Modified release gamma-hydroxybutyrate formulations having improved pharmacokinetics
Modified release formulations of gamma-hydroxybutyrate having improved dissolution and pharmacokinetic properties are provided, and therapeutic uses thereof.
1. A formulation of gamma-hydroxybutyrate comprising:
an immediate release portion comprising gamma-hydroxybutyrate;
a modified release portion comprising gamma-hydroxybutyrate;
a suspending or viscosifying agent selected from the group consisting of xanthan gum, carrageenan gum, gellan gum, guar gum, sodium alginate, calcium alginate, agar, sodium carboxymethyl cellulose, microcrystalline cellulose, hydroxyethyl cellulose, hydroxypropylmethyl cellulose, and mixtures thereof; and
an acidifying agent selected from the group consisting of malic acid, citric acid, tartaric acid, adipic acid, boric acid, maleic acid, phosphoric acid, ascorbic acid, oleic acid, capric acid, caprylic acid, and benzoic acid;
wherein the suspending or viscosifying agent and the acidifying agent are separate and distinct from the immediate release portion and the modified release portion; and
wherein the ratio of gamma-hydroxybutyrate in the immediate release portion and the modified release portion is from 10/90 to 65/35.
2. The formulation of claim 1 , wherein the suspending or viscosifying agent is present at 1% to 15% by weight of the formulation, and the acidifying agent is present at 1.2% to 15% by weight of the formulation.
3. The formulation of claim 2 , wherein:
the suspending or viscosifying agent is a mixture of xanthan gum, carrageenan gum, and hydroxyethylcellulose, or a mixture of xanthan gum and carrageenan gum, and
the acidifying agent is malic acid or tartaric acid.
4. The formulation of claim 1 , wherein the formulation further comprises a lubricant or glidant selected from the group consisting of magnesium stearate, calcium stearate, zinc stearate, glyceryl monostearate, glyceryl palmitostearate, glycerol behenate, sodium stearyl fumarate, talc, or colloidal silicon dioxide.
5. The formulation of claim 1 , wherein the formulation is a dry particulate formulation or a powdered formulation.
6. The formulation of claim 1 , wherein the formulation comprises 4.5 g, 6.0 g, 7.5 g, or 9.0 g of gamma-hydroxybutyrate.
7. The formulation of claim 1 , wherein the formulation comprises gamma-hydroxybutyrate in the form of sodium oxybate.
8. The formulation of claim 1 , wherein modified release portion comprises a hydrophobic compound having a melting point equal to or greater than 40° C.
9. The formulation of claim 1 , wherein a dose of the formulation achieves a relative bioavailability (RBA) of greater than 80% when compared to an equal dose of an immediate release liquid solution of sodium oxybate administered at t 0 and t 4h in equally divided doses, when administered approximately two hours after a standardized evening meal.
10. The formulation of claim 1 , wherein a dose of the formulation achieves a ratio of mean AUC 8h to mean AUC inf of greater than 0.80 when administered once approximately two hours after a standardized evening meal.
11. The formulation of claim 1 , wherein a dose of the formulation achieves a median T max within 150 minutes of the median T max of half the dose of an immediate release liquid solution of sodium oxybate, when administered approximately two hours after a standardized evening meal.
12. The formulation of claim 1 , wherein a dose of the formulation achieves a mean C 6h or mean C 7h greater than, and a mean C 10h less than, the mean C 4h of half the dose of an immediate release liquid solution of sodium oxybate, when administered approximately two hours after a standardized evening meal.
13. The formulation of claim 1 , wherein a dose of the formulation achieves a mean AUC inf of greater than 80% of the mean AUC inf provided by an equal dose of immediate release liquid solution of sodium oxybate administered at t 0 and t 4h in equally divided doses approximately two hours after a standardized evening meal, and a mean C 8h less than 95% of the mean C 8h provided by an equal dose of immediate release liquid solution of sodium oxybate administered at t 0 and t 4h in equally divided doses approximately two hours after a standardized evening meal.
14. The formulation of claim 1 , wherein the formulation releases at least 80% of its gamma-hydroxybutyrate at three hours when tested in a dissolution apparatus 2 according to USP 38 <711> in 900 mL of 0.05M monobasic potassium phosphate buffer pH 6.8 at a temperature of 37° C. and a paddle speed of 75 rpm.
