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Safety and Tolerability of Varying Load and Dose of ISIS 301012 in People With Elevated LDL-cholesterol Levels

Phase 2
Completed
Conditions
Hypercholesterolemia
Interventions
Drug: ISIS 301012 or Placebo
Registration Number
NCT00216463
Lead Sponsor
Kastle Therapeutics, LLC
Brief Summary

The aim of this study is to assess the safety and tolerability of varying dose and load regimens of ISIS 301012 in people who have elevated LDL-cholesterol levels.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
50
Inclusion Criteria
  • BMI >/= 25 to </= 32 kg/m^2
  • fasting stable LDL-cholesterol >/= 130 mg/dL (3.36 mmol/L) and triglycerides < 400 mg/dL (4.55 mmol/L)
  • Females not of childbearing potential
Exclusion Criteria
  • No endocrine, hematologic, renal, hepatic, metabolic, psychiatric, neurology, pulmonary or cardiovascular disease
  • Subjects who test positive for hepatitis B, C or HIV
  • Current diagnosis or known history of liver disease, such as acute or chronic hepatitis, liver cirrhosis, liver steatosis, or liver function abnormalities such as AST, ALT, GGT, or total bilirubin >/= 1.5 x ULN at Screening
  • A systolic blood pressure >/= 160 mmHg or a diastolic blood pressure >/= 95 mmHg on 2 occasions during Screening
  • Concomitant medications within 14 days of dosing, except hormone replacement therapy for post-menopausal women and acetylsalicylic acid or paracetamol dosed for fewer than five consecutive days
  • Subject has taken any lipid-lowering drug within 30 days or five half-lives (of the lipid-lowering drug) whichever is longer, prior to Screening
  • Alcohol or drug abuse within 2 years of Screening
  • Donated blood (450 mL) within the 3 months prior to Screening or suffered significant blood loss equal to a blood donor portion
  • Subject smokes > 10 cigarettes, or more than one pipe or one cigar per day

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
AISIS 301012 or PlaceboSlow load with every other week maintenance
BISIS 301012 or PlaceboSlow load with every other week maintenance
CISIS 301012 or PlaceboNo load; once weekly maintenance
DISIS 301012 or PlaceboNo load; once weekly maintenance
EISIS 301012 or PlaceboNo load; once weekly maintenance
Primary Outcome Measures
NameTimeMethod
Percent reduction in LDL-cholesterol from baseline14 days post dosing
Secondary Outcome Measures
NameTimeMethod
Percent reduction in apoB-100 from baseline14 days post dosing
Percent change from baseline in HDL-cholesterol, triglycerides, total cholesterol, non-HDL cholesterol, VLDL and LP(a)14 days post dosing
Percent change from baseline in LDL/HDL and apoB-100/apo-A1 ratios14 days post dosing
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