A Study to Evaluate 3 Different Dosing Regimens of Mipomersen Administered Via Subcutaneous Injections to Healthy Volunteers
Condition: Healthy Volunteer
Study type: Interventional
Phase: Phase 1

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.
    

Detailed description: 
      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.
    

Intervention name(s): mipomersen; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): 30 mg (cohort A), 70mg (cohort B) or 200mg (cohort C) subcutaneous (SC) dose of study drug daily for 3 weeks; 30 mg (cohort A), 70mg (cohort B), or 200mg (cohort C) subcutaneous (SC) dose of study drug daily for 3 weeks
Other intervention name(s): ISIS 301012
Intervention MeSH terms: Mipomersen
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: ApoB (Apolipoprotein B); LDL (low density lipoprotein); mipomersen; ISIS301012; antisense