15. The formulation of claim 1 , wherein the formulation releases from 10% to 65%, of its gamma-hydroxybutyrate at one hour and three hours when tested in a dissolution apparatus 2 according to USP 38 <711> in 900 mL of 0.1 N hydrochloric acid at a temperature of 37° C. and a paddle speed of 75 rpm.
16. The formulation of claim 1 , wherein the modified release portion releases greater than 80% of its gamma-hydroxybutyrate at three hours when tested in a dissolution apparatus 2 according to USP 38 <711> in 900 mL of 0.05M monobasic potassium phosphate buffer pH 6.8 at a temperature of 37° C. and a paddle speed of 75 rpm.
17. The formulation of claim 1 , wherein the modified release portion releases less than 20% of its gamma-hydroxybutyrate at one hour when tested in a dissolution apparatus 2 according to USP 38 <711> in 900 mL of 0.1 N hydrochloric acid at a temperature of 37° C. and a paddle speed of 75 rpm.
18. The formulation of claim 1 , wherein the modified release portion releases greater than 80% of its gamma-hydroxybutyrate at three hours in a dissolution test started in 750 mL of 0.1N hydrochloric acid for 2 hours then switched to 950 mL 0.05M monobasic potassium phosphate buffer adjusted to pH 6.8 at a temperature of 37° C. and a paddle speed of 75 rpm.
19. The formulation of claim 1 , wherein the immediate release portion releases greater than 80% of its gamma-hydroxybutyrate at one hour when tested in a dissolution apparatus 2 according to USP 38 <711> in 900 mL of 0.1 N hydrochloric acid at a temperature of 37° C. and a paddle speed of 75 rpm.
20. A formulation of gamma-hydroxybutyrate comprising:
an immediate release portion comprising gamma-hydroxybutyrate;
a modified release portion comprising gamma-hydroxybutyrate;
from 1% to 15% of a suspending or viscosifying agent; and
from 1.2% to 15% of an acidifying agent;
wherein the suspending or viscosifying agent and the acidifying agent are separate and distinct from the immediate release portion and the modified release portion;
wherein the ratio of gamma-hydroxybutyrate in the immediate release portion and the modified release portion is from 10/90 to 65/35;
wherein the formulation comprises an amount of gamma-hydroxybutyrate equivalent to from 3.0 g to 12.0 g of sodium oxybate; and
wherein the formulation is designed to be orally administered once-nightly to treat cataplexy in narcolepsy or excessive daytime sleepiness (“EDS”) in narcolepsy.
21. The formulation of claim 20 , wherein:
the suspending or viscosifying agent is selected from the group consisting of xanthan gum, carrageenan gum, gellan gum, guar gum, sodium alginate, calcium alginate, agar, sodium carboxymethyl cellulose, microcrystalline cellulose, hydroxyethyl cellulose, hydroxypropylmethyl cellulose, and mixtures thereof; and
the acidifying agent is selected from the group consisting of malic acid, citric acid, tartaric acid, adipic acid, boric acid, maleic acid, phosphoric acid, ascorbic acid, oleic acid, capric acid, caprylic acid, and benzoic acid.
22. The formulation of claim 20 , wherein:
the suspending or viscosifying agent is a mixture of xanthan gum, carrageenan gum, and hydroxyethylcellulose, or a mixture of xanthan gum and carrageenan gum, and
the acidifying agent is malic acid or tartaric acid.
23. The formulation of claim 20 , wherein the formulation further comprises a lubricant or glidant selected from the group consisting of magnesium stearate, calcium stearate, zinc stearate, glyceryl monostearate, glyceryl palmitostearate, glycerol behenate, sodium stearyl fumarate, talc, and colloidal silicon dioxide.
24. The formulation of claim 20 , wherein the formulation is a dry particulate formulation or a powdered formulation.
25. The formulation of claim 20 , wherein the formulation comprises 4.5 g, 6.0 g, 7.5 g, or 9.0 g of gamma-hydroxybutyrate.
26. The formulation of claim 20 , wherein the formulation comprises gamma-hydroxybutyrate in the form of sodium oxybate.
27. The formulation of claim 20 , wherein the modified release portion comprises a hydrophobic compound having a melting point equal to or greater than 40° C.
28. The formulation of claim 20 , wherein a dose of the formulation achieves a relative bioavailability (RBA) of greater than 80% when compared to an equal dose of an immediate release liquid solution of sodium oxybate administered at t 0 and t 4h in equally divided doses, when administered approximately two hours after a standardized evening meal.
