Hypercholesterolemia
Conditions
Keywords
LDL-cholesterol, apoB-100, apoB-48
Brief summary
The aim of this study is to assess the safety of varying doses of ISIS 301012 in subjects on Stable statin therapy.
Interventions
30 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, and 29
Sponsors
Ionis Pharmaceuticals, Inc.
Kastle Therapeutics, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* On a stable dose of \>/= 40 mg Simvastatin or atorvastatin daily for \>/= 3 months prior to baseline and expected to remain on this dose for the remainder of the study * LDL-cholesterol between 2.60 and 5.70 mmol/L (100 and 220 mg/dL), inclusive at screening * Females not of childbearing potential.
Exclusion criteria
* History of CHD or CHD-equivalent (such as diabetes mellitus, or another clinical form of atherosclerotic disease, e.g., peripheral arterial disease, abdominal aortic aneurysm, or symptomatic carotid artery disease) * Fasting triglyceride \>2.26 mmol/L (200 mg/dL) at screening * Any uncontrolled medical/surgical/psychiatric condition, including conditions that may predispose to secondary hypercholesterolemia * Current diagnosis or known history of complement deficiency or abnormality * A positive hepatitis B surface antigen or hepatitis C antibody, or a known positive HIV status * Current diagnosis or known history of liver disease, or has an ALT \>ULN at screening * Known history of fibromyalgia, myopathy, myositis, rhabdomyolysis, any unexplained muscle pain, or has a CPK \>ULN at screening * Malignancy within 5 years, except for basal or squamous cell carcinoma of the skin that has been adequately treated * The advisability of a subject taking any prescription medication (apart from simvastatin or atorvastatin) within 6 weeks prior to screening should be discussed with the Isis Medical Monitor * Subject unwilling to discontinue taking alternative/herbal medication for the duration of the study * History of drug abuse within 2 years of screening * Subject unwilling to limit alcohol consumption for the duration of the study: male subjects to a maximum of 3 drinks (30 g) per day, and \<12 drinks (120 g) per week; female subjects to a maximum of 2 drinks (20 g) per day, and \<8 drinks (80 g) per week * Known allergy or hypersensitivity to simvastatin * Undergoing or has undergone treatment with another investigational drug, biologic agent, or device within 3 months, or 3 half lives, prior to screening, whichever is longer
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percent reduction in LDL-cholesterol from baseline | From baseline measurement |
Secondary
| Measure | Time frame |
|---|---|
| Percent reduction in apoB-100 | From baseline measurement |
| Percent change in HDL-cholesterol, triglycerides, total cholesterol, non-HDL cholesterol, VLDL plus LDL-cholesterol and LDL-cholesterol particle size and concentration | From baseline measurement |
| Percent change from baseline in LDL/HDL and apoB-100/apo-A1 ratios | From baseline measurement |
| AEs, SAEs, physical examination data, vital signs, and laboratory analyzes | Duration of study |
Countries
Netherlands, United States
Outcome results
None listed