Apparatus and Method for Transdermal Delivery of Parathyroid Hormone Agents to Prevent or Treat Osteopenia

• US 20080039775A1
• Filed: 03/15/2007
• Published: 02/14/2008
• Est. Priority Date: 03/15/2006
• Status: Abandoned Application

• Current Assignee: ALZA Corporation (Johnson & Johnson)
• Original Assignee: ALZA Corporation (Johnson & Johnson)
• Inventors: Cormier, Michel, Maa, Yuh-Fun, Kamberi, Marika, Ameri, Mahmoud, Daddona, Peter
• Application Number:
  US11/686,909
• Publication Number:
  US 20080039775A1
• Time in Patent Office: Days
• US Class Current: 604/46
• CPC Class Codes: A61K 38/29 Parathyroid hormone, i.e. parathormone; Parathyroid hormone-related peptides
• CPC Class Codes: A61K 9/0021 Intradermal administration, e.g. through microneedle arrays, needleless injectors mechanical aspects A61M
• CPC Class Codes: A61M 2037/0023 Drug applicators using microneedles
• CPC Class Codes: A61M 2037/0046 Solid microneedles
• CPC Class Codes: A61M 2037/0061 Methods for using microneedles
• CPC Class Codes: A61M 37/0015 by using microneedles
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 5/18 of the parathyroid hormones

Abstract

An apparatus and method for transdermally delivering a biologically active agent to prevent or treat osteopenia, comprising a delivery system having a microprojection member (or system) that includes a plurality of microprojections (or array thereof) that are adapted to pierce through the stratum corneum into the underlying epidermis layer, or epidermis and dermis layers. In one embodiment, the PTH-based agent is contained in a biocompatible coating that is applied to the microprojection member.

Claims

1. A method for preventing or treating osteopenia, comprising the steps of:

providing a transdermal delivery device having disposed thereon at least one hPTH-based formulation;

applying said transdermal device to a skin site of said patient to deliver hPTH to said patient;

wherein said formulation achieves a mean Cmax value when applied to the thigh of said patient that is about 15% to about 75% of a mean Cmax value achieved by said formulation when applied to the abdomen of said patient.

2. The method of claim 1 wherein said formulation achieves a mean Cmax value when applied to the thigh of said patient that is about 20% to about 60% of a mean Cmax value achieved by said formulation when applied to the abdomen of said patient.

3. The method of claim 1 wherein said formulation achieves a mean Cmax value when applied to the thigh of said patient that is about 25% to about 35% of a mean Cmax value achieved by said formulation when applied to the abdomen of said patient.

4. The method of claim 1 wherein said formulation achieves a mean plasma hPTH Tmax of 5 minutes or less.

5. The method of claim 1, wherein said method comprises achieving a HPTH mean plasma Cmax value of at least 50 pg/mL.

6. The method of claim 1, wherein said method comprises achieving a hPTH mean plasma Cmax value of at least 100 pg/mL.

7. The method of claim 1, wherein after 3 hours from applying said transdermal device to the patient'"'"'s skin, said method achieves a hPTH plasma concentration of no more than about 10 pg/mL.

8. The method of claim 1, wherein after 2 hours from applying said transdermal device to the patient'"'"'s skin, said method achieves a hPTH plasma concentration of no more than about 20 pg/mL.

9. The method of claim 1, wherein after 1 hour from applying said transdermal device to the patient'"'"'s skin, said method achieves a hPTH plasma concentration of no more than about 30 pg/mL.

10. The method of claim 1, wherein the ratio between the Tmax achieved by said method and the Tmax achieved by subcutaneous administration of said hPTH-based agent is from about 1:

2 to about 1;

10.

11. The method of claim 1, wherein said device is applied to the abdomen of said patient and the ratio between the Tmax achieved by said method and the Tmax achieved by subcutaneous administration of said hPTH-based agent is from about 1:

4 to about 1;

6.

