METHODS COMPRISING DESMOPRESSIN

• US 20090291880A1
• Filed: 05/21/2009
• Published: 11/26/2009
• Est. Priority Date: 05/21/2008
• Status: Active Grant

• Current Assignee: Ferring BV (Ferring Holding SA)
• Original Assignee: Ferring International Center SA (Ferring Holding SA)
• Inventors: Klein, Bjarke Mimer, Shumel, Brad, Norgaard, Jens Peter
• Granted Patent: US 9,974,826 B2
• Time in Patent Office: Days
• US Class Current: 514/1.1
• CPC Class Codes: A61K 38/095 Oxytocins; Vasopressins; Related peptides
• CPC Class Codes: A61P 13/00 Drugs for disorders of the urinary system
• CPC Class Codes: A61P 13/02 of urine or of the urinary tract, e.g. urine acidifiers
• CPC Class Codes: A61P 13/10 of the bladder
• CPC Class Codes: A61P 25/20 Hypnotics; Sedatives
• CPC Class Codes: A61P 5/10 of the posterior pituitary hormones, e.g. oxytocin, ADH

Abstract

The present disclosure is directed to gender, age, and dose effects of desmopressin on reducing nocturnal voids, increasing an initial period of undisturbed sleep, and/or reducing nocturnal urine volume.

Claims

1. A method for increasing an initial period of undisturbed sleep in a patient in need thereof comprising:

administering to the patient prior to bedtime an orodispersible dose of desmopressin of 10 μ

g, wherein the dose is measured as the free base of desmopressin and the dose taken over a treatment period increases the patient'"'"'s initial period of undisturbed sleep.

2. The method according to claim 1, wherein the dose is taken from 0.8 to 3 hours prior to the patient'"'"'s bedtime.

3. The method according to claim 1, wherein the dose is taken once daily.

4. The method according to claim 1, wherein the dose of desmopressin free base is supplied in the form of the acetate salt of desmopressin.

5. The method according to claim 1, wherein the orodispersible dose of desmopressin is a dosage form comprising desmopressin acetate, gelatin, mannitol, and citric acid.

6. The method according to claim 1, wherein the patient in need thereof has nocturia or nocturnal polyuria.

7. The method according to claim 1, wherein the treatment period is 28 days.

8. The method according to claim 1, wherein the increase ranges from 48 to 54 minutes.

9. The method according to claim 8, wherein the increase is 51 minutes.

10. A method for reducing nocturnal urine volume in a patient in need thereof comprising:

administering to the patient prior to bedtime an orodispersible dose of desmopressin of 10 μ

g, wherein the dose is measured as the free base of desmopressin and the dose taken over a treatment period reduces the patient'"'"'s nocturnal urine volume.

11. The method according to claim 10, wherein the dose is taken from 0.8 to 3 hours prior to the patient'"'"'s bedtime.

12. The method according to claim 10, wherein the dose is taken once daily.

13. The method according to claim 10, wherein the dose of desmopressin free base is supplied in the form of the acetate salt of desmopressin.

14. The method according to claim 10, wherein the orodispersible dose of desmopressin is a dosage form comprising desmopressin acetate, gelatin, mannitol, and citric acid.

15. The method according to claim 10, wherein the patient in need thereof has nocturia or nocturnal polyuria.

16. The method according to claim 10, wherein the treatment period is 28 days.

17. The method according to claim 10, wherein the reduction ranges from 120 ml to 180 ml.

18. The method according to claim 17, wherein the reduction is 150 ml.

19. The method according to claim 10, wherein the patient has a rate of urine production during sleep that is greater than the patient'"'"'s overall average daily rate of urine production.

20. A method for reducing nocturnal voids in a female patient in need thereof comprising:

administering to the patient prior to bedtime an orodispersible dose of desmopressin of 10 μ

g or 25 μ

g, wherein the dose is measured as the free base of desmopressin and the dose taken over a treatment period reduces the patient'"'"'s nocturnal voids.

21. The method according to claim 20, wherein the dose is taken from 0.8 to 3 hours prior to the patient'"'"'s bedtime.

22. The method according to claim 20, wherein the dose is taken once daily.

23. The method according to claim 20, wherein the dose of desmopressin free base is supplied in the form of the acetate salt of desmopressin.

24. The method according to claim 20, wherein the orodispersible dose of desmopressin is a dosage form comprising desmopressin acetate, gelatin, mannitol, and citric acid.

