A Study to Evaluate 3 Different Dosing Regimens of Mipomersen Administered Via Subcutaneous Injections to Healthy Volunteers

Summary

Hypercholesterolemia is characterized by markedly elevated low density lipoproteins (LDL). Elevated LDL is a major risk factor for coronary heart disease (CHD). Mipomersen is an antisense drug that reduces a protein in the liver cells called apolipoprotein B-100 (apoB-100). ApoB-100 plays a role in producing low density lipoprotein cholesterol (LDL-C) (the 'bad' cholesterol) and moving it from the liver to one's bloodstream. High LDL-C is an independent risk factor for the development of coronary heart disease (CHD) or other diseases of blood vessels. It has been shown that lowering LDL-C reduces the risk of heart attacks and other major adverse cardiovascular events. Mipomersen is an investigational product being studied to determine if it is safe and effective in lowering LDL-C in specific populations of patients with hypercholesterolemia. This phase 1 study is being conducted to evaluate 3 different dosing regimens (daily, 3 times per week, or weekly) in healthy volunteers for a total of 3 weeks of dosing. Study procedures will include blood testing and physical examinations to assess the safety and tolerability of the different regimens. Tests will also be done to determine how much of the drug is present in the circulation (blood flow in the body). Specific pharmacokinetic (PK) tests on the blood samples will determine what the body does to the investigational product after it is injected, including how it is absorbed, distributed, the rate at which drug action begins and the duration of the effect. Eligible subjects will receive study injections of either mipomersen or placebo over a 3 week period followed by a 12 week safety follow-up period.

Timeline

Start

2010-01

Primary completion

2010-03

Completion

2010-06

Publications

• Flaim JD, Grundy JS, Baker BF, McGowan MP, Kastelein JJ. Changes in mipomersen dosing regimen provide similar exposure with improved tolerability in randomized placebo-controlled study of healthy volunteers. J Am Heart Assoc. 2014 Mar 13;3(2):e000560. doi: 10.1161/JAHA.113.000560.

Drugs

Indications

No indication recorded.