Coronary Heart Disease
Conditions
Keywords
Apolipoprotein A-I,, Atherosclerosis,, HDL,, Inflammation,
Brief 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
Interventions
DRUGAPL180
DRUGPlacebo
Sponsors
Novartis
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
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/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety and tolerability, pharmacokinetics and effects on biomarkers of HDL function of APL180 after a single and 7-daily infusions in healthy volunteers (HV) and in patients with coronary heart disease (CHD) | throughout the study |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetic/pharmacodynamic relationship after a single and 7 daily infusions in CHD patients | throughout the study |
Countries
Belgium, Denmark, Israel, Netherlands, South Africa, United Kingdom, United States
Outcome results
None listed