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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis
ClinicalTrials.gov Identifier:
NCT00568594
First received: December 5, 2007
Last updated: October 22, 2012
Last verified: October 2012
  Purpose

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


Condition Intervention Phase
Coronary Heart Disease
Drug: APL180
Drug: Placebo
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Basic Science
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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • Pharmacokinetic/pharmacodynamic relationship after a single and 7 daily infusions in CHD patients [ Time Frame: throughout the study ] [ Designated as safety issue: No ]

Enrollment: 176
Study Start Date: November 2007
Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: APL180
Placebo Comparator: 2 Drug: Placebo

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00568594

Locations
United States, Pennsylvania
Novartis Investigator Site
Philadelphia, Pennsylvania, United States
Belgium
Novartis Investigator Site
Antwerp, Belgium
Denmark
Novartis Investigator Site
Birkeroed, Denmark
Israel
Novartis Investigator Site
Jerusalem, Israel
Novartis Investigator Site
Tel-Aviv, Israel
Novartis Investigator Site
Tzrifin, Israel
Netherlands
Novartis Investigator Site
Groningen, Netherlands
South Africa
Novartis Investigator Site
Bloemfontein, South Africa
Novartis Investigator Site
George, South Africa
Novartis Investigator Site
Port Elizabeth, South Africa
United Kingdom
Novartis Investigator Site
Harrow, United Kingdom
Sponsors and Collaborators
Novartis
Investigators
Principal Investigator: NOVARTIS Novartis investigative site
  More Information

No publications provided

Responsible Party: Novartis
ClinicalTrials.gov Identifier: NCT00568594     History of Changes
Other Study ID Numbers: CAPL180A2201
Study First Received: December 5, 2007
Last Updated: October 22, 2012
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
United States: Food and Drug Administration
Israel: Ministry of Health
South Africa: Medicines Control Council
Belgium: Federal Agency for Medicinal Products and Health Products
Denmark: Danish Medicines Agency
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Novartis:
Apolipoprotein A-I,
Atherosclerosis,
HDL,
Inflammation,

Additional relevant MeSH terms:
Heart Diseases
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases

ClinicalTrials.gov processed this record on September 18, 2014