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

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