Hypercholesterolemia
Conditions
Keywords
LDL-cholesterol, apoB-100, apoB-48
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.
Interventions
200 mg subcutaneous injection - 4 loading doses within the first 11 days followed by: 200 mg subcutaneous injection - every other week for 11 weeks
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
* 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percent reduction in LDL-cholesterol from baseline | 14 days post dosing |
Secondary
| Measure | Time frame |
|---|---|
| Percent reduction in apoB-100 from baseline | 14 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 ratios | 14 days post dosing |
Countries
Germany
Outcome results
None listed