Claims for Patent: 8,992,975

Summary for Patent: 8,992,975

Title:	Combination composition comprising oxycodone and acetaminophen for rapid onset and extended duration of analgesia
Abstract:	The present disclosure provides an extended release pharmaceutical composition comprising oxycodone and acetaminophen that provides a rapid onset of analgesia, and reduced levels of acetaminophen near the end of the dosing interval. Also provided are methods for reducing the risk of acetaminophen-induced hepatic damage in a subject being treated with an acetaminophen containing composition, as well as methods for treating pain in a subject in need thereof.
Inventor(s):	Devarakonda; Krishna R. (St. Louis, MO), Giuliani; Michael J. (Creve Coeur, MO), Gupta; Vishal K. (Hillsborough, NJ), Heasley; Ralph A. (Webster Groves, MO), Shelby; Susan (Town and Country, MO)
Assignee:	Mallinckrodt LLC (Hazelwood, MO)
Application Number:	14/109,052
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,992,975
Patent Claims:	1. A pharmaceutical composition comprising: (a) at least one immediate release portion comprising about 125 mg to about 325 mg of acetaminophen and oxycodone or a pharmaceutically acceptable salt thereof in an amount selected from the group consisting of about 1 mg, 1.25 mg, 1.3 mg, 1.325 mg, 1.35 mg, 1.375 mg, 1.4 mg, 1.425 mg, 1.45 mg, 1.475 mg, 1.5 mg, 1.525 mg, 1.55 mg, 1.575 mg, 1.6 mg, 1.625 mg, 1.65 mg, 1.675 mg, 1.7 mg, 1.725 mg, 1.75 mg, 1.775 mg, 1.8 mg, 1.825 mg, 1.85 mg, 1.875 mg, 1.9 mg, 1.925 mg, 1.95 mg, 1.975 mg, 2.0 mg, 2.25 mg, 2.5 mg, 2.75 mg, 3.0 mg, 3.25 mg, 3.5 mg, 3.75 mg, and 4.0 mg; and (b) at least one extended release portion comprising about 125 mg to about 325 mg of acetaminophen and about 4.5 mg to about 6.5 mg oxycodone or a pharmaceutically acceptable salt thereof, and an extended release component; wherein the total amount of acetaminophen in the composition is 325 mg and the total amount of oxycodone or a pharmaceutically acceptable salt in the composition is about 7.5 mg; and wherein upon oral administration of a single dose of the composition to a subject, the composition provides a C.sub.max for oxycodone from about 0.9 ng/mL/mg to about 1.6 ng/mL/mg, a C.sub.max for acetaminophen from about 4.0 ng/mL/mg to about 11.0 ng/mL/mg, a T.sub.max for oxycodone from about 2 hours to about 7 hours, and a T.sub.max for acetaminophen from about 0.5 hour to about 6 hours. 2. The pharmaceutical composition of claim 1, wherein the C.sub.max for oxycodone is about 0.9 ng/mL/mg to about 1.2 ng/mL/mg. 3. The pharmaceutical composition of claim 1, wherein the C.sub.max for oxycodone is about 1.0 ng/mL/mg to about 1.5 ng/mL/mg. 4. The pharmaceutical composition of claim 1, wherein the C.sub.max for acetaminophen is about 6.5 ng/mL/mg to about 8.5 ng/mL/mg. 5. The pharmaceutical composition of claim 1, wherein the C.sub.max for acetaminophen is about 6.0 ng/mL/mg to about 9 ng/mL/mg. 6. The pharmaceutical composition of claim 1, wherein the T.sub.max for oxycodone is about 3.0 hours to about 6.0 hours. 7. The pharmaceutical composition of claim 1, wherein the T.sub.max for acetaminophen is about 0.75 hours to about 1.5 hours. 8. The pharmaceutical composition of claim 1, wherein upon oral administration of a single dose of the composition to a subject, the composition produces a blood plasma profile characterized by a AUC for oxycodone from about 9.0 nghr/mL/mg to about 18.5 nghr/mL/mg and a AUC for acetaminophen from about 35.0 nghr/mL/mg to about 80.0 nghr/mL/mg. 9. The pharmaceutical composition of claim 8, wherein the AUC for oxycodone is about 11.0 nghr/mL/mg to about 17.0 nghr/mL/mg. 10. The pharmaceutical composition of claim 8, wherein the AUC for acetaminophen is about 40.0 nghr/mL/mg to about 50.0 nghr/mL/mg. 11. The pharmaceutical composition of claim 1, wherein the composition is in the form of a bilayer tablet. 