Methods of treating, reducing the incidence of, and/or preventing ischemic events

• US 8,680,052 B1
• Filed: 05/29/2013
• Issued: 03/25/2014
• Est. Priority Date: 03/09/2013
• Status: Active Grant

• Current Assignee: Chiesi Farmaceutici SPA (Valline Srl)
• Original Assignee: Medicines Company (Novartis Ag)
• Inventors: Arculus-Meanwell, Clive Arthur, Skerjanec, Simona, Prats, Jayne, Schneider, David J.
• Primary Examiner(s): Tsang, Cecilia J
• Assistant Examiner(s): Lee, Li
• Application Number:
  US13/904,778
• Time in Patent Office: 300 Days
• Field of Search: None
• US Class Current: 514/14.7
• 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 31/4365 the heterocyclic ring system having sulfur as a ring hetero atom, e.g. ticlopidine
• CPC Class Codes: A61K 31/7076 containing purines, e.g. adenosine, adenylic acid
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/02 Inorganic compounds
• CPC Class Codes: 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
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/19 lyophilised , i.e. freeze-dried, solutions or dispersions lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00

Abstract

Methods of treating, reducing the incidence of, and/or preventing an ischemic event in a patient undergoing percutaneous coronary intervention (PCI), comprising administering to the patient a pharmaceutical composition comprising cangrelor. The method may further comprise administering an additional therapeutic agent to the patient, the additional therapeutic agent comprising a P2Y₁₂ inhibitor. Pharmaceutical compositions useful for treating, reducing the incidence of, and/or preventing an ischemic event in a patient undergoing PCI. The pharmaceutical compositions comprise cangrelor. Methods of preparing a pharmaceutical composition for treating, reducing the incidence of, and/or preventing an ischemic event in a patient undergoing PCI, comprising admixing cangrelor with one or more pharmaceutically acceptable excipients. An ischemic event may include stent thrombosis, myocardial infarction, ischemia-driven revascularization, and mortality.

Claims

1. A method of transitioning a patient from administration of cangrelor during percutaneous coronary intervention (PCI) to administration of ticagrelor for chronic treatment, the method comprising:

(1) administering intravenously a 30 μ

g/kg bolus of cangrelor before the start of PCI;

(2) administering intravenously a 4 μ

g/kg/min continuous infusion of cangrelor after administration of the bolus;

(3) continuing the administration of the continuous infusion for the longer of (a) at least two hours, or (b) the duration of PCI; and

(4) administering an oral dose of ticagrelor either (a) during administration of the continuous infusion, or (b) after discontinuation of the administration of the continuous infusion, wherein the oral dose comprises a 180 mg loading dose of ticagrelor.

2. The method of claim 1, wherein the patient received oral P2Y₁₂ therapy prior to the administration of cangrelor without attenuation of the effect of cangrelor.

3. The method of claim 2, wherein the oral P2Y₁₂ therapy is selected from the group consisting of clopidogrel, prasugrel, and ticagrelor.

4. The method of claim 1, wherein cangrelor is in a pharmaceutical composition comprising 200 μ

g/mL of cangrelor.

5. The method of claim 4, wherein the pharmaceutical composition further comprises sodium chloride injection 0.9% or 5% dextrose injection.

6. The method of claim 1, wherein the bolus is administered in less than one minute.

7. The method of claim 1, wherein the continuous infusion is continued for a total duration of up to about four hours.

8. The method of claim 1, wherein the method further comprises administering one or more oral doses of ticagrelor subsequent to the loading dose.

9. The method of claim 8, wherein the one or more subsequent oral doses comprise 90 mg of ticagrelor.

10. The method of claim 1, wherein the administration of the continuous infusion is started immediately after the administration of the bolus.

11. The method of claim 1, wherein the method further comprises administering aspirin before or during administration of the continuous infusion.

12. A method of transitioning a patient from administration of cangrelor during percutaneous coronary intervention (PCI) to administration of ticagrelor for chronic treatment, the method comprising:

(1) administering intravenously a 30 μ

g/kg bolus of cangrelor before the start of PCI;

(2) administering intravenously a 4 μ

g/kg/min continuous infusion of cangrelor after administration of the bolus;

(3) continuing the administration of the continuous infusion of cangrelor for the longer of (a) at least two hours, or (b) the duration of PCI; and

(4) administering an oral dose of ticagrelor during administration of the continuous infusion, wherein the oral dose comprises a 180 mg loading dose of ticagrelor.

13. The method of claim 12, wherein the patient received oral P2Y₁₂ therapy prior to the administration of cangrelor without attenuation of the effect of cangrelor.

14. The method of claim 13, wherein the oral P2Y₁₂ therapy is selected from the group consisting of clopidogrel, prasugrel, and ticagrelor.

15. The method of claim 12, wherein cangrelor is in a pharmaceutical composition comprising 200 μ

g/mL of cangrelor.

16. The method of claim 15, wherein the pharmaceutical composition further comprises sodium chloride injection 0.9% or 5% dextrose injection.

17. The method of claim 12, wherein the bolus is administered in less than one minute.

18. The method of claim 12, wherein the continuous infusion is continued for a total duration of up to about 4 hours.

19. The method of claim 12, wherein the method further comprises administering one or more oral doses of ticagrelor subsequent to the loading dose.

20. The method of claim 19, wherein the one or more subsequent oral doses comprise 90 mg of ticagrelor.

21. The method of claim 19, wherein the one or more subsequent oral doses continue after discontinuation of the administration of the continuous infusion.

22. A method of transitioning a patient from administration of cangrelor during percutaneous coronary intervention (PCI) to administration of ticagrelor for chronic treatment, the method comprising:

(1) administering intravenously a 30 μ

g/kg bolus of cangrelor before the start of PCI;

(2) administering intravenously a 4 μ

g/kg/min continuous infusion of cangrelor after administration of the bolus;

(3) continuing the administration of the continuous infusion for the longer of (a) at least two hours, or (b) the duration of PCI; and

(4) administering an oral dose of ticagrelor after discontinuation of the administration of the continuous infusion, wherein the oral dose comprises a 180 mg loading dose of ticagrelor.

23. The method of claim 22, wherein the patient received oral P2Y₁₂ therapy prior to the administration of cangrelor without attenuation of the effect of cangrelor.

24. The method of claim 23, wherein the oral P2Y₁₂ therapy is selected from the group consisting of clopidogrel, prasugrel, and ticagrelor.

25. The method of claim 22, wherein cangrelor is in a pharmaceutical composition comprising 200 μ

g/mL of cangrelor.

26. The method of claim 25, wherein the pharmaceutical composition further comprises sodium chloride injection 0.9% or 5% dextrose injection.

27. The method of claim 22, wherein the bolus is administered in less than one minute.

28. The method of claim 22, wherein the continuous infusion is continued for a total duration of up to about 4 hours.

29. The method of claim 22, wherein the method further comprises administering one or more oral doses of ticagrelor subsequent to the loading dose.

30. The method of claim 29, wherein the one or more subsequent oral doses comprise 90 mg of ticagrelor.