Claims for Patent: 9,713,642

Summary for Patent: 9,713,642

Title:	Itraconazole compositions and dosage forms, and methods of using the same
Abstract:	The disclosure relates to, among other things, pharmaceutical compositions, such as solid oral dosage forms, comprising itraconazole, methods of making the compositions, and methods of using the same for treating disorders including, but not limited to, fungal infections.
Inventor(s):	Mudge; Stuart James (Northcote, AU), Hayes; David (Rostrevor, AU), Lukas; Stefan (Manningham, AU)
Assignee:	MAYNE PHARMA INTERNATIONAL PTY. LTD. (Salisbury South, AU)
Application Number:	14/882,662
Patent Claims:	1. A method of treating a disease or condition in a subject, comprising administering to the subject an oral pharmaceutical composition comprising itraconazole and one or more pharmaceutically acceptable polymers, wherein the composition exhibits an AUC.sub.04 selected from the group consisting of: (a) an AUC.sub.0-t which is 80% to 125% of about 10 h*ng/ml to about 18.5 h*ng/ml per milligram of itraconazole following administration of the composition to the subject under fed conditions, (b) an AUC.sub.0-t which is 80% to 125% of about 6.9 h*ng/ml to about 13.8 h*ng/ml per milligram of itraconazole following administration of the composition to the subject under fasting conditions, (c) an AUC.sub.0-t which is 80% to 125% of about 8.8 h*ng/ml to about 14.8 h*ng/ml per milligram of itraconazole following administration of the composition to the subject under fed conditions, and (d) an AUC.sub.0-t which is 80% to 125% of about 7.0 h*ng/ml to about 12.4 h*ng/ml per milligram of itraconazole following administration of the composition to the subject under fasting conditions. 2. The method of claim 1, wherein the oral pharmaceutical composition is in solid dosage form. 3. The method of claim 2, wherein the oral pharmaceutical composition comprises one or more unit dosage forms. 4. The method of claim 1, wherein the disease or condition is fungal infection or cancer. 5. The method of claim 4, wherein the fungal infection is selected from the group consisting of onychomycosis, dermatomycoses, pityriasis versicolour, candidiasis, aspergillosis, and histoplasmosis. 6. The method of claim 4, wherein the cancer is prostate cancer, skin cancer, or lung cancer. 7. The method of claim 3, wherein the composition comprises about 65 mg of itraconazole in each unit dosage form and wherein the composition exhibits an AUC.sub.0-t which is 80% to 125% of about 650 h*ng/ml to about 1200 h*ng/ml following administration of the composition to the subject under fed conditions, and the composition under fed conditions is therapeutically similar to a composition containing about 100 mg of itraconazole, sugar spheres, hydroxypropyl methyl cellulose, and polyethylene glycol in a capsule shell, under fed conditions. 8. The method of claim 7, wherein the composition exhibits a C.sub.max which is 80% to 125% of about 65 ng/ml to about 100 ng/ml following administration of the composition to the subject under fed conditions. 9. The method of claim 7, wherein the composition under fasting conditions is therapeutically similar to a composition containing about 100 mg of itraconazole, sugar spheres, hydroxypropyl methyl cellulose, and polyethylene glycol in a capsule shell, under fed conditions. 10. The method of claim 1, wherein the composition comprises about 65 mg of itraconazole and wherein the composition exhibits an AUC.sub.0-t which is 80% to 125% of about 450 h*ng/ml to about 900 h*ng/ml following administration of the composition to the subject under fasting conditions, and the composition under fed conditions is therapeutically similar to a composition containing about 100 mg of itraconazole, sugar spheres, hydroxypropyl methyl cellulose, and polyethylene glycol in a capsule shell, under fed conditions. 11. The method of claim 1, wherein the composition exhibits an AUC.sub.0-t which is 80% to 125% of about 650 h*ng/ml to about 1200 h*ng/ml following administration of the composition to the subject under fed conditions. 12. The method of claim 7, wherein the composition exhibits a ratio in the range from about 0.70 to about 1.43 for AUC.sub.0-t between the oral pharmaceutical composition and a composition containing about 100 mg of itraconazole, sugar spheres, hydroxypropyl methyl cellulose, and polyethylene glycol in a capsule shell, with the 90% confidence interval. 13. The method of claim 3, wherein the composition comprises about 50 mg of itraconazole in each unit dosage form and wherein the composition exhibits an AUC.sub.0-t which is 80% to 125% of about 440 h*ng/ml to about 740 h*ng/ml following administration of the composition to the subject under fed conditions, and the composition under fed conditions is therapeutically similar to a composition containing about 100 mg of itraconazole, sugar spheres, hydroxypropyl methyl cellulose, and polyethylene glycol in a capsule shell, under fed conditions. 