Composition and method for treating neurological disease

• US 9,072,697 B2
• Filed: 01/07/2015
• Issued: 07/07/2015
• 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.
• Primary Examiner(s): ZAREK, PAUL E
• Application Number:
  US14/591,641
• Publication Number:
  US 20150126605A1
• Time in Patent Office: 181 Days
• US Class Current: 1/1
• 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 once-daily a composition consisting of

(i) a drug selected from the group consisting of amantadine and pharmaceutically acceptable salts thereof, and

(ii) at least one excipient,

wherein at least 50% of the drug in the composition is in an extended release form, and

wherein the composition has an in vitro dissolution profile ranging between 35% and 55% in 2 hours, 60% and 80% in 4 hours, and greater than 90% in 8 hours using a USP type 2 (paddle) dissolution system at 50 rpm at a temperature of 37±

0.5°

C. in water, and

wherein the daily dose of drug administered to the human subject is 200 to 500 mg.

4. The method of any one of claims 1 to 3, wherein the daily dose of drug administered is 300 to 500 mg.

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

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

7. The method of any one of claims 1 to 3, wherein at least some of the drug is in an immediate release form.

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

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

10. The method of claim 9, wherein the method reduces the frequency or severity of dyskinesia.

11. The method of claim 9, wherein the dyskinesia is levodopa-induced dyskinesia.

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

13. The method of any one of claims 1 to 3, wherein the composition 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.

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

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

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

2. A method comprising:

orally administering to a human subject with Parkinson'"'"'s disease once-daily a composition consisting of

(i) a drug selected from the group consisting of amantadine and pharmaceutically acceptable salts thereof, and

(ii) at least one excipient,

wherein at least 50% of the drug in the composition is in an extended release form and the extended release form of the composition has an in vitro dissolution profile ranging between 35% and 55% in 2 hours, 60% and 80% in 4 hours, and greater than 90% in 8 hours using a USP type 2 (paddle) dissolution system at 50 rpm at a temperature of 37±

0.5°

C. in water, and

wherein the daily dose of drug administered to the human subject is 200 to 500 mg.

3. A method comprising:

orally administering to a human subject with Parkinson'"'"'s disease once-daily a composition consisting of

(i) a drug selected from the group consisting of amantadine and pharmaceutically acceptable salts thereof, and (ii) at least one excipient,

wherein at least 50% of the drug in the composition is in an extended release form and the extended release form of the composition has an in vitro dissolution profile ranging between 60% and 80% in 4 hours, and greater than 90% in 8 hours using a USP type 2 (paddle) dissolution system at 50 rpm at a temperature of 37±

0.5°

C. in water, and

wherein the daily dose of drug administered to the human subject is 200 to 500 mg.