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

NCT00568594 | Completed Phase 1

• 1 other identifier: CAPL180A2201
• Study Type: interventional
• Target: 176
• Locations: 7 countries
• Sites: 11

Brief 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

Conditions

Coronary Heart Disease

Keywords

Apolipoprotein A-I,; Atherosclerosis,; HDL,; Inflammation,

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Pharmacokinetic/pharmacodynamic relationship after a single and 7 daily infusions in CHD patients

  throughout the study

Study Arms (2)

1

EXPERIMENTAL

Drug: APL180

2

PLACEBO COMPARATOR

Drug: Placebo

Interventions

APL180 DRUG

1

Placebo DRUG

2

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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)
• % 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis: lead

Study Sites (11)

Novartis Investigator Site

Philadelphia, Pennsylvania, United States

Location

Novartis Investigator Site

Antwerp, Belgium

Location

Novartis Investigator Site

Birkeroed, Denmark

Location

Novartis Investigator Site

Jerusalem, Israel

Location

Novartis Investigator Site

Tel Aviv, Israel

Location

Novartis Investigator Site

Tzrifin, Israel

Location

Novartis Investigator Site

Groningen, Netherlands

Location

Novartis Investigator Site

Bloemfontein, South Africa

Location

Novartis Investigator Site

George, South Africa

Location

Novartis Investigator Site

Port Elizabeth, South Africa

Location

Novartis Investigator Site

Harrow, United Kingdom

Location

Related Links

• Results for CAPL180A2201 from the Novartis Clinical Trials website

MeSH Terms

Conditions

Coronary Disease; Atherosclerosis; Inflammation

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• NOVARTIS

  Novartis investigative site

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 5, 2007
• First Posted: December 6, 2007
• Study Start: November 1, 2007
• Primary Completion: September 1, 2009
• Last Updated: December 24, 2020

Record last verified: 2012-10

Locations

DK (1); US (1); BE (1); IL (3); NL (1); ZA (3); GB (1)