Safety Study of ISIS 325568 in Healthy Volunteers

To evaluate the safety of a single subcutaneous injection of ISIS 325568 administered at four increasing dose levels (50, 100, 200, 400 mg/week) and to evaluate the safety and tolerability of multiple doses of ISIS 325568 (three intravenous doses during Study Week 1, followed by once weekly subcutaneous administration for 5 weeks) at each of the four dose levels

Inclusion criteria

• Age 18 to 65 years
• Males or females. Females must be non-pregnant and non-lactating, and either surgically sterile (hysterectomy, oophorectomy, or tubal ligation) or post-menopausal. Males must be surgically sterile, abstinent or if engaged in sexual relations of child-bearing potential, subject or partner must be using an acceptable contraceptive method during the trial and for 9 weeks after the last dose of study drug.
• Give written informed consent to participate in study and availability for all study requirements
• Fasting plasma glucose ≤ the upper limit of the laboratory's reference range (ULN)
• HbA1C ≤ ULN
• BMI < 30 kg/m2

Exclusion criteria

• Clinically significant abnormalities in medical history or physical examination
• Abnormalities on laboratory examination (ALT > ULN, AST > ULN, bilirubin > ULN, creatinine > ULN, urine protein positive by urine dipstick, platelets < lower limit of normal and any other clinically significant laboratory findings)
• History of clinically significant abnormalities in coagulation parameters
• Positive test result for HIV, hepatitis B virus, and/or hepatitis C virus
• Active infection requiring antiviral or antimicrobial therapy
• Subjects on chronic or acute prescription medication may be permitted after discussion with the Isis Medical Monitor.
• Malignancy (with the exception of basal or squamous cell carcinoma of the skin if adequately treated and no recurrence for > 1 year)
• Any other concurrent condition which, in the opinion of the Investigator, would preclude participation in this study or interfere with compliance
• History of alcohol or drug abuse
• Undergoing or have undergone treatment with another investigational drug, biologic agent or device within 90 days prior to Screening.
• Blood donation within three months of screening