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

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT00568594
• Date of registration: 05/12/2007
• Prospective Registration: No
• Primary sponsor: Novartis
• Public title: Safety and Efficacy of APL180 in Healthy Volunteers and Patients With Coronary Heart Disease (CHD)
• Scientific title: 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
• Date of first enrolment: November 2007
• Target sample size: 176
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT00568594
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Basic Science
• Phase: Phase 1/Phase 2

Countries of recruitment

Belgium, Denmark, Israel, Netherlands, South Africa, United Kingdom, United States

Contacts

• Name: NOVARTIS
• Affiliation: Novartis investigative site

Key inclusion & exclusion 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



Age minimum: 18 Years
Age maximum: 75 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Coronary Heart Disease

Intervention(s)

Drug: Placebo

Drug: APL180

Primary Outcome(s)

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]

Secondary Outcome(s)

Pharmacokinetic/pharmacodynamic relationship after a single and 7 daily infusions in CHD patients [Time Frame: throughout the study]

Secondary ID(s)

CAPL180A2201

Source(s) of Monetary Support

Please refer to primary and secondary sponsors