# US 2014/0155455 A1 · Pharmaceutical compositions comprising epa and a cardiovascular agent and methods of using the same

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- Number: US 2014/0155455 A1
- Document ID: US20140155455A1
- Status: Published application
- Kind: A1
- Application number: 14/175,515
- Filed: 2014-02-07
- Published: 2014-06-05
- Earliest claimed: 2009-04-29
- Assignees: Amarin Pharmaceuticals Ireland Limited
- Applicants: Amarin Pharmaceuticals Ireland Limited
- Inventors: Ian Osterloh; Pierre Wicker; Rene Braeckman; Paresh Soni; Mehar Manku
- Web page: https://patentgrep.com/patent/US20140155455A1

## CPC

- A61K 31/202: having three or more double bonds, e.g. linolenic (eicosanoids, e.g. leukotrienes A61K31/557)
- A61K 9/127: Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
- A61K 9/48: Preparations in capsules, e.g. of gelatin, of chocolate {(A61K9/0004 takes precedence; bite capsules A61K9/0056)}
- A61K 9/4858: {Organic compounds}
- A61K 31/222: with compounds having aromatic groups, e.g. dipivefrine, ibopamine
- A61K 31/232: having three or more double bonds, e.g. etretinate
- A61K 31/40: having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K 31/505: Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61K 47/22: Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
- A61K 47/26: Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
- A61K 47/34: Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers (A61K47/10 takes precedence)
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A61P 3/00: Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00)
- A61P 3/04: Anorexiants; Antiobesity agents
- A61P 3/08: for glucose homeostasis (pancreatic hormones A61P5/48)
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 7/02: Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
- A61P 7/12: Antidiuretics, e.g. drugs for diabetes insipidus (ADH A61P5/10)
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 9/04: Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
- A61P 9/06: Antiarrhythmics
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 9/12: Antihypertensives
- A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A61P 31/18: for HIV
- A61K 31/74: Synthetic polymeric materials
- A61P 3/06: Antihyperlipidemics
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present disclosure relates to, inter alia, methods of treating mixed dyslipidemia with ethyl eicosapentaenoate.

## Claims

### Claim 1

A composition comprising eicosapentaenoic acid and docosahexaenoic acid in free acid form, at least one surfactant and at least one cardiovascular agent.

### Claim 2 (depends on 1)

The composition of claim 1 further comprising at least one additional fatty acid selected from the group consisting of linolenic acid, arachidonic acid, alpha-linolenic acid, stearadonic acid, eicosatrienoic acid, docosapentaenoic acid, heneicosapentaenoate, gamma-linolenic acid, or ethyl esters or tryglycerides thereof.

### Claim 3 (depends on 1)

The composition of claim 1 further comprising oleic acid or a derivative thereof.

### Claim 4 (depends on 1)

The composition of claim 1 wherein the composition comprises at least 90% omega-3 fatty acids, by weight of total fatty acid present in the composition.

### Claim 5 (depends on 1)

The composition of claim 1 having a ratio of eicosapentaenoic acid to docosahexaenoic acid from about 2:1 to about 19:1, and wherein the eicosapentaenoic acid and docosahexaenoic acid combined comprise more than about 50% by weight of total fatty acid present in the composition.

### Claim 6 (depends on 1)

The composition of claim 1 wherein the at least one surfactant is selected from the group consisting of quaternary ammonium compounds, dioctyl sodium sulfosuccinate, polyoxyethylene alkylphenyl ethers, poloxamers, polyoxyethylene fatty acid glycerides and oils, polyoxyethylene alkyl ethers, polyoxyethylene fatty acid esters, polyoxyethylene sorbitan esters, propylene glycol fatty acid esters, sodium lauryl sulfate, glyceryl fatty acid esters, sorbitan esters, tyloxapol, and mixtures thereof.

### Claim 7 (depends on 1)

The composition of claim 1 wherein the at least one surfactant is selected from the group consisting of polysorbate 20, polysorbate 80, and mixtures thereof.

### Claim 8 (depends on 1)

The composition of claim 1 wherein the at least one surfactant is present in an amount of about 0.25% to about 15% by total weight of the composition.

### Claim 9 (depends on 1)

The composition of claim 1 wherein the at least one cardiovascular agent is an HMG-CoA reductase inhibitor.

### Claim 10 (depends on 9)

The composition of claim 9 wherein the HMG-CoA reductase inhibitor comprises lovastatin, mevastatin, pitavastatin, pravastatin, rosuvastatin, fluvastatin, atorvastatin, simvastatin, or combinations thereof.

