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
- 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
- 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
- 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
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.
- 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