Effect of Niacin on Transport of HDL and Relationship to Atherogenic Lipoproteins and Lipolysis

• Men and women between the ages of 18 and 75 inclusive
• HDL cholesterol >= 25 mg/dL in all subjects, and \<= 60 mg/dL in men and \<= 70 mg/dL in women
• Women must be of non-childbearing potential. They must have been surgically sterilized at least 6 months prior to screening or be postmenopausal. Postmenopausal women must have no regular menstrual bleeding for at least 2 years prior to inclusion.
• Subjects must be in good overall health.
• Subjects must be able to comprehend and willing to provide a signed Institutional Regulatory Board (IRB) approved Informed Consent Form.
• Subjects must be willing to comply with all study-related procedures.
• Subjects must weigh at least 140 pounds to participate in the HDL kinetics Substudy.

Exclusion Criteria:

• Clinically-manifest cardiovascular disease, including coronary disease, cerebrovascular disease, or peripheral vascular disease
• History of diabetes mellitus or fasting glucose > 126 mg/dL at the screening visit
• Presence of New York Heart Association (NYHA) Class III or IV chronic heart failure or unstable angina pectoris
• History of any other endocrine disease
• History of a non-skin malignancy within the previous 5 years
• Anemia defined as hemoglobin less than 12 g/dL
• Renal insufficiency as defined by creatinine ³ 1.3 mg/dl
• Any major active rheumatologic, pulmonary, or dermatologic disease or inflammatory condition
• Uncontrolled hypertension (Systolic >160 mm Hg and/or Diastolic >100 mmHg on two consecutive measurements
• Use of warfarin, or any known coagulopathy and /or elevated Prothrombin time/Partial Thromboplastin Time (PT/PTT) >1.5 x upper limit of normal (ULN)
• Self-reported history of Human immunodeficiency virus (HIV) positive
• Previous organ transplantation
• Clinical evidence of liver disease or liver injury as indicated by abnormal liver function tests such as Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2x ULN, or self-reported history of positive for Hepatitis B or Hepatitis C
• Any major surgical procedure that occurred within the previous 3 months of the screening visit
• History of illicit drug abuse (\< 1 year)
• Regular use of alcoholic beverages (> 2 drinks/day)
• Body mass index (BMI) > 35 kg/m2 or \< 18.5 kg/m2
• Administration of an investigational drug within 6 weeks prior to the screening visit
• Serious or unstable medical or psychological conditions that, in the opinion of the investigator, would compromise the subject's safety or successful participation in the study will be excluded.

• Use of daily lipid-altering therapy prior to the initiation of study medication is exclusionary under the following circumstances (washout of non-statins is permitted):

  • Statins within 4 weeks
  • Niacin > 250 mg/ day within 6 weeks: Advicor, Niaspan, Niacor, Simcor, Slo-Niacin, or supplemental niacin
  • Fibrates within 12 weeks: fenofibrate (Antara, Lofibra, Tricor, Triglide), gemfibrozil (Lopid), or clofibrate
  • Enterically active lipid-altering drugs within 4 weeks: colestipol (Colestid), cholestyramine (Questran), colesevelam (Welchol), ezetimibe (Zetia, Vytorin), orlistat (Xenical, Alli)
  • Red yeast rice
  • Fish oil > 2 g/day within 4 weeks: Lovaza (née Omacor), numerous supplements
  • Altered dose of a selective estrogen receptor modulator (SERM) within 4 weeks
• History of severe intolerance of niacin
• Men who plan to conceive a child within 3 months of the conclusion of the study.