IP Library › Granted Patent US 9,789,103
Granted Patent B2
US 9,789,103 · App. 14/336,753 · Granted Oct 17, 2017

Method of treating pain utilizing controlled release oxymorphone pharmaceutical compositions and instruction on dosing for renal impairment

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Quick Facts
Patent No.
US 9,789,103
App. No.
14/336,753
Granted
Oct 17, 2017
Kind
B2
Abstract

The invention pertains to a method of using oxymorphone in the treatment of pain by providing a patient with an oxymorphone dosage form and informing the patient or prescribing physician that the bioavailability of oxymorphone is increased in patients with renal impairment.

Claims (64)

1. A method of treating pain in a renally impaired patient comprising administering a pharmaceutical composition comprising about 5 mg to about 80 mg of oxymorphone or a pharmaceutically acceptable salt thereof as the sole active ingredient and a controlled release matrix, wherein the renally impaired patient is administered a dose of oxymorphone or a pharmaceutically acceptable salt thereof that is less than the dose administered to a comparable patient without renal impairment, and wherein the log transformed AUC of oxymorphone is about 1.05 to about 2.45 times greater than the log transformed AUC of a healthy patient if the healthy patient were to be administered the same dose.

2. A method of treating pain in a renally impaired patient comprising administering a pharmaceutical composition comprising about 5 mg to about 80 mg of oxymorphone or a pharmaceutically acceptable salt thereof as the sole active ingredient and a controlled release matrix, wherein

(a) the renally impaired patient is administered a dose of oxymorphone or a pharmaceutically acceptable salt thereof that is less than the dose administered to a comparable patient without renal impairment,

(b) the creatinine clearance rate of the patient is determining it to be about 51 mL/min to about 80 mL/min, and

(c) the renally impaired patient has mild renal impairment and the ratio of AUC of oxymorphone or pharmaceutically acceptable salt thereof in the renally impaired patient to the comparable patient without renal impairment is about 0.86 to about 1.84 when administered equal doses.

3. The method of claim 2 , wherein the ratio of AUC of oxymorphone or pharmaceutically acceptable salt thereof in the renally impaired patient to the comparable patient without renal impairment is about 1.26 when administered equal doses.

4. The method of claim 2 , wherein the ratio of Cmax of oxymorphone or pharmaceutically acceptable salt thereof in the renally impaired patient to the comparable patient without renal impairment is about 0.94 to about 2.03 when administered equal doses.

5. The method of claim 4 , wherein the ratio of Cmax of oxymorphone or pharmaceutically acceptable salt thereof in the renally impaired patient to the comparable patient without renal impairment is about 1.38 when administered equal doses.

6. The method of claim 5 , wherein the ratio of AUC of oxymorphone or pharmaceutically acceptable salt thereof in the renally impaired patient to the comparable patient without renal impairment is about 1.26 when administered equal doses.

7. The method of claim 1 , wherein the renally impaired patient has moderate renal impairment and the ratio of AUC of oxymorphone or pharmaceutically acceptable salt thereof in the renally impaired patient to the comparable patient without renal impairment is about 1.07 to about 2.31 when administered equal doses.

8. The method of claim 7 , wherein the ratio of AUC of oxymorphone or pharmaceutically acceptable salt thereof in the renally impaired patient to the comparable patient without renal impairment is about 1.57 when administered equal doses.

9. The method of claim 7 , wherein the ratio of Cmax of oxymorphone or pharmaceutically acceptable salt thereof in the renally impaired patient to the comparable patient without renal impairment is about 1.12 to about 2.43 when administered equal doses.

10. The method of claim 9 , wherein the ratio of Cmax of oxymorphone or pharmaceutically acceptable salt thereof in the renally impaired patient to the comparable patient without renal impairment is about 1.65 when administered equal doses.

11. The method of claim 10 , wherein the ratio of AUC of oxymorphone or pharmaceutically acceptable salt thereof in the renally impaired patient to the comparable patient without renal impairment is about 1.57 when administered equal doses.

12. The method of claim 1 , wherein the renally impaired patient has severe renal impairment and the ratio of AUC of oxymorphone or pharmaceutically acceptable salt thereof in the renally impaired patient to the comparable patient without renal impairment is about 1.13 to about 2.42 when administered equal doses.

13. The method of claim 12 , wherein the ratio of AUC of oxymorphone or pharmaceutically acceptable salt thereof in the renally impaired patient to the comparable patient without renal impairment is about 1.65 when administered equal doses.

14. The method of claim 12 , wherein the ratio of Cmax of oxymorphone or pharmaceutically acceptable salt thereof in the renally impaired patient to the comparable patient without renal impairment is about 1.23 to about 2.65 when administered equal doses.

15. The method of claim 14 , wherein the ratio of Cmax of oxymorphone or pharmaceutically acceptable salt thereof in the renally impaired patient to the comparable patient without renal impairment is about 1.80 when administered equal doses.

16. The method of claim 15 , wherein the ratio of AUC of oxymorphone or pharmaceutically acceptable salt thereof in the renally impaired patient to the comparable patient without renal impairment is about 1.265 when administered equal doses.

