PMID- 12455155
OWN - NLM
STAT- MEDLINE
DCOM- 20030507
LR  - 20181025
IS  - 1174-5886 (Print)
IS  - 1174-5886 (Linking)
VI  - 3
IP  - 5
DP  - 2002
TI  - Assessment of the effects of D-003, a new antiplatelet and lipid-lowering 
      compound, in healthy volunteers. A phase I clinical study.
PG  - 337-48
AB  - 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.
FAU - Castano, Gladys
AU  - Castano G
AD  - Medical Surgical Research Center, Havana City, Cuba.
FAU - Mas, Rosa
AU  - Mas R
FAU - Fernandez, Lilia
AU  - Fernandez L
FAU - Lopez, Ernesto
AU  - Lopez E
FAU - Gutierrez, Juan A
AU  - Gutierrez JA
FAU - Illnait, Jose
AU  - Illnait J
FAU - Fernandez, Julio C
AU  - Fernandez JC
FAU - Gamez, Rafael
AU  - Gamez R
FAU - Alvarez, Estrella
AU  - Alvarez E
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - New Zealand
TA  - Drugs R D
JT  - Drugs in R&D
JID - 100883647
RN  - 0 (D-003 sugarcane wax acid mixture)
RN  - 0 (Fatty Acids)
RN  - 0 (Hypolipidemic Agents)
RN  - 0 (Lipids)
RN  - 0 (Platelet Aggregation Inhibitors)
SB  - IM
MH  - Adult
MH  - Bleeding Time
MH  - Clinical Trials, Phase I as Topic
MH  - Dose-Response Relationship, Drug
MH  - Fatty Acids/administration & dosage/adverse effects/*pharmacology
MH  - Female
MH  - Humans
MH  - Hypolipidemic Agents/administration & dosage/adverse effects/*pharmacology
MH  - Lipids/blood
MH  - Male
MH  - Middle Aged
MH  - Platelet Aggregation Inhibitors/administration & dosage/adverse 
      effects/*pharmacology
MH  - Single-Blind Method
EDAT- 2002/11/29 04:00
MHDA- 2003/05/08 05:00
CRDT- 2002/11/29 04:00
PHST- 2002/11/29 04:00 [pubmed]
PHST- 2003/05/08 05:00 [medline]
PHST- 2002/11/29 04:00 [entrez]
AID - 10.2165/00126839-200203050-00008 [doi]
PST - ppublish
SO  - Drugs R D. 2002;3(5):337-48. doi: 10.2165/00126839-200203050-00008.