14. The method of claim 13, wherein the composition exhibits a C.sub.max which is 80% to 125% of about 60 ng/ml to about 75 ng/ml following administration of the composition to the subject under fed conditions. 15. The method of claim 1, wherein the composition exhibits reduced food effect as compared to a composition containing about 100 mg of itraconazole, sugar spheres, hydroxypropyl methyl cellulose, and polyethylene glycol in a capsule shell. 16. The method of claim 13, wherein the composition exhibits reduced intra-subject variability for the AUC.sub.0-t, C.sub.max, or T.sub.max as compared to a composition containing about 100 mg of itraconazole, sugar spheres, hydroxypropyl methyl cellulose, and polyethylene glycol in a capsule shell. 17. The method of claim 13, wherein the composition under fasting conditions is therapeutically similar to a composition containing about 100 mg of itraconazole, sugar spheres, hydroxypropyl methyl cellulose, and polyethylene glycol in a capsule shell, under fed conditions. 18. The method of claim 13, wherein the composition exhibits a ratio in the range from about 0.70 to about 1.43 for AUC.sub.0-t between the oral pharmaceutical composition and a composition containing about 100 mg of itraconazole, sugar spheres, hydroxypropyl methyl cellulose, and polyethylene glycol in a capsule shell, with the 90% confidence interval. 19. The method of claim 13, wherein the composition, upon administration under fed conditions, exhibits a relative bioavailability (F.sub.rel) of greater than about 150% relative to a composition containing about 100 mg of itraconazole, sugar spheres, hydroxypropyl methyl cellulose, and polyethylene glycol in a capsule shell, under fed conditions. 20. The method of claim 1, wherein the composition comprises about 50 mg of itraconazole and wherein the composition exhibits an AUC.sub.0-t which is 80% to 125% of about 350 h*ng/ml to about 620 h*ng/ml following administration of the composition to the subject under fasting conditions, and the composition under fed conditions is therapeutically similar to a composition containing about 100 mg of itraconazole, sugar spheres, hydroxypropyl methyl cellulose, and polyethylene glycol in a capsule shell, under fed conditions. 21. The method of claim 20, wherein the composition exhibits a C.sub.max which is 80% to 125% of about 30 ng/ml to about 60 ng/ml following administration of the composition to the subject under fasting conditions. 22. The method of claim 20, wherein the composition exhibits reduced intra-subject variability for the AUC.sub.0-t, C.sub.max, or T.sub.max as compared to a composition containing about 100 mg of itraconazole, sugar spheres, hydroxypropyl methyl cellulose, and polyethylene glycol in a capsule shell. 23. The method of claim 20, wherein the composition under fasting conditions is therapeutically similar to a composition containing about 100 mg of itraconazole, sugar spheres, hydroxypropyl methyl cellulose, and polyethylene glycol in a capsule shell, under fed conditions. 24. The method of claim 20, wherein the composition exhibits a ratio in the range from about 0.70 to about 1.43 for AUC.sub.0-t between the oral pharmaceutical composition and a composition containing about 100 mg of itraconazole, sugar spheres, hydroxypropyl methyl cellulose, and polyethylene glycol in a capsule shell, with the 90% confidence interval. 25. The method of claim 20, wherein the composition exhibits an AUC which is 80% to 125% of about 440 h*ng/ml to about 740 h*ng/ml following administration of the composition to a subject under fed conditions. 26. The method of claim 20, wherein the composition exhibits a C.sub.max which is 80% to 125% of about 60 ng/ml to about 75 ng/ml following administration of the composition to a subject under fed conditions. 27. The method of claim 1, wherein the composition comprises exhibits an AUC.sub.0-t which is 80% to 125% of about 8.8 h*ng/ml to about 14.8 h*ng/ml per milligram of itraconazole following administration of the composition to the subject under fed conditions, and the composition under fed conditions is therapeutically similar to a composition containing about 100 mg of itraconazole, sugar spheres, hydroxypropyl methyl cellulose, and polyethylene glycol in a capsule shell, under fed conditions. 28. The method of claim 27, wherein the composition exhibits a C.sub.max which is 80% to 125% of about 1.2 ng/ml to about 1.5 ng/ml per milligram of itraconazole following administration of the composition to the subject under fed conditions. 