A Phase II, Randomized, Double Blind, Placebo-Controlled Study to assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Varying Loading and Maintenance Dosing Regimens of ISIS 301012 Administered to Hypercholesterolemic Subjects.

Conditions: Hypercholesterolemia
MedDRA version: 7.0Level: LLTClassification code 10020604

Registration Number: EUCTR2004-003934-32-DE

Lead Sponsor: Isis Pharmaceuticals Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: Not specified

Inclusion Criteria

1. Age 18 to 65 years
2. Male or female gender.
Females: Must be post-menopausal or surgically sterile (complete cessation of menstrual periods for at least one year prior to randomization, hysterectomy, bilateral oopherectomy, or tubal ligation > 6 months prior to randomization).
Males: Must have been surgically sterilized by vasectomy, or is sexually abstinent, or using contraception with his partner from screening and throughout study participation. In addition, sexually active male subjects must also agree to continue to practice contraceptive methods for at least 6 months following the last dose of study drug.
3. Stable LDL-cholesterol = 130 mg/dL or 3.36 mmol/L (from at least one of the screening measurements) and triglycerides = 400 mg/dL or 4.55 mmol/L after at least a 12-hour fast
4. Body mass index (BMI) = 25 kg/m2 and = 32 kg/m2 and stable body weight (±5%) for at least 3 months prior to randomization. Subjects should not have been on any weight-altering or diet modification regimens for 3 months prior to randomization and agree to refrain from such regimens throughout the course of the study, including the post-dose follow-up.
5. Provide written informed consent to participate in the study prior to any study-specific procedures being performed.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Pregnant women, nursing mothers, or women of childbearing potential.
2. Subject is directly affiliated with the study, or is an immediate family member of any Study Center personnel directly affiliated with the study.
3. Subject currently employed by Isis Pharmaceuticals, Inc.
4. Current diagnosis or history of endocrine, hematologic, renal, hepatic, metabolic (except for primary hypercholesteremia), psychiatric, neurologic, pulmonary, or cardiovascular disease, including any condition that predisposes to secondary hyperlipidemia, such as diabetes mellitus and hypothyroidism.
5. Current diagnosis or known history of complement deficiency or abnormality.
6. Positive hepatitis B surface antigen, hepatitis C antibody, or HIV test at screening.
7. 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.
8. Active gallbladder or peptic ulcer disease, or known history of pancreatitis, arterial bleeding, or deep vein thrombosis.
9. Known history of fibromyalgia, myopathy, rhabdomyolysis, any unexplained muscle pain, or CPK = 1.5 x ULN at screening.
10. Current diagnosis or known history of a cardiac conditions.
11. A systolic blood pressure = 160 mmHg or a diastolic blood pressure = 95 mmHg on 2 occasions during screening.
12. History of cerebrovascular or peripheral vascular disease
13. History of syncope or seizures
14. Malignancy within 5 years (with the exception of basal or squamous cell carcinoma of the skin if adequately treated and no recurrence for > 1 year at the time of screening)
15. Clinically significant abnormalities in coagulation parameters, or is taking any medication that may affect coagulation, such as warfarin, heparin, or fractionated heparin products.
16. Active infection requiring antiviral or antimicrobial therapy
17. Currently taking, or taking within 14 days of dosing, any prescription or alternative medication including herbal medication and vitamins (excluding routine multivitamin therapy), which, in the opinion of the investigator, may interfere with the clinical assessment of ISIS 301012. Hormone replacement therapy for post-menopausal women is acceptable. Acetylsalicylic acid (> 75 mg daily), a non-steroidal anti-inflammatory drug, or paracetamol (> 4 g daily), dosed for longer than 5 consecutive days requires pre-approval from Isis. Any other anti-platelet or glycoprotein IIB/IIIa inhibitors should also be avoided. These include ticlopidine, clopidogrel, abciximab, tirofiban hydrochloride, eptifibatide, lamifiban, fradifiban.
18. 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
19. Alcohol or drug abuse within 2 years of screening
20. Donated blood (450 mL) within the 3 months prior to screening or suffered significant blood loss equal to a blood donor portion
21. Subject has known hypersensitivity to ISIS 301012 or similar drugs
22. Subject not available for follow-up assessment
23. Subject smokes > 10 cigarettes, or more than one pipe or one cigar per day
24. Undergoing or have undergone treatment with another investigational drug, biologic agent or device within 90 days prior to screening
25. Subject suffers any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply wit