Claims for Patent: 11,602,513

Summary for Patent: 11,602,513

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):	Jordan Dubow, Hervé Guillard, Claire Mégret, Jean-François DUBUISSON
Assignee:	Flamel Ireland Ltd
Application Number:	US17/497,393
Patent Claims:	1. A method of treating cataplexy or excessive daytime sleepiness in a human patient with narcolepsy, the method comprising orally administering to the patient a pharmaceutical formulation that comprises an immediate-release portion comprising an oxybate and a modified-release portion comprising an oxybate that may be the same as or different than the oxybate of the immediate-release portion, wherein the pharmaceutical formulation achieves a relative bioavailability of greater than 80% when compared to an equal dose of an immediate release liquid solution of sodium oxybate administered at t0 and t4h in equally divided doses, wherein the orally administering occurs only once per day at bedtime, and wherein the patient has statistically significant improvement on the Maintenance of Wakefulness Test (MWT) at a dosage of the pharmaceutical formulation equivalent to 4.5 g, 6 g, 7.5 g, or 9 g of sodium oxybate as compared to placebo. 2. The method of claim 1, wherein the patient has a latency to sleep onset about 5 minutes or more than placebo. 3. The method of claim 2, wherein the sleep latency is determined as the number of minutes a patient remains awake during the MWT. 4. The method of claim 2, wherein the patient has a reduction in weekly cataplexy attacks. 5. The method of claim 4, wherein the patient has an average total reduction in weekly cataplexy attacks from 4.83 to 6.65 as compared to placebo. 6. The method of claim 1, wherein the patient is concomitantly on a stimulant. 7. The method of claim 1, wherein the patient has an average improvement from 4.98 minutes to 6.21 minutes in the change from baseline in the MWT as compared to placebo. 8. The method of claim 1, wherein the patient has a 42.1% to 77.0% chance of being much improved or very much improved in a Clinical Global Impression-Improvement (CGI-I) score. 9. The method of claim 1, wherein the MWT measures latency to sleep onset in minutes averaged over five sessions at 2-hour intervals following nocturnal polysomnography. 10. A method of treating cataplexy or excessive daytime sleepiness in a human patient with narcolepsy, the method comprising: orally administering to the patient a pharmaceutical formulation that comprises an immediate-release portion comprising an oxybate and a modified-release portion comprising an oxybate that may be the same as or different than the oxybate of the immediate-release portion, wherein the pharmaceutical formulation achieves a relative bioavailability of greater than 80% when compared to an equal dose of an immediate release liquid solution of sodium oxybate administered at t0 and t4 h in equally divided doses, and wherein the orally administering occurs only once per day at bedtime at a dosage of the pharmaceutical formulation equivalent to 4.5 g, 6 g, 7.5 g, or 9 g of sodium oxybate, and inducing the patient to fall asleep within 15 minutes of the orally administering. 11. The method of claim 10, wherein the inducing comprising inducing the patient to fall asleep within 5 minutes of the orally administering due, at least in part, to the orally administering. 12. The method of claim 1, wherein the pharmaceutical formulation achieves a relative bioavailability of greater than 85%. 13. The method of claim 10, wherein the pharmaceutical formulation achieves a relative bioavailability of greater than 85%. 14. The method of claim 1, wherein the pharmaceutical formulation achieves a relative bioavailability of greater than 90%. 15. The method of claim 10, wherein the pharmaceutical formulation achieves a relative bioavailability of greater than 90%. 16. The method of claim 1, wherein the oxybate of the immediate-release portion is selected from the group consisting of pharmaceutically acceptable salts of gamma-hydroxybutyric acid, their hydrates, solvates, complexes or tautomers forms, and combinations thereof. 17. The method of claim 16, wherein the oxybate of the modified-release portion is selected from the group consisting of pharmaceutically acceptable salts of gamma-hydroxybutyric acid, their hydrates, solvates, complexes or tautomers forms, and combinations thereof. 