12. The method of claim 1, wherein said device is applied to the skin of said patient for a period of about 30 minutes and the residual hPTH remaining on said device after application is about 40% to about 75% of hPTH present on said device prior to application of said device to the skin of said patient.

13. The method of claim 1, wherein said skin site of said patient is on the abdomen of said patient.

14. The method of claim 1, wherein said formulation comprises a hPTH-based agent selected from the group consisting of hPTH (1-34), hPTH salts and analogs, teriparatide and related peptides.

15. The method of claim 14, wherein said hPTH salt is selected from group consisting of acetate, propionate, butyrate, pentanoate, hexanoate, heptanoate, levulinate, chloride, bromide, citrate, succinate, maleate, glycolate, gluconate, glucuronate, 3-hydroxyisobutyrate, tricarballylicate, malonate, adipate, citraconate, glutarate, itaconate, mesaconate, citramalate, dimethylolpropinate, tiglicate, glycerate, methacrylate, isocrotonate, β

-hydroxibutyrate, crotonate, angelate, hydracrylate, ascorbate, aspartate, glutamate, 2-hydroxyisobutyrate, lactate, malate, pyruvate, fumarate, tartarate, nitrate, phosphate, benzene, sulfonate, methane sulfonate, sulfate and sulfonate.

16. The method of claim 1, wherein said formulation comprises teriparatide (hPTH (1-34)) in the range of approximately 10-100 μ

g.

17. The method of claim 1, wherein the method prevents or delays onset of osteoporosis.

18. The method of claim 1, wherein the method prevents or delays the onset of osteoporotic fractures.

19. The method of claim 1, wherein the method reduces severity of osteoperosis deleterious effects.

20. The method of claim 1, wherein the method reduces severity of osteoporotic fractures.

21. A method for preventing or treating osteopenia, comprising the steps of:

providing a microprojection member having a plurality of stratum corneum-piercing microprotrusions;

said microprojection member having a coating disposed thereon, said coating including at least one hPTH-based formulation;

applying said microprojection member to a skin site of said patient, whereby said plurality of stratum corneum-piercing microprotrusions pierce the stratum corneum and deliver hPTH to said patient;

removing said microprojection member from said skin site;

wherein said formulation achieves a mean Cmax value when applied to the thigh of said patient that is about 15% to about 75% of a mean Cmax value achieved by said formulation when applied to the abdomen of said patient.

22. The method of claim 21 wherein said formulation achieves a mean Cmax value when applied to the thigh of said patient that is about 20% to about 60% of a mean Cmax value achieved by said formulation when applied to the abdomen of said patient.

23. The method of claim 21 wherein said formulation achieves a mean Cmax value when applied to the thigh of said patient that is about 25% to about 35% of a mean Cmax value achieved by said formulation when applied to the abdomen of said patient.

24. The method of claim 21 wherein said formulation achieves a mean plasma hPTH Tmax of 5 minutes or less.

25. The method of claim 21, wherein said method comprises achieving a hPTH mean plasma Cmax value of at least 50 pg/mL.

26. The method of claim 21, wherein said method comprises achieving a hPTH mean plasma Cmax value of at least 100 pg/mL.

27. The method of claim 21, wherein after 3 hours from applying said transdermal device to the patient'"'"'s skin, said method achieves a HPTH plasma concentration of no more than about 10 pg/mL.

28. The method of claim 21, wherein after 2 hours from applying said transdermal device to the patient'"'"'s skin, said method achieves a HPTH plasma concentration of no more than about 20 pg/mL.

29. The method of claim 21, wherein after 1 hour from applying said transdermal device to the patient'"'"'s skin, said method achieves a hPTH plasma concentration of no more than about 30 pg/mL.

30. The method of claim 21, wherein the ratio between the Tmax achieved by said method and the Tmax achieved by subcutaneous administration of said hPTH-based agent is from about 1:

2 to about 1;

10.

