A Prospective, Randomized, Double-Blind, Placebo-Controlled, Phase 1 Study to Evaluate the Relative Bioavailability, Pharmacokinetics, Safety, and Tolerability of Daily, Thrice Weekly, and Weekly Dosing Regimens of Mipomersen Administered Subcutaneously to Healthy Volunteers
A Prospective, Randomized, Double-Blind, Placebo-Controlled, Phase 1 Study to Evaluate the Relative Bioavailability, Pharmacokinetics, Safety, and Tolerability of Daily, Thrice Weekly, and Weekly Dosing Regimens of Mipomersen Administered Subcutaneously to Healthy Volunteers
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.
This is a prospective, randomized, double blind placebo-controlled, parallel-group, single center Phase 1 study to investigate the relative bioavailability, PK, safety, and tolerability of different sc dosing regimens of mipomersen in healthy volunteers. The bioavailability of 2 test regimens (Cohorts A and B) will be assessed relative to that of the reference treatment regimen (Cohort C). Approximately 84 subjects will be randomized equally to 1 of the 3 treatment regimens and then further randomized in a 3:1 ratio to mipomersen vs. placebo:
Cohort A/Test Treatment Regimen 1: up to 28 subjects will receive a 30 mg sc dose of study drug or matching volume of placebo daily for 3 weeks (21 doses; 630 mg total) Cohort B/Test Treatment Regimen 2: up to 28 subjects will receive a 70 mg sc dose of study drug or matching volume of placebo 3 times a week for 3 weeks (9 doses; 630 mg total) Cohort C/Reference Treatment Regimen: up to 28 subjects will receive a 200 mg sc dose of study drug or matching volume of placebo once a week for 3 weeks (3 doses; 600 mg total) Each subject will participate in a ≤ 6-week screening period, a 3-week treatment period, and a 12-week safety follow-up period.
Inclusion Criteria:
Exclusion Criteria: