Claims for Patent: 9,326,982

Summary for Patent: 9,326,982

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:	14/978,223
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 9,326,982
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 a starting dose of an oral dosage unit having hydrocodone bitartrate as the only active ingredient, wherein the starting dose is not adjusted relative to a patient without hepatic impairment; 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% and less than about 98% 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. 2. The method of claim 1, 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 469 ng*h/mL. 3. The method of claim 1, 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 18.7 ng/mL to about 25.3 ng/mL. 4. The method of claim 1, wherein the dosage unit comprises 15, 20, 30 or 40 mg of hydrocodone bitartrate. 5. The method of claim 1, wherein the dosage unit further comprises an immediate-release formulation of hydrocodone bitartrate. 6. The method of claim 5, wherein the extended release formulation of the dosage unit comprises 75% to 85% by weight of the total hydrocodone in the dosage unit and the immediate release formulation of the dosage unit comprises 15% to 25% by weight of the total hydrocodone in the dosage unit. 7. The method of claim 5, wherein the dosage unit comprises a first population of beads comprising the immediate release formulation of hydrocodone bitartrate and a second population of beads comprising the extended release formulation of hydrocodone bitartrate. 8. The method of claim 1, wherein the dosage unit provides a release profile of hydrocodone that does not increase average hydrocodone AUC.sub.0-inf in subjects suffering from mild hepatic impairment relative to subjects not suffering from renal or hepatic impairment in an amount of more than 30%, and the release profile of hydrocodone does not increase average hydrocodone AUC.sub.0-inf in subjects suffering from moderate hepatic impairment relative to subjects not suffering from renal or hepatic impairment in an amount of more than 50%. 9. The method of claim 1, wherein the dosage unit provides a release profile of hydrocodone that does not increase average hydrocodone C.sub.max in subjects suffering from mild hepatic impairment relative to subjects not suffering from renal or hepatic impairment in an amount of more than 25%, and the release profile of hydrocodone does not increase average hydrocodone C.sub.max in subjects suffering from moderate hepatic impairment relative to subjects not suffering from renal or hepatic impairment in an amount of more than 30%. 10. The method of claim 1, wherein the dosage unit is formulated to release about 15% to about 25% of the hydrocodone in the first hour and release about 65% and to about 95% of the hydrocodone during the first 12 hours after placement in a USP dissolution apparatus buffered at a pH of 6.8. 11. 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 a starting dose of an oral dosage unit having hydrocodone bitartrate as the only active ingredient, wherein the starting dose is not adjusted relative to a patient without hepatic impairment; 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% and less than about 98% of the hydrocodone during a first 12 hours after placement in a USP dissolution apparatus buffered at a pH of 6.8; and 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 312 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 352 ng*h/mL to about 564 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 405 ng*h/mL to about 666 ng*h/mL. 12. The method of claim 11, 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 317 ng*h/mL to about 465 ng*h/mL. 13. The method of claim 11, 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 suffering from mild hepatic impairment is in the range of about 316 ng*h/mL to about 564 ng*h/mL. 14. The method of claim 11, 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 suffering from moderate hepatic impairment is in the range of about 405 ng*h/mL to about 615 ng*h/mL. 15. The method of claim 11, 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. 16. The method of claim 11, wherein the dosage unit provides a release profile of hydrocodone such that the average hydrocodone C.sub.max 20 mg of hydrocodone bitartrate dosed to subjects suffering from mild hepatic impairment is in the range of about 19 ng/mL to about 29 ng/mL. 17. The method of claim 11, wherein the dosage unit provides a release profile of hydrocodone such that the average hydrocodone C.sub.max 20 mg of hydrocodone bitartrate dosed to subjects suffering from moderate hepatic impairment is in the range of about 20 ng/mL to about 30 ng/mL. 18. The method of claim 11, wherein the dosage unit comprises 15, 20, 30 or 40 mg of hydrocodone bitartrate. 19. The method of claim 11, wherein the dosage unit comprises a first population of beads comprising an immediate release formulation of hydrocodone bitartrate and a second population of beads comprising the extended release formulation of hydrocodone bitartrate. 20. The method of claim 11, wherein the dosage unit is formulated to release about 15% to about 25% of the hydrocodone in the first hour and release about 65% and to about 95% of the hydrocodone during the first 12 hours after placement in a USP dissolution apparatus buffered at a pH of 6.8.