Compositions comprising eicosapentaenoic acid and a hydroxyl compound and methods of use thereof

• US 9,855,240 B2
• Filed: 11/14/2016
• Issued: 01/02/2018
• Est. Priority Date: 02/19/2013
• Status: Active Grant

• Current Assignee: Amarin Pharmaceuticals Ireland Limited (Amarin Corporation plc)
• Original Assignee: Amarin Pharmaceuticals Ireland Limited (Amarin Corporation plc)
• Inventors: Zakrzewski, Joseph S.
• Primary Examiner(s): Henley, III, Raymond J
• Application Number:
  US15/350,312
• Publication Number:
  US 20170119721A1
• Time in Patent Office: 414 Days
• Field of Search: 514560
• 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 31/045 Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
• CPC Class Codes: A61K 31/047 having two or more hydroxy groups, e.g. sorbitol
• CPC Class Codes: A61K 31/10 Sulfides; Sulfoxides; Sulfones
• CPC Class Codes: A61K 31/145 having sulfur, e.g. thiurams (>N—C(S)—S—C(S)—N< and >N—C(S)—S—S—C(S)—N<), Sulfinylamines (—N=SO), Sulfonylamines (—N=SO2) isothiourea A61K31/155
• CPC Class Codes: A61K 31/19 Carboxylic acids, e.g. valproic acid salicylic acid A61K31/60
• CPC Class Codes: A61K 31/194 having two or more carboxyl groups, e.g. succinic, maleic or phthalic acid
• 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 31/22 of acyclic acids, e.g. pravastatin
• CPC Class Codes: A61K 31/232 having three or more double bonds, e.g. etretinate
• CPC Class Codes: A61K 31/275 Nitriles; Isonitriles
• CPC Class Codes: A61K 31/351 not condensed with another ring
• CPC Class Codes: A61K 31/365 Lactones
• CPC Class Codes: A61K 31/366 having six-membered rings, e.g. delta-lactones
• CPC Class Codes: A61K 31/41 having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
• CPC Class Codes: A61K 31/4166 having oxo groups directly attached to the heterocyclic ring, e.g. phenytoin
• CPC Class Codes: A61K 31/42 Oxazoles
• CPC Class Codes: A61K 31/4365 the heterocyclic ring system having sulfur as a ring hetero atom, e.g. ticlopidine
• CPC Class Codes: A61K 31/683 Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols

Abstract

The present invention relates to, inter alia, pharmaceutical compositions comprising a polyunsaturated fatty acid and to methods of using the same to treat or prevent cardiovascular-related diseases.

Claims

1. A composition comprising a hydroxyl compound and eicosapentaenoate or a pharmaceutically acceptable salt or ester thereof, wherein the hydroxyl compound is:

a compound of Formula I;

2. The composition of claim 1, wherein the composition comprises at least about 80%, by weight of all fatty acids present, eicosapentaenoate or a pharmaceutically acceptable salt or ester thereof.

3. The composition of claim 1, wherein the hydroxyl compound is present in an amount less than, about equal to, or greater than an effective amount of the hydroxyl compound when administered as a monotherapy.

4. The composition of claim 1, wherein the hydroxyl compound is present in an amount of about 5 mg to about 2000 mg.

5. The composition of claim 1, wherein the eicosapentaenoate or a pharmaceutically acceptable salt or ester thereof is present in an amount of about 400 mg to about 5000 mg.

6. The composition of claim 1, wherein the hydroxyl compound is dispersed or suspended in the eicosapentaenoate or a pharmaceutically acceptable salt or ester thereof.

7. The composition of claim 1, wherein the hydroxyl compound is 8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid.

8. A method of treating a cardiovascular-related disease or disorder in a subject comprising administering to the subject a composition comprising a hydroxyl compound and a composition comprising at least about 80%, by weight of all fatty acids present, eicosapentaenoate or a pharmaceutically acceptable salt or ester thereof, wherein the hydroxyl compound is:

a compound of Formula I;

9. The method of claim 8, wherein the cardiovascular-related disease or disorder is hyperlipidemia or homozygous familial hypercholesterolemia (HoFH).

10. The method of claim 8, wherein the subject has a baseline fasting triglyceride level of about 200 mg/dl to about 499 mg/dl.

11. The method of claim 9, wherein the subject is on statin therapy.

12. The method of claim 8, wherein the subject has a baseline fasting triglyceride level of at least about 500 mg/dl.

13. The method of claim 8, wherein the subject is administered the composition for a period of time to effect a reduction in triglyceride levels of at least about 5%.

14. The method of claim 13, wherein the reduction is in comparison to baseline, to placebo control or to a second subject or subject group who has received eicosapentaenoate or a pharmaceutically acceptable salt or ester thereof but not the hydroxyl compound.

15. The method of claim 13, wherein the reduction is in comparison to a second subject or subject group who has received the hydroxyl compound but not eicosapentaenoate or a pharmaceutically acceptable salt or ester thereof.

16. The method of claim 8, wherein the composition comprising the hydroxyl compound and the composition comprising eicosapentaenoate or a pharmaceutically acceptable salt or ester thereof are present in a single dosage form.

17. The method of claim 8, wherein the hydroxyl compound is in a dosage form separate from the eicosapentaenoate or a pharmaceutically acceptable salt or ester thereof.

18. A method of treating a cardiovascular-related disease or disorder in a subject receiving therapy including a hydroxyl compound, the method comprising administering to the subject a composition comprising at least about 80%, by weight of all fatty acids present, eicosapentaenoate or a pharmaceutically acceptable salt or ester thereof, wherein the hydroxyl compound is:

a compound of Formula I;

19. The method of claim 18, wherein the subject is administered the composition for a period of time to effect a reduction in triglyceride levels of at least about 5%.

20. The method of claim 19, wherein the reduction is in comparison to baseline, to placebo control, to a second subject or subject group who has received eicosapentaenoate but not the hydroxyl compound, or to a second subject or subject group who has received the hydroxyl compound but not eicosapentaenoate or a pharmaceutically acceptable salt or ester thereof.