ot applicable

Phase 1

Conditions: Cardiovascular Disease or at High Risk for Cardiovascular Disease
MedDRA version: 20.1Level: LLTClassification code 10020870Term: HypertriglyceridemiaSystem Organ Class: 100000004861
Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Registration Number: EUCTR2011-004726-10-PL

Lead Sponsor: Amarin Pharma Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 7990

Inclusion Criteria

1.Fasting TG levels of =200 mg/dL (2.26 mmol/L) and <500 mg/dL
(5.64 mmol/L).
2.LDL-C >40 mg/dL (1.04 mmol/L) and =100 mg/dL (2.60 mmol/L) and
on stable therapy with a statin (with or without ezetimibe) for at least 4
weeks prior to the LDL-C/TG baseline qualifying measurements for
randomization
•Stable therapy is defined as the same daily dose of the same statin for
at least 28 days before the lipid qualification measurements (TG and
LDL-C) and, if applicable, the same daily dose of ezetimibe for at least 28
days before the lipid qualification measurements (TG and LDL-C).
Patients who have their statin therapy or use of ezetimibe initiated at
Visit 1, or have their statin, statin dose and/or ezetimibe dose changed
at Visit 1, will need to go through a stabilization period of at least 28
days since initiation/change and have their qualifying lipid
measurements measured (TG and LDL-C) after the washout period (at
Visit 1.1).
•Statins may be administered with or without ezetimibe.
3.Either having established CVD (in CV Risk Category 1) or at high risk
for CVD (in CV Risk Category 2). The CV risk categories are defined as
follows:
CV Risk Category 1: defined as men and women =45 years of age with
one or more of the following:
o Documented coronary artery disease (CAD; one or more of the
following primary criteria must be satisfied):
•Documented multi vessel CAD (>50% stenosis in at least two major
epicardial coronary arteries – with or without antecedent
revascularization);
•Documented prior MI;
•Hospitalization for high-risk non-ST-segment elevation acute coronary
syndrome (NSTE-ACS) (with objective evidence of ischemia: ST-segment
deviation or biomarker positivity).
o Documented cerebrovascular or carotid disease (one of the following
primary criteria must be satisfied):
•Documented prior ischemic stroke;
•Symptomatic carotid artery disease with =50% carotid arterial
stenosis;
•Asymptomatic carotid artery disease with =70% carotid arterial
stenosis per angiography or duplex ultrasound;
•History of carotid revascularization (catheter-based or surgical).
o Documented peripheral arterial disease (PAD; one or more of the
following primary criteria must be satisfied):
•Ankle-brachial index (ABI) <0.9 with symptoms of intermittent
claudication;
•History of aorto-iliac or peripheral arterial intervention (catheter-based
or surgical).
OR
CV Risk Category 2: defined as patients with:
1.Diabetes mellitus (Type 1 or Type 2) requiring treatment with
medication AND
2.Men and women =50 years of age AND
3. One of the following at Visit 1 (additional risk factor for CVD):
• Men =55 years of age and Women =65 years of age;
• Cigarette smoker or stopped smoking within 3 months before Visit 1;
diastolic) or on antihypertensive medication;
• HDL-C =40 mg/dL for men or =50 mg/dL for women;
• Hs-CRP >3.00 mg/L (0.3 mg/dL);
• Renal dysfunction: Creatinine clearance (CrCL) >30 and <60 mL/min
(>0.50 and <1.00 mL/sec);
• Retinopathy, defined as any of the following: non-proliferative
retinopathy, pre-proliferative retinopathy, proliferative retinopathy,
maculopathy, advanced diabetic eye disease or a history of
photocoagulation;
• Micro- or macroalbuminuria. Microalbuminuria is defined as either a
positive micral or other strip test (may be obtained from medical
records), an albumin/creatinine ratio =2.5 mg/mmol or an albumin
excretion rate on timed collection =20 mg/min all on at least two
successive occasions; macroalbuminuria, defined as Albustix or other
dip

Exclusion Criteria

1. Severe (New York Heart Association [NYHA] class IV) heart failure.
2. Any life-threatening disease expected to result in death within the
next 2 years (other than CVD).
3. Active severe liver disease (evaluated at Visit 1): cirrhosis, active
hepatitis, alanine aminotransferase (ALT) or aspartate aminotransferase
(AST) >3 × the upper limit of normal (ULN), or biliary obstruction with
hyperbilirubinemia (total bilirubin >2 × ULN).
4. Hemoglobin A1c (HbA1c ) >10.0% (or >86 mmol/mol International
Federation of Clinical Chemistry [IFCC] units) at screening (Visit 1). If
patients fail this criterion (HbA1c >10.0% or >86 mmol/mol IFCC units)
at Visit 1, they may have their antidiabetic therapy optimized and be
retested at Visit 1.1.
5.Poorly controlled hypertension: blood pressure =200 systolic mmHg
OR =100 mmHg diastolic (despite antihypertensive therapy).
6.Planned coronary intervention (such as stent placement or heart
bypass) or any non-cardiac major surgical procedure. Patients can be
(re)evaluated for participation in the trial (starting with Visit 1.1) after
their recovery from the intervention/surgery.
7.Known familial lipoprotein lipase deficiency (Fredrickson Type I),
apolipoprotein C-II deficiency, or familial dysbetalipoproteinemia
(Fredrickson Type III).
8.Participation in another clinical trial involving an investigational agent
within 90 days prior to screening (Visit 1). Patients cannot participate in
any other investigational medication or medical device trial while
participating in this study (participation in a registry or observational
study without additional therapeutic intervention is allowed).
9.Intolerance or hypersensitivity to statin therapy.
10.Known hypersensitivity to any ingredients of the study product or
placebo (refer to Table 5); known hypersensitivity to fish and or
shellfish.
11.History of acute or chronic pancreatitis.
12.Malabsorption syndrome and/or chronic diarrhea. (Note: patients
who have undergone gastric/intestinal bypass surgery are considered to
have malabsorption, hence are excluded; patients who have undergone
gastric banding are allowed to enter the trial).
13. Non-study drug related, non-statin, lipid-altering medications,
supplements or foods:
• Patients are excluded if they used niacin >200 mg/day or fibrates
during the screening period (after Visit 1) and/or plan to use during the
study; patients who are taking niacin >200 mg/day or fibrates during
the last 28 days before Visit 1 need to go through washout of at least 28
days after their last use and have their qualifying lipids measured (TG
and LDL-C) after the washout period (Visit 1.1);
• Patients are excluded if they take any omega-3 fatty acid medications
(prescription medicines containing EPA and/or docosahexaenoic acid
[DHA]) during the screening period (after Visit 1) and/or plan to use
during the treatment/follow-up period of the study. To be eligible for
participation in the study, patients who are taking omega-3 fatty acid
medications during the last 28 days before Visit 1 (except patients in the
Netherlands), need to go through a washout period of at least 28 days
after their last use and have their qualifying lipid measurements
measured (TG and LDL-C) after the washout period (at Visit 1.1);
o For patients in the Netherlands only: patients being treated with
omega-3 fatty acid medications containing EPA and /or DHA are
excluded; no washout is allowed.
• Patients are excluded if they use dietary supplements containing
omega