12. The pharmaceutical composition of claim 11, wherein a single dose comprises two bilayer tablets. 13. A pharmaceutical composition comprising: (a) at least one immediate release portion comprising about 125 mg to about 325 mg of acetaminophen and oxycodone or a pharmaceutically acceptable salt thereof in an amount selected from the group consisting of about 1 mg, 1.25 mg, 1.3 mg, 1.325 mg, 1.35 mg, 1.375 mg, 1.4 mg, 1.425 mg, 1.45 mg, 1.475 mg, 1.5 mg, 1.525 mg, 1.55 mg, 1.575 mg, 1.6 mg, 1.625 mg, 1.65 mg, 1.675 mg, 1.7 mg, 1.725 mg, 1.75 mg, 1.775 mg, 1.8 mg, 1.825 mg, 1.85 mg, 1.875 mg, 1.9 mg, 1.925 mg, 1.95 mg, 1.975 mg, 2.0 mg, 2.25 mg, 2.5 mg, 2.75 mg, 3.0 mg, 3.25 mg, 3.5 mg, 3.75 mg, and 4.0 mg; and (b) at least one extended release portion comprising about 125 mg to about 325 mg of acetaminophen and about 4.5 mg to about 6.5 mg oxycodone or a pharmaceutically acceptable salt thereof, and an extended release component; wherein the total amount of acetaminophen in the composition is 325 mg and the total amount of oxycodone or a pharmaceutically acceptable salt in the composition is about 7.5 mg; and wherein upon oral administration of multiple doses of the composition to a subject, the composition produces a blood plasma profile characterized by a mean AUC for oxycodone from about 9.0 nghr/mL/mg to about 16.0 nghr/mL/mg , a mean AUC for acetaminophen from about 35.0 nghr/mL/mg to about 80.0 nghr/mL/mg, a C.sub.max for oxycodone from about 1.5 ng/mL/mg to about 2.0 ng/mL/mg, and a C.sub.max for acetaminophen from about 4.0 ng/mL/mg to about 11.0 ng/mL/mg. 14. The pharmaceutical composition of claim 13, wherein the C.sub.max for oxycodone is about 1.5 ng/mL/mg to about 2.0 ng/mL/mg. 15. The pharmaceutical composition of claim 13, wherein the C.sub.max for acetaminophen is about 6.5 ng/mL/mg to about 8.5 ng/mL/mg. 16. The pharmaceutical composition of claim 13, wherein upon oral administration of multiple doses of the composition to a subject, the composition produces a blood plasma profile characterized by a T.sub.max for oxycodone of about 3.0 hours to about 6 hours. 17. The pharmaceutical composition of claim 13, wherein upon oral administration of multiple doses of the composition to a subject, the composition produces a blood plasma profile characterized by a T.sub.max for acetaminophen of about 0.75 hours to about 1.5 hours. 18. The pharmaceutical composition of claim 13, wherein the AUC for oxycodone is about 13.0 nghr/ml/mg to about 15.0 nghr/mL/mg and the AUC for acetaminophen is about 35.0 ng/hr/mL/mg to about 45.0 nghr/mL/mg. 19. The pharmaceutical composition of claim 13, wherein the extended release component comprises polyethylene oxide. 20. The pharmaceutical composition of claim 19, wherein the polyethylene oxide has a molecular weight from about 500,000 Daltons to about 10,000,000 Daltons. 21. The pharmaceutical composition of claim 13, wherein the extended release component comprises a polymer selected from the group consisting of linear, branched, dendrimeric, or star polymers, hydrophilic polymers, and mixtures thereof 22. The pharmaceutical composition of claim 13, wherein the composition may be administered without regard to food. 23. A pharmaceutical composition comprising: (a) at least one immediate release portion comprising about 125 mg to about 325 mg of acetaminophen and oxycodone or a pharmaceutically acceptable salt thereof in an amount selected