Assessment of the effects of D-003, a new antiplatelet and lipid-lowering compound, in healthy volunteers. A phase I clinical study.
OBJECTIVE
To investigate the effects of D-003 on the bleeding time (BT) and lipid profile of healthy human volunteers.


METHODS
This single-blind, randomised, placebo-controlled, parallel-group study was conducted in healthy volunteers. Step 1 investigated the effects of single doses of D-003 5, 25 or 50 mg on BT in comparison with placebo. Step 2 investigated the effects of 30 days of D-003 5, 25 or 50 mg/day compared with placebo on lipid profile with an interim assessment at 14 days. BT, lipid profile, physical and haematological safety indicators were measured and adverse events (AEs) recorded. Both steps were followed by a 14- or 30-day washout period.


RESULTS
Step 1: D-003 25 and 50 mg significantly increased mean BT 2 hours after administration compared with baseline, but a significant difference versus placebo occurred only with the 50 mg dose. Individual values from participants taking this dose, however, remained within normal limits. This effect was reversible. BT values obtained 2 hours after drug administration showed a moderate dose-dependent relationship. No drug-related changes in safety indicators were found with D-003. Step 2: After 7 days on D-003 50 mg/day, BT was significantly increased compared with baseline and placebo up to the end of the active treatment period. However, all individual values for participants taking this dosage remained within the normal range. This effect was reversible by the end of the washout period. After 30 days, D-003 (5, 25 and 50 mg/day) significantly reduced serum TC (by 13.3 to 17.4%) and LDL-C (by 11.6 to 22.6%) levels, and raised HDL-C levels (by 14.6 to 29.7%), but did not affect triglyceride levels. The significant increase in HDL-C was observed after 14 days on treatment. The effects on the lipid profile were reversible by the end of the 30-day washout period, although after 14 days of washout the effects on HDL-C and LDL-C still remained significant, revealing a certain persistence of effect. Eight participants (four receiving placebo and four receiving D-003 5, 25 or 50 mg/day) reported a total of nine AEs, none of which were drug-related. Of these patients, only two treated with D-003 25 and 50 mg/day discontinued treatment.


CONCLUSIONS
D-003 in single or repeated doses (50 mg) induced significant and reversible increases in BT. In addition, repeated doses (5, 25 and 50 mg/day) significantly and reversibly lowered serum LDL-C and TC levels and significantly raised serum HDL-C levels. These effects were reversible by 30 days after the end of treatment.
Castaño
Gladys
G
Medical Surgical Research Center, Havana City, Cuba.
Más
Rosa
R
Fernández
Lilia
L
López
Ernesto
E
Gutiérrez
Juan A
JA
Illnait
José
J
Fernández
Julio C
JC
Gámez
Rafael
R
Alvarez
Estrella
E
D000328:Adult; D001760:Bleeding Time; D017321:Clinical Trials, Phase I as Topic; D004305:Dose-Response Relationship, Drug; D005227:Fatty Acids / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D005260:Female; D006801:Humans; D000960:Hypolipidemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D016037:Single-Blind Method
C418063:D-003 sugarcane wax acid mixture; D005227:Fatty Acids; D000960:Hypolipidemic Agents; D008055:Lipids; D010975:Platelet Aggregation Inhibitors