Method of treating cardiovascular events using colchicine concurrently with an antiplatelet agent

• US 10,206,891 B2
• Filed: 07/28/2017
• Issued: 02/19/2019
• Est. Priority Date: 11/02/2012
• Status: Active Grant

• Current Assignee: Murray & Poole Enterprises, Ltd.
• Original Assignee: Murray & Poole Enterprises, Ltd.
• Inventors: Nidorf, Mark
• Primary Examiner(s): Reese, Heidi
• Application Number:
  US15/663,148
• Publication Number:
  US 20170326083A1
• Time in Patent Office: 571 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 31/165 having aromatic rings, e.g. colchicine, atenolol, progabide
• CPC Class Codes: A61K 31/37 Coumarins, e.g. psoralen
• CPC Class Codes: A61K 31/4365 the heterocyclic ring system having sulfur as a ring hetero atom, e.g. ticlopidine
• CPC Class Codes: A61K 31/616 by carboxylic acids, e.g. acetylsalicylic acid
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• 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

Abstract

Methods of treating and/or preventing a cardiovascular event in a patient, the method comprising orally administering a colchicine to a patient who is receiving concurrent treatment with at least one antiplatelet agent, thereby treating and/or preventing the cardiovascular event in the patient are provided.

Claims

1. A method of treating and/or reducing the risk of a cardiovascular event in a subject, the method comprising:

administering colchicine, a salt thereof, and/or any combination thereof to a subject at risk of a cardiovascular event or who has had a cardiovascular event;

wherein the cardiovascular event is acute coronary syndrome, out-of-hospital cardiac arrest, or noncardioembolic ischemic stroke.

2. The method of claim 1, wherein the composition is administered once per day.

3. The method claim 1, wherein about 0.5 to about 0.75 mg of colchicine, a salt thereof, and/or any combination thereof is administered to the subject.

4. The method of claim 3, wherein about 0.5 to 0.6 mg of colchicine, a salt thereof, and/or any combination thereof is administered to the subject.

5. The method of claim 3, wherein about 0.6 mg of colchicine, a salt thereof, and/or any combination thereof is administered to the subject.

6. The method of claim 1, wherein the composition is administered orally, topically, parenterally, ophthalmically, intraventricularly, intracranially, intraperitoneally, buccally, rectally, vaginally, intranasally, or by aerosol administration and/or inhalation spray.

7. The method of claim 1, wherein the composition is administered in the form of a tablet, capsule, liquid dose, gel, or powder.

8. The method claim 1, wherein the subject receives concurrent treatment with at least one anticoagulant agent or antithrombotic agent.

9. The method claim 8, wherein the anticoagulant agent is one or more of novel oral anticoagulants (NOACs), coumarins or vitamin K antagonists, heparin, low molecular weight heparin, a synthetic pentasaccharide inhibitor of factor Xa, a factor Xa inhibitor, a thrombin inhibitor, and an antithrombin protein therapeutic.

10. The method of claim 9, wherein:

(a) the NOAC is dabigatran, rivaroxaban, apixaban, or a combination thereof;

(b) wherein the coumarin or vitamin K antagonist is one or more of warfarin, acenocoumarol, phenprocoumon, atromentin, brodifacoum, and phenindione;

(c) wherein the factor Xa inhibitor is one or more of rivaroxaban, apixaban, edoxaban, and darexaban; and

/or

(d) wherein the thrombin inhibitor is one or more of hirudin, lepirudin, bivalirudin, and ximelagatrain.

11. The method of claim 8, wherein the antithrombotic agent is an antiplatelet agent or a thrombolytic agent.

12. The method of claim 11, wherein the antiplatelet agent, the anticoagulant agent, and/or the thrombolytic agent is aspirin.

13. The method of claim 11, wherein the antiplatelet agent is one or more of an irreversible cyclooxygenase inhibitor, an adenosine diphosphate (ADP) receptor inhibitor, a phosphodiesterase inhibitor, a protease-activated receptor-1 (PAR-1) antagonist, a glycoprotein inhibitor, an adenosine reuptake inhibitor, and a thromboxane inhibitor.

14. The method of claim 13, wherein:

(a) the irreversible cyclooxygenase inhibitor is aspirin and/or triflusal;

(b) the ADP receptor inhibitor is clopidogrel, prasugrel, ticagrelor, ticlopidine, or a combination thereof;

(c) the phosphodiesterase inhibitor is cilostazol;

(d) the PAR-1 antagonist is vorapaxar;

(e) the glycoprotein inhibitor is abciximab, eptifibatide, tirofiban, or a combination thereof;

(f) the adenosine reuptake inhibitor is dipyridamole; and

/or

(g) the thromboxane inhibitor is terutroban.

15. The method of claim 11, wherein the thrombolytic agent is tissue plasminogen activator (t-PA).

16. The method of claim 15, wherein the t-PA is alteplase, reteplase, tenecteplase, anistreplase, streptokinase, urokinase, or a combination thereof.

17. The method of claim 1, further comprising co-administering to the subject a therapeutically effective amount of a second agent for the treatment and/or reduction of risk of the cardiovascular event.

18. The method of claim 17, wherein the second agent is a statin.

19. The method of claim 18, wherein the statin is atorvastatin, fluvastatin, lovastatin, pitavastatin, rosuvastatin, simvastatin, pravastatin, any salt thereof, or any combination thereof.

20. The method of claim 1, wherein the subject exhibits the symptoms of or is diagnosed with a coronary disease.

21. The method of claim 20, wherein the coronary disease is a clinically stable coronary disease.

22. The method of claim 1, wherein the subject has the symptoms of or is diagnosed with atherosclerotic vascular disease.

23. The method of claim 22, wherein the subject is concurrently administered an agent for the treatment and/or reduction of the risk of an atherosclerotic vascular disease.

24. The method of claim 23, wherein the atherosclerotic vascular disease is a coronary disease.

25. The method of claim 24, wherein the coronary disease is a clinically stable coronary disease.

26. The method of claim 23, wherein the agent is a statin.

27. The method of claim 26, wherein the statin is atorvastatin, fluvastatin, lovastatin, pitavastatin, rosuvastatin, simvastatin, pravastatin, a salt thereof, or any combination thereof.

28. The method of claim 1, wherein the composition of colchicine is administered as an immediate release formulation.

29. The method of claim 1, wherein the composition is administered for at least two years.

30. A method of treating and/or reducing the risk of acute coronary syndrome, out-of-hospital cardiac arrest, and/or noncardioembolic ischemic stroke in a human subject administered at least one of an antiplatelet agent, an anticoagulant agent, and an thrombolytic agent, the method comprising administering about 0.5 mg to about 0.75 mg of colchicine, a salt thereof, and/or any combination thereof to the subject.

31. A method of treating and/or reducing the risk of a cardiovascular event, which comprises administering about 0.5 mg to about 0.75 mg of colchicine, a salt thereof, and/or any combination thereof to a human subject,

wherein the human subject is concurrently administered an antiplatelet agent, an anticoagulant agent, a thrombolytic agent, or any combination thereof;

wherein the cardiovascular event is acute coronary syndrome, cardiac arrest, or noncardio-embolic ischemic stroke;

wherein acute coronary syndrome is acute myocardial infarction or unstable angina;

wherein cardiac arrest is associated with asystole, ventricular tachycardia, or ventricular fibrillation; and

wherein noncardio-embolic ischemic stroke is not attributable to atrial fibrillation or intracranial hemorrhage.