Use of GLP-1 compound for treatment of critically ill patients

• US 20030199445A1
• Filed: 02/06/2003
• Published: 10/23/2003
• Est. Priority Date: 02/07/2002
• Status: Abandoned Application

• Current Assignee: Novo Nordisk A/S
• Original Assignee: Novo Nordisk A/S
• Inventors: Selmer, Johan, Hansen, Kristian Tage, Knudsen, Lotte Bjerre
• Application Number:
  US10/359,324
• Publication Number:
  US 20030199445A1
• Time in Patent Office: Days
• US Class Current: 514/5.9
• CPC Class Codes: A61K 38/26 Glucagons
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/08 for glucose homeostasis pancreatic hormones A61P5/48
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/12 Antidiuretics, e.g. drugs for diabetes insipidus ADH A61P5/10

Abstract

Use of medicament for life saving treatment of critically ill patients and method of treatment. The medicament comprises a GLP-1 compound which effectively controls the blood glucose level.

Claims

1. Use of a GLP-1 compound for the manufacture of a medicament for treatment or cure of a critically ill patient and/or a CIPNP patient and/or a potential CIPNP patient.

2. The use according to claim 1, wherein the treatment or cure increases the survival rate of critically ill patients and/or CIPNP patients and/or potential CIPNP patients.

3. The use according to claim 1, wherein the treatment or cure reduces the time where a critically ill patient and/or a CIPNP patient and/or a potential CIPNP patient is hospitalized.

4. The use according to claim 3, wherein the patient is hospitalized in an ICU.

14. The use according to claim 1, wherein the treatment or cure reduces mortality, duration of hospitalization, frequency of bacteraemia, frequency of septicaemia, frequency of septic shock, need for dialysis, and/or need for ventilatory support in said patient.

16. The use according to any one of claims 1-15, wherein the GLP-1 compound is GLP-1(7-36)-amide, GLP-1(7-37), or an analogue thereof or a derivative thereof.

17. The use according to claim 16, wherein the GLP-1 compound is a derivative of GLP-1(7-36)-amide or GLP-1(7-37) which comprises a lipophilic substituent.

18. The use according to any one of claims 16-17, wherein the GLP-1 compound is Arg³⁴, Lys²⁶(N^ε

-(γ

-Glu(N^α

-hexadecanoyl)))-GLP-1(7-37).

19. The use according to claim 16, wherein the GLP-1 compound is selected from the group consisting of Gly⁸-GLP-1(7-36)-amide, Gly⁸-GLP-1(7-37), Val⁸-GLP-1(7-36)-amide, Val⁸-GLP-1(7-37), Val⁸Asp²²-GLP-1(7-36)-amide, Val⁸Asp²²-GLP-1(7-37), Val⁸Glu²²-GLP-1(7-36)-amide, Val⁸Glu²²-GLP-1(7-37), Val⁸Lys²²-GLP-1(7-36)-amide, Val⁸Lys²²-GLP-1(7-37, Val⁸Arg²²-GLP-1(7-36)-amide, Val⁸Arg²²-GLP-1(7-37), Val⁸His²²-GLP-1-36)-amide, Val⁸His²²-GLP-1(7-37), analogues thereof and derivatives thereof.

20. The use according to claim 16, wherein the GLP-1 compound is a stable GLP-1 analog/derivative.

21. The use according to any one of claims 1-15, wherein the GLP-1 compound is exendin-4 or an analogue thereof or a derivative thereof.

22. The use according to any one of claims 1-15 and 21, wherein the GLP-1 compound is a stable exendin-4 analog/derivative.

23. The use according to any one of claims 1-22, wherein the GLP-1 compound is to be administered parenterally.

24. The use according to claim 23, wherein the GLP-1 compound is administered by injection.

25. The use according to claim 23, wherein the GLP-1 compound is administered by infusion or drip.

26. The use according to any one of claims 23-25, wherein the dosage of GLP-1 compound is from about 0.5 μ

g/kg/day to about 20 μ

g/kg/day.

27. The use according to any one of claims 23-25, wherein the dosage of GLP-1 compound is from about 0.1 μ

g/kg/day to about 2 μ

g/kg/day.

28. The use according to any one of claims 1-25, wherein the GLP-1 compound is used such that the blood glucose level is kept below an upper limit which is about 110 mg/dL, about 120 mg/dL or about 130 mg/dL.

