Low Sodium Oxybate Once Nightly Composition
AssigneeTris Pharma, Inc.
InventorsAlfred Liang, Paras Rameshlal JAIN, Mahesh Chavan Patil, Hiren Patel, Devins Patel
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Abstract
Compositions providing a once-a-night dose of oxybate are provided. The compositions containing bilayer-coated oxybate anion exchange resin complex multiparticulates provide modified release of the oxybate for 5 to 8 hours post-dosing. Also provided are methods of treating patients in need thereof with pharmaceutical compositions containing the oxybate-anion exchange resin complex.
Claims16
An extended release oxybate powder for oral suspension (POS) which provides a once-a-night extended release oxybate dose, said powder for oral suspension comprising:
- (a) immediate release oxybate-anion exchange resin complex multiparticulates which comprises oxybate bound to ion exchange sites in an anion exchange resin;
- (b) at least two different extended release oxybate components comprising a drug-ion exchange resin complex;
- (c) less than the equivalent of 200 mg of total sodium per 9 gm oxybate dose of the POS,
- wherein post-administration to a patient, a suspension comprising the POS provides a pharmacokinetic profile for oxybate of at least one of:
- a Cmax of (i) 87.98 μg/mL to 126 μg/mL, or about 107 μg/mL, a Cmax of 85.6 μg/mL to 133.76 μg/mL, or 77.04 μg/mL to 117.711 μg/mL, as calculated using arithmetic mean and/or (ii) a Cmax of about 105 μg/mL, or 84.38 μg/mL to 131.84 μg/mL, 94.92 μg/mL to 116.01 μg/mL, as calculated using geometric mean;
- an AUCinf of (i) 518.20 hr*μg/mL to 719.725 hr*μg/mL;
- or about 575 hr*μg/mL, or of 304.11 hr*μg/mL to 846.67 hr*μg/mL, 460.62 hr*μg/mL to 719.725 hr*μg/mL, as calculated using arithmetic mean and/or (ii) an AUCinf of about 520 hr*μg/mL, or 428.58 hr*μg/mL to 669.66 hr*μg/mL;
- or about 482.16 hr*μg/mL to 589.30 hr*μg/mL, as calculated using geometric mean.
A method for treating narcolepsy, idiopathic hypersomnia, or cataplexy, said method comprising dosing a patient with a reconstituted suspension of an extended release oxybate powder for oral suspension (POS) which provides a once-a-night oxybate dose, said powder for oral suspension comprising a blend of oxybate-containing multiparticulates having different release profiles as defined in (a), (b) and (c):
- (a) immediate release oxybate-anion exchange resin complex multiparticulates which comprises oxybate bound to ion exchange sites in an anion exchange resin;
- (b) pH-independent diffusion barrier coated oxybate-anion exchange resin complex-optional matrix multiparticulates, wherein the pH-independent diffusion barrier coating layer comprises a water-insoluble film-forming polymer which confers an extended release to the oxybate, and wherein the pH-independent diffusion barrier coating layer is over the oxybate-anion exchange resin complex-optional matrix;
- (c) small intestine targeted drug coating system (SITCS) coated oxybate multiparticulates which comprise a blended coating layer over pH-independent diffusion barrier coated oxybate-anion exchange resin complex-optional matrix multiparticulates, wherein the pH-independent diffusion barrier coating layer comprises a water-insoluble film-forming polymer, and wherein the pH-independent diffusion barrier coating layer is over the oxybate-anion exchange resin complex-optional matrix;
- wherein the blended coating layer comprises a pH-dependent polymer and a pH-independent polymer, wherein the bilayer coating confers a delayed and extended release profile to the oxybate in the bilayer coated oxybate-anion exchange resin-optional matrix of (c), and
- wherein the oxybate-anion exchange resin complex-optional matrix of (a), (b) or (c) comprise oxybate bound to ion exchange sites in an anion exchange resin in an optional matrix which further comprises at least one hydrophilic or hydrophobic polymer, wherein the complex-optional matrix in each of (a), (b), or (c) may be the same or may differ from each other.
Dependencies are inferred from the claim text.