Claims for Patent: 12,201,596

Summary for Patent: 12,201,596

Title:	Levodopa dosing regimen
Abstract:	The invention is a method for treating patients with post-encephalitic parkinsonism, parkinsonism that may follow carbon monoxide intoxication, or parkinsonism that may follow manganese intoxication by orally administering a controlled release levodopa formulation and the method provides an improvement of a patient's total post-dose “Off” 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:	US18/823,153
Patent Claims:	1. A method for treating a patient diagnosed with Parkinson's disease comprising: i) selecting a patient diagnosed with Parkinson's disease selected from the group consisting of post-encephalitic parkinsonism, parkinsonism following carbon monoxide intoxication, and parkinsonism following manganese intoxication and being treated with oral immediate release levodopa tablets administered three, four, five or more times a day for a total daily levodopa dose of 500 mg or less; ii) determining the amount of levodopa administered to the patient with each administration of the one or more immediate release levodopa tablets of step (i); iii) discontinuing the administration of the immediate release levodopa tablets; and iv) orally administering one or more multiparticulate controlled release levodopa dosage forms twice or 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 one or more immediate release levodopa tablets of step (i), wherein the patient after receiving treatment with the multiparticulate controlled release levodopa dosage form exhibits a decrease of at least 5% of the patient's total post dose “Off” time as compared to post dose of the oral immediate release levodopa tablets; and wherein the multiparticulate controlled release dosage form comprises: (a) a plurality of controlled release components comprising a core comprising levodopa wherein the core is coated with a layer comprising a muco-adhesive polymer; and externally coated with a layer comprising an enteric coating polymer; and (b) an immediate release component comprising levodopa and carbidopa. 2. 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 (iv) is provided by administering one or a combination of the foregoing capsules per dosing time. 3. The method of claim 1 wherein the controlled release components (a) further comprise a rate-controlling polymer layer which undercoats the layer of muco-adhesive polymer within the controlled release component. 4. The method of claim 1 wherein the controlled release components (a) are formulated as beads. 5. The method of claim 4 wherein the beads are a size that passes through a 12, 14, and 16 mesh screen but are retained on a 18, 20, or 24 mesh screen. 6. The method of claim 1 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. 7. The method of claim 1 wherein after administration of the multiparticulate controlled release dosage form the patient exhibits a levodopa plasma level of from about 200 ng/mL to about 2000 ng/ml within 0.25 to 1 hour after administration. 8. The method of claim 1, wherein the administration of the multiparticulate controlled release dosage form provides a levodopa fluctuation index of about 1.7±0.5 hours. 9. The method of claim 1, wherein step (iii) further comprises initially administering one or more of the multiparticulate controlled release levodopa dosage forms to the patient twice a day for one to nine days and thereafter administering the multiparticulate controlled release levodopa dosage forms thrice a day. 10. A method for treating a patient diagnosed with Parkinson's disease comprising: i) selecting a patient diagnosed with Parkinson's disease selected from the group consisting of post-encephalitic parkinsonism, parkinsonism following carbon monoxide intoxication, and parkinsonism following manganese intoxication 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 100 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 capsules twice or thrice a day to the patient, wherein the one or more capsules comprise: (a) a plurality of controlled release beads comprising a core comprising levodopa wherein the core is coated with a layer comprising a muco-adhesive polymer and externally coated with a layer comprising an enteric coating polymer; and (b) an immediate release component comprising levodopa and carbidopa, wherein each administration of the one or more capsules comprises a total of 280 mg of levodopa; and wherein the patient after receiving treatment with the one or more capsules exhibits a decrease of at least 5% of the patient's total post dose “Off” time as compared to post dose of the oral immediate release levodopa tablets. 11. The method of claim 10 wherein the controlled release components (a) further comprise a rate-controlling polymer layer which undercoats the layer of muco-adhesive polymer within the controlled release component. 12. The method of claim 10 wherein the controlled release components (a) are formulated as beads. 13. The method of claim 12 wherein the beads are a size that passes through a 12, 14, and 16 mesh screen but are retained on a 18, 20, or 24 mesh screen. 14. A method for treating a patient diagnosed with Parkinson's disease comprising: i) selecting a patient diagnosed with Parkinson's disease selected from the group consisting of post-encephalitic parkinsonism, parkinsonism following carbon monoxide intoxication, and parkinsonism following manganese intoxication 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 100 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 capsules twice a day to the patient, wherein the one or more capsules comprise: (a) a plurality of controlled release beads comprising a core comprising levodopa wherein the core is coated with a layer comprising a muco-adhesive polymer and externally coated with a layer comprising an enteric coating polymer; and (b) an immediate release component comprising levodopa and carbidopa, wherein each administration of the one or more capsules comprises a total of 280 mg of levodopa; and wherein the patient after receiving treatment with the one or more capsules exhibits a decrease of at least 5% of the patient's total post dose “Off” time as compared to post dose of the oral immediate release levodopa tablets. 15. The method of claim 14 wherein the controlled release components (a) further comprise a rate-controlling polymer layer which undercoats the layer of muco-adhesive polymer within the controlled release component. 16. The method of claim 14 wherein the controlled release components (a) are formulated as beads. 17. The method of claim 16 wherein the beads are a size that passes through a 12, 14, and 16 mesh screen but are retained on a 18, 20, or 24 mesh screen.