Methods and materials useful for the treatment of arthritic conditions, inflammation associated with a chronic condition or chronic pain

• US 20050245557A1
• Filed: 10/15/2004
• Published: 11/03/2005
• Est. Priority Date: 10/15/2003
• Status: Abandoned Application

• Current Assignee: Pain Therapeutics, Inc.
• Original Assignee: Pain Therapeutics, Inc.
• Inventors: Schoenhard, Grant L., Friedmann, Nadav
• Application Number:
  US10/966,703
• Publication Number:
  US 20050245557A1
• Time in Patent Office: Days
• US Class Current: 514/282
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca

Abstract

Methods and materials, including novel compositions, dosage forms and methods of administration, useful for treating arthritic conditions, inflammation associated with a chronic condition, and/or chronic pain, including pain from arthritis and inflammation, using opioid antagonists, including combinations of opioid antagonists and opioid agonists. Methods and materials comprising opioid antagonists or combinations opioid antagonists and agonists may optionally include one or more additional therapeutic agents.

Claims

1. A method for treating an arthritic condition in a human subject comprising administering to the subject an opioid agonist and an opioid antagonist, wherein one or more symptoms or signs associated with the arthritic condition are alleviated.

4. The method of claim 1, wherein the arthritic condition is associated with a joint, hip, knee, back, neck, or lower back of the subject.

5. The method of claim 1, wherein the symptom or sign is pain.

6. The method of claim 5, wherein the pain is measured as pain intensity.

15. The method of claim 1, wherein the symptom or sign is stiffness.

21. The method of claim 1, wherein the symptom or sign is difficulty in physical function had by the subject.

27. The method of claim 1, wherein the total score of the subject on the WOMAC Osteoarthritis Index is attenuated.

82. The method of claim 1, 34 or 68 further comprising administering to the subject an additional therapeutic agent that is a non-steroidal anti-inflammatory drug, cytokine inhibitor, corticosteroid, anti-rheumatic drug, anticonvulsant agent, tricyclic antidepressant agent, anti-dynorphin agent, or glutamate receptor antagonist agent.

83. The method of claim 82, wherein the additional therapeutic agent is a TNF-α

inhibitor, corticosteroid, anti-rheumatic drug, non-steroidal anti-inflammatory drug, celecoxib, ropecoxib, valdecoxib, etanercept, infiximab, anti-TNF-α

, D2E7 human Mab, CDP-870, CDP-571, humicade, PEGylated soluble TNF-α

Receptor-1, TBP-1, PASSTNF-alpha, AGT-1, ienercept, CytoTAB, TACE, small molecule TNF mRNA synthesis inhibitor, PEGylated p75TNFR Fc mutein (Immunex), TNF-α

antisense inhibitor, methotrexate, leflunomide, D-Penicillamine, sulfasalazine, a gold composition, minocycline, azathioprine, hydroxychloroquine, an antimalarial drug, cyclosporine, or a biologic agent that designed to either inhibit or supplement a cytokine.

84. The method of claims 1, 34 or 68, wherein the agonist, the antagonist, or both the agonist and the antagonist is administered no more than twice in a 24-hour period.

85. The method of claims 1, 34 or 68, wherein the agonist, the antagonist, or both the agonist and the antagonist is administered no more than once in a 24-hour period.

86. The method of claims 1, 34 or 68, wherein the amount of the antagonist administered in a 24-hour period is less than 0.004 mg.

87. The method of claims 1, 34 or 68, wherein the amount of the antagonist administered in a 24-hour period is 0.002 mg or less.

88. The method of claims 1, 34 or 68, wherein the antagonist, the agonist, or both the antagonist and the agonist is administered in an oral dosage form.

89. The method of claim 88, wherein the oral dosage form is a solid oral dosage form or a liquid oral dosage form.

90. The method of claims 1, 34 or 68, wherein the agonist is oxycodone, oxymorphone, hydrocodone, hydromorphone, or morphine.

91. The method of claims 1, 34 or 68, wherein the antagonist is naltrexone, nalmefene, or naloxone.

92. The method of claims 1, 34 or 68, wherein the mode of administration is oral, intravenous, intrathecal, epidural, intramuscular, subcutaneous, perineural, intradermal, topical, or transcutaneous.

93. The method of claims 1, 34 or 68, wherein the agonist is selected from the group consisting of oxycodone, oxymorphone, hydrocodone, hydromorphone, and morphine, and the antagonist is naltrexone.

94. The method of claims 1, 34 or 68, wherein the agonist is oxycodone and the antagonist is naltrexone.

95. The method of claims 1, 34 or 68, wherein the amount of the agonist is from about 2.5 mg to about 160 mg.

96. The method of claims 1, 34 or 68, wherein the amount of the antagonist is from about 0.0001 mg to less than about 0.004 mg.

97. The method of claims 1, 34 or 68, wherein the amount of the agonist is selected from the group consisting of the amounts:

about 2.5 mg, about 5 mg, about 10 mg, about 15 mg, about 20 mg, about 30 mg, about 40 mg, about 80 mg, about 160 mg, and about 320 mg.

98. The method of claims 1, 34 or 68, wherein the amount of the antagonist administered is at least about 1250 fold less than the amount of the agonist administered.

99. The method of claims 1, 34 or 68, wherein the amount of the antagonist administered is at most about 1,600,000 fold less than the amount of the agonist administered.

100. The method of claims 1, 34 or 68, wherein the antagonist, the agonist, or both the antagonist and the agonist are administered once daily.

101. The method of claims 1, 34 or 68, wherein the antagonist, the agonist, or both the antagonist and the agonist are administered twice daily.

