FORMULATIONS COMPRISING IBRUTINIB

• US 20150140085A1
• Filed: 06/26/2013
• Published: 05/21/2015
• Est. Priority Date: 06/29/2012
• Status: Abandoned Application

• Current Assignee: Principia Biopharma Inc. (Sanofi )
• Original Assignee: Principia Biopharma Inc. (Sanofi )
• Inventors: Goldstein, David Michael
• Application Number:
  US14/403,927
• Publication Number:
  US 20150140085A1
• Time in Patent Office: Days
• US Class Current: 424/452
• 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 31/4184 condensed with carbocyclic rings, e.g. benzimidazoles
• CPC Class Codes: A61K 31/454 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• CPC Class Codes: A61K 9/2846 Poly(meth)acrylates
• CPC Class Codes: A61K 9/2866 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/4808 characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release capsules filled with granules or microparticles A61K9/16; filled with microcapsules or coated microparticles A61K9/50; with mixture of different granules, microcapsules, (coated) microparticles A61K9/5084
• CPC Class Codes: A61K 9/4825 Proteins, e.g. gelatin gelatin capsule shells with substantial amounts of other macromolecular substances A61K9/4816
• CPC Class Codes: A61K 9/4833 Encapsulating processes; Filling of capsules mechanical aspects A61J3/07
• CPC Class Codes: A61K 9/4875 Compounds of unknown constitution, e.g. material from plants or animals oils, fats, waxes, shellac A61K9/4858
• CPC Class Codes: A61K 9/4891 Coated capsules; Multilayered drug free capsule shells with drug coating for immediate release A61K9/4808; osmotic devices A61K9/0004
• CPC Class Codes: A61K 9/5026 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/5078 with drug-free core

Abstract

Oral pharmaceutical formulations of ibrutinib and/or a pharmaceutically acceptable salt thereof, methods for their administration, process of their production, and use of these formulations for the treatment of diseases treatable by ibrutinib such as cancer, inflammatory diseases, and autoimmune diseases.

Claims

1. A solid oral dosage form comprising:

(i) ibrutinib and/or a pharmaceutically acceptable salt thereof;

(ii) means for release of said ibrutinib and/or said pharmaceutically acceptable salt thereof in the intestine; and

(iii) at least one pharmaceutically acceptable excipient.

9. The solid oral dosage form of any of claims 1 to 8 wherein said solid oral dosage form contains from about 20 mg to about 450 mg of said ibrutinib and/or said pharmaceutically acceptable salt thereof.

10. The solid oral dosage form of any of claims 1 to 8 wherein said solid oral dosage form contains from about 20 mg to about 420 mg of said ibrutinib and/or said pharmaceutically acceptable salt thereof.

11. The solid oral dosage form of any of claims 1 to 8 wherein said solid oral dosage form contains from about 20 mg to about 300 mg of said ibrutinib and/or said pharmaceutically acceptable salt thereof.

12. The solid oral dosage form of any of claims 1 to 8 wherein said solid oral dosage form contains from about 50 mg to about 220 mg of said ibrutinib and/or said pharmaceutically acceptable salt thereof.

13. The solid oral dosage form of any of claims 1 to 12 wherein said solid oral dosage form is chosen from tablets and capsules.

14. The solid oral dosage form of any of claims 1 to 13 wherein said at least one pharmaceutically acceptable excipient is chosen from binders, surfactants, diluents, buffering agents, antiadherents, glidants, polymers, retardants, disintegrants, antioxidants, antifoaming agents, fillers, flavors, colors, lubricants, sorbents, preservatives, plasticizers, and sweeteners.

19. A method of increasing oral bioavailability of ibrutinib and/or a pharmaceutically acceptable salt thereof in a patient in recognized need thereof, which method comprises administering said ibrutinib and/or said pharmaceutically acceptable salt thereof to said patient a solid oral dosage form of any of claims 1 to 18.

2. A solid oral dosage form comprising:

(i) ibrutinib and/or a pharmaceutically acceptable salt thereof;

(ii) means for increasing oral bioavailability, as measured by the area under the curve (AUC), of said ibrutinib or said pharmaceutically acceptable salt thereof as compared to the oral bioavailability obtained from an immediate release solid oral dosage form comprising the same dose of said ibrutinib and/or said pharmaceutically acceptable salt thereof; and

(iii) at least one pharmaceutically acceptable excipient.

3. A solid oral dosage form comprising:

(i) ibrutinib and/or a pharmaceutically acceptable salt thereof;

(ii) at least one coating chosen from enteric coatings and non-enteric time-delayed release coatings; and

(ii) at least one pharmaceutically acceptable excipient.

