Methods of treating hypertriglyceridemia

• US 8,293,728 B2
• Filed: 01/12/2012
• Issued: 10/23/2012
• Est. Priority Date: 02/10/2009
• 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): SZNAIDMAN, MARCOS L
• Application Number:
  US13/349,153
• Publication Number:
  US 20120108659A1
• Time in Patent Office: 285 Days
• Field of Search: 514/183, 514/549, 424/451
• US Class Current: 514/183
• 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 31/397 having four-membered rings, e.g. azetidine
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: G16Z 99/00 Subject matter not provided for in other main groups of this subclass

Abstract

In various embodiments, the present invention provides methods of 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.

Claims

1. A method of reducing triglycerides in a subject having a fasting baseline triglyceride level of 500 mg/dl to about 1500 mg/dl who does not receive concurrent lipid altering therapy comprising:

administering orally to the subject about 4 g per day of a pharmaceutical composition comprising at least about 96%, by weight of all fatty acids present, ethyl eicosapentaenoate, and substantially no docosahexaenoic acid or its esters for a period of 12 weeks to effect a reduction in triglycerides without substantially increasing LDL-C compared to a second subject having a fasting baseline triglyceride level of 500 mg/dl to about 1500 mg/dl who has not received the pharmaceutical composition and a concurrent lipid altering therapy.

2. The method of claim 1, wherein the pharmaceutical composition is administered to the subject 1 to 4 times per day.

3. The method of claim 2 wherein, the pharmaceutical composition is present in one or more capsules.

4. The method of claim 1, wherein the subject and the second subject have one or more of:

a baseline fasting non-HDL-C of about 200 mg/dl to about 300 mg/dl, a baseline fasting total cholesterol of about 250 mg/dl to about 300 mg/dl, a baseline fasting VLDL-C of about 140 mg/dl to about 200 mg/dl, and/or a baseline fasting HDL-C of about 10 mg/dl to about 80 mg/dl.

5. The method of claim 4, comprising administering to the subject about 4 g of the pharmaceutical composition daily for the period of 12 weeks to effect a reduction in fasting non-HDL-C and a reduction in fasting VLDL-C compared to the second subject.

6. The method of claim 4, comprising administering to the subject about 4 g of the pharmaceutical composition daily for the period of 12 weeks to effect a reduction in fasting triglycerides of at least about 25% compared to the second subject.

7. The method of claim 4, comprising administering to the subject about 4 g of said pharmaceutical composition daily for the period of 12 weeks, to effect a reduction in fasting Lp-PLA2 of at least 10% compared to the second subject.

15. The method of claim 1, wherein the subject and the second subject consume a Western diet.

16. The method of claim 1, wherein no fatty acid of the pharmaceutical composition, except for ethyl-EPA, comprises more than about 0.6% by weight of all fatty acids combined.

8. A method of reducing triglycerides in a subject having a fasting baseline triglyceride level of 500 mg/dl to about 1500 mg/dl who does not receive concurrent lipid altering therapy comprising, administering to the subject, about 4 g per day of a pharmaceutical composition comprising at least about 96%, by weight of all fatty acids present, ethyl eicosapentaenoate and substantially no docosahexaenoic acid or its esters for a period of 12 weeks to effect a reduction in fasting triglycerides of at least about 15% without substantially increasing LDL-C compared to a second subject having fasting triglyceride of 500 mg/dl to about 1500 who has not received the pharmaceutical composition and concurrent lipid altering therapy.

9. The method of claim 8, wherein the pharmaceutical composition is administered to the subject 1 to 4 times per day.

10. The method of claim 9, wherein the pharmaceutical composition is present in one or more capsules.

11. The method of claim 8, wherein the subject and the second subject have one or more of:

a baseline fasting non-HDL-C of about 200 mg/dl to about 300 mg/dl, a baseline total cholesterol of about 250 mg/dl to about 300 mg/dl, a baseline fasting VLDL-C of about 140 mg/dl to about 200 mg/dl, and/or a baseline fasting HDL-C of about 10 mg/dl to about 80 mg/dl.

12. The method of claim 11, comprising administering to the subject about 4 g of the pharmaceutical composition daily for the period of 12 weeks to effect a reduction in fasting non-HDL-C and a reduction in fasting VLDL-C compared to the second subject.

13. The method of claim 8, comprising administering to the subject about 4 g of the pharmaceutical composition daily for the period of 12 weeks to effect a reduction in fasting triglycerides of at least about 25%.

14. The method of claim 11, comprising:

administering to the subject about 4 g of the pharmaceutical composition daily for the period of 12 weeks to effect a reduction in fasting Lp-PLA2 of at least 10% compared to the second subject.

17. The method of claim 8, wherein the subject and the second subject consume a Western diet.

18. The method of claim 8, wherein no fatty acid of the pharmaceutical composition, except for ethyl-EPA, comprises more than about 0.6% by weight of all fatty acids combined.

19. A method of lowering triglycerides in a subject having a fasting baseline triglyceride level of about 500 mg/dl to about 1500 mg/dl, who does not receive a concurrent lipid altering therapy comprising:

administering orally to the subject about 4 g per day of a pharmaceutical composition comprising at least about 96%, by weight of all fatty acids present, ethyl eicosapentaenoate and substantially no docosahexaenoic acid or its esters for a period of at least 12 weeks that is effective to reduce in a first patient population receiving 4 g per day of said composition without concurrent lipid altering therapy and having said baseline triglyceride level, a median triglyceride level by at least 5% without substantially increasing LDL-C, compared to a median triglyceride level and LDL-C level observed in a second patient population having said baseline triglyceride level who has not received the pharmaceutical composition and concurrent lipid altering therapy.