25. The method according to claim 20, wherein the patient in need thereof has nocturia or nocturnal polyuria.

26. The method according to claim 20, wherein the reduction is at least one nocturnal void.

27. The method according to claim 20, wherein the treatment period is chosen from 8 days, 15 days, 22 days, and 28 days.

28. A method for increasing an initial period of undisturbed sleep in a female patient in need thereof comprising:

administering to the patient prior to bedtime an orodispersible dose of desmopressin of 10 μ

g or 25 μ

g, wherein the dose is measured as the free base of desmopressin and the dose taken over a treatment period increases the patient'"'"'s initial period of undisturbed sleep.

29. The method according to claim 28, wherein the dose is taken from 0.8 to 3 hours prior to the patient'"'"'s bedtime.

30. The method according to claim 28, wherein the dose is taken once daily.

31. The method according to claim 28, wherein the dose of desmopressin free base is supplied in the form of the acetate salt of desmopressin.

32. The method according to claim 28, wherein the orodispersible dose of desmopressin is a fast dissolving tablet comprising desmopressin acetate, gelatin, mannitol, and citric acid.

33. The method according to claim 28, wherein the patient in need thereof has nocturia or nocturnal polyuria.

34. The method according to claim 28, wherein the treatment period is 28 days.

35. The method according to claim 28, wherein the increase ranges from 37 minutes to 114 minutes.

36. The method according to claim 35, wherein increase ranges from 37 to 55 minutes for the 10 μ

g dose of desmopressin.

37. The method according to claim 36, wherein the increase is 46 minutes.

38. The method according to claim 35, wherein the increase ranges from 76 to 114 minutes for the 25 μ

g dose of desmopressin.

39. The method according to claim 38, where in the increase is 95 minutes.

40. A method for reducing nocturnal urine volume in a female patient in need thereof comprising:

administering to the patient prior to bedtime an orodispersible dose of desmopressin of 10 μ

g or 25 μ

g, wherein the dose is measured as the free base of desmopressin and the dose taken over a treatment period reduces the patient'"'"'s nocturnal urine volume.

41. The method according to claim 40, wherein the dose is taken from 0.8 to 3 hours prior to the patient'"'"'s bedtime.

42. The method according to claim 40, wherein the dose is taken once daily.

43. The method according to claim 40, wherein the dose of desmopressin free base is supplied in the form of the acetate salt of desmopressin.

44. The method according to claim 40, wherein the orodispersible dose of desmopressin is a dosage form comprising desmopressin acetate, gelatin, mannitol, and citric acid.

45. The method according to claim 40, wherein the patient in need thereof has nocturia or nocturnal polyuria.

46. The method according to claim 40, wherein the treatment period is 28 days.

47. The method according to claim 40, wherein the reduction ranges from 143 ml to 358 ml.

48. The method according to claim 47, wherein the reduction ranges from 143 ml to 215 ml for the 10 μ

g dose of desmopressin.

49. The method according to claim 48, wherein the reduction is 179 ml.

50. The method according to claim 47, wherein the reduction is from 238 ml to 358 ml for the 20 μ

g dose of desmopressin.

51. The method according to claim 50, wherein the reduction is 298 ml.

52. A method for reducing nocturnal voids in a female patient above 50 years of age in need thereof comprising:

administering to the patient prior to bedtime an orodispersible dose of desmopressin of 10 μ

g or 25 μ

g, wherein the dose is measured as the free base of desmopressin and the dose taken over a treatment period reduces the patient'"'"'s nocturnal voids.

53. The method according to claim 52, wherein the dose is taken from 0.8 to 3 hours prior to the patient'"'"'s bedtime.

54. The method according to claim 52 wherein the dose is taken once daily.

55. The method according to claim 52, wherein the dose of desmopressin free base is supplied in the form of the acetate salt of desmopressin.

56. The method according to claim 52, wherein the orodispersible dose of desmopressin is a dosage form comprising desmopressin acetate, gelatin, mannitol, and citric acid.

57. The method according to claim 52, wherein the patient in need thereof has nocturia or nocturnal polyuria.

58. The method according to claim 52, wherein the reduction is at least one nocturnal void.

59. The method according to claim 52, wherein the treatment period is chosen from 8 days, 15 days, 22 days, and 28 days.

60. A method for increasing an initial period of undisturbed sleep in a female patient above 50 years of age in need thereof comprising:

administering to the patient prior to bedtime an orodispersible dose of desmopressin of 10 μ

g or 25 μ

g, wherein the dose is measured as the free base of desmopressin and the dose taken over a treatment period increases the patient'"'"'s initial period of undisturbed sleep.

61. The method according to claim 60, wherein the dose is taken from 0.8 to 3 hours prior to the patient'"'"'s bedtime.

62. The method according to claim 60, wherein the dose is taken once daily.

63. The method according to claim 60, wherein the dose of desmopressin free base is supplied in the form of the acetate salt of desmopressin.

