Claims for Patent: 12,109,185

Summary for Patent: 12,109,185

Title:	Levodopa dosing regimen
Abstract:	The invention provides oral dosing regimens of controlled release levodopa compositions for use in treating patients with Parkinson's disease, primary parkinsonism/idiopathic parkinsonism, post-encephalitic parkinsonism, parkinsonism that may follow carbon monoxide intoxication, or parkinsonism that may follow manganese intoxication and the dosing regimens provide an improvement of a patient's total post-dose “On” time or “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:	US18/634,040
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, administered three, four, five or more times a day for a total daily levodopa dose of greater than 500 mg; 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 form 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 dosage form exhibits an increase of at least 10% of the patient's total post-dose “On” time or “Good On” time compared to post-dose of the oral immediate release levodopa tablets, 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 patient after receiving treatment with the one or more multiparticulate controlled release dosage form exhibits an increase of at least 20 minutes of the patient's total post-dose “On” time or “Good On” time compared to post-dose of the oral immediate release levodopa tablets. 3. The method of claim 1, wherein the “On” time is measured per day or waking hours/per day. 4. 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. 5. The method of claim 1 wherein the controlled release components (a) further comprise a layer comprising a rate-controlling polymer wherein the layer comprising the rate-controlling polymer undercoats the layer comprising the muco-adhesive polymer within the controlled release component. 6. The method of claim 1 wherein after administration 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. 7. 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. 8. The method of claim 1, wherein in step (i) the patient is being treated with a stable dosing regimen of oral immediate release levodopa tablets, wherein the dosing regimen is stable for at least 5 days prior to step (iii). 9. The method of claim 8, wherein the stable dosing regimen includes no change in dose or dosing frequency. 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 three, four, five or more times a day for a total daily levodopa dose of greater than 500 mg; 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 form 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 10% of the patient's total post dose “Off” time as compared to post dose of the oral immediate release levodopa tablets, 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. 11. The method of claim 10, wherein the patient after receiving treatment with the one or more multiparticulate controlled release dosage form exhibits a decrease of at least 20 minutes of the patient's total post-dose “Off” time compared to post-dose of the oral immediate release levodopa tablets. 12. The method of claim 10, wherein the “Off” time is measured per day or waking hours/per day. 13. The method of claim 10, 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. 14. The method of claim 10, wherein the controlled release components (a) further comprise a layer comprising a rate-controlling polymer wherein the layer comprising the rate-controlling polymer undercoats the layer comprising the muco-adhesive polymer within the controlled release component. 15. The method of claim 10, wherein after administration 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. 16. The method of claim 10, wherein the administration of the multiparticulate controlled release dosage form provides a levodopa fluctuation index of about 1.7+0.5 hours. 17. 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, 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 form twice 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 dosage form exhibits an increase of at least 10% of the patient's total post-dose “On” time or “Good On” time compared to post-dose of the oral immediate release levodopa tablets, 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. 18. The method of claim 17, wherein the patient after receiving treatment with the one or more multiparticulate controlled release dosage form exhibits an increase of at least 20 minutes of the patient's total post-dose “On” time or “Good On” time compared to post-dose of the oral immediate release levodopa tablets. 19. The method of claim 17, wherein the “On” time is measured per day or waking hours/per day. 20. The method of claim 17, wherein the administration of the multiparticulate controlled release dosage form provides a levodopa fluctuation index of about 1.7±0.5 hours. 21. The method of claim 1, wherein the Parkinson's disease comprises primary parkinsonism/idiopathic parkinsonism. 22. The method of claim 1, wherein the Parkinson's disease comprises post-encephalitic parkinsonism. 23. The method of claim 1, wherein the Parkinson's disease comprises parkinsonism following carbon monoxide intoxication. 24. The method of claim 1, wherein the Parkinson's disease comprises parkinsonism following manganese intoxication. 25. The method of claim 10, wherein the Parkinson's disease comprises primary parkinsonism/idiopathic parkinsonism. 26. The method of claim 10, wherein the Parkinson's disease comprises post-encephalitic parkinsonism. 27. The method of claim 10, wherein the Parkinson's disease comprises parkinsonism following carbon monoxide intoxication. 28. The method of claim 10, wherein the Parkinson's disease comprises parkinsonism following manganese intoxication. 29. The method of claim 17, wherein the Parkinson's disease comprises primary parkinsonism/idiopathic parkinsonism. 30. The method of claim 17, wherein the Parkinson's disease comprises post-encephalitic parkinsonism. 31. The method of claim 17, wherein the Parkinson's disease comprises parkinsonism following carbon monoxide intoxication. 32. The method of claim 17, wherein the Parkinson's disease comprises parkinsonism following manganese intoxication.