Claims for Patent: 9,433,619

Summary for Patent: 9,433,619

Title:	Treating pain in patients with hepatic impairment
Abstract:	An extended release composition for an analgesic active pharmaceutical ingredient which may be an opioid, preferably hydrocodone as the only active ingredient. The extended release composition preferably comprises a extended release composition which may be in the form of beads contained in an oral dosage form such as gelatin capsules. The composition is designed to release hydrocodone in a way such that the increase in hydrocodone exposure in hepatically impaired patients is not clinically significant. The oral dosage units are supplied as part of a kit, which also includes a primary package and a package insert all sold as a commercially marketed product. The primary package and package insert are contained in an optional secondary package and the package insert does not contain a warning, a dosing instruction, or a dosing table specifically directed to patients suffering from mild, moderate or severe hepatic impairment, and preferably explicitly states that dosing adjustment is not required for mild or moderate hepatic impairment.
Inventor(s):	Hartman; Andrew (Belmont, CA), Rubino; Christopher M. (Williamsville, NY), Robinson; Cynthia Y. (Burlingame, CA)
Assignee:	Pemix Ireland Pain Limited (Dublin, IE)
Application Number:	15/154,527
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 9,433,619
Patent Claims:	1. A method of treating pain in a patient having mild or moderate hepatic impairment, the method comprising: administering to the patient having mild or moderate hepatic impairment an oral dosage unit having hydrocodone bitartrate as the only active ingredient; wherein the dosage unit comprises a first formulation of hydrocodone bitartrate and a second formulation of hydrocodone bitartrate, wherein the dosage unit provides a release profile of hydrocodone such that: (1) the average hydrocodone AUC.sub.0-inf per 20 mg of hydrocodone bitartrate dosed to subjects not suffering from renal or hepatic impairment is in the range of about 300 ng*h/mL to about 500 ng*h/mL; (2) the average hydrocodone AUC.sub.0-inf per 20 mg of hydrocodone bitartrate dosed to subjects suffering from mild hepatic impairment is in the range of about 300 ng*h/mL to about 570 ng*h/mL; and (3) the average hydrocodone AUC.sub.0-inf per 20 mg of hydrocodone bitartrate dosed to subjects suffering from moderate hepatic impairment is in the range of about 300 ng*h/mL to about 700 ng*h/mL. 2. The method of claim 1, wherein the dosage unit provides a plasma half-life of hydrocodone of about 8 hours in patients without hepatic impairment. 3. The method of claim 1, wherein the dosage unit provides a plasma half-life of hydrocodone of about 9 hours in patients with mild hepatic impairment. 4. The method of claim 1, wherein the dosage unit provides a plasma half-life of hydrocodone of about 10 hours in patients with moderate hepatic impairment. 5. The method of claim 1, wherein the first formulation comprises an immediate release component and the second formulation comprises a sustained release component. 6. The method of claim 5, wherein the immediate release component comprises a first population of particles and the sustained release component comprises a second population of particles. 7. The method of claim 1, wherein the first formulation comprises 15 to 25 percent by weight of the total hydrocodone in the oral dosage unit and the second formulation comprises 75 to 85 percent by weight of the total hydrocodone in the oral dosage unit. 8. The method of claim 1, wherein the dosage unit is formulated to release about 10% to about 30% of the hydrocodone in a first hour and release more than about 60% of the hydrocodone during a first 12 hours after placement in a USP dissolution apparatus buffered at a pH of 6. 9. A method of treating pain in a patient having mild or moderate hepatic impairment, the method comprising: administering to the patient having mild or moderate hepatic impairment an oral dosage unit having at least 20 mg of hydrocodone bitartrate as the only active ingredient, wherein the dosage unit comprises an extended release formulation of hydrocodone bitartrate. 10. The method of claim 9, wherein the dosage unit comprises a multiparticulate modified release composition. 11. The method of claim 10, wherein the dosage unit comprises a capsule containing the multiparticulate modified release composition. 12. The method of claim 11, wherein the multiparticulate modified release composition comprises a first population of beads containing 15 to 25% by weight of the total hydrocodone in the oral dosage unit as an immediate release population, and a second population of beads containing 75 to 85 percent by weight of the total hydrocodone in the oral dosage unit as a sustained release population. 13. The method of claim 12, wherein the multiparticulate modified release composition comprises a third population of beads which are different from beads in the first and second populations of beads. 14. The method of claim 12, wherein the second population of beads comprises a polymer coating comprising one or more of cellulose acetate phthalate, cellulose acetate trimaletate, hydroxy propyl methylcellulose phthalate, polyvinyl acetate phthalate, ammonio methacrylate copolymers, polyacrylic acid, polyacrylate and methacrylate copolymers, polyvinyl acetaldiethylamino acetate, hydroxypropyl methylcellulose acetate succinate and shellac. 15. The method of claim 14, wherein the polymer coating comprises ammonio methacrylate copolymers. 16. The method of claim 15, wherein the first population of beads and the second population of beads comprise sugar spheres as an inert core. 17. The method of claim 9, wherein the oral dosage unit contains 20 mg, 30 mg, 40 mg or 50 mg of hydrocodone bitartrate. 18. A method of treating pain in a patient having mild or moderate hepatic impairment, the method comprising: administering to the patient having mild or moderate hepatic impairment an oral dosage unit having hydrocodone bitartrate as the only active ingredient; wherein the dosage unit comprises an extended release formulation of hydrocodone bitartrate; wherein the dosage unit is formulated to release about 10% to about 30% of the hydrocodone in a first hour and release more than about 60 of the hydrocodone during a first 12 hours after placement in a USP dissolution apparatus buffered at a pH of 6.8; wherein the dosage unit provides a release profile of hydrocodone such that the average hydrocodone AUC.sub.0-inf per 20 mg of hydrocodone bitartrate dosed to subjects not suffering from renal or hepatic impairment is in the range of about 312 ng*h/mL to about 500 ng*h/mL; and wherein the dosage unit provides a release profile of hydrocodone such that the average hydrocodone C.sub.max per 20 mg of hydrocodone bitartrate dosed to subjects not suffering from renal or hepatic impairment is in the range of about 17 ng/mL to about 27 ng/mL. 19. The method of claim 18, wherein the dosage unit comprises at least 20 mg of hydrocodone bitartrate. 20. The method of claim 19, wherein the dosage unit contains 20 mg, 30 mg, 40 mg or 50 mg of hydrocodone bitartrate.