Claims for Patent: 8,916,588

Summary for Patent: 8,916,588

Title:	Methods for treatment of attention deficit hyperactivity disorder
Abstract:	Therapeutic compositions and methods for treatment of attention deficit disorder (ADD) or attention deficit hyperactivity disorder (ADHD) include dosage forms that deliver a therapeutic amount of active drug in a delayed and controlled release formulation. The dosage form can be administered at night and drug release is delayed for from 4 to 6 hours or longer, followed by an ascending release rate.
Inventor(s):	Lickrish; David (Camana Bay, KY), Zhang; Feng (Pflugerville, TX)
Assignee:	Ironshore Pharmaceuticals & Development, Inc. (Camana Bay, Grand Cayman, KY)
Application Number:	14/230,067
Patent Claims:	1. A method of treating a condition in a subject with a disorder or condition responsive to the administration of a methylphenidate, comprising orally administering to the subject an effective amount of methylphenidate or a pharmaceutical salt thereof in a formulation comprising a core comprising methylphenidate or a pharmaceutical salt thereof and at least one pharmaceutically acceptable excipient; a sustained release layer enclosing the core and a delayed release layer enclosing the sustained release layer, wherein when the formulation is administered to said subject it provides: (i) a lag period of at least 5 hours during which the plasma concentration of methylphenidate or a pharmaceutical salt thereof is less than 10% of the maximum concentration (C.sub.max); (ii) a plasma area under the curve at 10 hours (AUC.sub.0-10) after administration of less than about 7% of AUC.sub.0-48; and (iii) wherein the time to C.sub.max (T.sub.max) is between 12 and 19 hours after administration. 2. The method of claim 1, wherein the plasma area under the curve at 6 hours (AUC.sub.0-6) after administration is less than about 5% of the AUC.sub.0-48. 3. The method of claim 1, wherein the plasma area under the curve at 6 hours (AUC.sub.0-6) after administration is less than about 3% of the AUC.sub.0-48. 4. The method of claim 1, wherein the disorder or condition is attention deficit disorder, attention deficit hyperactivity disorder, excessive daytime sleepiness, major depressive disorder, bipolar depression, in schizophrenia, chronic fatigue, fatigue associated with chemotherapy or binge eating disorder. 5. The method of claim 1, wherein the disorder or condition is attention deficit disorder or attention deficit hyperactivity disorder. 6. The method of claim 1, wherein the disorder is binge eating disorder. 7. The method of claim 1, wherein administration of the formulation is timed to allow the subject to sleep during the lag period and to have absorbed a therapeutic plasma level of drug upon awakening. 8. The method of claim 7, wherein the lag period is followed by a period of sustained release. 9. The method of claim 1, wherein the methylphenidate or pharmaceutical salt thereof is administered in a solid pharmaceutical composition comprising: a water soluble capsule containing a plurality of beads, the beads comprising: a core comprising methylphenidate or a pharmaceutical salt thereof and at least one pharmaceutically acceptable excipient; a sustained release layer enclosing the core; and a delayed release layer enclosing the sustained release layer. 10. The method of claim 1, wherein the formulation is administered to a patient in a fasted state. 11. The method of claim 1, wherein the formulation is administered at night. 12. The method of claim 1, wherein the formulation releases no more than 10% of the total methylphenidate or a pharmaceutical salt thereof during the first five hours when the composition is placed in 700 ml aqueous solution of 0.1N HCl pH 1.1, for up to 2 hours followed by 2-6 hours in sodium phosphate buffer at pH 6.0; followed by 6-20 hours in sodium phosphate buffer, pH 7.2 at 37.degree. C..+-..0.5.degree. C., measured by the USP Apparatus I. 13. The method of claim 1, further comprising an abuse deterrent agent. 14. The method of claim 1, further comprising a nasal irritant. 15. The method of claim 14, wherein the nasal irritant is a capsaicinoid or sodium lauryl sulfate. 