from the group consisting of about 1 mg, 1.25 mg, 1.3 mg, 1.325 mg, 1.35 mg, 1.375 mg, 1.4 mg, 1.425 mg, 1.45 mg, 1.475 mg, 1.5 mg, 1.525 mg, 1.55 mg, 1.575 mg, 1.6 mg, 1.625 mg, 1.65 mg, 1.675 mg, 1.7 mg, 1.725 mg, 1.75 mg, 1.775 mg, 1.8 mg, 1.825 mg, 1.85 mg, 1.875 mg, 1.9 mg, 1.925 mg, 1.95 mg, 1.975 mg, 2.0 mg, 2.25 mg, 2.5 mg, 2.75 mg, 3.0 mg, 3.25 mg, 3.5 mg, 3.75 mg, and 4.0 mg; and (b) at least one extended release portion comprising about 125 mg to about 325 mg of acetaminophen and about 4.5 mg to about 6.5 mg oxycodone or a pharmaceutically acceptable salt thereof, and an extended release component; wherein the total amount of acetaminophen in the composition is about 325 mg and the total amount of oxycodone or a pharmaceutically acceptable salt in the composition is about 7.5 mg; wherein upon oral administration of the composition, the composition provides an AUC.sub.0-1.7h for acetaminophen of about 5.0 ngh/mL/mg to about 13.0 ngh/mL/mg; an AUC.sub.1.7-48h for acetaminophen of about 25.0 ngh/mL/mg to about 75.0 ngh/mL/mg, an AUC.sub.0-2.8h, for oxycodone of about 1.0 ngh/mL/mg to about 3.0 ngh/mL/mg; and AUC.sub.2.8-48h of about 7.5 ngh/mL/mg to about 15.0 ngh/mL/mg. 24. The pharmaceutical composition of claim 23, wherein the AUC.sub.0-1hr for acetaminophen is from about 1.25 nghr/mL/mg to about 3.25 nghr/mL/mg. 25. The pharmaceutical composition of claim 23, wherein the AUC.sub.0-2hr for acetaminophen is from about 4.25 nghr/mL/mg to about 8.75 nghr/mL/mg. 26. The pharmaceutical composition of claim 23, wherein the AUC.sub.0-4hr for acetaminophen is from about 10.0 nghr/mL/mg to about 20.0 nghr/mL/mg. 27. The pharmaceutical composition of claim 23, wherein the AUC.sub.0-1hr for oxycodone is from about 0.10 nghr/mL/mg to about 0.45 nghr/mL/mg. 28. The pharmaceutical composition of claim 23, wherein the AUC.sub.0-2hr for oxycodone is from about 0.65 nghr/mL/mg to about 1.35 nghr/mL/mg. 29. The pharmaceutical composition of claim 23, wherein the AUC.sub.0-4hr for oxycodone is from about 2.0 nghr/mL/mg to about 4.0 nghr/mL/mg. 30. A pharmaceutical composition as a solid oral dosage form comprising: (a) at least one immediate release portion comprising about 125 mg to about 325 mg of acetaminophen and oxycodone or a pharmaceutically acceptable salt thereof in an amount selected from the group consisting of about 1 mg, 1.25 mg, 1.3 mg, 1.325 mg, 1.35 mg, 1.375 mg, 1.4 mg, 1.425 mg, 1.45 mg, 1.475 mg, 1.5 mg, 1.525 mg, 1.55 mg, 1.575 mg, 1.6 mg, 1.625 mg, 1.65 mg, 1.675 mg, 1.7 mg, 1.725 mg, 1.75 mg, 1.775 mg, 1.8 mg, 1.825 mg, 1.85 mg, 1.875 mg, 1.9 mg, 1.925 mg, 1.95 mg, 1.975 mg, 2.0 mg, 2.25 mg, 2.5 mg, 2.75 mg, 3.0 mg, 3.25 mg, 3.5 mg, 3.75 mg, and 4.0 mg; and (b) at least one extended release portion comprising about 125 mg to about 325 mg of acetaminophen and about 4.5 mg to about 6.5 mg oxycodone or a pharmaceutically acceptable salt thereof, and an extended release component; wherein the total amount of acetaminophen in the composition is about 325 mg and the total amount of oxycodone or a pharmaceutically acceptable salt in the composition is about 7.5 mg; wherein upon oral administration of two solid oral dosage forms of the composition in an amount of about 15 mg of oxycodone or a pharmaceutically acceptable salt thereof and about 650 mg of acetaminophen, the composition provides an AUC.sub.0-1.7h for acetaminophen of about 5.0 ngh/mL/mg to about 13.0 ngh/mL/mg; an AUC.sub.1.7-48h for acetaminophen of about 25.0 ngh/mL/mg to about 75.0 ngh/mL/mg, an AUC.sub.0-2.8h, for oxycodone of about 1.0 ngh/mL/mg to about3.0 ngh/mL/mg; and AUC.sub.2.8-48h of about 7.5 ngh/mL/mg to about 15.0 ngh/mL/mg.