17. The method of claim 2 , wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average AUC of oxymorphone over a 12-hour period is less than 21 ng·hr/mL.

18. The method of claim 2 , wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average AUC of oxymorphone over a 12-hour period is less than 20 ng·hr/mL.

19. The method of claim 2 , wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average AUC of oxymorphone over a 12-hour period is less than 19 ng·hr/mL.

20. The method of claim 3 , wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average AUC of oxymorphone over a 12-hour period is less than 21 ng·hr/mL.

21. The method of claim 3 , wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average AUC of oxymorphone over a 12-hour period is less than 20 ng·hr/mL.

22. The method of claim 3 , wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average AUC of oxymorphone over a 12-hour period is less than 19 ng·hr/mL.

23. The method of claim 6 , wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average AUC of oxymorphone over a 12-hour period is less than 21 ng·hr/mL.

24. The method of claim 6 , wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average AUC of oxymorphone over a 12-hour period is less than 20 ng·hr/mL.

25. The method of claim 6 , wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average AUC of oxymorphone over a 12-hour period is less than 19 ng·hr/mL.

26. The method of claim 7 , wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average AUC of oxymorphone over a 12-hour period is less than 21 ng·hr/mL.

27. The method of claim 7 , wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average AUC of oxymorphone over a 12-hour period is less than 20 ng·hr/mL.

28. The method of claim 7 , wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average AUC of oxymorphone over a 12-hour period is less than 19 ng·hr/mL.

29. The method of claim 8 , wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average AUC of oxymorphone over a 12-hour period is less than 21 ng·hr/mL.

30. The method of claim 8 , wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average AUC of oxymorphone over a 12-hour period is less than 20 ng·hr/mL.

31. The method of claim 8 , wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average AUC of oxymorphone over a 12-hour period is less than 19 ng·hr/mL.

32. The method of claim 11 , wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average AUC of oxymorphone over a 12-hour period is less than 21 ng·hr/mL.

33. The method of claim 11 , wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average AUC of oxymorphone over a 12-hour period is less than 20 ng·hr/mL.

34. The method of claim 11 , wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average AUC of oxymorphone over a 12-hour period is less than 19 ng·hr/mL.

35. The method of claim 12 , wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average AUC of oxymorphone over a 12-hour period is less than 21 ng·hr/mL.

36. The method of claim 12 , wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average AUC of oxymorphone over a 12-hour period is less than 20 ng·hr/mL.

37. The method of claim 12 , wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average AUC of oxymorphone over a 12-hour period is less than 19 ng·hr/mL.

38. The method of claim 13 , wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average AUC of oxymorphone over a 12-hour period is less than 21 ng·hr/mL.

39. The method of claim 13 , wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average AUC of oxymorphone over a 12-hour period is less than 20 ng·hr/mL.

40. The method of claim 13 , wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average AUC of oxymorphone over a 12-hour period is less than 19 ng·hr/mL.

41. The method of claim 16 , wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average AUC of oxymorphone over a 12-hour period is less than 21 ng·hr/mL.

42. The method of claim 16 , wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average AUC of oxymorphone over a 12-hour period is less than 20 ng·hr/mL.

43. The method of claim 16 , wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average AUC of oxymorphone over a 12-hour period is less than 19 ng·hr/mL.

44. The method of claim 4 , wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average Cmax of oxymorphone over a 12-hour period is less than about 1.4 ngmL.

45. The method of claim 4 , wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average Cmax of oxymorphone over a 12-hour period is less than about 1.3 ng/mL.

46. The method of claim 4 , wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average Cmax of oxymorphone over a 12-hour period is less than about 1.2 ng/mL.

47. The method of claim 5 , wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average Cmax of oxymorphone over a 12-hour period is less than about 1.4 ng/mL.

48. The method of claim 5 , wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average Cmax of oxymorphone over a 12-hour period is less than about 1.3 ng/mL.

49. The method of claim 5 , wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average Cmax of oxymorphone over a 12-hour period is less than about 1.2 ng/mL.

50. The method of claim 9 , wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average Cmax of oxymorphone over a 12-hour period is less than about 1.4 ng/mL.

51. The method of claim 9 , wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average Cmax of oxymorphone over a 12-hour period is less than about 1.3 ng/mL.

52. The method of claim 9 , wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average Cmax of oxymorphone over a 12-hour period is less than about 1.2 ng/mL.

53. The method of claim 10 , wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average Cmax of oxymorphone over a 12-hour period is less than about 1.4 ng/mL.

54. The method of claim 10 , wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average Cmax of oxymorphone over a 12-hour period is less than about 1.3 ng/mL.

55. The method of claim 10 , wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average Cmax of oxymorphone over a 12-hour period is less than about 1.2 ng/mL.

56. The method of claim 14 , wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average Cmax of oxymorphone over a 12-hour period is less than about 1.4 ng/mL.

57. The method of claim 14 , wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average Cmax of oxymorphone over a 12-hour period is less than about 1.3 ng/mL.

58. The method of claim 14 , wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average Cmax of oxymorphone over a 12-hour period is less than about 1.2 ng/mL.