16. The method of claim 1, wherein during at least two one-hour periods prior to the maximum concentration (T.sub.max), the total plasma concentration of methylphenidate or a pharmaceutical salt thereof increases at an increased rate with respect to the rate of increase for the previous one-hour period. 17. A method of treating attention deficit disorder or attention deficit hyperactivity disorder in a subject comprising orally administering to the subject a unit dose of methylphenidate or a pharmaceutical salt thereof in a unit dose that comprises a sustained release formulation comprising the methylphenidate or a pharmaceutical salt thereof enclosed in an outer coating that is insoluble in an aqueous medium at pH below 5.5, wherein the unit dose provides a lag period of at least 5 hours during which the subject's plasma concentration of methylphenidate or a pharmaceutical salt thereof is less than 10% of the maximum concentration (C.sub.max), wherein the plasma area under the curve at 10 hours (AUC.sub.0-10) after administration is less than about 7% of AUC.sub.0-48 and wherein the time to C.sub.max (T.sub.max) is between 12 and 19 hours after administration. 18. The method of claim 17, wherein the plasma area under the curve at 6 hours (AUC.sub.0-6) after administration is less than about 5% of the AUC.sub.0-48. 19. The method of claim 17, wherein the plasma area under the curve at 6 hours (AUC.sub.0-6) after administration is less than about 3% of the AUC.sub.0-48. 20. The method of claim 17, wherein the outer coating comprises methacrylic acid copolymer type-B, mono- and di-glycerides and polysorbate 80. 21. The method of claim 17, wherein the sustained release formulation comprises a drug-containing core enclosed in a coating comprising ethyl cellulose and hydroxypropyl cellulose in a ratio of about 1:3 to 1:5, dibutyl sebacate and from 25% to 50% magnesium stearate. 22. The method of claim 17, wherein the unit dose releases no more than 10% of the total methylphenidate or a pharmaceutical salt thereof during the first five hours when the composition is placed in 700 ml aqueous solution of 0.1N HCl pH 1.1, for up to 2 hours followed by 2-6 hours in sodium phosphate buffer at pH 6.0; followed by 6-20 hours in sodium phosphate buffer, pH 7.2 at 37.degree. C..+-..0.5.degree. C., measured by the USP Apparatus I. 23. The method of claim 17, wherein during at least two one-hour periods prior to the maximum concentration (T.sub.max) the total plasma concentration of methylphenidate or a pharmaceutical salt thereof increases at an increased rate with respect to the rate of increase for the previous one-hour period. 24. A method of treating attention deficit disorder or attention deficit hyperactivity disorder in a subject comprising orally administering to the subject a unit dose of methylphenidate or a pharmaceutical salt thereof in a unit dose that comprises: a water soluble capsule containing a plurality of beads, the beads comprising: (a) a core comprising methylphenidate or a pharmaceutical salt thereof and at least one pharmaceutically acceptable excipient; (b) a sustained release layer enclosing the core and comprising ethyl cellulose and hydroxypropyl cellulose in a ratio of about 1:3 to 1:5, dibutyl sebacate and from 25% to 50% magnesium stearate; and (c) a delayed release layer enclosing the sustained release layer and comprising methacrylic acid copolymer type-B, mono- and di-glycerides and polysorbate 80. 25. The method of claim 24, wherein the core comprises a substantially spherical bead. 26. The method of claim 24, wherein the core comprises a non-pareil bead coated with a layer comprising methylphenidate or a pharmaceutical salt thereof. 27. The method of claim 24, wherein the unit dose comprises from 5 mg to 150 mg methylphenidate or a pharmaceutical salt thereof. 28. The method of claim 24, wherein the unit dose comprises 80 mg methylphenidate or a pharmaceutical salt thereof. 29. The method of claim 24, wherein the unit dose comprises a dose that provides a mean area under the plasma concentration/time curve from the time point of administration to the point of the last quantifiable time point (AUC.sub.0-t) of from about 83 to about 210 ng-hr/ml when orally administered to human subjects.