Method of administering amantadine prior to a sleep period

• US 9,877,933 B2
• Filed: 02/09/2017
• Issued: 01/30/2018
• Est. Priority Date: 12/02/2009
• Status: Active Grant

• Current Assignee: Adamas Pharma, LLC (Supernus Pharmaceuticals, Inc.)
• Original Assignee: Adamas Pharma, LLC (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:
  US15/428,878
• Publication Number:
  US 20170151183A1
• Time in Patent Office: 355 Days
• Field of Search: None
• 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 treating a patient with Parkinson'"'"'s disease, comprising administering once daily, 0 to 4 hours before bedtime, to said patient with Parkinson'"'"'s disease, a pharmaceutical composition comprising:

(i) 220 mg to 455 mg of a drug selected from the group consisting of amantadine and a pharmaceutically acceptable salt thereof; and

(ii) one or more excipients, wherein at least one of said one or more excipients modifies the release of said drug to provide an extended release dosage form,

wherein ON time without troublesome dyskinesia is increased in said patient with Parkinson'"'"'s disease, and

wherein when said pharmaceutical composition is dosed in a single dose, fasted, human pharmacokinetic study in healthy subjects, the Tmax for the drug is 8 to 20 hours.

2. The method of claim 1, wherein said increased ON time without troublesome dyskinesia is determined from a Parkinson'"'"'s disease home diary.

3. The method of claim 1, wherein said Tmax is 9 to 18 hours.

4. The method of claim 1, wherein said Tmax is 11 to 18 hours.

5. The method of claim 1, wherein when said pharmaceutical composition is dosed in a single dose, fasted, human pharmacokinetic study in healthy subjects, the AUC_0-inf for the drug is 40 to 75 ng*hr/ml per mg of the drug.

6. The method of claim 1, wherein when said pharmaceutical composition is dosed in a multiple dose, fasted, human pharmacokinetic study in healthy subjects, the steady state AUC_0-24 for the drug is 44 to 83 ng*hr/ml per mg of the drug.

7. The method of claim 1, wherein said pharmaceutical composition is administered to said patient once daily, 0 to 3 hours before bedtime.

8. The method of claim 1, wherein said pharmaceutical composition comprises 1 or 2 unit dosage forms.

9. The method of claim 1, wherein said pharmaceutical composition comprises one, two, or three capsules.

24. The method of claim 1, wherein said drug is a pharmaceutically acceptable salt of amantadine.

25. The method of claim 1, wherein said drug is amantadine hydrochloride.

26. The method of claim 1, wherein said pharmaceutical composition is selected from the group consisting of one unit dosage form comprising 340 mg of said drug and two unit dosage forms each comprising 170 mg of said drug.

27. The method of claim 26, wherein said drug is a pharmaceutically acceptable salt of amantadine.

28. The method of claim 26, wherein said drug is amantadine hydrochloride.

29. The method of claim 1, wherein when said pharmaceutical composition is dosed in a single dose, fasted, human pharmacokinetic study in healthy subjects, the Cmax for the drug is 1.0 to 2.8 ng/ml per mg of the drug.

30. The method of claim 29, wherein the Cmax for the drug is 1.0 to 2.4 ng/ml per mg of the drug.

10. A method of treating a patient with Parkinson'"'"'s disease, comprising administering once daily, 0 to 4 hours before bedtime, to said patient with Parkinson'"'"'s disease, a pharmaceutical composition comprising:

(i) 220 mg to 445 mg of a drug selected from the group consisting of amantadine and a pharmaceutically acceptable salt thereof; and

(ii) one or more excipients, wherein at least one of said one or more excipients modifies the release of said drug to provide an extended release dosage form,

wherein ON time without troublesome dyskinesia is increased in said patient with Parkinson'"'"'s disease, and

wherein when said pharmaceutical composition is dosed in a single dose, fasted, human pharmacokinetic study in healthy subjects, the Cmax for the drug is 1.0 to 2.8 ng/ml per mg of the drug and the AUC_0-inf for the drug is 40 to 75 ng*h/ml per mg of the drug.

11. The method of claim 10, wherein said increased ON time without troublesome dyskinesia is determined from a Parkinson'"'"'s disease home diary.

12. The method of claim 10, wherein when said pharmaceutical composition is dosed in a single dose, fasted, human pharmacokinetic study in healthy subjects, the Tmax for the drug is 8 to 18 hours.

13. The method of claim 10, wherein when said pharmaceutical composition is dosed in a single dose, fasted, human pharmacokinetic study in healthy subjects, the Tmax for the drug is 9 to 18 hours.

14. The method of claim 10, wherein when said pharmaceutical composition is dosed in a single dose, fasted, human pharmacokinetic study in healthy subjects, the Tmax for the drug is 11 to 18 hours.

15. The method of claim 10, wherein when said pharmaceutical composition is dosed in a multiple dose, fasted, human pharmacokinetic study in healthy subjects, the steady state AUC_0-24 for the drug is 44 to 83 ng*hr/ml per mg of the drug.

16. The method of claim 10, wherein said pharmaceutical composition is administered to said patient once daily, 0 to 3 hours before bedtime.

17. The method of claim 10, wherein said pharmaceutical composition comprises 1 or 2 unit dosage forms.

18. The method of claim 10, wherein said pharmaceutical composition comprises one, two, or three capsules.

19. The method of claim 10, wherein said drug is a pharmaceutically acceptable salt of amantadine.

20. The method of claim 10, wherein said drug is amantadine hydrochloride.

21. The method of claim 10, wherein said pharmaceutical composition is selected from the group consisting of one unit dosage form comprising 340 mg of said drug and two unit dosage forms each comprising 170 mg of said drug.

22. The method of claim 21, wherein said drug is a pharmaceutically acceptable salt of amantadine.

23. The method of claim 21, wherein said drug is amantadine hydrochloride.

31. The method of claim 10, wherein the Cmax for the drug is 1.0 to 2.4 ng/ml per mg of the drug.