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

Study Overview
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Brief Summary
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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

Official Title
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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

Conditions
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Coronary Heart Disease

Intervention / Treatment
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* Drug: APL180
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: APL180<br> <br> |
| Placebo Comparator: 2<br> | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic/pharmacodynamic relationship after a single and 7 daily infusions in CHD patients |  | throughout the study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Apolipoprotein A-I,, Atherosclerosis,, HDL,, Inflammation,