### Claim 11 (depends on 9)

The composition of claim 9 wherein the HMG-CoA reductase inhibitor is present in an amount from about 1 mg to about 1000 mg.

### Claim 12 (depends on 1)

The composition of claim 1 further comprising at least one antioxidant.

### Claim 13 (depends on 12)

The composition of claim 12 wherein the at least one antioxidant is a tocopherol.

### Claim 14 (depends on 12)

The composition of claim 12 wherein the antioxidant is present in an amount from about 0.0001% to about 5% of the total weight of the composition.

### Claim 15

A method of treating a cardiovascular-related disease in a subject in thereof, the method comprising administering to the subject a therapeutically effective amount of a composition comprising: eicosapentaenoic acid, docosahexaenoic acid, at least one surfactant; and at least one cardiovascular agent.

### Claim 16 (depends on 15)

The method of claim 15 wherein the cardiovascular-related disease is selected from the group consisting of any disease or disorder of the heart or blood vessels or any symptom thereof, including, for example, acute cardiac ischemic events, acute myocardial infarction, angina, angina pectoris, arrhythmia, atrial fibrulation, atherosclerosis, arterial fibrillation, cardiac insufficiency, cardiovascular disease, chronic heart failure, chronic stable angina, congestive heart failure, coronary artery disease, coronary heart disease, deep vein thrombosis, diabetes, diabetes mellitus, diabetic neuropathy, diastolic dysfunction in subjects with diabetes mellitus, edema, essential hypertension, eventual pulmonary embolism, fatty liver disease, heart disease, heart failure, homozygous familial hypercholesterolemia (HoFH), homozygous familial sitosterolemia, hypercholesterolemia, ischemic complications in unstable angina and myocardial infarction, low blood pressure, metabolic syndrome, moderate to mild heart failure, myocardial infarction, obesity management, paroxysmal atrial/arterial fibrillation/fibrulation/flutter, paroxysmal supraventricular tachycardias (PSVT), particularly severe or rapid onset edema, platelet aggregation, primary hypercholesterolemia, primary hyperlipidemia, pulmonary arterial hypertension, pulmonary hypertension, recurrent hemodynamically unstable ventricular tachycardia (VT), recurrent ventricular arrhythmias, recurrent ventricular fibrillation (VF), ruptured aneurysm, sitisterolemia, stroke, supraventricular tachycardia, symptomatic atrial fibrillation/flutter, tachycardia, type-II diabetes, vascular disease, venous thromboembolism, ventricular arrhythmias, and combinations thereof.

### Claim 17 (depends on 17)

The method of claim 17 wherein the cardiovascular-related disease is selected from the group consisting of hyperlipidemia, hypertension, mixed dyslipidemia, and combinations thereof.

### Claim 18 (depends on 17)

The method of claim 17 wherein the cardiovascular-related disease is hypertriglyceridemia.

### Claim 19 (depends on 17)

The method of claim 17 wherein the administering step reduces fasting triglycerides by at least 10% compared to baseline or a placebo arm.

### Claim 20 (depends on 17)

The method of claim 17 wherein the administering step reduces fasting triglycerides by at least 15% compared to baseline or a placebo arm.

### Claim 21 (depends on 17)

The method of claim 17 wherein the administering step reduces fasting triglycerides by at least 20% compared to baseline or a placebo arm.

### Claim 22 (depends on 17)

The method of claim 17 wherein the administering step reduces fasting triglycerides by at least 25% and LDL-C by at least 5% compared to baseline or a placebo arm.

### Claim 23 (depends on 17)

The method of claim 17 wherein the administering step reduces fasting apolipoprotein B compared to baseline or a placebo arm.

### Claim 24 (depends on 17)

The method of claim 17 wherein the administering step reduces fasting apolipoprotein B by at least 5% compared to baseline or a placebo arm.

### Claim 25 (depends on 17)

The method of claim 17 wherein the administering step reduces fasting VLDL-C compared to baseline or a placebo arm.

### Claim 26 (depends on 17)

The method of claim 17 wherein the administering step reduces fasting VLDL-C by at least 15% compared to baseline or a placebo arm.

### Claim 27 (depends on 17)

The method of claim 17 wherein the pharmaceutical composition is administered to the subject in 1 to about 10 dosage units per day.

### Claim 28 (depends on 27)

The method of claim 27 wherein the dosage units comprise capsules.

### Claim 29 (depends on 17)

The method of claim 17 wherein the pharmaceutical composition is administered to the subject in 1 to about 4 dosage units per day.

### Claim 30 (depends on 31)

The method of claim 31 wherein the dosage units comprise capsules.