2-3. -3. (canceled)

7-14. -14. (canceled)

16-20. -20. (canceled)

22-26. -26. (canceled)

28-33. -33. (canceled)

34. A method for treating inflammation associated with a chronic condition in a human subject comprising administering to the subject an opioid agonist and an opioid antagonist, wherein one or more signs or symptoms associated with the inflammation is alleviated.

35. The method of claim 34, wherein the chronic condition is an arthritic condition.

38. The method of claim 35, wherein the arthritic condition is associated with a joint, hip, knee, back, neck, or lower back of the subject.

39. The method of claim 34, wherein the symptom or sign is pain.

40. The method of claim 39, wherein the pain is measured as pain intensity.

55. The method of claim 34, wherein the symptom or sign is difficulty in physical function had by the subject.

61. The method of claim 34, wherein the total score of the subject on the WOMAC Osteoarthritis index is attenuated.

36-37. -37. (canceled)

41-54. -54. (canceled)

56-60. -60. (canceled)

62-67. -67. (canceled)

68. A method for treating chronic pain comprising administering to a human subject with chronic pain an opioid agonist and an opioid antagonist, wherein the chronic pain is attenuated.

69. The method of claim 68, wherein the chronic pain is associated with an arthritic condition.

72. The method of claim 68, wherein the chronic pain is associated with a joint, hip, knee, back, neck, or lower back of the subject.

73. The method of claim 68 wherein the pain is measured as pain intensity.

70-71. -71. (canceled)

74-81. -81. (canceled)

102-103. -103. (canceled)

104. A method for treating an arthritic condition comprising administering to a human subject a dosage form for oral administration, wherein the dosage form comprises no more than about 80.4 pgs, about 40.2 μ

gs, about 20 μ

gs, about 10 μ

gs, about 5 μ

gs, about 2.5 μ

gs, about 1.2 μ

gs, about 0.6 μ

g, about 0.3 μ

g, or about 0.12 μ

g of the opioid antagonist.

105. The method of claim 104, wherein the dosage form comprises at least about 0.0002 μ

g, about 0.1 μ

g, about 0.2 μ

g, about 0.4 μ

g, about 0.8 μ

g, about 1.6 μ

g, about 3.3 μ

g, or about 6.6 μ

g of the opioid antagonist.

106. A method for treating inflammation associated with a chronic condition comprising administering to a human subject a dosage form for oral administration, wherein the dosage form comprises no more than about 80.4 μ

gs, about 40.2 μ

gs, about 20 μ

gs, about 10 μ

gs, about 5 μ

gs, about 2.5 μ

gs, about 1.2 μ

gs, about 0.6 μ

g, about 0.3 μ

g, or about 0.12 μ

g of the opioid antagonist.

107. The method of claim 106, wherein the dosage form comprises at least about 0.0002 μ

g, about 0.1 μ

g, about 0.2 μ

g, about 0.4 μ

g, about 0.8 μ

g, about 1.6 μ

g, about 3.3 μ

g, or about 6.6 μ

g of the opioid antagonist.

108. A method for treating chronic pain comprising administering to a human subject with chronic pain a dosage form for oral administration, wherein the dosage form comprises no more than about 80.4 μ

gs, about 40.2 μ

gs, about 20 μ

gs, about 10 μ

gs, about 5 μ

gs, about 2.5 μ

gs, about 1.2 μ

gs, about 0.6 μ

g, about 0.3 μ

g, or about 0.12 μ

g of the opioid antagonist.

109. The method of claim 108, wherein the dosage form comprises at least about 0.0002 μ

g, about 0.1 μ

g, about 0.2 μ

g, about 0.4 μ

g, about 0.8 μ

g, about 1.6 μ

g, about 3.3 μ

g, or about 6.6 μ

g of the opioid antagonist.

110-112. -112. (canceled)

113. A method for treating chronic pain comprising in a human subject comprising:

administering an opioid agonist to the human subject; and

administering an opioid antagonist to the human subject no more than twice-a-day.

114. The method of claim 113, wherein the opioid antagonist is administered twice-a-day.

115. The method of claim 113, wherein the opioid antagonist is administered once-a-day.

116. The method of claim 113, wherein the opioid antagonist is orally administered.

117. The method of claim 113, wherein the opioid agonist is orally administered.

118. The method of claim 113, wherein the opioid agonist and the opioid antagonist are each orally administered in a dose amount twice-a-day.

119. The method of claim 118, wherein the dose amount of the opioid agonist is about 1 mg and the dose amount of opioid antagonist is from about 0.041 μ

g to about 0.119 μ

g, or the dose amount of the opioid agonist is about 2.5 mg and the dose amount of opioid antagonist is from about 0.103 μ

g to about 0.297 μ

g, or the dose amount of the opioid agonist is about 5 mg and the dose amount of opioid antagonist is from about 0.207 μ

g to about 0.593 μ

g, or the dose amount of the opioid agonist is about 10 mg and the dose amount of opioid antagonist is from about 0.415 μ

g to about 1.19 μ

gs, or the dose amount of the opioid agonist is about 20 mg and the dose amount of the opioid antagonist is from about 0.829 μ

g to about 2.37 μ

gs, or the dose amount of the opioid agonist is about 40 mg and the dose amount of the opioid antagonist is from about 1.66 μ

gs to about 4.74 μ

gs, or the dose amount of the opioid agonist is about 80 mg and the dose amount of the opioid antagonist is from about 3.32 μ

gs to about 9.48 μ

gs, or the dose amount of the opioid agonist is about 160 mg and the dose amount of the opioid antagonist is from about 6.64 μ

gs to about 18.96 μ

gs, or or the dose amount of the opioid agonist is about 320 mg and the dose amount of the opioid antagonist is from about 13.28 μ

gs to about 37.92 μ

gs.

120-168. -168. (canceled)