29. The formulation of claim 20 , wherein a dose of the formulation achieves a ratio of mean AUC 8h to mean AUC inf of greater than 0.80 when administered once approximately two hours after a standardized evening meal.
30. The formulation of claim 20 , wherein a dose of the formulation achieves a median T max within one hundred fifty minutes of the median T max of half the dose of an immediate release liquid solution of sodium oxybate, when administered approximately two hours after a standardized evening meal.
31. The formulation of claim 20 , wherein a dose of the formulation achieves a mean C 6h or mean C 7h greater than, and a mean C 10h less than, the mean C 4h of half the dose of an immediate release liquid solution of sodium oxybate, when administered approximately two hours after a standardized evening meal.
32. The formulation of claim 20 , wherein a dose of the formulation achieves a mean AUC inf of greater than 80% of the mean AUC inf provided by an equal dose of immediate release liquid solution of sodium oxybate administered at t 0 and t 4h in equally divided doses approximately two hours after a standardized evening meal, and a mean C 8h less than 95% of the mean C 8h provided by an equal dose of immediate release liquid solution of sodium oxybate administered at t 0 and t 4h in equally divided doses approximately two hours after a standardized evening meal.
33. The formulation of claim 20 , wherein the formulation releases at least 80% of its gamma-hydroxybutyrate at three hours when tested in a dissolution apparatus 2 according to USP 38 <711> in 900 mL of 0.05M monobasic potassium phosphate buffer pH 6.8 at a temperature of 37° C. and a paddle speed of 75 rpm.
34. The formulation of claim 20 , wherein the formulation releases from 10% to 65%, of its gamma-hydroxybutyrate at one hour and three hours when tested in a dissolution apparatus 2 according to USP 38 <711> in 900 mL of 0.1 N hydrochloric acid at a temperature of 37° C. and a paddle speed of 75 rpm.
35. The formulation of claim 20 , wherein the modified release portion releases greater than 80% of its gamma-hydroxybutyrate at three hours when tested in a dissolution apparatus 2 according to USP 38 <711> in 900 mL of 0.05M monobasic potassium phosphate buffer pH 6.8 at a temperature of 37° C. and a paddle speed of 75 rpm.
36. The formulation of claim 20 , wherein the modified release portion releases less than 20% of its gamma-hydroxybutyrate at one hour when tested in a dissolution apparatus 2 according to USP 38 <711> in 900 mL of 0.1 N hydrochloric acid at a temperature of 37° C. and a paddle speed of 75 rpm.
37. The formulation of claim 20 , wherein the modified release portion releases greater than 80% of its gamma-hydroxybutyrate at three hours in a dissolution test started in 750 mL of 0.1N hydrochloric acid for 2 hours then switched to 950 mL 0.05M monobasic potassium phosphate buffer adjusted to pH 6.8 at a temperature of 37° C. and a paddle speed of 75 rpm.
38. The formulation of claim 20 , wherein the immediate release portion releases greater than 80% of its gamma-hydroxybutyrate at one hour when tested in a dissolution apparatus 2 according to USP 38 <711> in 900 mL of 0.1 N hydrochloric acid at a temperature of 37° C. and a paddle speed of 75 rpm.
39. A formulation of gamma-hydroxybutyrate comprising:
an immediate release portion comprising gamma-hydroxybutyrate;
a modified release portion comprising gamma-hydroxybutyrate;
a suspending or viscosifying agent for improving the formulation's viscosity and pourabilty after mixing with a liquid, the suspending or viscosifying agent being selected from the group consisting of xanthan gum, carrageenan gum, gellan gum, guar gum, sodium alginate, calcium alginate, agar, sodium carboxymethyl cellulose, microcrystalline cellulose, hydroxyethyl cellulose, hydroxypropylmethyl cellulose, and mixtures thereof; and
an acidifying agent for ensuring that the formulation's release profile remains unchanged for at least 15 minutes after mixing with a liquid, the acidifying agent being selected from the group consisting of malic acid, citric acid, tartaric acid, adipic acid, boric acid, maleic acid, phosphoric acid, ascorbic acid, oleic acid, capric acid, caprylic acid, and benzoic acid;
wherein the ratio of gamma-hydroxybutyrate in the immediate release portion and the modified release portion is from 10/90 to 65/35.
