Compositions and methods of using modified release solabegron for lower urinary tract symptoms

1. A method for treating LUTS in a patient in need thereof, comprising: administering once a day to the patient a pharmaceutical composition for the delivery of a therapeutically effective amount of solabegron, comprising: an immediate release composition, comprising solabegron and at least one pharmaceutically acceptable carrier or diluent; and a delayed release composition, comprising solabegron and at least one pharmaceutically acceptable carrier or diluent to the patient, wherein the immediate release composition achieves a first plasma C max , the delayed release composition achieves a second plasma C max , a first plasma C min is achieved after the first plasma C max and before the second plasma C max and a second plasma C min is achieved after the second plasma C max ; wherein the first plasma C max is about 0.5 ug/ml to about 4.0 ug/ml in about 0.75 to about 4 hours after administration of the pharmaceutical composition; wherein the first plasma C min is about 0.25 ug/ml to about 1.5 ul/ml in about 4 to about 8 hours after administration of the pharmaceutical composition; wherein the second plasma C max is about 0.5 ug/ml to about 4 ug/ml in about 2 to about 8 hours after the first plasma C min ; wherein the second plasma C min is about 0.01 ug/ml to about 1.0 ug/ml before about 24 hours after administration of the pharmaceutical composition; wherein the pharmaceutical composition reduces desensitization of the beta-3 adrenoceptor, when compared to an immediate release pharmaceutical composition of solabegron administered twice daily.

2. The method according to claim 1 , further comprising administering one or more additional therapeutic agents or treatments useful for the treatment of LUTS, wherein the one more additional therapeutic agents or treatments are selected from the groups consisting of: antimuscarinic agents; alpha adrenoceptor blockers; botulinum toxin; purinergics; cannabinoids; transient receptor potential (TRP) protein inhibitors; prostaglandins; percutaneous tibial nerve stimulation; 5-alpha reductase inhibitors; and phosphodiesterase-5 inhibitors.

3. The method according to claim 2 , wherein the one or more additional therapeutic agents may be administered prior to, simultaneously with, or following the administration of the pharmaceutical composition comprising solabegron.

4. The method of claim 1 , wherein said LUTS is selected from overactive bladder and a prostate disorder.

5. The method of claim 4 , wherein treating overactive bladder comprises treating one or more symptoms of OAB selected from the group consisting of: frequency of urinary urgency; nocturia; increase in urinary micturition frequency; and urinary incontinence, voided volume, post-void residual volume and patient reported outcomes.

6. The method of claim 1 , wherein the immediate release comprises about 75 mg to about 250 mg of solabegron.

7. The method of claim 1 , wherein the delayed release comprises about 100 mg to about 400 mg of solabegron.

8. The method of claim 1 , wherein the immediate release comprises 50, 55, 60, 65, 75, 80, 85, 90, 95, 100, 105, 110, 115, 120, 125, 130, 135, 140, 145 or 150 mg of solabegron.

9. The method of claim 1 , wherein the delayed release comprises 100, 105, 110, 115, 120, 125, 130, 135, 140, 145, 150, 155, 160, 165, 170, 175, 180, 185, 190, 195, 200, 205, 210, 215, 220, 225, 230, 235, 240, 245, 250, 255, 260, 265, 270, 275, 280, 285, 290, 295, 300, 305, 310, 315, 320, 325, 330, 335, 340, 345 or 350 mg of solabegron.

10. The method of claim 1 , wherein the immediate release composition is an immediate release drug layer and the delayed release composition is a delayed release core, wherein the immediate release drug layer is coated on the delayed release core.

11. The method of claim 1 , wherein the pharmaceutical composition is a single unit dose.

12. The method according to claim 1 , wherein the first plasma C max is about 0.5 μg/ml to about 3.5 μg/ml.

13. The method according to claim 1 , wherein the first plasma C max is about 1 μg/ml to about 3.5 μg/ml.

14. The method according to claim 1 , wherein the first plasma C max is about 1 μg/ml to about 2 μg/ml.

15. The method according to claim 1 , wherein the first plasma C max is about 1.5 μg/ml to about 4 μg/ml.

16. The method according to claim 1 , wherein the first plasma C max is about 1.5 μg/ml to about 3.5 μg/ml.

17. The method according to claim 1 , wherein the first plasma C max is about 1.5 μg/ml to about 3.0 μg/ml.

18. The method according to claim 1 , wherein the first plasma C max is about 2.0 μg/ml to about 3.5 μg/ml.

19. The method according to claim 1 , wherein the first plasma C max is about 2.0 μg/ml to about 3.0 μg/ml.

20. The method according to claim 1 , wherein the first plasma C max is achieved about 1.5 hours to about 3 hours after administration of the pharmaceutical composition.

