Effects of D-003 on the Lipid Profile of Patients with Type II Hypercholesterolaemia : A Phase II Clinical Study.

BACKGROUND: D-003 is a cholesterol-lowering agent that is isolated and purified from sugarcane wax and has concomitant antiplatelet effects.

OBJECTIVE: To evaluate lipid profile responses to different doses of D-003 in patients with type II hypercholesterolaemia.

STUDY DESIGN: An 8-week, double-blind, placebo-controlled, parallel-group clinical study.

METHODS: After concluding a 5-week diet-only baseline period, 55 patients were randomly allocated to receive either placebo or D-003 at 5, 10, 20 or 40mg once daily with their evening meal for 8 weeks. An interim check-up was performed at week 4. The primary efficacy variable was the reduction of serum low-density lipoprotein-cholesterol (LDL-C) from baseline compared with placebo. Drug safety and tolerability were assessed on the basis of changes in physical, haematological and blood biochemical indicators and on questioning about adverse experiences (AEs).

RESULTS: After 8 weeks of therapy, D-003 significantly lowered (p < 0.0001 vs baseline and placebo) serum LDL-C in a dose-related manner, with reductions of 20.5-26.1% from the lowest to the highest dose investigated. At study completion, 43 of 44 (97.7%) randomised patients treated with D-003 reached LDL-C reductions >15% compared with baseline, while 30 of 44 patients (68.2%) reached LDL-C targets according to their individual global coronary risk status. Decreases in total cholesterol (TC) and the ratios of TC/high-density lipoprotein-cholesterol (HDL-C) and LDL-C/HDL-C were also significant (p < 0.0001) and dose related. Changes in LDL-C, TC and both ratios were significant from the interim check-up. D-003 significantly increased HDL-C values (11.7-16.7%), but the increase was not dose related. No significant changes in lipid profile variables were observed with placebo. D-003 was well tolerated. The treatment did not affect any physical, haematological or blood safety indicators. All included patients completed the study. Four patients reported mild AEs during the study: headache (one patient treated with placebo and one treated with D-003 20 mg/day), insomnia (one patient treated with D-003 5 mg/day) and polyuria (one patient treated with D-003 40 mg/day).

CONCLUSIONS: D-003 was effective in dose dependently reducing LDL-C in patients with type II hypercholesterolaemia, as documented by average percentage reductions and the percentage of patients achieving decreases >15% from baseline and LDL-C goals. The treatment was well tolerated by patients and did not affect any safety indicator. Further studies corroborating these results and exploring the effect of lower doses of D-003 and a longer treatment duration must be carried out, however, before definitive conclusions can be reached. These results encourage continuing clinical investigation on this drug.