Pharmacokinetic/pharmacodynamic assessment of a novel, pharmaceutical lipid–aspirin complex: results of a randomized, crossover, bioequivalence study

Dominick J. Angiolillo, Deepak L. Bhatt, Frank Lanza, Byron Cryer, Jin fei Dong, Walter Jeske, Ronald R. Zimmerman, Estela von Chong, Jayne Prats, Efthymios N. Deliargyris, Upendra Marathi

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Aspirin (acetylsalicylic acid, ASA) can lead to gastrointestinal mucosal injury through disruption of its protective phospholipid bilayer. A liquid formulation of a novel pharmaceutical lipid–aspirin complex (PL-ASA) was designed to prevent this disruption. We sought to determine the pharmacokinetic (PK)/pharmacodynamic (PD) characteristics of PL-ASA compared with immediate release aspirin (IR-ASA). In this active-control crossover study, 32 healthy volunteers were randomized to receive 1 of 2 dose levels (a single dose of 325 mg or 650 mg) of either PL-ASA or IR-ASA. After a 2-week washout period between treatment assignments, subjects received a single dose of the alternative treatment, at the same dose level. The primary objectives of the study were to assess, for PL-ASA and IR-ASA at 325 mg and 650 mg dose levels, PK and PD bioequivalence, and safety, over a 24–h period after administration of both drugs. PK parameters were similar for PL-ASA and IR-ASA, and met FDA-criteria for bioequivalence. Regarding PD, both drugs also showed Cmin TxB2 values below 3.1 ng/mL (cut-off associated with decreased cardiovascular events) and > 99% inhibition of serum TxB2 (≥ 95% inhibition represents the cut-off for aspirin responders) along with similar results in several secondary PK/PD parameters. There were no serious adverse events or changes from baseline in vital signs or laboratory values in either of the 2 treatment groups. PL-ASA’s novel liquid formulation has similar PK and PD performance compared with IR-ASA, supporting functional and clinical equivalence. These data coupled with the improved gastric safety of PL-ASA suggest that this novel formulation may exhibit an improved benefit-risk profile, warranting evaluation in future trials. Clinical trial registration:http://www.clinicaltrials.gov. Unique Identifier: NCT04008979.

Original languageEnglish (US)
Pages (from-to)554-562
Number of pages9
JournalJournal of Thrombosis and Thrombolysis
Volume48
Issue number4
DOIs
StatePublished - Nov 1 2019
Externally publishedYes

Keywords

  • Aspirin
  • Bioequivalence
  • Pharmacodynamic
  • Pharmacokinetic
  • Platelet

ASJC Scopus subject areas

  • Hematology
  • Cardiology and Cardiovascular Medicine

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    Angiolillo, D. J., Bhatt, D. L., Lanza, F., Cryer, B., Dong, J. F., Jeske, W., Zimmerman, R. R., von Chong, E., Prats, J., Deliargyris, E. N., & Marathi, U. (2019). Pharmacokinetic/pharmacodynamic assessment of a novel, pharmaceutical lipid–aspirin complex: results of a randomized, crossover, bioequivalence study. Journal of Thrombosis and Thrombolysis, 48(4), 554-562. https://doi.org/10.1007/s11239-019-01933-7