Claims for Patent: 12,303,478

Summary for Patent: 12,303,478

Title:	Gamma-hydroxybutyrate compositions having improved pharmacokinetics in the fed state
Abstract:	Oral pharmaceutical compositions of sodium oxybate having improved pharmacokinetic properties when administered less than two hours after eating are provided, and therapeutic uses thereof.
Inventor(s):	Julien Grassot, Cendrine Grangeon, Jordan Dubow
Assignee:	Flamel Ireland Ltd
Application Number:	US18/898,132
Patent Claims:	1. A method of decreasing excessive daytime sleepiness in a human patient, the method comprising: orally administering a formulation that comprises an immediate-release portion and a modified-release portion to the patient, wherein the formulation comprises an amount of gamma-hydroxybutyrate equivalent to from 3.0 g to 12 g of sodium oxybate, wherein the orally administering occurs only once daily at bedtime, wherein, the administered formulation releases gamma-hydroxybutyrate info the blood stream of the patient, and wherein the Cmax of the formulation is dose proportional. 2. The method of claim 1, wherein the formulation decreases daytime sleepiness as measured by the Maintenance of Wakefulness Test. 3. The method of claim 1, wherein the formulation decreases excessive daytime sleepiness (EDS) as measured by the Epworth Sleepiness Scale (ESS). 4. The method of claim 1, wherein the formulation reduces frequency of cataplectic attacks. 5. The method of claim 1, wherein the formulation decreases disturbed nocturnal sleep (DNS) as determined by polysomnographic (PSG) measures of sleep fragmentation. 6. The method of claim 1, wherein the formulation decreases hypnogogic hallucinations (HH) or sleep paralysis (SP). 7. The method of claim 1, wherein the Cmax of the formulation is dose proportional by a factor of about 1 to about 1.3. 8. The method of claim 1, wherein the Cmax of the formulation is dose proportional by a factor of about 1. 9. The method of claim 1, wherein the Cmax of the formulation increases 2.0-fold as a once daily dose of the formulation increases from an amount equivalent to 4.5 g to 9 g of sodium oxybate. 10. The method of claim 1, wherein the AUC of the formulation is more than dose proportional across once-daily dosages of the formulation. 11. The method of claim 10, wherein the AUC of the formulation increases 2.3-fold as a once daily dose of the formulation increases from an amount equivalent to 4.5 g to 9 g of sodium oxybate. 12. The method of claim 1, wherein the AUC of the formulation is dose proportional by a factor of about 1.3. 13. The method of claim 1, wherein the formulation provides an AUCinf bioequivalent to the AUCinf as depicted in a figure selected from FIGS. 4A, 5A, 5B, 6A, 6B, or 7A. 14. The method of claim 1, wherein the formulation provides a mean blood concentration (ug/ml) at 8 hours similar to that of twice-nightly IR sodium oxybate. 15. The method of claim 1, wherein the formulation comprises an amount of gamma-hydroxybutyrate equivalent to 6 g of sodium oxybate, the administering occurs less than two hours after eating, and the formulation achieves a mean AUCinf of greater than 230 hr*microgram/mL. 16. The method of claim 15, wherein the mean AUCinf has an upper limit of 300 hr*microgram/mL. 17. The method of claim 15, wherein the mean AUCinf has an upper limit of 350 hr*microgram/mL. 18. The method of claim 1, wherein the formulation comprises an amount of gamma-hydroxybutyrate equivalent to 6 g of sodium oxybate, the administering occurs less than two hours after eating, and the formulation achieves a mean Cmax of greater than 50 μg/mL. 19. The method of claim 18, wherein the mean Cmax has an upper limit of 75 μg/mL. 20. The method of claim 18, wherein the mean Cmax has an upper limit of 90 μg/mL. 21. The method of claim 1, wherein the formulation comprises an amount of gamma-hydroxybutyrate equivalent to 6 g of sodium oxybate, the administering occurs less than two hours after eating, and the formulation achieves a mean AUC8h of greater than 1, 2, 3, 4, 5, or 6 μg/mL. 22. The method of claim 1, wherein the formulation comprises an amount of gamma-hydroxybutyrate equivalent to 6 g of sodium oxybate, the administering occurs less than two hours after eating, and the formulation achieves a mean t1/2 of greater than 0.5, 1, or 1.5 hours. 23. The method of claim 1, wherein the formulation comprises an amount of gamma-hydroxybutyrate equivalent to 9 g of sodium oxybate, the administering occurs less than two hours after eating, and the formulation achieves a mean AUCinf of greater than 350 hr*microgram/mL. 24. The method of claim 23, wherein the mean AUCinf has an upper limit of 550 hr*microgram/mL. 25. The method of claim 23, wherein the mean AUCinf has an upper limit of 600 hr*microgram/mL. 26. The method of claim 1, wherein the formulation comprises an amount of gamma-hydroxybutyrate equivalent to 9 g of sodium oxybate, the administering occurs less than two hours after eating, and the formulation achieves a mean Cmax of greater than 60 g/mL. 27. The method of claim 26, the mean Cmax has an upper limit of 100 μg/mL. 28. The method of claim 26, wherein the mean Cmax has an upper limit of 125 μg/mL. 29. A method of decreasing excessive daytime sleepiness in a human patient, the method comprising: orally administering a formulation that comprises an immediate-release portion and a modified-release portion to the patient, wherein the formulation comprises an amount of gamma-hydroxybutyrate equivalent to from 3.0 g to 12 g of sodium oxybate, wherein the orally administering occurs only once daily at bedtime, wherein the administered formulation releases gamma-hydroxybutyrate info the blood stream of the patient, and wherein the formulation exhibits predictable increases in plasma levels with increasing doses of the formulation. 30. The method of claim 29, wherein the formulation achieves pharmacokinetics that are dose proportional.