40. A formulation of gamma-hydroxybutyrate comprising:
an immediate release portion comprising gamma-hydroxybutyrate;
a modified release portion comprising gamma-hydroxybutyrate;
from 1% to 15% of a suspending or viscosifying agent for improving the formulation's viscosity and pourabilty after mixing with a liquid; and
from 1.2% to 15% of an acidifying agent for ensuring that the formulation's release profile remains unchanged for at least 15 minutes after mixing with a liquid;
wherein the ratio of gamma-hydroxybutyrate in the immediate release portion and the modified release portion is from 10/90 to 65/35;
wherein the formulation comprises an amount of gamma-hydroxybutyrate equivalent to from 3.0 g to 12.0 g of sodium oxybate; and
wherein the formulation is designed to be orally administered once-nightly to treat cataplexy in narcolepsy or excessive daytime sleepiness (“EDS”) in narcolepsy.
41. A formulation of gamma-hydroxybutyrate comprising:
an immediate release portion comprising gamma-hydroxybutyrate;
a modified release portion comprising gamma-hydroxybutyrate and a coating comprising a hydrophobic compound having a melting point equal to or greater than 40° C.;
a suspending or viscosifying agent selected from the group consisting of xanthan gum, carrageenan gum, gellan gum, guar gum, sodium alginate, calcium alginate, agar, sodium carboxymethyl cellulose, microcrystalline cellulose, hydroxyethyl cellulose, hydroxypropylmethyl cellulose, and mixtures thereof; and
an acidifying agent selected from the group consisting of malic acid, citric acid, tartaric acid, adipic acid, boric acid, maleic acid, phosphoric acid, ascorbic acid, oleic acid, capric acid, caprylic acid, and benzoic acid;
wherein the ratio of gamma-hydroxybutyrate in the immediate release portion and the modified release portion is from 10/90 to 65/35.
42. A formulation of gamma-hydroxybutyrate comprising:
an immediate release portion comprising gamma-hydroxybutyrate;
a modified release portion comprising gamma-hydroxybutyrate and a coating comprising a hydrophobic compound having a melting point equal to or greater than 40° C.;
from 1% to 15% of a suspending or viscosifying agent; and
from 1.2% to 15% of an acidifying agent;
wherein the ratio of gamma-hydroxybutyrate in the immediate release portion and the modified release portion is from 10/90 to 65/35;
wherein the formulation comprises an amount of gamma-hydroxybutyrate equivalent to from 3.0 g to 12.0 g of sodium oxybate; and
wherein the formulation is designed to be orally administered once-nightly to treat cataplexy in narcolepsy or excessive daytime sleepiness (“EDS”) in narcolepsy.
43. A formulation of gamma-hydroxybutyrate comprising:
an immediate release portion comprising gamma-hydroxybutyrate;
a modified release portion comprising gamma-hydroxybutyrate;
a suspending or viscosifying agent selected from the group consisting of xanthan gum, carrageenan gum, gellan gum, guar gum, sodium alginate, calcium alginate, agar, sodium carboxymethyl cellulose, microcrystalline cellulose, hydroxyethyl cellulose, hydroxypropylmethyl cellulose, and mixtures thereof; and
an acidifying agent selected from the group consisting of malic acid, citric acid, tartaric acid, adipic acid, boric acid, maleic acid, phosphoric acid, ascorbic acid, oleic acid, capric acid, caprylic acid, and benzoic acid;
wherein the ratio of gamma-hydroxybutyrate in the immediate release portion and the modified release portion is from 10/90 to 65/35; and
wherein a dose of the formulation achieves a relative bioavailability (RBA) of greater than 80% when compared to an equal dose of an immediate release liquid solution of sodium oxybate administered at t 0 and t 4h in equally divided doses, when administered approximately two hours after a standardized evening meal.
44. A formulation of gamma-hydroxybutyrate comprising:
an immediate release portion comprising gamma-hydroxybutyrate;
a modified release portion comprising gamma-hydroxybutyrate;
from 1% to 15% of a suspending or viscosifying agent; and
from 1.2% to 15% of an acidifying agent;
wherein the ratio of gamma-hydroxybutyrate in the immediate release portion and the modified release portion is from 10/90 to 65/35;
wherein the formulation comprises an amount of gamma-hydroxybutyrate equivalent to from 3.0 g to 12.0 g of sodium oxybate;
wherein the formulation is designed to be orally administered once-nightly to treat cataplexy in narcolepsy or excessive daytime sleepiness (“EDS”) in narcolepsy; and
wherein a dose of the formulation achieves a relative bioavailability (RBA) of greater than 80% when compared to an equal dose of an immediate release liquid solution of sodium oxybate administered at t 0 and t 4h in equally divided doses, when administered approximately two hours after a standardized evening meal.
