Claims for Patent: 12,263,148

Summary for Patent: 12,263,148

Title:	Levodopa dosing regimen
Abstract:	The invention is a method for 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 provides 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:	US18/802,458
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 most frequent immediate release levodopa dose from each administration of immediate release tablets of step (i); iii) discontinuing the administration of the immediate release levodopa tablets to the patient of step (i); and iv) 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 immediate release levodopa dose of step (ii); 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 wherein the multiparticulate controlled release dosage form comprises: (a) a plurality of controlled release components comprising levodopa, a controlled release material, and a coating comprising an enteric polymer surrounding the levodopa and controlled release material wherein the controlled release components pass through a 12 mesh screen; and (b) an immediate release component comprising levodopa, and carbidopa; and wherein the multiparticulate controlled release dosage form when administered to an adult human subject after an overnight fast and at a dose of 280 mg of levodopa and 70 mg of carbidopa produces a Cmax of from about 1410±418 ng/ml to about 1425±527 ng/ml wherein the plurality of controlled release components are free of carbidopa; and wherein the controlled release dosage form when tested using a USP Type I apparatus at 37° C.±0.5° C. with a rotational speed of 75 rpm and about 900 ml of simulated gastric fluid for 2 hours and pH 6.8 phosphate buffer thereafter, about 75% to about 100% of CD is released within 30 minutes; about 15% to about 45% of LD is released within 30 minutes and not less than 85% of the LD is released after 7 hours; wherein the simulated gastric fluid has a pH of from about 1 to about 4.0. 2. The method of claim 1 wherein the human subject has a body mass index of about 18.5 to 30 kg/m2. 3. The method of claim 1 wherein the patient after receiving treatment with the multiparticulate controlled release dosage form exhibits a decrease of at least 20 minutes of the patient's total “Off” time compared to the patient's total “Off” time while receiving the oral immediate release levodopa tablets of step (i). 4. The method of claim 1 wherein the “Off” time is measured per day or waking hours/per day. 5. 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 (iv). 6. The method of claim 5, wherein the stable dosing regimen includes no change in dose or dosing frequency. 7. The method of claim 1, wherein the Parkinson's disease comprises primary parkinsonism/idiopathic parkinsonism. 8. The method of claim 1, wherein the Parkinson's disease comprises post-encephalitic parkinsonism. 9. The method of claim 1, wherein the Parkinson's disease comprises parkinsonism following carbon monoxide intoxication. 10. The method of claim 1, wherein the Parkinson's disease comprises parkinsonism following manganese intoxication. 11. 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 most frequent immediate release levodopa dose from each administration of immediate release tablets of step (i); iii) discontinuing the administration of the immediate release levodopa tablets to the patient of step (i); and iv) 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 the most frequent immediate release levodopa dose of step (ii); 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 wherein the multiparticulate controlled release dosage form comprises: (a) a plurality of controlled release components comprising a core comprising levodopa, a controlled release material, and a coating comprising an enteric polymer surrounding the levodopa and controlled release material wherein the controlled release components pass through a 12 mesh screen; and (b) an immediate release component comprising levodopa, and carbidopa; and wherein the multiparticulate controlled release dosage form when administered to an adult human subject after an overnight fast and at a dose of 280 mg of levodopa and 70 mg of carbidopa produces an AUCtau of from about 5752±1771 ng*h/mL to about 6037±2648 ng*h/mL wherein the plurality of controlled release components are free of carbidopa; and wherein the controlled release dosage form when tested using a USP Type I apparatus at 37° C.±0.5° C. with a rotational speed of 75 rpm and about 900 ml of simulated gastric fluid for 2 hours and pH 6.8 phosphate buffer thereafter, about 75% to about 100% of CD is released within 30 minutes; about 15% to about 45% of LD is released within 30 minutes and not less than 85% of the LD is released after 7 hours; wherein the simulated gastric fluid has a pH of from about 1 to about 4.0. 12. The method of claim 11 wherein the adult human subject has a body mass index of about 18.5 to 30 kg/m2. 13. The method of claim 11 wherein the patient after receiving treatment with the multiparticulate controlled release dosage form exhibits a decrease of at least 20 minutes of the patient's total “Off” time compared to the patient's total “Off” time while receiving the oral immediate release levodopa tablets of step (i). 14. The method of claim 11 wherein the “Off” time is measured per day or waking hours/per day. 15. The method of claim 11, wherein in step (i) the patient is being treated with a stable dosing regimen of oral immediate release levodopa tablets comprising 100 mg of levodopa, esters or salts thereof, wherein the dosing regimen is stable for at least 5 days prior to step (iii). 16. The method of claim 15, wherein the stable dosing regimen includes no change in dose or dosing frequency. 17. The method of claim 11, wherein the Parkinson's disease comprises primary parkinsonism/idiopathic parkinsonism. 18. The method of claim 11, wherein the Parkinson's disease comprises post-encephalitic parkinsonism. 19. The method of claim 11, wherein the Parkinson's disease comprises parkinsonism following carbon monoxide intoxication. 20. The method of claim 11, wherein the Parkinson's disease comprises parkinsonism following manganese intoxication. 21. The method of claim 1 wherein the multiparticulate controlled release dosage form is a capsule. 22. The method of claim 1 wherein the multiparticulate controlled release dosage form is a tablet. 23. The method of claim 1 wherein the plurality of controlled release components comprise beads with a spheronized core comprising levodopa. 24. The method of claim 23 wherein the beads past through a 14 mesh screen but are retained on 24 mesh screen. 25. The method of claim 11 wherein the multiparticulate controlled release dosage form is a capsule. 26. The method of claim 11 wherein the multiparticulate controlled release dosage form is a tablet. 27. The method of claim 11 wherein the plurality of controlled release components comprise beads with a spheronized core comprising levodopa. 28. The method of claim 27 wherein the beads past through a 14 mesh screen but are retained on 24 mesh screen.