29. The use according to any one of claims 1-25, wherein the GLP-1 compound is used such that the blood glucose level is kept within a range where the lower limit is about 60 mg/dL, about 70 mg/dL or about 80 mg/dL and the upper limit is about 110 mg/dL, about 120 mg/dL or about 130 mg/dL, preferably in the range of 80 to about 110 mg/dL.

30. The use according to any one of claims 1-25, wherein the GLP-1 compound is used such that the blood glucose level is kept within a range from about 60 mg/dL to about 130 mg/dL, preferably from about 70 mg/dL to about 120 mg/dL, more preferred from about 80 mg/dL to about 110 mg/dL.

31. The use according to any one of claims 28-30, wherein the blood glucose level is kept within the specified range for a period of more than about 8 hours, preferably for more than about 24 hours, more preferred for more than about 2 days, even more preferred for more than about 4 days, and even more preferred for more than about 7 days.

32. The use according to any one of claims 1-31, wherein a second blood glucose regulator is used.

33. The use according to claim 32, wherein the second blood glucose-regulator is selected from insulin, insulin analogs, insulin derivatives, insulin secretagogues, insulin compounds that stimulate signal transduction mediated by an insulin receptor type tyrosine kinase in a cell, protein-tyrosine phosphatases and Type II antidiabetica.

34. The use according to claim 32, wherein the second blood glucose regulator is selected from insulin, an insulin analog, an insulin derivative, a GLP-1 compound and an orally administered blood glucose regulator.

35. The use according to any one of claims 32-34, wherein treatment, curing or prevention is performed by administering an effective amount of the second blood glucose regulator.

36. The use according to any one of claims 1-35, wherein the patient is a non-diabetic patient.

37. The use according to any one of claims 1-36, wherein the patient is a human.

38. The use according to any one of claims 1-37, wherein the patient is in need of cardiac surgery, cerebral surgery, thoracic surgery, abdominal surgery, vascular surgery, or transplantation, or a patient suffering from neurological diseases, cerebral trauma, respiratory insufficiency, abdominal peritonitis, multiple trauma, severe burns, or CIPNP.

39. The use according to any one of claims 1-38, wherein the patient is fed parenterally.

40. The use according to any one of claims 1-39, wherein the patient receives at least about one third of the caloric need through the normal enteral route, preferably at least about half of the caloric need through the normal enteral route, most preferable at least about two third of the caloric need through the normal enteric route.

41. The use according to any one of claims 1-40, wherein treatment, curing or prevention is performed by administering an effective amount of the GLP-1 compound.

44. The use according to any one of claims 42-43, wherein said use is to attain the clinical benefits mentioned in any one of the preceding claims.

5. Use of a GLP-1 compound for the manufacture of a medicament for preventing that a patient becomes critically ill or develops CIPNP.

6. Use of a GLP-1 compound for the manufacture of a medicament for prevention, treatment or cure of SIRS in a patient.

7. Use of a GLP-1 compound for the manufacture of a medicament for preventing or reducing the likelihood of a patient suffering from bacteraemia, septicaemia and/or septic shock during hospitalization.

8. The use according to claim 7, where the hospitalization is in an ICU.

9. The use according to any one of claims 7-8, wherein the patient is selected from a critically ill patient, a CIPNP patient, a potential CIPNP patient, a SIRS patient and a potential SIRS patient.

10. Use of a GLP-1 compound for manufacturing a medicament for preventing or reducing the likelihood that a critically ill patient and/or a CIPNP patient and/or a potential CIPNP patient acquires an infectious disease.

11. The use according to claim 10, wherein the infectious disease has a mortal outcome.

12. Use of a GLP-1 compound for manufacturing a medicament for preventing or reducing the likelihood that a critically ill patient and/or a CIPNP patient and/or a potential CIPNP patient dies due to an infection.

13. Use of a GLP-1 compound for manufacturing a medicament for reducing the rate of infection with mortal outcome in critically ill patients and/or CIPNP patients and/or potential CIPNP patients in an ICU.

