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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01057654
Other study ID # LIF293/95apoB
Secondary ID
Status Completed
Phase Phase 3
First received January 26, 2010
Last updated January 26, 2010
Start date January 1996
Est. completion date June 1998

Study information

Verified date January 2010
Source University Hospital, Bonn
Contact n/a
Is FDA regulated No
Health authority Germany: Federal Institute for Drugs and Medical Devices
Study type Interventional

Clinical Trial Summary

Lifibrol is a new lipid-lowering drug which lowers cholesterol to an extent in the order of magnitude of the statins. The mechanism of action of this compound is different from the one of statins but remains unknown. The current study will investigate the mechanism of action using stable-isotope turnover methods. The study will be done in healthy male volunteers.


Description:

Elevated lipoprotein concentrations are a major risk factor for the development of atherosclerotic cardiovascular disease. Effective reduction of low density lipoprotein (LDL)-cholesterol concentrations has been shown to greatly reduce this risk. The most widely used lipid-lowering agents are the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins), which have been shown to reduce morbidity and mortality from coronary heart disease (CHD) in large prospective clinical trials. However, despite significant LDL-C reduction approximately 70% of the events are still not avoided and the search for improved or alternative lipid-modifying drug therapies continuous. HDL-C has been addressed as a potential modifiable target for decreasing this residual risk, since a low HDL-C concentration is an acknowledged independent risk factor for CHD. However, recent studies showed that an increase in HDL-C concentrations was surprisingly not associated with a decrease in atherosclerosis, but with a possible increase. Therefore it seems that not the concentrations of HDL-C should be targeted but HDL function in reverse cholesterol transport.

Lifibrol is a lipid-modifying drug which has been shown to improve HDL particle flux via increased apoA-I production, while not having HDL-raising properties. Furthermore, it decreases dose-dependently LDL-C by up to 40%. It is of major interest to clarify the, apparently unique, mechanisms of action of a compound, whose LDL-lowering effects are comparable in magnitude to the ones of statins.

The mechanisms of lifibrol's LDL-lowering effects are not completely clarified. There is evidence suggesting that it increases hepatic LDL receptor expression by a sterol-independent mechanism, i.e. not through a reduction in cholesterol synthesis, the mechanism of action of statins. ApoB turnover studies have indicated that increased catabolism of LDL rather than a decrease in hepatic apoB production may be responsible for its cholesterol-lowering effects. Since apoB metabolism and cholesterol synthesis are closely related, we designed a study to investigate the effects of lifibrol on the metabolism of apoB-100-containing lipoproteins and on endogenous sterol synthesis in parallel, using stable isotope methods. In addition, since lifibrol may inhibit cholesterol synthesis at steps earlier than HMG-CoA reductase, we investigated [13C]acetate catabolism analyzing 13CO2 appearance in breath. The HMG-CoA-reductase inhibitor pravastatin was used as comparator, since its mode of action is well characterized. The principle questions addressed were (i) whether lifibrol exerts its cholesterol-lowering effects through decreased synthesis/enhanced catabolism of apoB-100-containing lipoproteins or through inhibition of sterol de novo synthesis and (ii) whether these effects are interrelated.


Recruitment information / eligibility

Status Completed
Enrollment 18
Est. completion date June 1998
Est. primary completion date April 1996
Accepts healthy volunteers Accepts Healthy Volunteers
Gender Male
Age group 18 Years to 35 Years
Eligibility Inclusion Criteria:

- male volunteers

- 18 to 35 years old

- good clinical condition

- normal eating habits

- mental abilities to be able to understand the study procedures

- written informed consent

Exclusion Criteria:

- relevant pathological findings in the baseline examination

- known allergic predisposition

- concomitant drugs

- alcohol or nicotine abuse

- participation in other clinical trials in the last 30 days

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Basic Science


Intervention

Drug:
Pravastatin
Pravastatin 40 mg
Lifibrol
Lifibrol (K12.148; 4-(4'-tert. butylphenyl)-1-(4'-carboxyphenoxy)-2-butanol) given as a 600 mg film-coated tablet

Locations

Country Name City State
Germany Dept. of Clinical Pharmacology, University of Bonn Bonn

Sponsors (1)

Lead Sponsor Collaborator
University Hospital, Bonn

Country where clinical trial is conducted

Germany, 

Outcome

Type Measure Description Time frame Safety issue
Primary LDL cholesterol lowering 4 weeks No
Secondary Changes in other lipoprotein concentrations 4 weeks No
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