Claims for Patent: 12,458,616

Summary for Patent: 12,458,616

Title:	Levodopa dosing regimen
Abstract:	The invention is a method for treating patients with Parkinson's disease by orally administering a controlled release levodopa formulation and the method provides an improvement of a patient's total post-dose “Off” time, total post dose “On” time and total post dose “Good On” time compared to post-dose of treatment regimens with oral immediate release levodopa tablets.
Inventor(s):	Richard D'Souza, Hester Visser, Suneel Gupta
Assignee:	Amneal Pharmaceuticals LLC
Application Number:	US19/022,256
Patent Claims:	1. A method for treating a patient diagnosed with Parkinson's disease comprising: (i) selecting a patient diagnosed with Parkinson's disease and being treated with oral immediate release levodopa tablets for a total daily levodopa dose of 500 mg or more; (ii) determining the amount of levodopa administered to the patient with each administration of the immediate release levodopa tablets of step (i); (iii) determining the patient's most frequent dose of immediate release levodopa tablets from step (ii); (iv) discontinuing the administration of the immediate release levodopa tablets; and (v) orally administering one or more multiparticulate controlled release levodopa dosage forms thrice a day to the patient, wherein the amount of levodopa administered with each administration of the multiparticulate controlled release levodopa dosage form is 2.8 times the amount of levodopa the patient was receiving with each administration of the most frequent dose of immediate release levodopa tablets of step (iii), wherein the patient after receiving treatment with the multiparticulate controlled release levodopa dosage form exhibits an increase of at least 5% of the patient's total post dose “On” time or “Good On” time as compared to post dose of the oral immediate release levodopa tablets; and wherein the multiparticulate controlled release dosage form is free of a catechol-O-methyl transferase inhibitor and comprises: (a) a controlled release component comprising a plurality of beads that passes through a 12 mesh screen but are retained on a 24 mesh screen wherein the beads are substantially free of carbidopa and comprise: (i) a core comprising levodopa, (ii) a controlled release coating surrounding the core, (iii) a coating comprising a muco-adhesive polymer surrounding the controlled release coating, and (iv) a coating comprising an enteric coating polymer surrounding the coating comprising the muco-adhesive polymer; and (b) an immediate release component comprising levodopa and carbidopa. 2. The method of claim 1, wherein the Parkinson's disease is primary parkinsonism, post-encephalitic parkinsonism, parkinsonism following carbon monoxide intoxication, or parkinsonism following manganese intoxication. 3. The method of claim 1, wherein the multiparticulate controlled release dosage form is a capsule comprising: 140 mg of levodopa and 35 mg of carbidopa; 210 mg of levodopa and 52.5 mg of carbidopa; 280 mg of levodopa and 70 mg of carbidopa; or 350 mg of levodopa and 87.5 mg of carbidopa; and the dose of levodopa administered in step (v) is provided by administering one or a combination of the foregoing capsules per dosing time. 4. The method of claim 3, wherein the immediate release component comprise from about 90% to about 100% of the total amount of carbidopa in the multiparticulate controlled release formulation. 5. The method of claim 4, wherein the multiparticulate controlled release dosage form when tested using a USP Apparatus I at 75 rpms and 37°±0.5° C. with 500-900 ml of simulated gastric fluid for 2 hours and pH 6.8 phosphate buffer thereafter exhibits the following levodopa release profile: 20% to 60% of levodopa is released after 2 hours; 40% to 80% of levodopa is released after 3 hours; 60% to 100% of levodopa is released after 4 hours; and not less than 80% is released after 7 hours, wherein the simulated gastric fluid has a pH of about 1 to about 4. 6. The method of claim 4, wherein the controlled release coating comprises a controlled release material selected from the group consisting of ethyl cellulose, cellulose acetate, and mixtures thereof. 7. The method of claim 4, wherein the mucoadhesive polymer is capable of forming a positive ionic charge at pHs present in the human gastrointestinal tract. 8. The method of claim 7, wherein the mucoadhesive polymer is an amino methacrylate copolymer. 9. The method of claim 8, wherein the amino methacrylate copolymer is poly(butyl methacrylate-co-(2-dimethylaminoethyl)methacrylate-co-methylmethacrylate). 10. A method for treating a patient diagnosed with Parkinson's disease comprising: i) selecting a patient diagnosed with Parkinson's disease and being treated with oral immediate release levodopa tablets administered four or five times a day with each dose of oral immediate release levodopa tablets comprising 150 mg of levodopa; ii) discontinuing the administration of the immediate release levodopa tablets to the patient of step (i); and iii) orally administering one or more controlled release levodopa capsules three times a day to the patient, wherein the one or more capsules are free of a catechol-O-methyl transferase inhibitor and comprise: (a) a controlled release component comprising a plurality of beads that pass through a 12 mesh screen but are retained on a 24 mesh screen wherein the beads are substantially free of carbidopa and comprise: (i) a core comprising levodopa, (ii) a controlled release coating surrounding the core, (iii) a coating comprising a muco-adhesive polymer surrounding the controlled release coating, and (iv) a coating comprising an enteric coating polymer surrounding the coating comprising the muco-adhesive polymer; and (b) an immediate release component comprising levodopa and carbidopa, wherein each administration of the one or more capsules comprises a total of 420 mg of levodopa; and wherein the patient after receiving treatment with the one or more capsules exhibits an increase of at least 5% of the patient's total post dose “On” time or “Good On” time as compared to post dose of the oral immediate release levodopa tablets. 