Claims for Patent: 11,065,224

Summary for Patent: 11,065,224

Title:	Modified release gamma-hydroxybutyrate formulations having improved pharmacokinetics
Abstract:	Modified release formulations of gamma-hydroxybutyrate having improved dissolution and pharmacokinetic properties are provided, and therapeutic uses thereof.
Inventor(s):	Megret Claire, Guillard Herve, Dubuisson Jean-Francois
Assignee:	Flamel Ireland Limited
Application Number:	US16527633
Patent Claims:	1. A pharmaceutical composition that releases gamma-hydroxybutyrate in the blood stream of a human subject , wherein the composition is designed to be administered only once per night , wherein the composition is effective to induce sleep for at least six consecutive hours , and wherein upon administration to a human subject approximately two hours after a standardized evening meal and{'figref': {'@idref': 'DRAWINGS', 'FIG. 12'}, 'at a dose equivalent to 4.5 g or 6.0 g of sodium oxybate, the composition yields a plasma concentration versus time curve bioequivalent to the plasma concentration versus time curve depicted in for the corresponding dose;'}{'figref': {'@idref': 'DRAWINGS', 'FIG. 13'}, 'at a dose equivalent to 4.5 g, 6.0 g, or 7.5 g of sodium oxybate, the composition yields a plasma concentration versus time curve bioequivalent to the plasma concentration versus time curve depicted in for the corresponding dose; or'}{'figref': {'@idref': 'DRAWINGS', 'FIG. 90'}, 'at a dose equivalent to 4.5 g, 7.5 g, or 9.0 g of sodium oxybate, the composition yields a plasma concentration versus time curve bioequivalent to the plasma concentration versus time curve depicted in for the corresponding dose.'}2. The pharmaceutical composition of claim 1 , wherein the composition yields dissolution profiles bioequivalent to the dissolution profiles depicted in and .3. The pharmaceutical composition of claim 1 , wherein the composition yields dissolution profiles bioequivalent to the dissolution profiles depicted in and .4. The pharmaceutical composition of claim 1 , wherein the composition yields a dissolution profile between the minimum and maximum values depicted in and .5. The pharmaceutical composition of claim 1 , wherein the composition yields a dissolution profile between the minimum and maximum values depicted in and .6. The pharmaceutical composition of claim 1 , wherein the composition yields a dissolution profile between the minimum and maximum values depicted in and .7. The pharmaceutical composition of claim 1 , wherein the composition is defined based on the concentration of gamma-hydroxybutyrate in the blood stream 8 hours after administration to a patient claim 1 , and further wherein a dose equivalent to a 4.5 g dose of sodium oxybate achieves a mean Cof from 4.7 to 9.0 microgram/mL.8. The pharmaceutical composition of claim 1 , wherein the composition is defined based on the concentration of gamma-hydroxybutyrate in the blood stream 8 hours after administration to a patient claim 1 , and further wherein a dose equivalent to a 4.5 g dose of sodium oxybate achieves a mean Cof from 3.5 to 4.7 microgram/mL.9. The pharmaceutical composition of claim 1 , wherein the composition is defined based on the concentration of gamma-hydroxybutyrate in the blood stream 8 hours after administration to a patient claim 1 , and further wherein a dose equivalent to a 6.0 g dose of sodium oxybate achieves a mean Cof from 6.3 to 16.7 microgram/mL.10. The pharmaceutical composition of claim 1 , wherein the composition is defined based on the concentration of gamma-hydroxybutyrate in the blood stream 8 hours after administration to a patient claim 1 , and further wherein a dose equivalent to a 6.0 g dose of sodium oxybate achieves a mean Cof from 7.3 to 15.4 microgram/mL.11. The pharmaceutical composition of claim 1 , wherein the composition is defined based on the concentration of gamma-hydroxybutyrate in the blood stream 8 hours after administration to a patient claim 1 , and further wherein a dose equivalent to a 7.5 g dose of sodium oxybate achieves a mean Cof from 13.0 to 40.3 microgram/mL.12. The pharmaceutical composition of claim 1 , wherein the composition is defined based on the concentration of gamma-hydroxybutyrate in the blood stream 8 hours after administration to a patient claim 1 , and further wherein a dose equivalent to a 7.5 g dose of sodium oxybate achieves a mean Cof from 24.7 to 37.2 