29. The method of claim 27, wherein the composition exhibits reduced food effect as compared to a composition containing about 100 mg of itraconazole, sugar spheres, hydroxypropyl methyl cellulose, and polyethylene glycol in a capsule shell. 30. The method of claim 27, wherein the composition exhibits reduced intra-subject variability for the AUC.sub.0-t, C.sub.max, or T.sub.max as compared to a composition containing about 100 mg of itraconazole, sugar spheres, hydroxypropyl methyl cellulose, and polyethylene glycol in a capsule shell. 31. The method of claim 27, wherein the composition under fasting conditions is therapeutically similar to a composition containing about 100 mg of itraconazole, sugar spheres, hydroxypropyl methyl cellulose, and polyethylene glycol in a capsule shell, under fed conditions. 32. The method of claim 27, wherein the composition exhibits a ratio in the range from about 0.70 to about 1.43 for AUC.sub.0-t between the oral pharmaceutical composition and a composition containing about 100 mg of itraconazole, sugar spheres, hydroxypropyl methyl cellulose, and polyethylene glycol in a capsule shell, with the 90% confidence interval. 33. The method of claim 27, wherein the composition, upon administration under fed conditions, exhibits a relative bioavailability (F.sub.rel) of greater than about 150% relative to a composition containing about 100 mg of itraconazole, sugar spheres, hydroxypropyl methyl cellulose, and polyethylene glycol in a capsule shell, under fed conditions. 34. The method of claim 1, wherein the composition exhibits an AUC.sub.0-t which is 80% to 125% of about 7.0 h*ng/ml to about 12.4 h*ng/ml per milligram of itraconazole following administration of the composition to the subject under fasting conditions, and the composition under fed conditions is therapeutically similar to a composition containing about 100 mg of itraconazole, sugar spheres, hydroxypropyl methyl cellulose, and polyethylene glycol in a capsule shell, under fed conditions. 35. The method of claim 34, wherein the composition exhibits a C.sub.max which is 80% to 125% of about 1.2 ng/ml to about 1.5 ng/ml per milligram of itraconazole following administration of the composition to the subject under fasting conditions. 36. The method of claim 34, wherein the composition exhibits reduced food effect as compared to a composition containing about 100 mg of itraconazole, sugar spheres, hydroxypropyl methyl cellulose, and polyethylene glycol in a capsule shell. 37. The method of claim 34, wherein the composition exhibits reduced intra-subject variability for the AUC.sub.0-t, C.sub.max, or T.sub.max as compared to a composition containing about 100 mg of itraconazole, sugar spheres, hydroxypropyl methyl cellulose, and polyethylene glycol in a capsule shell. 38. The method of claim 34, wherein the composition under fasting conditions is therapeutically similar to a composition containing about 100 mg of itraconazole, sugar spheres, hydroxypropyl methyl cellulose, and polyethylene glycol in a capsule shell, under fed conditions. 39. The method of claim 34, wherein the composition exhibits a ratio in the range from about 0.70 to about 1.43 for AUC.sub.0-t between the oral pharmaceutical composition and a composition containing about 100 mg of itraconazole, sugar spheres, hydroxypropyl methyl cellulose, and polyethylene glycol in a capsule shell, with the 90% confidence interval. 40. The method of claim 34, wherein the composition, upon administration under fed conditions, exhibits a relative bioavailability (F.sub.rel) of greater than about 150% relative to a composition containing about 100 mg of itraconazole, sugar spheres, hydroxypropyl methyl cellulose, and polyethylene glycol in a capsule shell, under fed conditions. 41. The method of claim 10, wherein the composition exhibits a C.sub.max which is 80% to 125% of about 36 ng/ml to about 70 ng/ml following administration of the composition to a subject under fasting conditions. 42. The method of claim 4, wherein the composition exhibits an AUC/MIC ratio of greater than 25, under the fed and fasting conditions. 43. The method of claim 1, wherein the oral pharmaceutical composition comprises about 50 mg to about 65 mg of itraconazole, and the composition exhibits an AUC.sub.0-t which is selected from the group consisting of: (a) 80% to 125% of about 650 h*ng/ml to about 1200 h*ng/ml following administration of the composition to the subject under fed conditions, (b) 80% to 125% of about 450 h*ng/ml to about 900 h*ng/ml following administration of the composition to the subject under fasting conditions, (c) 80% to 125% of about 440 h*ng/ml to about 740 h*ng/ml following administration of the composition to the subject under fed conditions, and (d) 80% to 125% of about 350 h*ng/ml to about 620 h*ng/ml following administration of the composition to the subject under fasting conditions.