31. The method of claim 21, wherein said device is applied to the abdomen of said patient and the ratio between the Tmax achieved by said method and the Tmax achieved by subcutaneous administration of said hPTH-based agent is from about 1:

4 to about 1;

6.

32. The method of claim 21, wherein said device is applied to the skin of said patient for a period of about 30 minutes and the residual HPTH remaining on said device after application is about 40% to about 75% of hPTH present on said device prior to application of said device to the skin of said patient.

33. The method of claim 21, wherein said skin site of said patient is on the abdomen of said patient.

34. The method of claim 21, wherein said formulation comprises a hPTH-based agent selected from the group consisting of HPTH (1-34), hPTH salts and analogs, teriparatide and related peptides.

35. The method of claim 34, wherein said hPTH salt is selected from group consisting of acetate, propionate, butyrate, pentanoate, hexanoate, heptanoate, levulinate, chloride, bromide, citrate, succinate, maleate, glycolate, gluconate, glucuronate, 3-hydroxyisobutyrate, tricarballylicate, malonate, adipate, citraconate, glutarate, itaconate, mesaconate, citramalate, dimethylolpropinate, tiglicate, glycerate, methacrylate, isocrotonate, β

-hydroxibutyrate, crotonate, angelate, hydracrylate, ascorbate, aspartate, glutamate, 2-hydroxyisobutyrate, lactate, malate, pyruvate, fumarate, tartarate, nitrate, phosphate, benzene, sulfonate, methane sulfonate, sulfate and sulfonate.

36. The method of claim 21, wherein said formulation comprises teriparatide (HPTH (1-34)) in the range of approximately 10-100 μ

g.

37. The method of claim 21, wherein said formulation comprises teriparatide (hPTH (1-34)) in a dose of approximately 10 μ

g.

38. The method of claim 21, wherein said formulation comprises teriparatide (hPTH (1-34)) in a dose of approximately 20 μ

g.

39. The method of claim 21, wherein said formulation comprises teriparatide (hPTH (1-34)) in a dose of approximately 30 μ

g.

40. The method of claim 21, wherein said formulation comprises teriparatide (HPTH (1-34)) in a dose of approximately 40 μ

g.

41. The method of claim 21, wherein the method prevents or delays onset of osteoporosis.

42. The method of claim 21, wherein the method prevents or delays the onset of osteoporotic fractures.

43. The method of claim 21, wherein the method reduces severity of osteoperosis deleterious effects.

44. The method of claim 21, wherein the method reduces severity of osteoporotic fractures.

45. A method for preventing or treating osteopenia, comprising the steps of:

providing a transdermal delivery device having disposed thereon at least one hPTH-based formulation;

applying said transdermal device to a skin site located on the abdomen of said patient to deliver hPTH to said patient;

wherein said formulation achieves a mean tmax value of 30 minutes or less.

46. The method of claim 45, wherein said formulation achieves a mean tmax value of 20 minutes or less.

47. The method of claim 45, wherein said formulation achieves a mean tmax value of 10 minutes or less.

48. The method of claim 45, wherein said formulation achieves a mean tmax value of 5 minutes or less.

49. A method for preventing or treating osteopenia, comprising the steps of:

providing a transdermal delivery device having disposed thereon at least one hPTH-based formulation;

applying said transdermal device to a skin site located on the thigh of said patient to deliver HPTH to said patient;

wherein said formulation achieves a mean tmax value of 30 minutes or less.

50. The method of claim 49, wherein said formulation achieves a mean tmax value of 20 minutes or less.

51. The method of claim 49, wherein said formulation achieves a mean tmax value of 10 minutes or less.

52. The method of claim 49, wherein said formulation achieves a mean tmax value of 5 minutes or less

53. A method for preventing or treating osteopenia, comprising the steps of:

providing a microprojection member having a plurality of stratum corneum-piercing microprotrusions;

said microprojection member having a coating disposed thereon, said coating including at least one hPTH-based formulation;

applying said microprojection member to a skin site located on the abdomen of said patient, wherein said formulation achieves a mean tmax value of 30 minutes or less.

