (AUICt) were calculated. Non-inferiority was assumed if the lower limits of the 95 % confidence intervals (CIs) for the two pharmacodynamic parameters were above 85 %. The 95 % CI lower limits were 95.35 % for I max and 86.12 % for AUICt, i.e. within the pre-specified delta. Time to achieve I max did not differ between treatments (p = 0.88). The two formulations were bioequivalent as regards the extent of ASA exposure (area under the plasma concentration-time curve from zero to time t [AUCt] 90 % CIs 96.67-113.37); a delayed ASA absorption (later time to reach maximum plasma concentration [t max], lower maximum plasma concentration [C max]) was observed for the test product. No treatment-related adverse events were reported. In healthy subjects, the 75 mg soft-gel capsules were not inferior to the oral solution in terms of serum TXB2 inhibition, indicating that the novel formulation could be an effective alternative in the secondary prevention of cardiovascular events.