4. The solid oral dosage form of claim 3 wherein said dosage form is coated with said at least one coating chosen from enteric coatings and non-enteric time-delayed release coatings.

5. The solid oral dosage form of claim 3 wherein said ibrutinib and/or said pharmaceutically acceptable salt thereof is coated with at least one coating chosen from enteric coatings and non-enteric time-delayed release coatings.

6. The solid oral dosage form of any of claims 3 to 5 wherein the said at least one coating is chosen from enteric coatings.

7. The solid oral dosage form of claim 6 wherein the said enteric coatings are chosen from polymeric coatings.

8. The solid oral dosage form of claim 7 wherein the said polymeric coatings are chosen from polymethacrylates, cellulose-based polymers, and polyvinyl derivatives.

15. A solid oral dosage form comprising:

(i) about 20 mg to about 450 mg of ibrutinib and/or a pharmaceutically acceptable salt thereof;

(ii) at least one coating chosen from an enteric coating and a non-enteric time-delayed release coating; and

(iii) at least one pharmaceutically acceptable excipient;

wherein said oral dosage form increases the oral bioavailability, as measured by the area under the curve (AUC), of said ibrutinib or said pharmaceutically acceptable salt thereof by at least 20% as compared to the bioavailability obtained from an immediate release solid oral dosage form comprising the same dose of said ibrutinib and/or said pharmaceutically acceptable salt thereof.

16. The solid oral dosage form of claim 15 wherein said solid oral dosage form increases the oral bioavailability by at least 50%.

17. The solid oral dosage form of claim 15 wherein said solid oral dosage form increases the bioavailability by at least 75%.

18. The solid oral dosage form of claim 15 wherein said solid oral dosage form increases the bioavailability by at least 95%.

20. A method of treating a disease treatable by inhibition of a tyrosine kinase in a patient in recognized need thereof which method comprises administering to said patient, in single or multiple doses, a therapeutically effective amount of ibrutinib and/or a pharmaceutically acceptable salt thereof in a dosage form that releases said ibrutinib and/or said pharmaceutically acceptable salt thereof in the intestine.

21. The method of claim 20 wherein the tyrosine kinase is chosen from BLK, BMX, EGFR, HER2, HER4, ITK, TEC, BTK, and TXK.

22. The method of claim 20 wherein the tyrosine kinase is BTK.

23. The method of any of claims 20 to 22 wherein said ibrutinib and/or said pharmaceutically acceptable salt thereof is released in the small intestine.

24. The method of any of claims 20 to 23 wherein said therapeutically effective amount of said ibrutinib and/or said pharmaceutically acceptable salt thereof is from about 20 mg/day to about 450 mg/day.

25. The method of claim 24 wherein said therapeutically effective amount of said ibrutinib and/or said pharmaceutically acceptable salt thereof is from about 30 mg/day to about 300 mg/day.

26. The method of claim 24 wherein said therapeutically effective amount of said ibrutinib and/or said pharmaceutically acceptable salt thereof is from about 50 mg/day to about 220 mg/day.

27. The method of any of claims 20 to 26 wherein said solid dosage form comprises at least one coating chosen from enteric coatings and non-enteric time-delayed release coatings;

and at least one pharmaceutically acceptable excipient.

28. The method of claim 27 wherein said dosage form is coated with said at least one coating chosen from enteric coatings and non-enteric time-delayed release coatings

29. The method of claim 27 wherein said ibrutinib or said pharmaceutically acceptable salt thereof is coated with at least one coating chosen from enteric coatings and non-enteric time-delayed release coatings.

30. The method of any of claims 27 to 29 wherein the said at least one coating is chosen from an enteric coating.

31. The method of claim 30 wherein the said enteric coatings are polymeric coatings chosen from polymethacrylates, cellulose-based polymers, and polyvinyl derivatives.

32. The method of any of claims 20 to 31 wherein the disease is selected from an autoimmune disease, cancer and an inflammatory disease.

33. The method of any of claims 20 to 31, wherein the disease is leukemia or lymphoma.

34. The method of claim 33 wherein the leukemia is chosen from chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), multiple myeloma, mantle cell lymphoma, and B-cell non-Hodgkin lymphoma.

35. The method of any of claims 20 to 34 wherein said dosage form is administered in combination with at least one additional agent chosen from anti-inflammatory and antiproliferative agents.

36. The method of any of claims 20 to 34 wherein said dosage form is administered in combination with at least one additional agent chosen from of atumumab, bendamustine, and rituaximab.

37. The method of claim 35 or 36 wherein the combination administration is simultaneously or sequentially.

38. The method of any of claims 20 to 35 wherein said ibrutinib and/or said pharmaceutically acceptable salt thereof is released from said dosage form at or above about pH 5.