Claims for Patent: 12,295,931

Summary for Patent: 12,295,931

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:	US18/823,575
Patent Claims:	1. A dosing regimen comprising orally administering a controlled release levodopa dosage form twice, thrice, or four times a day to a Parkinson's disease patient, wherein the patient prior to receiving the controlled release levodopa dosage form was being treated with oral immediate release levodopa tablets, wherein the administration of the oral immediate release levodopa tablets was discontinued and replaced with the dosing regimen of controlled release levodopa dosage forms, wherein the amount of levodopa administered with each administration of the discontinued immediate release levodopa tablets was determined, and 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 discontinued immediate release levodopa tablets prior to the administration of the controlled release dosage form, wherein the patient after receiving the treatment with the controlled release dosage form exhibits a decrease of at least 5% of the patient's post-dose “Off”′ time as compared to patient's post-dose “Off”′ time during the treatment with the oral immediate release levodopa tablets, wherein the controlled release dosage form comprises one or more immediate release components comprising levodopa and a decarboxylase inhibitor, and 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 the plurality of 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 the decarboxylase inhibitor is released within 30 minutes; and about 15% to about 45% of levodopa is released within 30 minutes; and the simulated gastric fluid has a pH of from about 1 to about 4.0. 2. The dosing regimen of claim 1, wherein the Parkinson's disease is selected from the group consisting of primary parkinsonism/idiopathic parkinsonism, post-encephalitic parkinsonism, parkinsonism following carbon monoxide intoxication, and parkinsonism following manganese intoxication. 3. The dosing regimen of claim 1, wherein the decarboxylase inhibitor is carbidopa, and 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 via the controlled release dosage form is provided by administering one or a combination of the foregoing capsules per dosing time. 4. The dosing regimen 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. 5. The dosing regimen of claim 1, wherein the administration of the controlled release dosage form provides a levodopa fluctuation index of about 1.7±0.5 hours. 6. The dosing regimen of claim 1, wherein the patient prior to receiving the controlled release levodopa dosage form was being treated with a stable dosing regimen of oral immediate release levodopa tablets, wherein the dosing regimen was stable for at least 5 days prior to discontinuing the oral immediate release tablets. 7. The dosing regimen of claim 6, wherein the stable dosing regimen includes no change in dose or dosing frequency. 8. The dosing regimen of claim 1, wherein the amount of levodopa administered to the patient with each administration of the immediate release levodopa tablets was the most frequent single dose of immediate-release levodopa tablets the patient was receiving prior to discontinuation of administration of immediate release levodopa tablets. 9. The dosing regimen of claim 8, wherein the most-frequent single dose of the immediate release levodopa tablets was the highest most-frequent dose of immediate release levodopa tablets the patient was receiving prior to discontinuation of administration of immediate release levodopa tablets. 10. The dosing regimen of claim 3, 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. 11. The dosing regimen of claim 10, wherein the “On” time is measured per day or waking hours/per day. 12. A dosing regimen comprising orally administering a controlled release levodopa dosage form twice or thrice a day to a Parkinson's disease patient, wherein the patient prior to receiving the controlled release levodopa dosage form was being treated with oral immediate release levodopa tablets for a total daily levodopa dose of less than 500 mg, wherein the amount of levodopa administered with each administration of immediate release levodopa tablets was determined, and administration of oral immediate release levodopa tablets was discontinued and replaced with the dosing regimen of controlled release levodopa dosage forms, 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 discontinued immediate release levodopa tablets prior to the administration of the controlled release dosage form, and wherein the patient after receiving the treatment with the controlled release dosage form exhibits a decrease of at least 5% of the patient's post-dose “Off′ time as compared to the patient's post-dose “Off” time during treatment with oral immediate release levodopa tablets, wherein the controlled release dosage form comprises one or more immediate release components comprising levodopa and a decarboxylase inhibitor, and 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 the plurality of 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 the decarboxylase inhibitor 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. 13. The dosing regimen of claim 12, wherein the Parkinson's disease is selected from the group consisting of primary parkinsonism/idiopathic parkinsonism, post-encephalitic parkinsonism, parkinsonism following carbon monoxide intoxication, and parkinsonism following manganese intoxication. 14. The dosing regimen of claim 12, wherein the patient is a Parkinson's disease patient experiencing an average of at least 2.5 hours per day of “Off” time. 15. The dosing regimen of claim 12, wherein the decarboxylase inhibitor is carbidopa, and 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 via the controlled release dosage form is provided by administering one or a combination of the foregoing capsules per dosing time. 16. The dosing regimen of claim 12, 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. 17. The dosing regimen of claim 12, wherein the administration of the controlled release dosage form provides a levodopa fluctuation index of about 1.7±0.5 hours. 18. The dosing regimen of claim 12, wherein the patient prior to receiving the controlled release levodopa dosage form was being treated with a stable dosing regimen of oral immediate release levodopa tablets, wherein the dosing regimen was stable for at least 5 days prior to discontinuing the oral immediate release tablets. 19. The dosing regimen of claim 18, wherein the stable dosing regimen includes no change in dose or dosing frequency. 20. The dosing regimen of claim 12, wherein the amount of levodopa administered to the patient with each administration of the immediate release levodopa tablets was the most frequent single dose of immediate-release levodopa tablets the patient was receiving prior to discontinuation of administration of immediate release levodopa tablets. 21. The dosing regimen of claim 20, wherein the most-frequent single dose of the immediate release levodopa tablets was the highest most-frequent dose of immediate release levodopa tablets the patient was receiving prior to discontinuation of administration of immediate release levodopa tablets. 22. The dosing regimen of claim 15, 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. 23. A dosing regimen comprising orally administering a controlled release levodopa dosage form twice, thrice, or four times a day to a Parkinson's disease patient, wherein the patient prior to receiving the controlled release levodopa dosage form was being treated with oral immediate release levodopa tablets for a total daily levodopa dose of greater than 500 mg, wherein the amount of levodopa administered with each administration of immediate release levodopa tablets was determined, and administration of the oral immediate release levodopa tablets was discontinued and replaced with the dosing regimen of controlled release levodopa dosage form, 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 discontinued immediate release levodopa tablets prior to the administration of the controlled release dosage form, and wherein the patient after receiving the treatment with the controlled release dosage form exhibits a decrease of at least 5% of the patient's post-dose “Off” time as compared to the patient's post-dose “Off”′ time during treatment with the oral immediate release levodopa tablets, wherein the controlled release dosage form comprises one or more immediate release components comprising levodopa and a decarboxylase inhibitor, and 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 the plurality of 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 the decarboxylase inhibitor 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. 24. The dosing regimen of claim 23, wherein the Parkinson's disease is selected from the group consisting of primary parkinsonism/idiopathic parkinsonism, post-encephalitic parkinsonism, parkinsonism following carbon monoxide intoxication, and parkinsonism following manganese intoxication. 25. The dosing regimen of claim 23, wherein the patient is a Parkinson's disease patient experiencing an average of at least 2.5 hours per day of “Off” time.