59. The method of claim 15 , wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average Cmax of oxymorphone over a 12-hour period is less than about 1.4 ng/mL.

60. The method of claim 15 , wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average Cmax of oxymorphone over a 12-hour period is less than about 1.3 ng/mL.

61. The method of claim 15 , wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average Cmax of oxymorphone over a 12-hour period is less than about 1.2 ng/mL.

Assignments (10)
RELEASE OF SECURITY INTEREST Recorded Jul 31, 2026
From: COMPUTERSHARE TRUST COMPANY, NATIONAL ASSOCIATION
To: ENDO OPERATIONS LIMITED
Reel/Frame 075485/0685 →
SECURITY INTEREST Recorded Jul 22, 2024
From: ENDO BIOLOGICS LIMITED; ENDO OPERATIONS LIMITED
To: COMPUTERSHARE TRUST COMPANY, NATIONAL ASSOCIATION
Reel/Frame 068469/0001 →
SECURITY INTEREST Recorded Jul 19, 2024
From: ENDO BIOLOGICS LIMITED; ENDO OPERATIONS LIMITED
To: GOLDMAN SACHS BANK USA
Reel/Frame 068461/0692 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 27, 2024
From: ENDO USA, INC.
To: ENDO OPERATIONS LIMITED
Reel/Frame 067245/0492 →
RELEASE OF SECURITY INTEREST Recorded Apr 26, 2024
From: WILMINGTON TRUST, NATIONAL ASSOCIATION
To: ACTIENT PHARMACEUTICALS LLC; ASTORA WOMEN’S HEALTH HOLDINGS, LLC; ASTORA WOMEN’S HEALTH LLC; AUXILIUM PHARMACEUTICALS, LLC; AUXILIUM US HOLDINGS, LLC; BIOSPECIFICS TECHNOLOGIES CORP.; BIOSPECIFICS TECHNOLOGIES LLC; DAVA INTERNATIONAL, LLC; DAVA PHARMACEUTICALS, LLC; ENDO GENERIC HOLDINGS, INC. (FORMERLY KNOWN AS PAR PHARMACEUTICALS COMPANIES, INC.); ENDO PHARMACEUTICALS INC.; ENDO PHARMACEUTICALS SOLUTIONS INC. (FORMERLY KNOWN AS INDEVUS PHARMACEUTICALS, INC.); GENERICS BIDCO I, LLC; GENERICS INTERNATIONAL (US), INC.; PAR PHARMACEUTICAL, INC.; PAR STERILE PRODUCTS, LLC (FORMERLY KNOWN AS JHP PHARMACEUTICALS, LLC); QUARTZ SPECIALTY PHARMACEUTICALS, LLC; SLATE PHARMACEUTICALS, LLC; VINTAGE PHARMACEUTICALS, LLC
Reel/Frame 067240/0001 →
RELEASE OF SECURITY INTEREST Recorded Apr 25, 2024
From: WILMINGTON TRUST, NATIONAL ASSOCIATION
To: ACTIENT PHARMACEUTICALS LLC; ASTORA WOMEN’S HEALTH LLC; AUXILIUM PHARMACEUTICALS, LLC; AUXILIUM US HOLDINGS, LLC; BIOSPECIFICS TECHNOLOGIES CORP.; BIOSPECIFICS TECHNOLOGIES LLC; DAVA INTERNATIONAL, LLC; DAVA PHARMACEUTICALS, LLC; ENDO PHARMACEUTICALS INC.; ENDO PHARMACEUTICALS SOLUTIONS INC. (FORMERLY KNOWN AS INDEVUS PHARMACEUTICALS, INC.); GENERICS BIDCO I, LLC; GENERICS INTERNATIONAL (US), INC.; PAR PHARMACEUTICAL, INC.; PAR PHARMACEUTICAL COMPANIES, INC.; PAR STERILE PRODUCTS, LLC (FORMERLY KNOWN AS JHP PHARMACEUTICALS, LLC); QUARTZ SPECIALTY PHARMACEUTICALS, LLC; SLATE PHARMACEUTICALS, LLC; VINTAGE PHARMACEUTICALS, LLC
Reel/Frame 067239/0491 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 23, 2024
From: ENDO PHARMACEUTICALS INC.
To: ENDO USA, INC.
Reel/Frame 067203/0398 →
CONFIRMATORY GRANT OF SECURITY INTEREST IN UNITED STATES PATENTS Recorded Sep 17, 2021
From: ASTORA WOMEN'S HEALTH LLC; ENDO PHARMACEUTICALS SOLUTIONS INC.; ENDO PHARMACEUTICALS INC.; PAR PHARMACEUTICAL, INC.
To: WILMINGTON TRUST, NATIONAL ASSOCIATION
Reel/Frame 057538/0978 →
SECURITY INTEREST Recorded Jun 8, 2017
From: ENDO PHARMACEUTICALS INC
To: WILMINGTON TRUST, NATIONAL ASSOCIATION, AS COLLATERAL TRUSTEE
Reel/Frame 042742/0922 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 16, 2014
From: AHDIEH, HARRY
To: ENDO PHARMACEUTICALS INC.
Reel/Frame 033751/0785 →