microgram/mL.13. The pharmaceutical composition of claim 1 , wherein the composition is defined based on the time required to reach maximum blood concentration of gamma-hydroxybutyrate to a patient claim 1 , and further achieves a median Tof 1.25 to 3.25 hours when administered once approximately two hours after a standardized evening meal.14. The pharmaceutical composition of claim 1 , wherein the composition is defined based on the time required to reach maximum blood concentration of gamma-hydroxybutyrate to a patient claim 1 , and further achieves a median Tof 0.5 to 3.25 hours when administered once approximately two hours after a standardized evening meal.15. The pharmaceutical composition of claim 1 , wherein the composition yields a dissolution profile bioequivalent to the dissolution profile depicted in .16. The pharmaceutical composition of claim 1 , wherein the composition yields a dissolution profile bioequivalent to the dissolution profile depicted in .17. The pharmaceutical composition of claim 1 , wherein the composition yields a dissolution profile bioequivalent to the dissolution profile depicted in .18. The pharmaceutical composition of claim 1 , wherein the composition yields a dissolution profile bioequivalent to the dissolution profile depicted in .19. The pharmaceutical composition of claim 1 , wherein the composition yields dissolution profiles bioequivalent to the dissolution profiles depicted in and .20. The pharmaceutical composition of claim 1 , wherein the composition yields dissolution profiles bioequivalent to the dissolution profiles depicted in and .21. The pharmaceutical composition of claim 1 , wherein the composition yields dissolution profiles bioequivalent to the dissolution profiles depicted in and .22. The pharmaceutical composition of claim 1 , wherein the composition yields a dissolution profile bioequivalent to the dissolution profile depicted in .23. The pharmaceutical composition of claim 1 , wherein the composition yields dissolution profiles bioequivalent to the dissolution profiles depicted in and .24. The pharmaceutical composition of claim 1 , wherein the composition yields dissolution profiles bioequivalent to the dissolution profiles depicted in and .25. The pharmaceutical composition of claim 1 , wherein the composition yields dissolution profiles bioequivalent to the dissolution profiles depicted in and .26. The pharmaceutical composition of claim 1 , wherein the composition yields a dissolution profile bioequivalent to the dissolution profile depicted in .27. The pharmaceutical composition of claim 1 , wherein the composition yields dissolution profiles bioequivalent to the dissolution profiles depicted in and .28. The pharmaceutical composition of claim 1 , wherein the composition yields dissolution profiles bioequivalent to the dissolution profiles depicted in and .29. The pharmaceutical composition of claim 1 , wherein the composition yields dissolution profiles bioequivalent to the dissolution profiles depicted in and .30. The pharmaceutical composition of claim 1 , wherein the composition yields dissolution profiles bioequivalent to the dissolution profiles depicted in and .31. The pharmaceutical composition of claim 1 , wherein the composition yields dissolution profiles bioequivalent to the dissolution profiles depicted in and .32. The pharmaceutical composition of claim 1 , wherein the composition yields dissolution profiles bioequivalent to the dissolution profiles depicted in and .33. The pharmaceutical composition of claim 1 , wherein the composition yields dissolution profiles bioequivalent to the dissolution profiles depicted in and .34. The pharmaceutical composition of claim 1 , wherein the composition yields dissolution profiles bioequivalent to the dissolution profiles depicted in and .35. The pharmaceutical composition of claim 1 , wherein the composition yields dissolution profiles bioequivalent to the dissolution profiles depicted in and .36. The pharmaceutical composition of claim 1 , wherein the composition yields dissolution profiles bioequivalent to the dissolution profiles depicted in and .37. The pharmaceutical composition of claim 1 , wherein the composition yields dissolution profiles bioequivalent to the dissolution profiles depicted in and .38. The pharmaceutical composition of claim 1 , wherein the composition is effective to induce sleep for at least eight consecutive hours.