Effects of D-003, a New Compound Purified from Sugarcane Wax, on Platelet Aggregation in Healthy Volunteers: A Randomised, Double-Blind Clinical Study.

Background: D-003 is a mixture of long-chain aliphatic primary acids purified from sugarcane wax with experimentally demonstrated antiplatelet effects. D-003 shows hypocholesterolaemic effects in rabbits and healthy volunteers, lowering serum total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C), but increasing high-density lipoprotein-cholesterol (HDL-C). Objective: To investigate the effects of D-003 administered for 10 days on platelet aggregation in healthy volunteers. Participants: Healthy men and women aged 20-55 years. Methods: The present double-blind, randomised, placebo-controlled study investigated the effects of D-003 (5, 10 and 20 mg/day), on platelet aggregation induced by arachidonic acid (AA) [0.75 and 1.5 mmol/L], collagen (1 mg/L) and adenosine diphosphate (ADP) [1 and 2 μmol/L]. The reversibility of the effects was also investigated. Forty-one subjects were randomised to receive placebo or D-003 at 5, 10 and 20 mg/day for 10 days followed by a washout period of 7 days. At baseline and after active treatment and washout completion, platelet aggregation, lipid profile and safety indicators were assessed. Results: D-003 significantly, markedly and reversibly inhibited platelet aggregation induced by AA 0.75 and 1.5 mmol/L in a dose-dependent manner. D-003 at 10 mg/day significantly inhibited (p < 0.05) aggregation induced by AA 0.75 mmol/L from 60.4-21.0% and that induced by AA 1.5 mmol/L from 61.5-26.8%. The dosage of 20 mg/day inhibited platelet aggregation induced by AA 0.75 mmol/L from 57.2-11.2%, and platelet aggregation induced by AA 1.5 mmol/L from 65.1- 21.6%. D-003 at 10 and 20 mg/day also inhibited platelet aggregation induced by collagen 1 mg/L, the effect being moderate, not dose related and reversible after washout. Platelet aggregation induced by ADP and coagulation time were unaffected by the treatment. D-003 at 5 mg/day was ineffective in inhibiting platelet aggregation. TC and triglycerides remained unchanged after therapy, as was expected for such a short duration of administration. Nevertheless, D-003 (10 and 20 mg/day) significantly (p < 0.05 vs baseline and placebo ) raised HDL-C by 20%, an effect that was not dose dependent and was partially reversible after washout. As a consequence, final values of LDL-C were lower (p < 0.05) in the 20 mg/day group than in the placebo group. No significant changes in lipid profiles occurred with placebo. No drug-related changes in safety indicators were observed. Four subjects, one from each group, withdrew from the study, none because of adverse events (AEs). No patients reported AEs during the study. Conclusions: D-003 at 10 and 20 mg/day for 10 days significantly inhibited AA- and collagen-induced platelet aggregation, without changes in ADP-induced platelet aggregation or coagulation time. The effects on AA-induced aggregation were marked, dose dependent and reversible, whereas the effects on collagen-induced aggregation were moderate and not dose dependent. D-003 (10 and 20 mg/day) also significantly but not dose dependently raised HDL-C. D-003 was well tolerated, with no AEs being reported and no changes in safety indicators being observed. The effects described suggest that D-003 is a promising agent with concomitant antiplatelet and lipid-profile modifying effects, and is potentially useful for the treatment and/or prevention of atherothrombotic disorders. Clinical investigation of D-003 is justified and further studies are needed to demonstrate such a hypothesis. [ABSTRACT FROM AUTHOR]