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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

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Abstract

Background

Low-dose acetylsalicylic acid (ASA; aspirin) is well-established as a platelet anti-aggregating agent for the secondary prevention of cardiovascular events.

Objectives

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.

Methods

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 %.

Results

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.

Conclusions

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.

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Acknowledgments

We would like to gratefully acknowledge CROSS Research S.A. (Arzo, Switzerland) for study coordination, Analytisch Biochemisch Laboratorium BV (Assen, The Netherlands) for TXB2 analysis and Anapharm Inc. (Quebec City, Canada) for ASA analysis.

This study was funded by IBSA Institut Biochimique SA. (Pambio-Noranco, Switzerland).

Claudia Scarsi is an employee of IBSA Institut Biochimique SA. Luca Loprete, Chiara Leuratti and Milko Radicioni are employees of CROSS SA and its affiliated company CROSS Research S.A., which have been contracted by IBSA Institut Biochimique SA as Contract Research Organisations for the conduction of this study, and have received financial support for their services. The authors declare that they have no other relationships or activities that could appear to have influenced the submitted work.

The MedDRA® trademark is owned by the International Federation of Pharmaceutical Manufacturers and Associations (IFPMA) on behalf of the ICH.

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Authors and Affiliations

  1. CROSS Research S.A., via F.A. Giorgioli 14, 6864, Arzo, Switzerland

    Luca Loprete, Chiara Leuratti & Milko Radicioni

  2. IBSA Institut Biochimque S.A., Pambio-Noranco, Switzerland

    Claudia Scarsi

Authors
  1. Luca Loprete
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  2. Chiara Leuratti
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  3. Claudia Scarsi
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  4. Milko Radicioni
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Correspondence to Luca Loprete.

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Loprete, L., Leuratti, C., Scarsi, C. et al. 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. Clin Drug Investig 34, 19–25 (2014). https://doi.org/10.1007/s40261-013-0145-2

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