45. A formulation of gamma-hydroxybutyrate comprising:
an immediate release portion comprising gamma-hydroxybutyrate;
a modified release portion comprising gamma-hydroxybutyrate;
a suspending or viscosifying agent selected from the group consisting of xanthan gum, carrageenan gum, gellan gum, guar gum, sodium alginate, calcium alginate, agar, sodium carboxymethyl cellulose, microcrystalline cellulose, hydroxyethyl cellulose, hydroxypropylmethyl cellulose, and mixtures thereof; and
an acidifying agent selected from the group consisting of malic acid, citric acid, tartaric acid, adipic acid, boric acid, maleic acid, phosphoric acid, ascorbic acid, oleic acid, capric acid, caprylic acid, and benzoic acid;
wherein the ratio of gamma-hydroxybutyrate in the immediate release portion and the modified release portion is from 10/90 to 65/35; and
wherein a dose of the formulation achieves a ratio of mean AUC 8h to mean AUC inf of greater than 0.80 when administered once approximately two hours after a standardized evening meal.
46. A formulation of gamma-hydroxybutyrate comprising:
an immediate release portion comprising gamma-hydroxybutyrate;
a modified release portion comprising gamma-hydroxybutyrate;
from 1% to 15% of a suspending or viscosifying agent; and
from 1.2% to 15% of an acidifying agent;
wherein the ratio of gamma-hydroxybutyrate in the immediate release portion and the modified release portion is from 10/90 to 65/35;
wherein the formulation comprises an amount of gamma-hydroxybutyrate equivalent to from 3.0 g to 12.0 g of sodium oxybate;
wherein the formulation is designed to be orally administered once-nightly to treat cataplexy in narcolepsy or excessive daytime sleepiness (“EDS”) in narcolepsy; and
wherein a dose of the formulation achieves a ratio of mean AUC 8h to mean AUC inf of greater than 0.80 when administered once approximately two hours after a standardized evening meal.
47. A formulation of gamma-hydroxybutyrate comprising:
an immediate release portion comprising gamma-hydroxybutyrate;
a modified release portion comprising gamma-hydroxybutyrate;
a suspending or viscosifying agent selected from the group consisting of xanthan gum, carrageenan gum, gellan gum, guar gum, sodium alginate, calcium alginate, agar, sodium carboxymethyl cellulose, microcrystalline cellulose, hydroxyethyl cellulose, hydroxypropylmethyl cellulose, and mixtures thereof; and
an acidifying agent selected from the group consisting of malic acid, citric acid, tartaric acid, adipic acid, boric acid, maleic acid, phosphoric acid, ascorbic acid, oleic acid, capric acid, caprylic acid, and benzoic acid;
wherein the ratio of gamma-hydroxybutyrate in the immediate release portion and the modified release portion is from 10/90 to 65/35; and
wherein a dose of the formulation achieves a median T max within 150 minutes of the median T max of half the dose of an immediate release liquid solution of sodium oxybate, when administered approximately two hours after a standardized evening meal.
48. A formulation of gamma-hydroxybutyrate comprising:
an immediate release portion comprising gamma-hydroxybutyrate;
a modified release portion comprising gamma-hydroxybutyrate;
from 1% to 15% of a suspending or viscosifying agent; and
from 1.2% to 15% of an acidifying agent;
wherein the ratio of gamma-hydroxybutyrate in the immediate release portion and the modified release portion is from 10/90 to 65/35;
wherein the formulation comprises an amount of gamma-hydroxybutyrate equivalent to from 3.0 g to 12.0 g of sodium oxybate;
wherein the formulation is designed to be orally administered once-nightly to treat cataplexy in narcolepsy or excessive daytime sleepiness (“EDS”) in narcolepsy; and
wherein a dose of the formulation achieves a median T max within 150 minutes of the median T max of half the dose of an immediate release liquid solution of sodium oxybate, when administered approximately two hours after a standardized evening meal.
