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

Coronary Heart Disease Clinical Trial

Official 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00568594
• Other study ID #: CAPL180A2201
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: November 2007

Study information

• Verified date: October 2012
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 176
• Est. primary completion date: September 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Coronary Heart Disease
• Heart Diseases
• Myocardial Ischemia

Intervention

Drug:
• APL180

• Placebo

Locations

Country	Name	City	State
Belgium	Novartis Investigator Site	Antwerp
Denmark	Novartis Investigator Site	Birkeroed
Israel	Novartis Investigator Site	Jerusalem
Israel	Novartis Investigator Site	Tel-Aviv
Israel	Novartis Investigator Site	Tzrifin
Netherlands	Novartis Investigator Site	Groningen
South Africa	Novartis Investigator Site	Bloemfontein
South Africa	Novartis Investigator Site	George
South Africa	Novartis Investigator Site	Port Elizabeth
United Kingdom	Novartis Investigator Site	Harrow
United States	Novartis Investigator Site	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Novartis

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Pharmacokinetic/pharmacodynamic relationship after a single and 7 daily infusions in CHD patients		throughout the study

External Links

•   Results for CAPL180A2201 from the Novartis Clinical Trials website