11. The method of claim 10, wherein the Parkinson's disease is primary parkinsonism, postencephalitic parkinsonism, parkinsonism following carbon monoxide intoxication, or parkinsonism following manganese intoxication. 12. The method of claim 10 wherein the controlled release levodopa capsule comprises 210 mg of levodopa and 52.5 mg of carbidopa; and the dose of levodopa administered in step (iii) is provided by administering 2 capsules per dosing time. 13. The method of claim 12, wherein the immediate release component comprises from about 90% to about 100% of the total amount of carbidopa in the controlled release levodopa capsule. 14. The method of claim 13, wherein the controlled release levodopa capsule when tested using a USP Apparatus I at 75 rpms and 37°±0.5° C. with 500-900 ml of simulated gastric fluid for 2 hours and pH 6.8 phosphate buffer thereafter exhibits the following levodopa release profile: 20% to 60% of levodopa is released after 2 hours; 40% to 80% of levodopa is released after 3 hours; 60% to 100% of levodopa is released after 4 hours; and not less than 80% is released after 7 hours, wherein the simulated gastric fluid has a pH of about 1 to about 4. 15. The method of claim 13, wherein the controlled release coating comprises a controlled release material selected from the group consisting of ethyl cellulose, cellulose acetate, and mixtures thereof. 16. The method of claim 13, wherein the mucoadhesive polymer is capable of forming a positive ionic charge at pHs present in the human gastrointestinal tract. 17. The method of claim 16, wherein the mucoadhesive polymer is an amino methacrylate copolymer. 18. The method of claim 17, wherein the amino methacrylate copolymer is a poly(butyl methacrylate-co-(2-dimethylaminoethyl)methacrylate-co-methylmethacrylate). 19. A method for treating a patient diagnosed with Parkinson's disease comprising: i) selecting a patient diagnosed with Parkinson's disease and being treated with oral immediate release levodopa tablets administered three, four or five times a day with each dose of oral immediate release levodopa tablets comprising 200 mg of levodopa; ii) discontinuing the administration of the immediate release levodopa tablets to the patient of step (i); and iii) orally administering one or more controlled release levodopa capsules three times a day to the patient, wherein the one or more capsules are free of a catechol-O-methyl transferase inhibitor and comprise: (a) a controlled release component comprising a plurality of beads that pass through a 12 mesh screen but are retained on a 24 mesh screen wherein the beads are substantially free of carbidopa and comprise: (i) a core comprising levodopa, (ii) a controlled release coating surrounding the core, (iii) a coating comprising a muco-adhesive polymer surrounding the controlled release coating, and (iv) a coating comprising an enteric coating polymer surrounding the coating comprising the muco-adhesive polymer; and (b) an immediate release component comprising levodopa and carbidopa, wherein each administration of the one or more capsules comprises a total of 560 mg of levodopa; and wherein the patient after receiving treatment with the one or more capsules exhibits an increase of at least 5% of the patient's total post dose “On” time or “Good On” time as compared to post dose of the oral immediate release levodopa tablets. 20. The method of claim 19, wherein the Parkinson's disease is primary parkinsonism, postencephalitic parkinsonism, parkinsonism following carbon monoxide intoxication, or parkinsonism following manganese intoxication. 21. The method of claim 19 wherein the controlled release levodopa capsule comprises 280 mg of levodopa and 52.5 mg of carbidopa; and the dose of levodopa administered in step (iii) is provided by administering 2 capsules per dosing time. 22. The method of claim 21, wherein the immediate release component comprises from about 90% 80% to about 100% of the total amount of carbidopa in the controlled release levodopa capsule. 23. The method of claim 22, wherein the controlled release coating comprises a controlled release material selected from the group consisting of ethyl cellulose, cellulose acetate, and mixtures thereof. 24. The method of claim 22, wherein the mucoadhesive polymer is capable of forming a positive ionic charge at pHs present in the human gastrointestinal tract. 25. The method of claim 24, wherein the mucoadhesive polymer is an amino methacrylate copolymer. 26. The method of claim 25, wherein the amino methacrylate copolymer is a poly(butyl methacrylate-co-(2-dimethylaminoethyl)methacrylate-co-methylmethacrylate).