Claims for Patent: 12,194,150

Summary for Patent: 12,194,150

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.
Inventor(s):	Richard D'Souza, Hester Visser, Suneel Gupta
Assignee:	Amneal Pharmaceuticals LLC
Application Number:	US17/558,337
Patent Claims:	1. A method for treating a levodopa naïve patient with Parkinson's disease comprising an oral administration of a controlled release levodopa dosage form comprising: a) one or more controlled release components comprising levodopa, and a mucoadhesive polymer; and b) one or more immediate release components comprising levodopa, and carbidopa; wherein the mucoadhesive polymer is a material capable of forming a positive ionic charge at pHs present in the human gastro-intestinal tract, wherein the controlled release dosage form is administered twice a day with each dose administered each time comprising 140 mg of levodopa and a total daily administered levodopa dose of 280 mg; wherein the patient is not being treated with a catechol-O-methyl transferase inhibitor and the patient has not been previously treated with levodopa; wherein the twice a day dosing provides an improvement of at least 10% in the patient's tremor, dyskinesia, and/or mobility as measured by a Kinesia 360 Sensor; wherein the one or more controlled release components are substantially free of carbidopa; wherein the controlled release dosage form is free of a catechol-O-methyl transferase inhibitor; 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; and about 15% to about 45% of LD 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 after administration the controlled release dosage form provides a levodopa plasma level of at least about 300 ng/mL within about 1 hour after administration and after twice a day administration of the controlled release dosage form for at least 7 days provides a minimum levodopa plasma level at least about 250 ng/mL at about six hours after dosing. 3. The method of claim 2, wherein after administration of the controlled release dosage form twice a day for at least 7 days, the minimum carbidopa plasma level is at least about 40 ng/mL seven to eight hours after dosing. 4. The method of claim 1 wherein the patient is newly diagnosed with Parkinson's disease. 5. A method for treating a levodopa naïve patient with Parkinson's disease comprising an oral administration of a controlled release levodopa dosage form comprising: a) one or more controlled release components comprising levodopa, and a mucoadhesive polymer; and b) one or more immediate release components comprising levodopa and carbidopa; wherein the mucoadhesive polymer is a material capable of forming a positive ionic charge at pHs present in the human gastro-intestinal tract, wherein the controlled release dosage form is administered twice a day with each dose administered each time comprising 140 mg of levodopa and a total daily administered levodopa dose of 280 mg, wherein the patient is not being treated with a catechol-O-methyl transferase inhibitor and the patient has not been previously treated with levodopa; wherein twice a day dosing improves the patient's motor state as determined by patient's Parkinsons disease diary; wherein the one or more controlled release components are substantially free of carbidopa; wherein the controlled release dosage form is free of a catechol-O-methyl transferase inhibitor; 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; and about 15% to about 45% of LD is released within 30 minutes; wherein the simulated gastric fluid has a pH of from about 1 to about 4.0. 6. A method for treating a levodopa naïve patient with Parkinson's disease comprising an oral administration of a controlled release levodopa dosage form comprising: a) one or more controlled release components comprising levodopa, and a mucoadhesive polymer; and b) one or more immediate release components comprising levodopa and carbidopa; wherein the mucoadhesive polymer is a material capable of forming a positive ionic charge at the pHs present in the human gastro-intestinal tract, wherein the controlled release dosage form is administered twice a day with each dose administered each time comprising 140 mg of levodopa and a total daily administered levodopa dose of 280 mg, wherein the patient is not being treated with a catechol-O-methyl transferase inhibitor and has not been previously treated with levodopa; wherein the twice a day dosing reduces the patient's Movement Disorders Society version of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) scores by at least 3 points; and wherein the one or more controlled release components are substantially free of carbidopa; wherein the controlled release dosage form is free of a catechol-O-methyl transferase inhibitor; 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; and about 15% to about 45% of LD is released within 30 minutes; wherein the simulated gastric fluid has a pH of from about 1 to about 4.0. 7. The method of claim 6 wherein the twice a day dosing reduces the patient's MDS-UPDRS scores from about 3 points to about 15 points. 8. The method of claim 5 wherein after administration the controlled release dosage form provides a levodopa plasma level of at least about 300 ng/ml within about 1 hour after administration and after twice a day administration of the controlled release dosage form for at least 7 days provides a minimum levodopa plasma level at least about 250 ng/mL six hours after dosing. 9. The method of claim 6 wherein after administration the controlled release dosage form provides a levodopa plasma level of at least about 300 ng/ml within about 1 hour after administration and after twice a day administration of the controlled release dosage form for at least 7 days provides a minimum levodopa plasma level at least about 250 ng/mL six hours after dosing. 10. The method of claim 1, wherein the Parkinson's disease comprises primary parkinsonism. 11. The method of claim 1, wherein the twice-a-day administration provides a reduction of from about 10%-40% in the patient's tremor, dyskinesia, and/or mobility as measured by a Kinesia 360 Sensor. 12. The method of claim 5, wherein the Parkinson's disease comprises primary parkinsonism. 13. The method of claim 5, wherein the twice-a-day dosing improves patient's motor state by at least 10%. 14. The method of claim 6, wherein the Parkinson's disease comprises primary parkinsonism.