No Effect of Omega-3 Carboxylic Acids on Pharmacokinetics/Pharmacodynamics of Warfarin or on Platelet Function When Co-administered with Acetylsalicylic Acid: Results of Two Phase I Studies in Healthy Volunteers

Abstract

Background: Omega-3 carboxylic acids (OM3-CA) can lower triglyceride levels. Objective: Our objective was to assess the effects of OM3-CA on warfarin pharmacokinetics and pharmacodynamics and on acetylsalicylic acid (ASA)-dependent and independent platelet activation when co-administered with ASA in two phase I studies. Methods: In ECLIPSE II (NCT01431690), 26 participants received warfarin 25 mg on days 1 and 22 and OM3-CA 4 g once daily from day 8 to day 28. In OM-EPA-007 (NCT01486433), 52 participants received simvastatin 40 mg plus ASA 81 mg once daily for 14 days, with or without OM3-CA 4 g. Lack of a drug–drug interaction was indicated when 90% confidence intervals (CIs) fell entirely within the range 80–125% for least-squares mean (LSM) ratios of area under the concentration–time curve (AUC), maximum observed plasma concentration (Cmax), international normalized ratio (INR) AUC to 168 h and maximum INR. Results: In ECLIPSE II, 90% CIs for LSM ratios of with:without OM3-CA fell within 80–125% for AUC and Cmax of S- and R-warfarin enantiomers. The 90% CIs for LSM ratios of with:without OM3-CA fell within 80–125% for INR AUC to 168 h after dosing and for maximum INR of warfarin. In OM-EPA-007, no significant effect of OM3-CA was observed on ASA-dependent or ASA-independent platelet activation. No deaths or serious adverse events occurred in either study. Conclusion: OM3-CA did not affect the pharmacokinetics or pharmacodynamics of warfarin or the pharmacodynamic effects of ASA. OM3-CA did not affect platelet function when co-administered with ASA.