Methods of treating pulmonary disorders with liposomal amikacin formulations
View Patent ↗Disclosed herein are methods of treating pulmonary disorders comprising administering to the patient an effective dose of a nebulized liposomal amikacin formulation for at least one treatment cycle, wherein: the treatment cycle comprises an administration period of 15 to 75 days, followed by an off period of 15 to 75 days; and the effective dose comprises 100 to 2500 mg of amikacin daily during the administration period.
1. A method for improving lung function in a human patient suffering from a Pseudomonas aeruginosa infection, the method comprising administering to the human patient an effective dose of a nebulized liposomal amikacin formulation for at least one treatment cycle,
wherein the at least one treatment cycle comprises an administration period of 20 to 35 days, followed by an off period of 25 to 75 days, during which an improvement in lung function is maintained for at least 15 days after the administration period ends,
wherein the improvement in lung function comprises an increase in Forced Expiratory Volume in one second (FEV 1 ) as compared to the human patient prior to the at least one treatment cycle, or an untreated human patient suffering from a Pseudomonas aeruginosa infection; and
wherein the lipid component of the liposome comprises dipalmitoylphosphatidylcholine (DPPC) and cholesterol, and the effective dose comprises 510 mg to 610 mg of amikacin daily during the administration period.
2. The method of claim 1 , wherein the treatment cycle is followed at least twice.
3. The method of claim 1 , wherein the administration period is about 28 days.
4. The method of claim 1 , wherein the off period is about 28 days.
5. The method of claim 1 , wherein the off period is 35 to 75 days.
6. The method of claim 1 , wherein the off period is 45 to 75 days.
7. The method of claim 1 , wherein the off period is about 56 days.
8. The method of claim 1 , wherein the administration period is about 28 days and the off period is about 28 days.
9. The method of claim 1 , wherein the administration period is about 28 days and the off period is about 56 days.
10. The method of claim 1 , wherein the Pseudomonas aeruginosa infection is a chronic Pseudomonas aeruginosa infection.
11. The method of claim 1 , wherein the human patient has a serum C max of amikacin of less than about 10 mcg/mL during the administration period.
12. The method of claim 1 , wherein the human patient has a sputum C max of amikacin of at least 1000 mcg per gram of sputum.
13. The method of claim 10 , wherein a sputum C max of amikacin is at least 1000 mcg per gram of sputum during the administration period.
14. The method of claim 10 , wherein a sputum C max of amikacin is at least 1000 mcg per gram of sputum for at least 15 days after the administration.
15. The method of claim 10 , wherein the human patient has a reduction in log 10 Colony Forming Unit (CFU) of the bacterial infection in the lungs of at least 0.5 for at least 15 days after the administration period ends.
16. The method of claim 15 , wherein the reduction in the log 10 Colony Forming Unit (CFU) is at least 1.0.
17. The method of claim 1 , wherein the improvement further comprises an increase in blood oxygen saturation in the human patient.
18. The method of claim 1 , wherein the human patient has a Forced Expiratory Volume in one second (FEV 1 ) that is increased by at least 5% over the Forced Expiratory Volume in one second (FEV 1 ) prior to the treatment cycle.
19. The method of claim 1 , wherein the Forced Expiratory Volume in one second (FEV 1 ) is increased by about 5 to about 50%.
20. The method of claim 1 , wherein the Forced Expiratory Volume in one second (FEV 1 ) of the human patient is increased by about 25 to about 500 mL over the Forced Expiratory Volume in one second (FEV 1 ) prior to the treatment cycle.
21. The method of claim 17 , wherein the blood oxygen saturation is increased by at least 1% over blood oxygen saturation prior to the at least one treatment cycle.
22. The method of claim 1 , wherein a time to pulmonary exacerbation in the patient is about 20 days or longer.
23. The method of claim 1 , wherein a time to rescue treatment in the patient is about 20 days or longer.
24. The method of claim 1 , wherein the lipid component to amikacin ratio is about 0.3:1 to about 1.0:1 by weight.
25. The method of claim 24 , wherein the lipid component to amikacin ratio is about 0.5:1 to about 0.7:1 by weight.
26. The method of claim 24 , wherein the lipid component to amikacin ratio is about 0.6:1 by weight.
27. The method of claim 1 , wherein the liposomal amikacin formulation comprises dipalmitoylphosphatidylcholine (DPPC) and cholesterol in about a 2 to 1 ratio by weight.