15. The use of a GLP-1 compound for the manufacture of a medicament to treat a critically ill patient and/or a CIPNP-patient and/or a potential CIPNP-patient so that the patient is no longer in need of vital organ system support or to treat a critically ill patient and/or a CIPNP-patient and/or a potential CIPNP-patient so that it is considered sufficient for the patient to receive at least about two third of the caloric need through the normal enteral route to reduce the risk or likelihood from multiple organ failure, to reduce the risk or likelihood from multiple organ failure with a proven septic focus on post-mortem examination, to reduce mortality, for example, in-hospital mortality, to reduce the use of mechanical ventilatory support, to reduce the likelihood of renal replacement therapy and/or renal failure, to reduce the likelihood of disturbed kidney function parameters, to reduce the likelihood of hyperbilirubinemia, to reduce the likelihood for blood stream infections, to reduce the likelihood of disturbance in markers of inflammations and/or inflammatory responses, to reduce the use of antibiotics, to reduce the amount of red cell transfusion, or to reduce stress induced hyperglycaemia, or to reduce the likelihood of the critically ill patient and/or the CIPNP-patient and/or the potential CIPNP-patient having repetitive positive EMGs, or to prevent or reduce the amount of ultimately futile intensive care to a critically ill patient and/or a CIPNP-patient and/or a potential CIPNP-patient, or to protect a critically ill patient and/or a CIPNP-patient and/or a potential CIPNP-patient from cholestasis, or to reduce the need for invasive treatment in a critically ill patient and/or a CIPNP-patient and/or a potential CIPNP-patient.

42. Use of a GLP-1 compound for the treatment or cure of critically ill patients and/or CIPNP patients and/or potential CIPNP patients.

43. The use according to claim 42, wherein said treatment or cure comprises a pharmaceutically effective composition comprising the GLP-1 compound.

45. A kit of parts comprising

a medicament wherein is a GLP-1 compound and

an insert label stating the use of said medicament for treating critically ill patients within an ICU.

46. A method of marketing a GLP-1 compound, said method comprising the dissemination of information about the indications, utilities and benefits of a GLP-1 compound or a pharmaceutical composition comprising a GLP-1 compound, said indications, utilities, benefits and GLP-1 compounds being described in the preceding claims.

47. The method according to claim 46, wherein the information is disseminated by means of printed material, oral presentation or electromagnetic signals, such as via internet, telephone, television, radio or computer.

48. The method according to any one of claims 46-47, wherein the information is disseminated to physicians and/or persons responsible for health care budgets, preferably to physicians working in an ICU and persons responsible for an ICU budget.

49. Advertising medium to disseminate information about the indications, utilities and benefits of a GLP-1 compound or a pharmaceutical composition comprising a GLP-1 compound, said indications, utilities, benefits and GLP-1 compounds being described in the preceding claims.

50. The advertising medium according to claim 49, wherein said advertising medium is selected from the group consisting of a brochure, pamphlet, prospectus, videotape, DVD disk and CD disk.

51. A method for treating a critically ill patient and/or a patient having critical illness polyneuropathy (CIPNP) and/or a patient having systemic inflammatory response syndrome (SIRS), said method comprising administering to said patient a therapeutically effective amount of a GLP-1 compound.

52. The method according to claim 51, wherein the GLP-1 compound is GLP-1(7-36)-amide, GLP-1(7-37), or an analogue thereof or a derivative thereof.

53. The method according to claim 52, wherein the GLP-1 compound is a derivative of GLP-1(7-36)-amide or GLP-1(7-37) which comprises a lipophilic substituent.

54. The method according to claim 53, wherein the GLP-1 compound is Arg³⁴, Lys²⁶(N^ε

-(γ

-Glu(N^α

-hexadecanoyl)))-GLP-1(7-37).

55. The method according to claim 52, wherein the GLP-1 compound is selected from the group consisting of Gly⁸-GLP-1(7-36)-amide, Gly⁸-GLP-1(7-37), Val⁸-GLP-1(7-36)-amide, Val⁸-GLP-1(7-37), Val⁸Asp²²-GLP-1(7-36)-amide, Val⁸Asp²²-GLP-1(7-37), Val^8Glu22-GLP-1(7-36)-amide, Val⁸Glu²²-GLP-1(7-37), Val⁸Lys²²-GLP-1(7-36)-amide, Val⁸Lys²²-GLP-1(7-37), Val⁸Arg²²-GLP-1(7-36)-amide, Val⁸Arg²²-GLP-1(7-37), Val⁸His²²-GLP-1(7-36)-amide, Val⁸His²²-GLP-1(7-37), and analogues and derivatives thereof.