18. The method of claim 1, wherein the oxybate of the modified-release portion is selected from the group consisting of pharmaceutically acceptable salts of gamma-hydroxybutyric acid, their hydrates, solvates, complexes or tautomers forms, and combinations thereof. 19. The method of claim 10, wherein the oxybate of the immediate-release portion is selected from the group consisting of pharmaceutically acceptable salts of gamma-hydroxybutyric acid, their hydrates, solvates, complexes or tautomers forms, and combinations thereof. 20. The method of claim 19, wherein the oxybate of the modified-release portion is selected from the group consisting of pharmaceutically acceptable salts of gamma-hydroxybutyric acid, their hydrates, solvates, complexes or tautomers forms, and combinations thereof. 21. The method of claim 10, wherein the oxybate of the modified-release portion is selected from the group consisting of pharmaceutically acceptable salts of gamma-hydroxybutyric acid, their hydrates, solvates, complexes or tautomers forms, and combinations thereof. 22. The method of claim 1, wherein the oxybate of the immediate-release portion is selected from the group consisting of the sodium salt of gamma-hydroxybutyric acid, the potassium salt of gamma-hydroxybutyric acid, the magnesium salt of gamma-hydroxybutyric acid, the calcium salt of gamma-hydroxybutyric acid, the lithium salt of gamma-hydroxybutyric, the tetra ammonium salt of gamma-hydroxybutyric acid, any other pharmaceutically acceptable salt forms of gamma-hydroxybutyric acid, and combinations thereof. 23. The method of claim 22, wherein the oxybate of the modified-release portion is selected from the group consisting of the sodium salt of gamma-hydroxybutyric acid, the potassium salt of gamma-hydroxybutyric acid, the magnesium salt of gamma-hydroxybutyric acid, the calcium salt of gamma-hydroxybutyric acid, the lithium salt of gamma-hydroxybutyric, the tetra ammonium salt of gamma-hydroxybutyric acid, any other pharmaceutically acceptable salt forms of gamma-hydroxybutyric acid, and combinations thereof. 24. The method of claim 1, wherein the oxybate of the modified-release portion is selected from the group consisting of the sodium salt of gamma-hydroxybutyric acid, the potassium salt of gamma-hydroxybutyric acid, the magnesium salt of gamma-hydroxybutyric acid, the calcium salt of gamma-hydroxybutyric acid, the lithium salt of gamma-hydroxybutyric, the tetra ammonium salt of gamma-hydroxybutyric acid, any other pharmaceutically acceptable salt forms of gamma-hydroxybutyric acid, and combinations thereof. 25. The method of claim 10, wherein the oxybate of the immediate-release portion is selected from the group consisting of the sodium salt of gamma-hydroxybutyric acid, the potassium salt of gamma-hydroxybutyric acid, the magnesium salt of gamma-hydroxybutyric acid, the calcium salt of gamma-hydroxybutyric acid, the lithium salt of gamma-hydroxybutyric, the tetra ammonium salt of gamma-hydroxybutyric acid, any other pharmaceutically acceptable salt forms of gamma-hydroxybutyric acid, and combinations thereof. 26. The method of claim 25, wherein the oxybate of the modified-release portion is selected from the group consisting of the sodium salt of gamma-hydroxybutyric acid, the potassium salt of gamma-hydroxybutyric acid, the magnesium salt of gamma-hydroxybutyric acid, the calcium salt of gamma-hydroxybutyric acid, the lithium salt of gamma-hydroxybutyric, the tetra ammonium salt of gamma-hydroxybutyric acid, any other pharmaceutically acceptable salt forms of gamma-hydroxybutyric acid, and combinations thereof. 27. The method of claim 10, wherein the oxybate of the modified-release portion is selected from the group consisting of the sodium salt of gamma-hydroxybutyric acid, the potassium salt of gamma-hydroxybutyric acid, the magnesium salt of gamma-hydroxybutyric acid, the calcium salt of gamma-hydroxybutyric acid, the lithium salt of gamma-hydroxybutyric, the tetra ammonium salt of gamma-hydroxybutyric acid, any other pharmaceutically acceptable salt forms of gamma-hydroxybutyric acid, and combinations thereof.