Claims for Patent: 11,504,347

Summary for Patent: 11,504,347

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):	Grassot Julien, Guillard Hervé, Mégret Claire, Dubuisson Jean-François
Assignee:	Flamel Ireland Limited
Application Number:	US17497366
Patent Claims:	1. A composition comprising a blend of granules for suspension in water , the blend of granules comprising an immediate release portion and a modified release portion , the granules comprising sodium oxybate , wherein the composition;is provided in a single dose packet,comprises 3.0 g, 4.5 g, 6 g, 7.5 g, or 9 g of sodium oxybate,is for the treatment of narcolepsy or a symptom thereof,is administered orally only once nightly,is effective to induce sleep in a human subject in need thereof for at least six hours, and{'sub': 'max', 'provides a Cwhich increases approximately 2-fold, and more than dose proportionally for AUC increasing approximately 2.3-fold, as a total daily dose is doubled.'}2. The composition of claim 1 , further comprising carrageenan claim 1 , hydrogenated vegetable oil claim 1 , hydroxyethyl cellulose claim 1 , magnesium stearate claim 1 , malic acid claim 1 , methacrylic acid copolymer claim 1 , microcrystalline cellulose claim 1 , povidone claim 1 , and/or xanthan gum.3. A composition comprising a blend of granules for suspension in water claim 1 , the blend of granules comprising an immediate release portion and a modified release portion claim 1 , the granules comprising sodium oxybate claim 1 , wherein the composition:is packaged in a once-nightly dose packet,comprises 3.0 g, 4.5 g, 6 g, 7.5 g, or 9 g of sodium oxybate,is for the treatment of narcolepsy or a symptom thereof,is administered orally only once nightly,is effective to induce sleep in a human subject in need thereof for at least six hours, and{'sub': 'max', 'provides a Cwhich increases approximately 2-fold, and more than dose proportionally for AUC increasing approximately 2.3-fold as a total daily dose is doubled.'}4. The composition of claim 1 , wherein the single dose packet is provided as part of a total of 7 or 30 single dose packets per package.5. The composition of claim 1 , wherein the composition is provided with a prepackaged mixing cup.6. The composition of claim 1 , further comprising approximately one-third of a cup of water to be used in forming a suspension with the composition.7. The composition of claim 1 , further comprising approximately 80 mL of water.8. The composition of claim 7 , wherein the water temperature is 50° C. or less.9. The composition of claim 1 , wherein the granules of the modified release portion are coated with a coating comprising:a polymer carrying free carboxylic groups, anda hydrophobic compound having a melting point equal or greater than 40° C.10. The composition of claim 1 , wherein the amount of sodium oxybate in the immediate release portion is equal to the amount of sodium oxybate in the modified release portion.11. The composition of claim 9 , wherein the polymer carrying free carboxylic groups has a pH trigger from 5.5 to 6.97.12. The composition of claim 9 , wherein the free carboxylic groups are ionized at pH 7.5.13. The composition of in an amount effective to treat narcolepsy Type 1 or Type 2 claim 1 , wherein said treatment of narcolepsy or a symptom thereof comprises reducing excessive daytime sleepiness claim 1 , reducing the frequency of cataplectic attacks claim 1 , or a combination thereof.14. The composition of in an amount effective to induce sleep for at least eight consecutive hours.15. The composition of claim 1 , wherein the ratio of sodium oxybate in the immediate release portion and the modified release portion is from 10/90 to 65/35.16. The composition of claim 1 , wherein the ratio of sodium oxybate in the immediate release portion and the modified release portion is from 40/60 to 60/40.17. The composition of claim 1 , wherein the granules of the immediate release portion have a mean diameter from 10 to 1000 microns claim 1 , and the granules of the modified release portion have a mean diameter from 100 to 1200 microns.18. The composition of claim 1 , wherein the granules comprising sodium oxybate in the immediate release portion have a mean diameter from 150 to 400 microns claim 1 , and the particles granules comprising sodium oxybate in the modified release portion have a mean diameter from 200 to 800 microns.19. The composition of claim 3 , wherein the composition provides a lower risk of causing a confusional state in a patient as compared to a twice-nightly oxybate composition.20. The composition of claim 3 , wherein the composition provides a 50% lower risk of causing a confusional state in a patient as compared to a twice-nightly oxybate composition.21. The composition of claim 3 , further comprising hydroxyethyl cellulose claim 3 , malic acid claim 3 , methacrylic acid copolymer claim 3 , microcrystalline cellulose claim 3 , and povidone.22. The composition of claim 3 , further comprising carrageenan claim 3 , hydrogenated vegetable oil claim 3 , hydroxyethyl cellulose claim 3 , malic acid claim 3 , methacrylic acid copolymer claim 3 , microcrystalline cellulose claim 3 , povidone claim 3 , and/or xanthan gum.23. The composition of claim 1 , further comprising a suspending agent that prevents the granules from settling in less than 1 minute when suspended in water.24. A composition comprising a blend of granules for suspension in water claim 1 , the granules comprising from 3.0 to 9.0 g sodium oxybate claim 1 , wherein the composition:is packaged in a once-nightly dose packet,is for the treatment of narcolepsy or a symptom thereof,is effective to induce sleep in a human subject in need thereof,is administered orally only once nightly, and{'sub': 'max', 'produces a dose-proportional C.'}25. A composition comprising a blend of granules for suspension in water claim 1 , the granules comprising from 3.0 to 9.0 g sodium oxybate claim 1 , wherein the composition:is packaged in a once-nightly dose packet,is for the treatment of narcolepsy or a symptom thereof,is effective to induce sleep in a human subject in need thereof,is administered orally only once nightly, and{'sub': 'inf', 'produces a more than dose-proportional in AUC.'}