54. The method of claim 53, wherein said formulation achieves a mean tmax value of 20 minutes or less.

55. The method of claim 53, wherein said formulation achieves a mean tmax value of 10 minutes or less.

56. The method of claim 53, wherein said formulation achieves a mean tmax value of 5 minutes or less.

57. A method for preventing or treating osteopenia, comprising the steps of:

providing a microprojection member having a plurality of stratum corneum-piercing microprotrusions;

said microprojection member having a coating disposed thereon, said coating including at least one hPTH-based formulation;

applying said microprojection member to a skin site located on the thigh of said patient, wherein said formulation achieves a mean tmax value of 30 minutes or less.

58. The method of claim 57, wherein said formulation achieves a mean tmax value of 20 minutes or less.

59. The method of claim 57, wherein said formulation achieves a mean tmax value of 10 minutes or less.

60. The method of claim 57, wherein said formulation achieves a mean tmax value of 5 minutes or less.

61. A method for preventing or treating osteopenia, comprising the steps of:

providing a transdermal delivery device having disposed thereon at least one hPTH-based formulation comprising teriparatide (hPTH (1-34)) in a dose of approximately 40 μ

g;

applying said transdermal device to a skin site of said patient to deliver hPTH to said patient;

wherein said formulation achieves a mean tmax value of 30 minutes or less.

62. The method of claim 61, wherein said formulation achieves a mean tmax value of 20 minutes or less.

63. The method of claim 61, wherein said formulation achieves a mean tmax value of 10 minutes or less.

64. The method of claim 61, wherein said formulation achieves a mean tmax value of 5 minutes or less.

65. A method for preventing or treating osteopenia, comprising the steps of:

providing a transdermal delivery device having disposed thereon at least one hPTH-based formulation comprising teriparatide (hPTH (1-34)) in a dose of approximately 40 μ

g;

applying said transdermal device to a skin site of said patient to deliver HPTH to said patient;

wherein said formulation achieves a mean tmax value of 30 minutes or less.

66. The method of claim 65, wherein said formulation achieves a mean tmax value of 20 minutes or less.

67. The method of claim 65, wherein said formulation achieves a mean tmax value of 10 minutes or less.

68. The method of claim 65, wherein said formulation achieves a mean tmax value of 5 minutes or less

69. A method for preventing or treating osteopenia, comprising the steps of:

providing a microprojection member having a plurality of stratum corneum-piercing microprotrusions;

said microprojection member having a coating disposed thereon, said coating including at least one hPTH-based formulation comprising teriparatide (hPTH (1-34)) in a dose of approximately 40 μ

g;

applying said microprojection member to a skin site of said patient, wherein said formulation achieves a mean tmax value of 30 minutes or less.

70. The method of claim 69, wherein said formulation achieves a mean tmax value of 20 minutes or less.

71. The method of claim 69, wherein said formulation achieves a mean tmax value of 10 minutes or less.

72. The method of claim 69, wherein said formulation achieves a mean tmax value of 5 minutes or less.

73. A method for preventing or treating osteopenia, comprising the steps of:

providing a microprojection member having a plurality of stratum corneum-piercing microprotrusions;

said microprojection member having a coating disposed thereon, said coating including at least one hPTH-based formulation comprising teriparatide (hPTH (1-34)) in a dose of approximately 40 μ

g;

applying said microprojection member to a skin site of said patient, wherein said formulation achieves a mean tmax value of 30 minutes or less.

74. The method of claim 73, wherein said formulation achieves a mean tmax value of 20 minutes or less.

75. The method of claim 73, wherein said formulation achieves a mean tmax value of 10 minutes or less.

76. The method of claim 73, wherein said formulation achieves a mean tmax value of 5 minutes or less.