Claims for Patent: 12,303,481

Summary for Patent: 12,303,481

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:	US18/802,151
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 less than 500 mg; (ii) determining the amount of levodopa administered to the patient with each administration of the immediate release levodopa tablets of step (i); selecting the most frequent dose of the patient's dosing regimen of the immediate release tablets from step (ii); (iv) discontinuing the administration of the immediate release levodopa tablets; and (v) orally administering a controlled release levodopa dosage form twice or thrice a day to the patient, wherein the amount of levodopa administered with each administration of the 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 the immediate release levodopa tablets of step (iii), wherein the patient after receiving treatment with the controlled release dosage form exhibits an increase of at least 5% 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 controlled release dosage form comprises: (a) a plurality of controlled release components comprising a core comprising levodopa and a controlled release material, and a coating comprising an enteric polymer surrounding the levodopa and controlled release material; and (b) one or more immediate release components comprising levodopa and carbidopa; wherein the controlled release components are substantially 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 carbidopa is released within 30 minutes; and about 15% to about 45% of levodopa is released within 30 minutes; wherein the simulated gastric fluid has a pH of from about 1 to about 4.0. 2. The method of claim 1, wherein the patient after receiving treatment with the 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 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 after administration of the 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. 6. The method of claim 1, wherein the administration of the controlled release dosage form provides a levodopa fluctuation index of about 1.7±0.5 hours. 7. 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). 8. The method of claim 7, wherein the stable dosing regimen includes no change in dose or dosing frequency. 9. The method of claim 1, wherein the most frequent single dose of the immediate release levodopa tablets is the highest dose of immediate release levodopa tablets the patient is receiving prior to step (iii). 10. The method of claim 1, wherein the Parkinson's disease comprises primary parkinsonism/idiopathic parkinsonism. 11. The method of claim 1, wherein the Parkinson's disease comprises post-encephalitic parkinsonism. 12. The method of claim 1, wherein the Parkinson's disease comprises parkinsonism following carbon monoxide intoxication. 13. The method of claim 1, wherein the Parkinson's disease comprises parkinsonism following manganese intoxication. 14. The method of claim 1, wherein the twice or thrice a day administration of the controlled release dosage form provides a total “On” time of at least about 5 hours per day. 15. 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 with each dose of oral immediate release levodopa tablets comprising 100 mg of levodopa; ii) discontinuing the administration of the immediate release levodopa tablets; and iii) orally administering a controlled release levodopa dosage form twice, thrice, or four times a day to the patient, wherein the amount of levodopa administered with each administration of the controlled release levodopa dosage form comprises 280 mg of levodopa, wherein the patient after receiving treatment with the controlled release dosage form exhibits an increase of at least 5% 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 controlled release dosage form comprises: (a) a plurality of controlled release components comprising a core comprising levodopa and a controlled release material, and a coating comprising an enteric polymer surrounding the levodopa and controlled release material; and (b) one or more immediate release components comprising levodopa and carbidopa; wherein the controlled release components are substantially free of carbidopa; and wherein the 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 carbidopa is released within 30 minutes; and about 15% to about 45% of levodopa is released within 30 minutes; wherein the simulated gastric fluid has a pH of from about 1 to about 4.0. 16. The method of claim 15, wherein the Parkinson's disease patient in step (i) is being treated with oral immediate release levodopa tablets for a total daily levodopa dose of less than 500 mg. 17. The method of claim 16, wherein the Parkinson's disease patient in step (iii) is being orally administered the controlled release levodopa dosage form twice a day. 18. The method of claim 15, wherein the Parkinson's disease comprises primary parkinsonism/idiopathic parkinsonism. 19. The method of claim 15, wherein the Parkinson's disease comprises post-encephalitic parkinsonism. 20. The method of claim 15, wherein the Parkinson's disease comprises parkinsonism following carbon monoxide intoxication. 21. The method of claim 15, wherein the Parkinson's disease comprises parkinsonism following manganese intoxication.