Compositions and methods for lowering levels of high-sensitivity C-reactive protein (HS-CRP) in a subject

• US 9,827,219 B2
• Filed: 01/07/2013
• Issued: 11/28/2017
• Est. Priority Date: 01/06/2012
• Status: Active Grant

• Current Assignee: Amarin Pharmaceuticals Ireland Limited (Amarin Corporation plc)
• Original Assignee: Amarin Pharmaceuticals Ireland Limited (Amarin Corporation plc)
• Inventors: Manku, Mehar, Osterloh, Ian, Wicker, Pierre, Braeckman, Rene, Soni, Paresh
• Primary Examiner(s): TRAN, SUSAN T
• Application Number:
  US13/735,660
• Publication Number:
  US 20130189355A1
• Time in Patent Office: 1,786 Days
• Field of Search: None
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/202 having three or more double bonds, e.g. linolenic eicosanoids, e.g. leukotrienes A61K31/557
• CPC Class Codes: A61K 31/232 having three or more double bonds, e.g. etretinate
• CPC Class Codes: A61K 31/366 having six-membered rings, e.g. delta-lactones
• CPC Class Codes: A61K 31/40 having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
• CPC Class Codes: A61K 31/505 Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
• CPC Class Codes: A61K 9/48 Preparations in capsules, e.g. of gelatin, of chocolate A61K9/0004 takes precedence; bite capsules A61K9/0056
• CPC Class Codes: A61K 9/4866 Organic macromolecular compounds
• CPC Class Codes: 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
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/06 Antiarrhythmics
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/12 Antihypertensives

Abstract

The present disclosure provides methods for treating and/or preventing cardiovascular-related disease and, in particular, a method of blood lipid therapy comprising administering to a subject in need thereof a pharmaceutical composition comprising eicosapentaenoic acid or a derivative thereof. In some embodiments, the method comprises lowering high sensitivity CRP (hs-CRP) levels in a subject including, for example, a subject with a HbA_1c value of about 5.00 %-8.50 % or at least about 6.8 %.

Claims

1. A method of lowering a high-sensitivity CRP (hs-CRP) level in a subject having a baseline HbA_1c, level of at least 6.8 %, the method comprising administering to the subject daily a pharmaceutical composition comprising about 3.5 g to about 4 g of eicosapentaenoic acid or a derivative thereof for a period of time effective to lower the hs-CRP level and maintain or improve glycemic control in the subject.

2. The method of claim 1, wherein the subject has a baseline triglyceride level of about 150-499 mg/dl.

3. The method of claim 2, wherein the subject is on statin therapy or stable statin therapy.

4. The method of claim 1, wherein the pharmaceutical composition comprises at least 90%, by weight of all fatty acids present, ethyl eicosapentaenoate.

5. The method of claim 1, wherein the pharmaceutical composition is encapsulated in a capsule.

6. The method of claim 5, wherein the capsule comprises gelatin.

7. The method of claim 6, wherein 1 to 4 of said capsules are administered to the subject each day.

8. The method of claim 1, wherein the period of time is about 12 weeks and the hs-CRP level is lowered in the subject by at least about 5% compared to a placebo controlled subject who is on stable statin therapy and has not received the pharmaceutical composition.

9. The method of claim 8, wherein the hs-CRP level is reduced by at least about 10%, compared to the placebo controlled subject.

10. A method of lowering high-sensitivity CRP (hs-CRP) in a subject on stable statin therapy with a baseline HbA_1c, level of at least 6.8% and baseline triglycerides of about 150 to 499 mg/dl, the method comprising administering to the subject a pharmaceutical composition comprising about 3.5 to about 4 g of eicosapentaenoic acid or a derivative thereof for a period of about 12 weeks to reduce the hs-CRP level of the subject compared to baseline and maintain or improve glycemic control in the subject.

11. The method of claim 10 further comprising identifying a baseline HbA_1c, value of at least 6.8% in the subject before administering the pharmaceutical composition.

12. The method of claim 10 further comprising confirming a reduction in HbA_1c level of at least 5% after administering the pharmaceutical composition.

13. The method of claim 12, wherein the hsCRP level is reduced by at least 5% compared to a placebo controlled subject on stable statin therapy and having a baseline HbA_1c, value of at least 6.8% and baseline triglycerides of about 150-499 mg/dl who has not received the pharmaceutical composition.

14. The method of claim 13, wherein the statin is selected from the group consisting of atorvastatin, rosuvastatin and simvastatin.

15. The method of claim 14, wherein the subject and the placebo controlled subject are not on concomitant niacin or fibrate therapy.

16. The method of claim 13, wherein the subject and the placebo controlled subject have a baseline sitting systolic blood pressure less than or equal to about 160 mmHg and a baseline sitting diastolic blood pressure less than about 100 mmHg.

17. The method of claim 10, wherein the pharmaceutical composition comprises at least 90%, by weight of all fatty acids present, ethyl eicosapentaenoate.