56. The method according to claim 51, wherein the GLP-1 compound is a stable GLP-1 analog/derivative.

57. The method according to claim 51, wherein the GLP-1 compound is exendin-4 or an analogue thereof or a derivative thereof.

58. The method according to claim 51, wherein the GLP-1 compound is a stable exendin-4 analog/derivative.

59. The method according to claim 51, wherein the GLP-1 compound is administered parenterally.

60. The method according to claim 51, wherein the GLP-1 compound is administered by injection.

61. The method according to claim 51, wherein the GLP-1 compound is administered by infusion or drip.

62. The method according to claim 51, wherein the GLP-1 compound is administered at a dosage of from about 0.5 μ

g/kg/day to about 20 μ

g/kg/day.

63. The method according to claim 51, wherein the GLP-1 compound is administered at a dosage of from about 0.1 μ

g/kg/day to about 2 μ

g/kg/day.

64. The method according to claim 51, wherein said administration of the GLP-1 compound results in said patient'"'"'s blood glucose level being kept below an upper limit of about 110 mg/dL.

65. The method according to claim 51, wherein said administration of the GLP-1 compound results in said patient'"'"'s blood glucose level being kept below an upper limit which is about 120 mg/dL.

66. The method according to claim 51, wherein said administration of the GLP-1 compound results in said patient'"'"'s blood glucose level being kept below an upper limit which is about 130 mg/dL.

67. The method according to claim 51, wherein said administration of the GLP-1 compound results in said patient'"'"'s blood glucose level being kept within a range between about 60 mg/dL and about 130 mg/dL.

68. The method according to claim 51, wherein said administration of the GLP-1 compound results in said patient'"'"'s blood glucose level being kept within a range between about 70 mg/dL and about 120 mg/dL.

69. The method according to claim 51, wherein said administration of the GLP-1 compound results in said patient'"'"'s blood glucose level being kept within a range between about 80 mg/dL and about 110 mg/dL.

70. The method according to claim 51, wherein said patient is further administered a blood glucose regulator.

71. The method according to claim 70, wherein the blood glucose regulator is selected from the group consisting of insulin, insulin analogs, insulin derivatives, insulin secretagogues, insulin compounds that stimulate signal transduction mediated by an insulin receptor type tyrosine kinase in a cell, protein-tyrosine phosphatases and Type II antidiabetic compounds.

72. The method according to claim 70, wherein the blood glucose regulator is selected from the group consisting of insulin, an insulin analog, an insulin derivative, a second GLP-1 compound and an orally administered blood glucose regulator.

73. The method according to claim 51, wherein the patient is a non-diabetic.

74. The method according to claim 51, wherein the patient is a human.

75. The method according to claim 51, wherein the patient is in need of a surgery selected from the group consisting of cardiac surgery, cerebral surgery, thoracic surgery, abdominal surgery, vascular surgery, and transplantation.

76. The method according to claim 51, wherein the patient is suffering from a condition selected from the group consisting of neurological diseases, cerebral trauma, respiratory insufficiency, abdominal peritonitis, multiple trauma, and severe burns.

77. The method according to claim 51, wherein the patient is fed parenterally.

78. The method according to claim 51, wherein at least about one third of said patient'"'"'s caloric intake is through the normal enteric route.

79. The method according to claim 51, wherein at least about half of said patient'"'"'s caloric intake is through the normal enteric route.

80. The method according to claim 51, wherein at least about two third of said patient'"'"'s caloric intake is through the normal enteric route.

81. The method according to claim 67, wherein said patient'"'"'s blood glucose level is kept within the specified range for a period of more than about 8 hours.

82. The method according to claim 67, wherein said patient'"'"'s blood glucose level is kept within the specified range for a period of more than about 24 hours.

83. The method according to claim 67, wherein said patient'"'"'s blood glucose level is kept within the specified range for a period of more than about 2 days.

84. The method according to claim 67, wherein said patient'"'"'s blood glucose level is kept within the specified range for a period of more than about 4 days.

85. The method according to claim 67, wherein said patient'"'"'s blood glucose level is kept within the specified range for a period of more than about about 7 days.