safety and efficacy of apl180 in healthy volunteers and patients with coronary heart disease (chd)

Conditions: Coronary Heart Disease

Summary: the purpose of this study is to determine: (1) the safety and pharmacokinetics of apl180 administered as a single intravenous infusion in healthy volunteers, and (2) the safety, pharmacokinetics and pharmacodynamics of single and multiple daily intravenous infusions of apl018 in patients with chd


Eligibility criteria:
inclusion criteria: * male and female healthy volunteers (ages 18-55 years) and patients with chd (ages 18 to 75 years) on stable statin therapy for at least 8 weeks, with normal liver and kidney function. * women who are post-menopausal, surgically sterile, or practicing effective contraception. additional birth control details to be provided at screening. * body mass index (bmi) must be within the range of 20 to 35 for chd patients or chd equivalents. * clinical chd: * myocardial infarction (mi), angina, revascularization (e.g. cabg, stent) at least 6 months prior to inclusion * chd equivalents: * symptomatic carotid artery disease (e.g. transient ischemic attack or stroke of carotid origin) or peripheral artery disease or abdominal aortic aneurysm or diabetes mellitus (hba1c ≤9) * 20% 10 year risk of chd (framingham point score: ≥16 (men), ≥23 (women)) * other clinical forms of atherosclerotic disease including \>50 percent stenosis on angiography or ultrasound * male subjects, when sexually active, using one form of highly effective contraception (e.g. condom) exclusion criteria for both healthy volunteers and patients: * smokers (use of tobacco products in the previous 3 months). smokers who report cigarette use of more then 10 cigarette per day or have a urinary cotinine level greater then 500 ng/ml. * pregnancy. * use of any prescription drugs within four (4) weeks prior dosing, or over-the-counter (otc) medication (vitamins, herbal supplements, dietary supplements) within two (2) weeks prior to dosing. significant illness within two weeks prior to dosing. * significant illness within two weeks prior to dosing. * a past medical history of clinically significant ecg abnormalities or a family history of a prolonged qt-interval syndrome. * history of clinically significant drug allergy or history of atopic allergy (asthma, urticaria, eczematous dermatitis). a known hypersensitivity to the study drug or drugs similar to the study drug or any allergic reaction to prior receipt of protein therapies or vaccines. * presence of nyha class iii or iv chf or unstable angina pectoris. * mi or within angioplasty (including stenting), acute coronary syndrome (acs), unstable angina or arterial embolic disease within 6 months prior to dosing. * use of certain medications prohibited by the protocol. * uncontrolled diabetes (hba1c \> 9). * uncontrolled hypertension (systolic bp \>160 mm hg and/or diastolic bp \>100 mmhg on two consecutive measurements). * liver or kidney disease confirmed by abnormal lab values or function. * serum creatine kinase ck (cpk) total \> 2x. * chd equivalent patients with a history of early positive exercise stress test. other protocol-defined inclusion/exclusion criteria may apply

Keywords: apolipoprotein a-i, atherosclerosis, hdl, inflammation,