28. The method of claim 27 , wherein the liposomal amikacin formulation has a lipid component to amikacin ratio of about 0.3:1 to about 1.0:1 by weight.
29. The method of claim 28 , wherein the lipid component to amikacin ratio is about 0.5:1 to about 0.7:1 by weight.
30. The method of claim 28 , wherein the lipid component to amikacin ratio is about 0.6:1 by weight.
31. The method of claim 1 , wherein a time to pulmonary exacerbation in the human patient administered with the nebulized liposomal amikacin formulation is at least twice the time to pulmonary exacerbation in the untreated human patient.
32. A method for increasing blood oxygen saturation in a human patient suffering from a Pseudomonas aeruginosa infection, the method comprising administering to the human patient an effective amount of a nebulized liposomal amikacin formulation for at least one treatment cycle comprising an administration period of 20 to 35 days and an off period of 25 to 75 days,
wherein the lipid component of the liposome comprises dipalmitoylphosphatidylcholine (DPPC) and cholesterol, and the effective amount comprises 510 mg to 610 mg of amikacin per day during the administration period; and
wherein the effective amount of the nebulized liposomal amikacin formulation is effective to increase blood oxygen concentration in the human patient by at least 1% as compared to the blood oxygen concentration in an untreated human patient suffering from the Pseudomonas aeruginosa infection.
33. The method of claim 32 , wherein the Pseudomonas aeruginosa infection is a chronic Pseudomonas aeruginosa infection.
34. The method of claim 32 , wherein the human patient has a serum C max of amikacin of less than about 10 mcg/mL during the administration period.
35. The method of claim 32 , wherein the human patient has a sputum C max of amikacin of at least 1000 mcg per gram of sputum.
36. The method of claim 33 , wherein a sputum C max of amikacin in the human patient is at least 1000 mcg per gram of sputum during the administration.
37. The method of claim 33 , wherein a sputum C max of amikacin in the human patient is at least 1000 mcg per gram of sputum for at least 15 days after administration.
38. The method of claim 33 , wherein the patient has a reduction in log 10 Colony Forming Unit (CFU) of the bacterial infection in lungs of at least 0.5 for at least 15 days following administration.
39. The method of claim 38 , wherein the reduction in the log 10 Colony Forming Unit (CFU) is at least 1.0.
40. The method of claim 32 , wherein a time to pulmonary exacerbation in the human patient administered with the nebulized liposomal amikacin formulation is at least twice the time to pulmonary exacerbation in the untreated human patient.
41. The method of claim 32 , wherein a time to pulmonary exacerbation in the human patient is at least 20 days.
42. The method of claim 32 , wherein a time to rescue treatment is at least 20 days.
43. The method of claim 32 , wherein the lipid component to amikacin ratio of the liposomal amikacin formulation is about 0.3:1 to about 1.0:1 by weight.
44. The method of claim 43 , wherein the lipid component to amikacin ratio is about 0.5:1 to about 0.7:1 by weight.
45. The method of claim 43 , wherein the lipid component to amikacin ratio is about 0.6:1 by weight.
46. The method of claim 32 , wherein the liposomal amikacin formulation comprises dipalmitoylphosphatidylcholine (DPPC) and cholesterol in about a 2 to 1 ratio by weight.
47. The method of claim 46 , wherein the liposomal amikacin formulation has a lipid component to amikacin ratio of about 0.3:1 to about 1.0:1 by weight.
48. The method of claim 47 , wherein the lipid component to amikacin ratio is about 0.5:1 to about 0.7:1 by weight.
49. The method of claim 47 , wherein the lipid component to amikacin ratio is about 0.6:1 by weight.
50. The method of claim 1 , wherein the human patient is a cystic fibrosis patient.
51. The method of claim 10 , wherein the human patient is a cystic fibrosis patient.
52. The method of claim 32 , wherein the human patient is a cystic fibrosis patient.
53. The method of claim 33 , wherein the human patient is a cystic fibrosis patient.