Method for administering an NMDA receptor antagonist to a subject

• US 8,598,233 B2
• Filed: 01/28/2013
• Issued: 12/03/2013
• Est. Priority Date: 11/23/2004
• 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., Meyerson, Laurence R.
• Primary Examiner(s): Carter, Kendra D
• Application Number:
  US13/751,876
• Publication Number:
  US 20130165527A1
• Time in Patent Office: 309 Days
• Field of Search: 514/597, 514/766, 424/400
• US Class Current: 514/597
• CPC Class Codes: A61K 31/13 Amines A61K31/04 takes precedence
• 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: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/08 Antiepileptics; Anticonvulsants
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/24 Antidepressants
• 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
• CPC Class Codes: A61P 25/30 for treating abuse or dependence

Abstract

Compositions and methods for administering memantine to a subject are provided. In particular, a solid pharmaceutical composition in a unit dosage form for once daily oral administration is provided. The compositions comprises an extended release formulation of 22.5 mg to 33.75 mg memantine, or a pharmaceutically acceptable salt thereof, wherein administration of a dose of the composition to a human subject provides a mean plasma memantine concentration profile characterized by a change in memantine concentration as a function of time (dC/dT) that is less than 50% of the dC/dT provided by the same quantity of an immediate release form of memantine, determined in a time period between 0 hours to 6 hours after administration of memantine, and wherein dC/dT is measured in a single-dose human PK study. Methods of treating dementia, in particular Alzheimer'"'"'s diseases, using the compositions are provided.

Claims

1. A solid pharmaceutical composition in a unit dosage form for once daily oral administration comprising an extended release formulation of 22.5 mg to 33.75 mg memantine, or a pharmaceutically acceptable salt thereof, wherein administration of a dose of the composition to a human subject provides a mean plasma memantine concentration profile characterized by a change in memantine concentration as a function of time (dC/dT) that is less than 50% of the dC/dT provided by the same quantity of an immediate release form of memantine, determined in a time period between 0 hours to 6 hours after administration of memantine, and wherein dC/dT is measured in a single-dose human PK study.

2. The composition of claim 1, comprising 22.5 mg to 30 mg memantine or a pharmaceutically acceptable salt thereof.

3. The composition of claim 1, comprising 28 mg memantine or a pharmaceutically acceptable salt thereof.

4. The composition of claim 1, wherein administration of a dose of the composition to a human subject provides a mean plasma memantine concentration profile characterized by dC/dT that is 2.1 ng/ml/hr or less, determined in a time period of 0 hours to 4 hours after administration of memantine, and wherein dC/dT is measured in a single-dose human PK study.

5. The composition of claim 4, wherein the dC/dT of 2.1 ng/ml/hr or less is determined in a time period of 2 hours to 4 hours after administration of memantine.

6. The composition of claim 2, wherein administration of a dose of the composition to a human subject provides a mean plasma memantine concentration profile characterized by dC/dT that is 2.1 ng/ml/hr or less, determined in a time period of 0 hours to 4 hours after administration of memantine, and wherein dC/dT is measured in a single-dose human PK study.

7. The composition of claim 6, wherein the dC/dT of 2.1 ng/ml/hr or less is determined in a time period of 2 hours to 4 hours after administration of memantine.

8. The composition of claim 3, wherein administration of a dose of the composition to a human subject provides a mean plasma memantine concentration profile characterized by dC/dT that is 2.1 ng/ml/hr or less, determined in a time period of 0 hours to 4 hours after administration of memantine, and wherein dC/dT is measured in a single-dose human PK study.

9. The composition of claim 8, wherein the dC/dT of 2.1 ng/ml/hr or less is determined in a time period of 2 hours to 4 hours after administration of memantine.

10. A solid pharmaceutical composition in an unit dosage form consisting essentially of 22.5 to 37.5 mg memantine or a pharmaceutically acceptable salt thereof provided in an extended release dosage form, wherein administration of the dosage form provides a mean plasma memantine concentration profile characterized by a change in memantine concentration of memantine as a function of time (dC/dT) that is less than about 50% of the dC/dT provided by the same quantity of an immediate release form of memantine, determined in a time period between 0 hours to 6 hours of administration of memantine, and wherein dC/dT is measured in a single-dose human PK study.

11. The composition of claim 10, comprising 22.5 mg to 30 mg memantine or a pharmaceutically acceptable salt thereof.

12. The composition of claim 10, comprising 28 mg memantine or a pharmaceutically acceptable salt thereof.

13. The composition of claim 10, wherein administration of a dose of the composition to a human subject provides a mean plasma memantine concentration profile characterized by dC/dT that is 2.1 ng/ml/hr or less, determined in a time period of 0 hours to 4 hours after administration of memantine, and wherein dC/dT is measured in a single-dose human PK study.

14. The composition of claim 13, wherein the dC/dT of 2.1 ng/ml/hr or less is determined in a time period of 2 hours to 4 hours after administration of memantine.

15. The composition of claim 11, wherein administration of a dose of the composition to a human subject provides a mean plasma memantine concentration profile characterized by dC/dT that is 2.1 ng/ml/hr or less, determined in a time period of 0 hours to 4 hours after administration of memantine, and wherein dC/dT is measured in a single-dose human PK study.

16. The composition of claim 15, wherein the dC/dT of 2.1 ng/ml/hr or less is determined in a time period of 2 hours to 4 hours after administration of memantine.

17. The composition of claim 12, wherein administration of a dose of the composition to a human subject provides a mean plasma memantine concentration profile characterized by dC/dT that is 2.1 ng/ml/hr or less, determined in a time period of 0 hours to 4 hours after administration of memantine, and wherein dC/dT is measured in a single-dose human PK study.

18. The composition of claim 17, wherein the dC/dT of 2.1 ng/ml/hr or less is determined in a time period of 2 hours to 4 hours after administration of memantine.