Claims for Patent: 12,128,021

Summary for Patent: 12,128,021

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):	Claire Mégret, Hervé Guillard, Jean-François DUBUISSON
Assignee:	Flamel Ireland Ltd
Application Number:	US18/643,773
Patent Claims:	1. A method of treating a disorder treatable with gamma-hydroxybutyrate in a human subject in need thereof, the method comprising: initiating a dosage of a pharmaceutical formulation equivalent to 4.5 g of sodium oxybate once per night orally, wherein the pharmaceutical formulation comprises an immediate-release (IR) portion and a modified-release (MR) portion; up-titrating the once per night dosage in an amount equivalent to 1.5 g of sodium oxybate; maintaining the up-titrated once per night dosage for at least a week before any further up-titrating; and ceasing any further up-titrating upon effect. 2. The method of claim 1, wherein the once per night dosage is increased by an amount equivalent to 1.5 g of sodium oxybate per night to an effective dosage range of an amount equivalent to 6 g to 9 g of sodium oxybate per night. 3. The method of claim 2, wherein the once per night dosage is increased by an amount equivalent to 1.5 g of sodium oxybate per night to an effective dosage amount equivalent to 6 g of sodium oxybate per night. 4. The method of claim 2, wherein the once per night dosage is increased by an amount equivalent to 1.5 g of sodium oxybate per night to an effective dosage amount equivalent to 7.5 g of sodium oxybate per night. 5. The method of claim 2, wherein the once per night dosage of sodium oxybate is increased by an amount equivalent to 1.5 g of sodium oxybate per night to an effective dosage amount equivalent to 9 g of sodium oxybate per night. 6. The method of claim 1, wherein the up-titrated once per night dosage is maintained for at least two weeks before any further up-titrating occurs. 7. The method of claim 1, wherein initiating comprises dosing at an amount equivalent to 4.5 g of sodium oxybate for week 1, and then up-titrating to a dosage amount equivalent to 6 g of sodium oxybate once per night dosage for at least weeks 2-3. 8. The method of claim 7, wherein the method comprises up-titrating to a dosage amount equivalent to 7.5 g of sodium oxybate once per night dosage for at least weeks 4-8. 9. The method of claim 8, wherein the method comprises up-titrating to a dosage amount equivalent to 9 g of sodium oxybate once per night dosage for at least weeks 9-13. 10. The method of claim 1, wherein the ceasing comprises maintaining a stable dosage amount equivalent to 6 g, 7.5 g, or 9 g of sodium oxybate once per night orally. 11. The method of claim 1, wherein the once per night dosage does not change once a dosage amount equivalent to 9 g of sodium oxybate per night is reached. 12. The method of claim 1, further comprising administering a stimulant to the human patient. 13. The method of claim 1, wherein doses higher than an amount equivalent to 9 g of sodium oxybate per night are not to be administered to the human patient. 14. A method of treating a disorder treatable with gamma-hydroxybutyrate in a human subject in need thereof, the method comprising: initiating a dosage of a pharmaceutical formulation equivalent to 4.5 g of sodium oxybate once per night orally, wherein the pharmaceutical formulation comprises an immediate-release (IR) portion and a modified-release (MR) portion; and up-titrating the once per night dosage to effect in increments equivalent to 1.5 g of sodium oxybate per night; maintaining each up-titrated once per night dosage for at least one week before any further up-titrating. 15. The method of claim 14, wherein the effective once per night dosage is equivalent to 6 g of sodium oxybate per night. 16. The method of claim 14, wherein the effective once per night dosage is equivalent to 7.5 g of sodium oxybate per night. 17. The method of claim 14, wherein the effective once per night dosage is equivalent to 9 g of sodium oxybate per night. 18. The method of claim 14, wherein the up-titrating occurs over a period of at least three weeks. 19. The method of claim 14, wherein the up-titrating occurs over a period of at least five weeks. 20. A method of treating a disorder treatable with gamma-hydroxybutyrate in a human subject in need thereof, the method comprising: initiating a dosage of a pharmaceutical formulation equivalent to 4.5 g of sodium oxybate once per night orally, wherein the pharmaceutical formulation comprises an immediate-release (IR) portion and a modified-release (MR) portion; and maintaining the dosage at an amount equivalent to 4.5 g of sodium oxybate once per night for week 1; up-titrating the dosage to an amount equivalent to 6 g of sodium oxybate once per night; and maintaining the up-titrated dosage for at least weeks 2-3. 21. The method of claim 20, further comprising: further up-titrating the dosage to an amount equivalent to 7.5 g of sodium oxybate once per night; and maintaining the further up-titrated dosage for at least weeks 4-8. 22. The method of claim 21, further comprising: still further up-titrating the dosage to an amount equivalent to 9 g of sodium oxybate once per night; and maintaining the still further up-titrated dosage for at least weeks 9-13. 23. A method of treating a disorder treatable with gamma-hydroxybutyrate in a human subject in need thereof, the method comprising: initiating a dosage of a pharmaceutical formulation equivalent to 4.5 g of sodium oxybate once per night orally, wherein the pharmaceutical formulation comprises an immediate-release portion and a modified-release portion; and up-titrating the once per night dosage to effect in increments equivalent to 1.5 g of sodium oxybate per night at weekly intervals for at least one week. 24. The method of claim 23, wherein the once per night dosage is increased by an amount equivalent to 1.5 g of sodium oxybate per night at weekly intervals to an effective dosage range of an amount equivalent to 6 g to 9 g of sodium oxybate once per night orally. 25. The method of claim 23, wherein the titrating occurs over a period of eight weeks. 26. The method of claim 23, further comprising maintaining a stable dosage amount equivalent to 6 g, 7.5 g, or 9 g of sodium oxybate once per night, wherein the maintaining occurs after the up-titrating.