49. A formulation of gamma-hydroxybutyrate comprising:
an immediate release portion comprising gamma-hydroxybutyrate;
a modified release portion comprising gamma-hydroxybutyrate;
a suspending or viscosifying agent selected from the group consisting of xanthan gum, carrageenan gum, gellan gum, guar gum, sodium alginate, calcium alginate, agar, sodium carboxymethyl cellulose, microcrystalline cellulose, hydroxyethyl cellulose, hydroxypropylmethyl cellulose, and mixtures thereof; and
an acidifying agent selected from the group consisting of malic acid, citric acid, tartaric acid, adipic acid, boric acid, maleic acid, phosphoric acid, ascorbic acid, oleic acid, capric acid, caprylic acid, and benzoic acid;
wherein the ratio of gamma-hydroxybutyrate in the immediate release portion and the modified release portion is from 10/90 to 65/35; and
wherein a dose of the formulation achieves a mean C 6h or mean C 7h greater than, and a mean C 10h less than, the mean Co of half the dose of an immediate release liquid solution of sodium oxybate, when administered approximately two hours after a standardized evening meal.
50. A formulation of gamma-hydroxybutyrate comprising:
an immediate release portion comprising gamma-hydroxybutyrate;
a modified release portion comprising gamma-hydroxybutyrate;
from 1% to 15% of a suspending or viscosifying agent; and
from 1.2% to 15% of an acidifying agent;
wherein the ratio of gamma-hydroxybutyrate in the immediate release portion and the modified release portion is from 10/90 to 65/35;
wherein the formulation comprises an amount of gamma-hydroxybutyrate equivalent to from 3.0 g to 12.0 g of sodium oxybate;
wherein the formulation is designed to be orally administered once-nightly to treat cataplexy in narcolepsy or excessive daytime sleepiness (“EDS”) in narcolepsy; and
wherein a dose of the formulation achieves a mean C 6h or mean C 7h greater than, and a mean C 10h less than, the mean Co of half the dose of an immediate release liquid solution of sodium oxybate, when administered approximately two hours after a standardized evening meal.
51. A formulation of gamma-hydroxybutyrate comprising:
an immediate release portion comprising gamma-hydroxybutyrate;
a modified release portion comprising gamma-hydroxybutyrate;
a suspending or viscosifying agent selected from the group consisting of xanthan gum, carrageenan gum, gellan gum, guar gum, sodium alginate, calcium alginate, agar, sodium carboxymethyl cellulose, microcrystalline cellulose, hydroxyethyl cellulose, hydroxypropylmethyl cellulose, and mixtures thereof; and
an acidifying agent selected from the group consisting of malic acid, citric acid, tartaric acid, adipic acid, boric acid, maleic acid, phosphoric acid, ascorbic acid, oleic acid, capric acid, caprylic acid, and benzoic acid;
wherein the ratio of gamma-hydroxybutyrate in the immediate release portion and the modified release portion is from 10/90 to 65/35; and
wherein a dose of the formulation achieves a mean AUC inf of greater than 80% of the mean AUC inf provided by an equal dose of immediate release liquid solution of sodium oxybate administered at t 0 and t 4h in equally divided doses approximately two hours after a standardized evening meal, and a mean C 8h less than 95% of the mean C 8h provided by an equal dose of immediate release liquid solution of sodium oxybate administered at t 0 and t 4h in equally divided doses approximately two hours after a standardized evening meal.
52. A formulation of gamma-hydroxybutyrate comprising:
an immediate release portion comprising gamma-hydroxybutyrate;
a modified release portion comprising gamma-hydroxybutyrate;
from 1% to 15% of a suspending or viscosifying agent; and
from 1.2% to 15% of an acidifying agent;
wherein the ratio of gamma-hydroxybutyrate in the immediate release portion and the modified release portion is from 10/90 to 65/35;
wherein the formulation comprises an amount of gamma-hydroxybutyrate equivalent to from 3.0 g to 12.0 g of sodium oxybate;
wherein the formulation is designed to be orally administered once-nightly to treat cataplexy in narcolepsy or excessive daytime sleepiness (“EDS”) in narcolepsy; and
wherein a dose of the formulation achieves a mean AUC inf of greater than 80% of the mean AUC inf provided by an equal dose of immediate release liquid solution of sodium oxybate administered at t 0 and t 4h in equally divided doses approximately two hours after a standardized evening meal, and a mean C 8h less than 95% of the mean C 8h provided by an equal dose of immediate release liquid solution of sodium oxybate administered at t 0 and t 4h in equally divided doses approximately two hours after a standardized evening meal.