Clinical trial NCT00568594: Safety and Efficacy of APL180 in Healthy Volunteers and Patients With Coronary Heart Disease (CHD)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Coronary Heart Disease
Keywords: Apolipoprotein A-I,
Atherosclerosis,
HDL,
Inflammation,
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2007-12-06
Enrollment: 176
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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


Eligibility 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

Primary outcomes:
measure: 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)
timeFrame: throughout the study
Secondary outcomes:
measure: Pharmacokinetic/pharmacodynamic relationship after a single and 7 daily infusions in CHD patients
timeFrame: throughout the study
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Novartis Investigator Site
state: Pennsylvania
city: Antwerp
country: Belgium
facility: Novartis Investigator Site
city: Birkeroed
country: Denmark
facility: Novartis Investigator Site
city: Jerusalem
country: Israel
facility: Novartis Investigator Site
city: Tel-Aviv
country: Israel
facility: Novartis Investigator Site
city: Tzrifin
country: Israel
facility: Novartis Investigator Site
city: Groningen
country: Netherlands
facility: Novartis Investigator Site
city: Bloemfontein
country: South Africa
facility: Novartis Investigator Site
city: George
country: South Africa
facility: Novartis Investigator Site
city: Port Elizabeth
country: South Africa
facility: Novartis Investigator Site
city: Harrow
country: United Kingdom
facility: Novartis Investigator Site
Study officials:
affiliation: Novartis investigative site
name: NOVARTIS
role: PRINCIPAL_INVESTIGATOR
References: