Hypercholesterolemia MedDRA version: 7.0 Level: LLT Classification code 10020604
Conditions
Interventions
Product Code: ISIS 301012
Pharmaceutical Form: Solution for injection
CAS Number: 629167-92-6
Current Sponsor code: ISIS 301012
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: eq
Sponsors
Isis Pharmaceuticals Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
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
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To examine the safety and tolerability of varying load and maintenance dose/regimen of ISIS 301012 in hypercholesterolemic subjects ;Secondary Objective: To determine optimal load and maintenance dose/regimen for ISIS 301012 activity in hypercholesterolemic subjects. To characterize the pharmacokinetics and pharmacodynamics of ISIS 301012 during and following 3 months of treatment in hypercholesterolemic subjects;Primary end point(s): Primary Efficacy Endpoint: % reduction in LDL-cholesterol from Baseline to PD14. Secondary Efficacy Endpoint: % reduction in apoB-100 from Baseline. %Change from Baseline in HDL-cholesterol, Triglycerides, Total , non-HDL Cholesterol, VLDL, and Lp(a) % Change from Baseline in LDL/HDL and apoB-100/apo-A1 ratios. Safety and PK Endpoints: All AEs and SAEs Physical examination data, vital signs. Hepatic, renal, coagulation profiles as measured by AST, ALT, alkaline phosphatase, GGT, total bilirubin, total protein, albumin, BUN, creatinine, aPTT, and PT levels. | — |
Countries
Germany
Outcome results
None listed