Safety and Efficacy of APL180 in Healthy Volunteers and Patients With Coronary Heart Disease (CHD)

• Status: Completed
• Trial end date: 1969-12-31
• Target enrollment: 0
• Participant gender: All

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

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Novartis

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