Method of administering amantadine prior to a sleep period

• US 8,741,343 B2
• Filed: 12/02/2010
• Issued: 06/03/2014
• Est. Priority Date: 12/02/2009
• Status: Active Grant

• Current Assignee: Adamas Pharma, LLC (Supernus Pharmaceuticals, Inc.)
• Original Assignee: Adamas Pharmaceuticals, Inc. (Supernus Pharmaceuticals, Inc.)
• Inventors: Went, Gregory T., Sathyan, Gayatri, Vermani, Kavita, Ganapati, Gangadhara, Coffee, Michael, Shek, Efraim, Katdare, Ashok
• Primary Examiner(s): Orwig, Kevin S
• Application Number:
  US12/959,321
• Publication Number:
  US 20110189273A1
• Time in Patent Office: 1,279 Days
• Field of Search: None
• US Class Current: 424/457
• CPC Class Codes: A61K 31/13 Amines A61K31/04 takes precedence
• 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 9/0002 Galenical forms characterised by the drug release technique; Application systems commanded by energy
• 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 9/14 Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles microspheres A61K9/16; microcapsules A61K9/50; nanocapsules, nanoparticles of the matrix type A61K9/51
• CPC Class Codes: A61K 9/48 Preparations in capsules, e.g. of gelatin, of chocolate A61K9/0004 takes precedence; bite capsules A61K9/0056
• 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 9/4891 Coated capsules; Multilayered drug free capsule shells with drug coating for immediate release A61K9/4808; osmotic devices A61K9/0004
• CPC Class Codes: A61K 9/50 Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals A61K9/2081 takes precedence; particles with a single coating comprising drug A61K9/167
• CPC Class Codes: A61K 9/5015 Organic compounds, e.g. fats, sugars
• CPC Class Codes: A61K 9/5026 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• 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 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/20 Hypnotics; Sedatives
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia

Abstract

Methods of nighttime administration of amantadine to reduce sleep disturbances in patient undergoing treatment with amantadine are described, as well as compositions of extended release amantadine that are suitable for nighttime administration.

Claims

1. A method of administering amantadine, or a pharmaceutically acceptable salt thereof, to a human subject in need thereof, said method comprising the steps of:

providing an extended release (ER) composition comprising 220 mg to 445 mg of amantadine, or a pharmaceutically acceptable salt thereof, and at least one release modifying excipient, said composition having a median amantadine Tmax between 8 and 18 hours, as determined by a single dose, fasting human pharmacokinetic study, and

orally administering said composition once daily 0 to 4 hours before bedtime to a human subject.

2. The method of claim 1, wherein the method comprises reducing sleep disturbance in a human subject undergoing treatment with amantadine.

3. The method of claim 1, wherein the method comprises treating levodopa-induced dyskinesia in a patient with Parkinson'"'"'s disease.

4. The method of claim 1, wherein the composition is administered 0 to 3 hours before bedtime.

5. The method of claim 1, wherein the composition is administered 0 to 2 hours before bedtime.

6. The method of claim 1, wherein the composition is administered as two or three unit dosage forms each comprising 110 to 210 mg of extended release amantadine, or a pharmaceutically acceptable salt thereof, and the amantadine, or pharmaceutically acceptable salt thereof in the unit dosage forms together totals 220 mg to 445 mg.

7. The method of claim 1, wherein the composition is administered as two or three unit dosage forms each comprising 130 mg of amantadine, or a pharmaceutically acceptable salt thereof.

8. The method of claim 1, wherein the composition is administered as two or three unit dosage forms each comprising 140 mg of amantadine, or a pharmaceutically acceptable salt thereof.

9. The method of claim 1, wherein the composition is administered as two unit dosage forms each comprising 170 mg of amantadine, or a pharmaceutically acceptable salt thereof.

10. A method of administering amantadine, or a pharmaceutically acceptable salt thereof, to a human subject in need thereof, said method comprising the steps of:

providing an extended release (ER) composition comprising 220 mg to 445 mg of amantadine, or a pharmaceutically acceptable salt thereof and at least one release modifying excipient, said composition having a mean Cmax for amantadine of 1.0 to 2.8 ng/mL/mg amantadine and a mean amantadine AUC_0-inf of 40 to 75 ng·

hr/mL/mg, as determined by a single dose, fasting human pharmacokinetic study, and

orally administering said composition once daily, 0 to 4 hours before bedtime to a human subject.

11. The method of claim 10, wherein said composition has a mean AUC per mg of amantadine equivalent to a mean AUC per mg of amantadine for a 100 mg tablet of an immediate release formulation of amantadine HCl.

12. The method of claim 10, wherein the method comprises reducing sleep disturbance in a human subject undergoing treatment with amantadine.

13. The method of claim 10, wherein the method comprises treating levodopa-induced dyskinesia in a patient with Parkinson'"'"'s disease.

14. The method of claim 10, wherein the composition is administered 0 to 3 hours before bedtime.

15. The method of claim 10, wherein the composition is administered 0 to 2 hours before bedtime.

16. The method of claim 10, wherein the composition is administered as one or two or three unit dosage forms each comprising 110 to 210 mg of extended release amantadine, or a pharmaceutically acceptable salt thereof, and the amantadine, or pharmaceutically acceptable salt thereof in the unit dosage forms together totals 220 mg to 445 mg.

17. The method of claim 10, wherein the composition is administered as two or three unit dosage forms each comprising 130 mg of amantadine, or a pharmaceutically acceptable salt thereof.

18. The method of claim 10, wherein the composition is administered as two or three unit dosage forms each comprising 140 mg of amantadine, or a pharmaceutically acceptable salt thereof.

19. The method of claim 10, wherein the composition is administered as two unit dosage forms each comprising 170 mg of amantadine, or a pharmaceutically acceptable salt thereof.

20. The method of claim 10, wherein administration of a dose of the composition to a human subject in a single-dose human pharmacokinetic study provides a mean amantadine Cmax of 1.0 to 2.4 ng/mL/mg.

21. The method of claim 20, wherein said composition has a mean AUC per mg of amantadine equivalent to a mean AUC per mg of amantadine for a 100 mg tablet of an immediate release formulation of amantadine HCl.

22. The method of claim 20, wherein the method comprises reducing sleep disturbance in a human subject undergoing treatment with amantadine.

23. The method of claim 20, wherein the method comprises treating levodopa-induced dyskinesia in a patient with Parkinson'"'"'s disease.

24. The method of claim 20, wherein the composition is administered 0 to 3 hours before bedtime.

25. The method of claim 20, wherein the composition is administered 0 to 2 hours before bedtime.

26. The method of claim 20, wherein the composition is administered as one or two or three unit dosage forms each comprising 110 to 210 mg of extended release amantadine, or a pharmaceutically acceptable salt thereof, and the amantadine, or pharmaceutically acceptable salt thereof in the unit dosage forms together totals 220 mg to 445 mg.

27. The method of claim 20, wherein the composition is administered as two or three unit dosage forms each comprising 130 mg of amantadine, or a pharmaceutically acceptable salt thereof.

28. The method of claim 20, wherein the composition is administered as two or three unit dosage forms each comprising 140 mg of amantadine, or a pharmaceutically acceptable salt thereof.

29. The method of claim 20, wherein the composition is administered as two unit dosage forms each comprising 170 mg of amantadine, or a pharmaceutically acceptable salt thereof.