A Study to Evaluate 3 Different Dosing Regimens of Mipomersen Administered Via Subcutaneous Injections 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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Bio-availability Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||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|
- Incidence of treatment-emergent AEs and SAEs [ Time Frame: Assessed at each study visit through 21 weeks ] [ Designated as safety issue: Yes ]
- Maximum plasma concentration (Cmax) [ Time Frame: variable up to 105 days ] [ Designated as safety issue: No ]
- time to maximal concentration (Tmax) [ Time Frame: variable up to 105 days ] [ Designated as safety issue: No ]
- area under the curve (AUC) based on PK profiles following the first and last dose [ Time Frame: variable up to 105 days ] [ Designated as safety issue: No ]
|Study Start Date:||January 2010|
|Study Completion Date:||June 2010|
|Primary Completion Date:||March 2010 (Final data collection date for primary outcome measure)|
30 mg (cohort A), 70mg (cohort B) or 200mg (cohort C) SC daily
30 mg (cohort A), 70mg (cohort B) or 200mg (cohort C) subcutaneous (SC) dose of study drug daily for 3 weeks
Other Name: ISIS 301012
Placebo Comparator: Placebo
30 mg (cohort A), 70mg (cohort B), or 200mg (cohort C) SC daily
30 mg (cohort A), 70mg (cohort B), or 200mg (cohort C) subcutaneous (SC) dose of study drug daily for 3 weeks
This is a prospective, randomized, double blind placebo-controlled, parallel-group, singlecenter 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.