Pharmacokinetic and pharmacodynamic profiles of a novel phospholipid-aspirin complex liquid formulation and low dose enteric-coated aspirin: results from a prospective, randomized, crossover study

Francesco Franchi; David J Schneider; Jayne Prats; Weihong Fan; Fabiana Rollini; Latonya Been; Heidi S Taatjes-Sommer; Deepak L Bhatt; Efthymios N Deliargyris; Dominick J Angiolillo

doi:10.1007/s11239-022-02687-5

Pharmacokinetic and pharmacodynamic profiles of a novel phospholipid-aspirin complex liquid formulation and low dose enteric-coated aspirin: results from a prospective, randomized, crossover study

J Thromb Thrombolysis. 2022 Oct;54(3):373-381. doi: 10.1007/s11239-022-02687-5. Epub 2022 Aug 29.

Affiliations

¹ Division of Cardiology, University of Florida College of Medicine - Jacksonville, 655 West 8th Street, Jacksonville, FL, 32209, USA.
² Department of Medicine, Cardiovascular Research Institute, The University of Vermont, Burlington, VT, USA.
³ Elysis LLC, Carlisle, MA, USA.
⁴ PLx Pharma, Inc., Sparta, NJ, USA.
⁵ Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁶ Science and Strategy Consulting Group, Basking Ridge, NJ, USA.
⁷ Division of Cardiology, University of Florida College of Medicine - Jacksonville, 655 West 8th Street, Jacksonville, FL, 32209, USA. dominick.angiolillo@jax.ufl.edu.

Abstract

Low dose enteric-coated aspirin (EC-ASA) is routinely used for secondary cardiovascular event prevention. However, absorption of EC tablets is poor, which can result in subtherapeutic antiplatelet effects. Phospholipid-aspirin liquid filled capsules (PL-ASA) are a novel FDA-approved immediate-release formulation designed to reduce gastrointestinal (GI) injury by limiting direct contact with the stomach lining. We compared the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of PL-ASA versus EC-ASA at a low dose. This randomized, open-label, crossover study assessed PK and PD following a single 81-mg dose of PL-ASA versus EC-ASA under fasting conditions in 36 volunteers without cardiovascular disease between 18 and 75 years of age. Volunteers were randomly assigned 1:1 to either PL-ASA then EC-ASA or vice versa with a minimum 14-day washout. Assessments included PK parameters for acetylsalicylic acid and salicylic acid, platelet aggregation in response to arachidonic acid (AA), and serum thromboxane B2 (TxB₂) assessments over 24 h. PL-ASA was rapidly absorbed. PL-ASA reached T_max 3 h earlier (1.01 vs. 4.00 h, p < 0.0001), with almost double the C_max (720 vs. 368 ng/mL, p < 0.0001) and overall 44% higher exposure of acetylsalicylic acid (AUC_0-t: 601 vs. 416 h*ng/mL, p = 0.0013) compared with EC-ASA. Within 1 h of dosing, PL-ASA achieved significantly lower residual platelet aggregation, which persisted for the full 24 h (median AA-LTA was 47% with PL-ASA vs. 80.5% with EC-ASA; p = 0.0022 at hour-24). Treatment with PL-ASA also resulted in significantly lower serum TxB₂ concentrations at each time point compared with EC-ASA (all p-values < 0.05). PL-ASA resulted in faster and more complete aspirin absorption paralleled by more prompt and potent platelet inhibition compared with EC-ASA after a single 81 mg dose. PL-ASA represents an attractive novel aspirin formulation for the secondary prevention of cardiovascular events.Clinical Trial Registration ClinicalTrials.gov identifier: NCT04811625.

Keywords: Aspirin; PL-ASA; Pharmacodynamic; Pharmacokinetic; Platelet.

Publication types

Randomized Controlled Trial

MeSH terms

Arachidonic Acid
Aspirin* / pharmacokinetics
Aspirin* / pharmacology
Capsules
Cross-Over Studies
Humans
Phospholipids
Platelet Aggregation Inhibitors* / pharmacokinetics
Platelet Aggregation Inhibitors* / pharmacology
Prospective Studies
Salicylic Acid
Tablets
Thromboxane B2

Substances

Capsules
Phospholipids
Platelet Aggregation Inhibitors
Tablets
Arachidonic Acid
Thromboxane B2
Salicylic Acid
Aspirin

Associated data

ClinicalTrials.gov/NCT04811625