# US 2023/0054825 A1 · Levodopa dosing regimen > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2023/0054825 A1 - Document ID: US20230054825A1 - Status: Published application - Kind: A1 - Application number: 17/967,332 - Filed: 2022-10-17 - Published: 2023-02-23 - Earliest claimed: 2020-12-22 - Assignees: Amneal Pharmaceuticals, LLC - Applicants: Amneal Pharmaceuticals LLC - Inventors: Richard D'Souza; Hester Visser; Suneel Gupta - Web page: https://patentgrep.com/patent/US20230054825A1 ## CPC - A61K 31/198: Alpha-amino acids, e.g. alanine or edetic acid [EDTA] (betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00) - A61K 9/5005: {Wall or coating material} - A61K 9/5073: {having two or more different coatings optionally including drug-containing subcoatings} - A61P 25/16: Anti-Parkinson drugs - A61K 9/4825: {Proteins, e.g. gelatin (gelatin capsule shells with substantial amounts of other macromolecular substances A61K9/4816)} - A61K 9/5026: {obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates} - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## 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. ## Claims ### Claim 1 A method for treating a patient diagnosed with Parkinson's disease comprising the oral administration of a controlled release dosage form comprising levodopa and a controlled release excipient and/or a muco-adhesive excipient; wherein the composition is administered twice a day with a starting dose comprising a total daily dose of levodopa of form is about 400 mg to about 1,400 mg; wherein the dose of levodopa administered each time is from the controlled release dosage form is from about 200 mg to about 700 mg, and wherein the patient prior to receiving the controlled release dosage form of levodopa was being treated with a total daily dose of about 500 mg or less of levodopa administered in three, four or more doses in a twenty-four hour period. ### Claim 2 (depends on 1) The method of claim 1 wherein the dose of levodopa administered every six to twelve hours from the controlled release dosage form is about 200 mg to about 600 mg. ### Claim 3 (depends on 1) The method of claim 1 wherein the dose of levodopa administered every 6 to 9 hours from the controlled release dosage form is about 200 mg to about 600 mg. ### Claim 4 (depends on 1) The method of claim 1 wherein the controlled release dosage form further comprises carbidopa. ### Claim 5 (depends on 4) The method of claim 4 wherein the controlled release dosage form comprises one or more capsules comprising: (a) 140 mg of levodopa and 35 mg of carbidopa; (b) 210 mg of levodopa and 52.5 mg of carbidopa; (c) 280 mg of levodopa and 70 mg of carbidopa; (d) 350 mg of levodopa and 87.5 mg of carbidopa; or (e) a combination of the foregoing. ### Claim 6 (depends on 1) The method of claim 1 wherein the controlled release dosage form when tested using a USP Apparatus I at 75 rpms and 37°±0.5° C. with 500-900 ml of simulated gastric fluid for 2 hours and pH 6.8 phosphate buffer thereafter exhibits the following levodopa release profile: 20% to 60% of levodopa is released after 2 hours; 40% to 80% of levodopa is released after 3 hours; 60% to 100% of levodopa is release after 4 hours; and not less than 80% is released after 7 hours. ### Claim 7 (depends on 1) The method of claim 1 wherein after administration the controlled release dosage form produces a levodopa plasma level of at least 300 ng/mL within 0.25 to 1 hour after administration. ### Claim 8 (depends on 1) The method of claim 1 wherein 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 to eight hours after dosing. ### Claim 9 (depends on 4) The method of claim 4 wherein after administration the controlled release dosage twice a day for at least 7 days, the minimum carbidopa plasma level is a at least about 40 ng/mL seven to eight hours after dosing. ### Claim 10 (depends on 1) The method of claim 1 wherein the patient is a newly diagnosed with Parkinson's disease or is a levodopa naïve patient. ### Claim 11 A method for treating a patient diagnosed with Parkinson's disease comprising the oral administration of a controlled release dosage form comprising levodopa and a controlled release excipient and/or a muco-adhesive excipient; the administration of the controlled release dosage form occurs every 6 to 12 hours and the patient exhibits: (i) a total “Off” time during a 24 hour period and/or or during waking hours in a 24 hour period of less than 5 hours. ### Claim 12 (depends on 11) The method of claim 11, wherein the patient exhibits a total “On” time at and/or a total “Good On” time of 5 hours or more during the dosing time interval. ### Claim 13 (depends on 11) The method of claim 11, wherein the patient exhibits an increase of at least 20 minutes of the patient's total “On” time and/or a total “Good On” time per dose, per day and/or during waking hours per day compared to a comparable oral immediate release CD-LD dose or the total immediate release CD-LD doses per day or per waking hours. ### Claim 14 (depends on 11) The method of claim 11 wherein the controlled release dosage form comprises one or more capsules comprising: (a) 140 mg of levodopa and 35 mg of carbidopa; (b) 210 mg of levodopa and 52.5 mg of carbidopa; (c) 280 mg of levodopa and 70 mg of carbidopa; (d) 350 mg of levodopa and 87.5 mg of carbidopa; or (e) a combination of the foregoing. ### Claim 15 A method for treating a patient diagnosed with Parkinson's disease comprising the oral administration of a controlled release dosage form comprising levodopa and a controlled release excipient and/or a muco-adhesive excipient; the administration of the controlled release dosage form occurs twice or thrice daily and the patient exhibits at least a 5% reduction in total “Off” time during waking hours compared to the patient receiving treatment with an immediate release levodopa and carbidopa oral dosage form administered five times a day. ### Claim 16 (depends on 15) The method of claim 15 wherein the controlled release dosage form comprises one or more capsules comprising: (a) 140 mg of levodopa and 35 mg of carbidopa; (b) 210 mg of levodopa and 52.5 mg of carbidopa; (c) 280 mg of levodopa and 70 mg of carbidopa; (d) 350 mg of levodopa and 87.5 mg of carbidopa; or (e) a combination of the foregoing. ### Claim 17 (depends on 15) The method of claim 15 wherein the administration of the controlled release dosage form occurs at a dosing interval of every six to twelve hours and the patient exhibits a total “Off” time during the dosing interval of 240 minutes or less. ### Claim 18 (depends on 15) The method of claim 15 wherein the administration of the controlled release dosage form occurs every six to twelve hours and the patient is administered a bedtime dose of the controlled release dosage form about 30 minutes or less before bedtime and the patient will wake in about 6 to about 9 hours after the bedtime dose in an “On” or “Good On” state. ### Claim 19 (depends on 15) The method of claim 15 wherein the administration of the controlled release dosage form occurs every six to twelve hour dosing interval and the patient is administered the same dose at each of the dosing interval. ### Claim 20 (depends on 15) The method of claim 15 wherein the controlled release dosage form when administered in a fed condition provides similar or increased levodopa maximum plasma concentration (Cmax) and levodopa area under the plasma concentration time curve compared to administration under fasting conditions. ### Claim 21 (depends on 15) The method of claim 15 wherein the time to maximum levodopa plasma concentration (Tmax levodopa) or the time to maximum carbidopa plasma concentration (Tmax carbidopa) when the controlled release dosage form is administered under fed conditions is ±5 hours of the Tmax levodopa or Tmax carbidopa when the controlled release dosage form is administered under fasting conditions.