64. The method according to claim 60, wherein the orodispersible dose of desmopressin is a fast dissolving tablet comprising desmopressin acetate, gelatin, mannitol, and citric acid.

65. The method according to claim 60, wherein the patient in need thereof has nocturia or nocturnal polyuria.

66. The method according to claim 60, wherein the patient does not develop hyponatremia during the treatment period.

67. The method according to claim 60, wherein the treatment period is 28 days.

68. The method according to claim 60, wherein the increase ranges from 22 minutes to 115 minutes.

69. The method according to claim 68, wherein the increase ranges from 22 minutes to 32 minutes for the 10 μ

g dose of desmopressin.

70. The method according to claim 69, wherein the increase is 27 minutes.

71. The method according to claim 68, wherein increase ranges from 77 minutes to 115 minutes for the 25 μ

g dose of desmopressin.

72. The method according to claim 71, wherein the increase is 96 minutes.

73. A method for reducing nocturnal urine volume in a female patient above 50 years of age in need thereof comprising:

administering to the patient prior to bedtime an orodispersible dose of desmopressin of 10 μ

g or 25 μ

g, wherein the dose is measured as the free base of desmopressin and the dose taken over a treatment period reduces the patient'"'"'s nocturnal urine volume.

74. The method according to claim 73, wherein the dose is taken from 0.8 to 3 hours prior to the patient'"'"'s bedtime.

75. The method according to claim 73, wherein the dose is taken once daily.

76. The method according to claim 73, wherein the dose of desmopressin free base is supplied in the form of the acetate salt of desmopressin.

77. The method according to claim 73, wherein the orodispersible dose of desmopressin is a dosage form comprising desmopressin acetate, gelatin, mannitol, and citric acid.

78. The method according to claim 73, wherein the patient in need thereof has nocturia or nocturnal polyuria.

79. The method according to claim 73, wherein the treatment period is 28 days.

80. The method according to claim 73, wherein the reduction ranges from 120 ml to 460 ml.

81. The method according to claim 80, wherein the reduction ranges from 120 ml to 180 ml for the 10 μ

g dose of desmopressin.

82. The method according to claim 81, wherein the reduction is 150 ml.

83. The method according to claim 80, wherein the reduction ranges from 306 ml to 460 ml for the 20 μ

g dose of desmopressin.

84. The method according to claim 83, wherein the reduction is 383 ml.

85. A method for reducing nocturnal voids in a female patient above 65 years of age in need thereof comprising:

administering to the patient prior to bedtime an orodispersible dose of desmopressin of 25 μ

g, wherein the dose is measured as the free base of desmopressin and the dose taken over a treatment period reduces the patient'"'"'s nocturnal voids.

86. The method according to claim 85, wherein the dose is taken from 0.8 to 3 hours prior to the patient'"'"'s bedtime.

87. The method according to claim 85, wherein the dose is taken once daily.

88. The method according to claim 85, wherein the dose of desmopressin free base is supplied in the form of the acetate salt of desmopressin.

89. The method according to claim 85, wherein the orodispersible dose of desmopressin is a dosage form comprising desmopressin acetate, gelatin, mannitol, and citric acid.

90. The method according to claim 85, wherein the patient in need thereof has nocturia or nocturnal polyuria.

91. The method according to claim 85, wherein reduction is at least 0.5 nocturnal void.

92. The method according to claim 85, wherein the treatment period is chosen from 8 days, 15 days, 22 days, and 28 days.

93. A method for increasing an initial period of undisturbed sleep in a female patient above 65 years of age in need thereof comprising:

administering to the patient prior to bedtime an orodispersible dose of desmopressin of 25 μ

g, wherein the dose is measured as the free base of desmopressin and the dose taken over a treatment period increases the patient'"'"'s initial period of undisturbed sleep.

94. The method according to claim 93, wherein the dose is taken from 0.8 to 3 hours prior to the patient'"'"'s bedtime.

95. The method according to claim 93, wherein the dose is taken once daily.

96. The method according to claim 93, wherein the dose of desmopressin free base is supplied in the form of the acetate salt of desmopressin.

97. The method according to claim 93, wherein the orodispersible dose of desmopressin is a fast dissolving tablet comprising desmopressin acetate, gelatin, mannitol, and citric acid.

98. The method according to claim 93, wherein the patient in need thereof has nocturia or nocturnal polyuria.

99. The method according to claim 93, wherein the treatment period is 28 days.

100. The method according to claim 93, wherein the increase ranges from 90 minutes to 136 minutes.

101. The method according to claim 100, wherein the increase ranges from 102 minutes to 124 minutes.

102. The method according to claim 101, wherein the increase is 113 minutes.

103. A method for reducing nocturnal urine volume in a female patient above 65 years of age in need thereof comprising:

administering to the patient prior to bedtime an orodispersible dose of desmopressin of 25 μ

g, wherein the dose is measured as the free base of desmopressin and the dose taken over a treatment period reduces the patient'"'"'s nocturnal urine volume.

