| Safety and Efficacy of APL180 in Healthy Volunteers and Patients With Coronary Heart Disease (CHD) |
| A First-in-Human, Randomized, Double-Blind, Placebo-Controlled, Single-Ascending Dose (Healthy Volunteers and CHD Patients) and Multiple Dose (CHD Patients) Study to Assess Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of APL180 |
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 |
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| Phase I, Phase II |
| Interventional |
| Basic Science, Randomized, Double Blind (Subject, Investigator), Active Control, Parallel Assignment, Safety Study |
| 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) [ Time Frame: throughout the study ] [ Designated as safety issue: No ] |
| Pharmacokinetic/pharmacodynamic relationship after a single and 7 daily infusions in CHD patients [ Time Frame: throughout the study ] [ Designated as safety issue: No ] |
| Coronary Heart Disease (CHD) |
Drug: APL180
Drug: Placebo |
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| Recruiting |
| 120 |
| November 2007 |
| December 2008 |
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 |
| Both |
| 18 Years to 75 Years |
| Yes |
| Contact: NOVARTIS |
+41 61 324 1111 |
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| United States, Belgium, Denmark, Israel, Netherlands, South Africa, United Kingdom |
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| NCT00568594 |
| CAPL180A2201 |
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| Novartis |
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| Principal Investigator: |
NOVARTIS |
Novartis investigative site |
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| Novartis |
| June 2008 |
| December 5, 2007 |
| June 17, 2008 |