Claims for Patent: 11,000,520

Summary for Patent: 11,000,520

Title:	Buprenorphine dosing regimens
Abstract:	The disclosure provides a dosage regimen using sustained-release buprenorphine formulations to produce therapeutic levels of buprenorphine in patients for the treatment of pain or opioid use disorders.
Inventor(s):	Nasser; Azmi (Richmond, VA), Laffont; Celine M (Richmond, VA), Heidbreder; Christian (Richmond, VA)
Assignee:	Indivior UK Limited (Hull, GB)
Application Number:	15/523,986
Patent Claims:	1. A method of treating opioid use disorder in a human in need thereof, the method comprising the steps of: (a) administering a first composition comprising about 300 mg of buprenorphine to the human once per month by subcutaneous injection for two months; wherein the first composition comprises (i) about 18 wt % of buprenorphine free base; (ii) about 32 wt % of a poly(DL-lactide-co-glycolide) copolymer; and (iii) about 50 wt % of N-methyl-2-pyrrolidone; and (b) administering a second composition comprising about 100 mg of buprenorphine to the human once per month by subcutaneous injection beginning with a third month and for at least four months; wherein the second composition comprises (i) about 18 wt % of buprenorphine free base; (ii) about 32 wt % of a poly(DL-lactide-co-glycolide) copolymer; and (iii) about 50 wt % of N-methyl-2-pyrrolidone; to treat the opioid use disorder. 2. The method of claim 1, wherein the opioid use disorder is moderate opioid use disorder or severe opioid use disorder. 3. The method of claim 1, wherein the poly(DL-lactide-co-glycolide) copolymer in the first composition and the second composition is a 50:50 poly(DL-lactide-co-glycolide) copolymer. 4. A method of treating opioid use disorder in a human in need thereof, the method comprising the steps of: (a) administering a first composition comprising about 300 mg of buprenorphine or a pharmaceutically acceptable salt thereof to the human once per month by injection for two months; and (b) administering a second composition comprising about 100 mg of buprenorphine or a pharmaceutically acceptable salt thereof to the human once per month by injection beginning with a third month and for at least four months; to treat the opioid use disorder. 5. The method of claim 4, wherein the buprenorphine is in the form of a free base. 6. The method of claim 4, wherein the method produces an average buprenorphine plasma concentration of at least 2 ng/mL. 7. The method of claim 4, wherein the method produces an average buprenorphine plasma concentration of about 2 ng/mL to about 5 ng/mL. 8. The method of claim 4, wherein the method produces a .mu.-opioid receptor occupancy as measured by a maximum effect model of Equation 1 of at least 70%. 9. The method of claim 4, wherein the injection is a subcutaneous injection. 10. The method of claim 4, wherein the method of treating opioid use disorder is a method of suppressing opioid withdrawal signs and symptoms. 11. The method of claim 4, wherein the first composition and the second composition each comprise: (i) about 18 wt % of buprenorphine free base; (ii) about 32 wt % of a 50:50 poly(DL-lactide-co-glycolide) copolymer; and (iii) about 50 wt % of N-methyl-2-pyrrolidone. 12. The method of claim 4, wherein the first composition and the second composition each comprise: (i) about 14 wt % to about 22 wt % of buprenorphine free base; (ii) about 22 wt % to about 42 wt % of a 50:50 to 80:20 poly(DL-lactide-co-glycolide) copolymer; and (iii) about 40 wt % to about 60 wt % of N-methyl-2-pyrrolidone. 13. The method of claim 4, wherein the first composition and the second composition each comprise: (i) about 10 wt % to about 30 wt % of buprenorphine free base; (ii) about 10 wt % to about 60 wt % of a 50:50 to 95:5 poly(DL-lactide-co-glycolide) copolymer; and (iii) about 30 wt % to about 70 wt % of N-methyl-2-pyrrolidone. 14. The method of claim 1, wherein the poly(DL-lactide-co-glycolide) copolymer in the first composition and the second composition is a 50:50 poly(DL-lactide-co-glycolide) copolymer having a carboxy terminal group and having an average molecular weight of about 9,000 Daltons to about 19,000 Daltons. 15. The method of claim 11, wherein the 50:50 poly(DL-lactide-co-glycolide) copolymer has a carboxy terminal group and has an average molecular weight of about 9,000 Daltons to about 19,000 Daltons. 16. The method of claim 12, wherein the 50:50 to 80:20 poly(DL-lactide-co glycolide) copolymer is a 50:50 to 80:20 poly(DL-lactide-co-glycolide) copolymer having an average molecular weight of about 5,000 Daltons to about 30,000 Daltons. 17. The method of claim 13, wherein the 50:50 to 95:5 poly(DL-lactide-co-glycolide) copolymer is a 50:50 to 95:5 poly(DL-lactide-co-glycolide) copolymer having an average molecular weight of about 5,000 Daltons to about 40,000 Daltons. 18. The method of claim 4, wherein the opioid use disorder is moderate opioid use disorder or severe opioid use disorder. 19. The method of claim 1, further comprising transmucosally administering to the patient a composition comprising buprenorphine prior to step (a). 20. The method of claim 1, further comprising sublingually administering to the patient a composition comprising buprenorphine prior to step (a). 21. The method of claim 1, further comprising inducting and stabilizing the patient on a transmucosal composition comprising buprenorphine prior to step (a). 22. The method of claim 1, further comprising inducting and stabilizing the patient on a sublingual composition comprising buprenorphine prior to step (a). 23. A method of treating opioid addiction in a human in need thereof, the method comprising the steps of: (a) transmucosally administering a composition comprising buprenorphine; (b) subcutaneously administering a first composition comprising about 300 mg of buprenorphine once per month for two months; wherein the first composition comprises (i) about 18 wt % of buprenorphine free base; (ii) about 32 wt % of a poly(DL-lactide-co-glycolide) copolymer; and (iii) about 50 wt % of N-methyl-2-pyrrolidone; and (c) subcutaneously administering a second composition comprising about 100 mg of buprenorphine once per month beginning with a third month and for at least four months; wherein the second composition comprises (i) about 18 wt % of buprenorphine free base; (ii) about 32 wt % of a poly(DL-lactide-co-glycolide) copolymer; and (iii) about 50 wt % of N-methyl-2-pyrrolidone.