104. The method according to claim 103, wherein the dose is taken from 0.8 to 3 hours prior to the patient'"'"'s bedtime.

105. The method according to claim 103, wherein the dose is taken once daily.

106. The method according to claim 103, wherein the dose of desmopressin free base is supplied in the form of the acetate salt of desmopressin.

107. The method according to claim 103, wherein the orodispersible dose of desmopressin is a dosage form comprising desmopressin acetate, gelatin, mannitol, and citric acid.

108. The method according to claim 103, wherein the patient in need thereof has nocturia or nocturnal polyuria.

109. The method according to claim 103, wherein the treatment period is 28 days.

110. The method according to claim 103, wherein the reduction ranges from 306 ml to 460 ml.

111. The method according to claim 110, wherein the reduction ranges from 345 to 421 ml.

112. The method according to claim 111, wherein the reduction is 383 ml.

113. The method according to claim 103, wherein the patient has a rate of urine production during sleep that is greater than the patient'"'"'s overall average daily rate of urine production.

114. A method for reducing nocturnal urine volume in a male patient in need thereof comprising:

measuring the patient'"'"'s serum sodium level;

administering to the patient, with a serum sodium level of at least 135 mmol/L, prior to bedtime an orodispersible dose of desmopressin of 100 μ

g, wherein the dose is measured as the free base of desmopressin;

measuring the patient'"'"'s serum sodium level at a time interval after administration;

continuing the administration of the dose of desmopressin with the patient having at least 130 mmol/L serum sodium level;

wherein the dose administered over a treatment period reduces the patient'"'"'s nocturnal urine volume.

115. The method according to claim 114, wherein the time interval ranges from 4 days to 28 days.

116. The method according to claim 115, wherein the time interval is 4 days.

117. The method according to claim 115, wherein the time interval is 28 days.

118. The method according to claim 114, wherein the dose is taken from 0.8 to 3 hours prior to the patient'"'"'s bedtime.

119. The method according to claim 114, wherein the dose is taken once daily.

120. The method according to claim 114, wherein the dose of desmopressin free base is supplied in the form of the acetate salt of desmopressin.

121. The method according to claim 114, wherein the orodispersible dose of desmopressin is a dosage form comprising desmopressin acetate, gelatin, mannitol, and citric acid.

122. The method according to claim 114, wherein the patient in need thereof has nocturia or nocturnal polyuria.

123. The method according to claim 114, wherein the treatment period is 28 days.

124. The method according to claim 114, wherein the reduction ranges from 211 ml to 317 ml.

125. The method according to claim 124, wherein the reduction ranges from 238 to 290 ml.

126. The method according to claim 125, wherein reduction is 264 ml.

127. The method according to claim 114, wherein the patient has a rate of urine production during sleep that is greater than the patient'"'"'s overall average daily rate of urine production.

128. The method according to claim 114, wherein the patient is over 65 years of age with a serum sodium level of at least 135 after administration.

129. A method of treating nocturia comprising administering sublingually to a subject in need thereof a dose of desmopressin, wherein the dose is measured as the free base and is selected from the group consisting of 10 μ

g, 25 μ

g, 50 μ

g, and 100 μ

g of desmopressin daily.

130. The method of claim 129, wherein the dose of desmopressin free base is supplied in the form of the acetate salt of desmopressin.

131. The method of claim 129, wherein the desmopressin is administered once daily one hour before bedtime.

132. The method of claim 129, wherein the desmopressin is administered for a period of at least 28 days.

133. The method of claim 129, wherein the desmopressin is administered as an oral lyophilisate of desmopressin acetate.

134. The method of claim 129, wherein the desmopressin is administered once daily before bedtime as a desmopressin fast dissolving tablet comprising desmopressin acetate in a freeze-dried presentation formulated with gelatin, mannitol and citric acid.

135. The method of claim 129, wherein the subject in need thereof has nocturnal polyuria.

136. The method of claim 129, wherein a treated subject has an average of a least 0.5 fewer nocturnal urinary voids per night after 28 days of treatment with desmopressin.

137. The method of claim 129, wherein the subject in need thereof is less than 65 years old.

138. The method of claim 129, wherein the subject in need thereof is at least 65 years old.

139. The method of claim 129, wherein the subject does not have a low serum sodium level before treatment with desmopressin.

140. The method of claim 129, wherein the subject has a statistically significant increase in the duration of the initial period of undisturbed sleep after treatment with desmopressin.