21. The method according to claim 1 , wherein the first plasma C max is achieved about 1 hours to about 3 hours after administration of the pharmaceutical composition.

22. The method according to claim 1 , wherein the first plasma C max is about 1.5 μg/ml to about 4.0 μg/ml.

23. The method according to claim 1 , wherein the second plasma C max is about 1.5 μg/ml to about 3.0 μg/ml.

24. The method according to claim 1 , wherein the second plasma C max is about 2.5 μg/ml to about 4.0 μg/ml.

25. The method according to claim 1 , wherein the second plasma C max is about 2.0 μg/ml to about 4.0 μg/ml.

26. The method according to claim 1 , wherein the second plasma C max is about 2.0 μg/ml to about 3.0 μg/ml.

27. The method according to claim 1 , wherein the second plasma C max is about 3.0 μg/ml to about 4.0 μg/ml.

28. The method according to claim 1 , wherein the second plasma C max is achieved in about 4 to about 6 hours after the first blood plasma C min .

29. The method according to claim 1 , wherein the second plasma C max is achieved in about 14 to about 16 hours after administration of the pharmaceutical composition.

30. The method according to claim 1 , wherein the first plasma C min is from about 0.25 μg/ml to about 1 μg/ml.

31. The method according to claim 1 , wherein the first plasma C min is from about 0.5 μg/ml to about 1.5 μg/ml.

32. The method according to claim 1 , wherein the first plasma C min is from about 0.5 μg/ml to about 1.0 μg/ml.

33. The method according to claim 1 , wherein the first plasma C min is from about 0.75 μg/ml to about 1.5 μg/ml.

34. The method according to claim 1 , wherein the first plasma C min is from about 0.25 μg/ml to about 1.25 μs/ml.

35. The method according to claim 1 , wherein the first plasma C min is achieved about 5 to about 6 hours after administration of the pharmaceutical composition.

36. The method according to claim 1 , wherein the second plasma C min is from about 0.01 μg/ml to about 0.5 μg/ml.

37. The method according to claim 1 , wherein the second plasma C min is from about 0.1 μg/ml to about 1.0 μg/ml.

38. The method according to claim 1 , wherein the second plasma C min is from about 0.25 μg/ml to about 1.0 μg/ml.

39. The method according to claim 1 , wherein the second plasma C min is from about 0.5 μg/ml to about 1.0 μg/ml.

40. The method according to claim 1 , wherein the second plasma C min is from about 0.75 μg/ml to about 1.0 μg/ml.

41. The method according to claim 1 , wherein the second plasma C min is less than about 0.5 μg/ml.

42. The method according to claim 1 , wherein the second plasma C min is achieved before about 20 hours after administration of the pharmaceutical composition.

43. The method according to claim 1 , wherein the second plasma C min is achieved before about 16 hours after administration of the pharmaceutical composition.

44. The method according to claim 1 , wherein the pharmaceutical composition achieves a plasma concentration of about 1 μg/ml or below for about 6 to about 9 hours during a 24 hour period.

45. The method according to claim 1 , wherein the pharmaceutical composition achieves a plasma concentration of about 1 μg/ml or below for about 7 to about 8 hours during a 24 hour period.

46. The method according to claim 1 , wherein the pharmaceutical composition achieves a plasma concentration of about 0.5 μg/ml or below for about 12 to about 18 hours.

47. The method according to claim 1 , wherein the pharmaceutical composition achieves an area under the curve (AUC) of about 11,000 ng hr/ml to about 30,000 ng hr/ml over a 24 hour period.

48. The method according to claim 1 , wherein the time between the first plasma C max and the second blood plasma C max is about 3 hours to about 7 hours.

49. The method according to claim 1 , wherein the time between the first plasma C max and the second blood plasma C max is about 4 hours to about 6 hours.

50. The method of claim 1 , wherein the immediate release comprises about 30 mg to about 500 mg of solabegron.

51. The method of claim 1 , wherein the immediate release comprises about 75 mg to about 400 mg of solabegron.

52. The method of claim 1 , wherein the immediate release comprises about 75 mg to about 250 mg of solabegron.

53. The method of claim 1 , wherein the immediate release comprises about 100 mg to about 300 mg of solabegron.

54. The method of claim 1 , wherein the immediate release comprises about 125 mg of solabegron.

55. The method of claim 1 , wherein the immediate release comprises about 200 mg of solabegron.

56. The method of claim 1 , wherein the delayed release comprises about 75 mg to about 400 mg of solabegron.

57. The method of claim 1 , wherein the delayed release comprises about 100 mg to about 300 mg of solabegron.

58. The method of claim 1 , wherein the delayed release comprises about 30 mg to about 500 mg of solabegron.

59. The method of claim 1 , wherein the delayed release comprises about 125 mg of solabegron.

60. The method of claim 1 , wherein the delayed release comprises about 200 mg of solabegron.