Composition and method for treating neurological disease

• US 8,895,617 B1
• Filed: 08/04/2014
• Issued: 11/25/2014
• Est. Priority Date: 11/24/2004
• Status: Active Grant

• Current Assignee: Adamas Pharma, LLC (Supernus Pharmaceuticals, Inc.)
• Original Assignee: Adamas Pharmaceuticals, Inc. (Supernus Pharmaceuticals, Inc.)
• Inventors: Went, Gregory T., Fultz, Timothy J., Porter, Seth, Meyerson, Laurence R., Burkoth, Timothy S.
• Primary Examiner(s): ZAREK, PAUL E
• Application Number:
  US14/451,273
• Publication Number:
  US 20140343154A1
• Time in Patent Office: 113 Days
• Field of Search: 514/565, 514/656
• US Class Current: 514/565
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/13 Amines A61K31/04 takes precedence
• CPC Class Codes: A61K 31/197 the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid carnitine A61K31/205
• CPC Class Codes: 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
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61K 9/16 Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction A61K9/20 takes precedence if the final form is a tablet; microspheres with drug-free outer coating, microcapsules A61K9/50; mixture of different granules, microcapsules, (coated) microparticles A61K9/5084; nanoparticles A61K9/51
• CPC Class Codes: A61K 9/1617 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/1652 Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin homeopathic globules A61K9/1623
• CPC Class Codes: A61K 9/2009 Inorganic compounds
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2846 Poly(meth)acrylates
• CPC Class Codes: A61K 9/4808 characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release capsules filled with granules or microparticles A61K9/16; filled with microcapsules or coated microparticles A61K9/50; with mixture of different granules, microcapsules, (coated) microparticles A61K9/5084
• CPC Class Codes: A61K 9/5021 Organic macromolecular compounds
• CPC Class Codes: A61K 9/5047 Cellulose ethers containing no ester groups, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/5078 with drug-free core
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs

Abstract

Disclosed are compositions comprising amantadine, or a pharmaceutically acceptable salt thereof, and one or more excipients, wherein at least one of the excipients modifies release of amantadine. Methods of administering the same are also provided.

Claims

1. A method comprising:

orally administering to a human subject with Parkinson'"'"'s disease a once-daily dose consisting of (i) 200 mg to 500 mg of a drug selected from the group consisting of amantadine and pharmaceutically acceptable salts thereof, and (ii) at least one excipient, wherein the drug in the dose comprises an extended release form, and wherein the extended release form of the drug in the dose provides a mean change in amantadine plasma concentration as a function of time (dC/dT) that is less than 40% of the dC/dT provided by the same quantity of the drug in an immediate release form, wherein the dC/dT values are measured in a single dose human pharmacokinetic study over the time period between 0 and 4 hours after administration.

4. The method of any of claims 1 to 3, wherein the amount of drug is 300 to 500 mg.

5. The method of any of claims 1 to 3, wherein at least 50% of the drug in the dose is in an extended release form.

6. The method of any of claims 1 to 3, wherein at least 75% of the drug in the dose is in an extended release form.

7. The method of any of claims 1 to 3, wherein at least 90% of the drug in the dose is in an extended release form.

8. The method of any of claims 1 to 3, wherein the dose additionally comprises the drug in an immediate release form.

9. The method of any of claims 1 to 3, the dose administered is therapeutically effective for the treatment of Parkinson'"'"'s disease.

10. The method of any of claims 1 to 3, wherein the human subject with Parkinson'"'"'s disease suffers from dyskinesia.

11. The method of claim 10, wherein the method reduces the frequency or severity of dyskinesia.

12. The method of claim 10, wherein the dyskinesia is levodopa-induced dyskinesia.

13. The method of any of claims 1 to 3, additionally comprising administering to the subject a pharmaceutically effective amount of levodopa/carbidopa.

14. The method of any of claims 1 to 3, wherein the dose provides a shift in amantadine Tmax of 2 hours to 16 hours relative to an immediate release form of amantadine, wherein the Tmax is measured in a single dose human pharmacokinetic study.

15. The method of any of claims 1 to 3, wherein the dose comprises an osmotic device which utilizes an osmotic driving force to provide extended release of the drug.

16. The method of any of claims 1 to 3, wherein the extent of drug bioavailability is maintained.

17. The method of any of claims 1 to 3, wherein the once-daily dose is administered at a therapeutically-effective dose from the onset of therapy.

2. A method comprising:

orally administering to a human subject with Parkinson'"'"'s disease a once-daily dose consisting of (i) 200 mg to 500 mg of a drug selected from the group consisting of amantadine and pharmaceutically acceptable salts thereof, and (ii) at least one excipient, wherein the drug in the dose comprises an extended release form, and wherein the extended release form of the drug in the dose provides a mean change in amantadine plasma concentration as a function of time (dC/dT) that is less than 40% of the dC/dT provided by the same quantity of the drug in an immediate release form, wherein the dC/dT values are measured in a single dose human pharmacokinetic study over the time period between administration and Tmax of the immediate release form.

3. A method comprising:

orally administering to a human subject with Parkinson'"'"'s disease a once-daily dose consisting of (i) 200 mg to 500 mg of a drug selected from the group consisting of amantadine and pharmaceutically acceptable salts thereof, and (ii) at least one excipient, wherein the drug in the dose comprises an extended release form, and wherein the extended release form of the drug in the dose provides a mean change in amantadine plasma concentration as a function of time (dC/dT) that is less than 40% of the dC/dT provided by the same quantity of the drug in an immediate release form, wherein the dC/dT of the extended release form of the drug in the dose is measured in a single dose human pharmacokinetic study over the time period between 2 hours and 4 hours after administration and the dC/dT provided by the same quantity of the drug in an immediate release form is measured in a single dose human pharmacokinetic study over the time period between administration and Tmax of the immediate release form.