Dose-escalating Safety Study in Subjects on Stable Statin Therapy
Phase 2
Completed
- Conditions
- Hypercholesterolemia
- Interventions
- Drug: ISIS 301012 or Placebo
- Registration Number
- NCT00231569
- Lead Sponsor
- Kastle Therapeutics, LLC
- Brief Summary
The aim of this study is to assess the safety of varying doses of ISIS 301012 in subjects on Stable statin therapy.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 74
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort A ISIS 301012 or Placebo Loading doses followed by weekly maintenance doses Cohort D ISIS 301012 or Placebo Loading doses followed by weekly maintenance doses Cohort B ISIS 301012 or Placebo Loading doses followed by weekly maintenance doses Cohort C ISIS 301012 or Placebo Loading doses followed by weekly maintenance doses Cohort E ISIS 301012 or Placebo Loading doses followed by weekly maintenance doses Cohort F ISIS 301012 or Placebo Loading doses followed by extended weekly maintenance doses Cohort G ISIS 301012 or Placebo Loading doses followed by extended weekly maintenance doses
- Primary Outcome Measures
Name Time Method Percent reduction in LDL-cholesterol from baseline From baseline measurement
- Secondary Outcome Measures
Name Time Method 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