Method and composition for administering an NMDA receptor antagonist to a subject

• US 8,173,708 B2
• Filed: 04/09/2010
• Issued: 05/08/2012
• 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): Padmanabhan, Sreeni
• Assistant Examiner(s): Carter, Kendra D
• Application Number:
  US12/757,819
• Publication Number:
  US 20100260838A1
• Time in Patent Office: 760 Days
• Field of Search: 514/597, 514/400, 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

The invention provides methods and compositions for administering an NMDA receptor antagonist (e.g., memantine) to a subject.

Claims

1. A method of administering memantine to a human subject in need thereof comprising:

administering to said subject once daily a sustained release oral dosage form comprising 5 to 40 mg of memantine or a pharmaceutically acceptable salt thereof and a component that sustains release of said memantine or salt thereof,

wherein said sustained release memantine provides a change in plasma concentration 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, wherein the dC/dT is measured in a single dose human PK study between the time period of 0 to Tmax of the immediate release form of memantine;

and wherein the subject has a condition selected from the group consisting of Alzheimer'"'"'s disease, dementia, Parkinson'"'"'s disease, and neuropathic pain.

2. The method of claim 1, wherein the sustained release component comprises a sustained release coating.

3. The method of claim 1, wherein the dosage form comprises 12.5-40 mg of memantine or salt thereof.

4. The method of claim 1, wherein the dosage form comprises 25-40 mg of memantine or salt thereof.

5. The method of claim 1, wherein the dosage form has a memantine in vitro dissolution profile ranging between 0.1-20% in one hour, 5-30% in two hours, 40-80% in six hours, and 50 to 90% in 10 hours, wherein the dissolution profile is determined using a USP type 2 (paddle) dissolution system at 50 rpm, at a temperature of 37±

0.5°

C., in 500 ml water.

6. A method of reducing the potential for an adverse effect while administering memantine to a human subject in need thereof, comprising:

orally administering to the human subject once per day a sustained release oral dosage form comprising 5-40 mg of memantine or a pharmaceutically acceptable salt thereof and a component that sustains release of the memantine or salt thereof,

wherein said sustained release memantine provides a change in plasma concentration 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, wherein the dC/dT is measured in a single dose human PK study between the time period of 0 to Tmax of the immediate release form of memantine; and

wherein the subject has a condition selected from the group consisting of Alzheimer'"'"'s disease, dementia, Parkinson'"'"'s disease, and neuropathic pain.

7. The method of claim 6, wherein the dosage form comprises 12.5 to 40 mg of memantine or salt thereof.

8. The method of claim 6, wherein the dosage form comprises 25 to 40 mg of memantine or salt thereof.

9. The method of claim 6, wherein the dosage form has a memantine in vitro dissolution profile ranging between 0.1-20% in one hour, 5-30% in two hours, 40-80% in six hours, and 50 to 90% in 10 hours, wherein the dissolution profile is determined using a USP type 2 (paddle) dissolution system at 50 rpm, at a temperature of 37±

0.5°

C., in 500 ml water.

10. A method of administering memantine to a human subject in need thereof comprising:

administering to said subject once daily a sustained release oral dosage form comprising 5 to 40 mg of memantine or a pharmaceutically acceptable salt thereof and a component that sustains release of said memantine or salt thereof,

wherein said sustained release memantine provides a change in plasma concentration as a function of time (dC/dT) in a defined time period of 0 to 6 hours after administration as measured in a single dose human PK study that is less than about 50% of the dC/dT provided by the same quantity of an immediate release form of memantine in said defined time period;

and wherein the subject has a condition selected from the group consisting of Alzheimer'"'"'s disease, dementia, Parkinson'"'"'s disease, and neuropathic pain.

11. The method of claim 10, wherein the sustained release component comprises a sustained release coating.

12. The method of claim 10, wherein the dosage form comprises 12.5-40 mg of memantine or salt thereof.

13. The method of claim 10, wherein the dosage form comprises 25-40 mg of memantine or salt thereof.

14. The method of claim 10, wherein the dosage form has a memantine in vitro dissolution profile ranging between 0.1-20% in one hour, 5-30% in two hours, 40-80% in six hours, and 50 to 90% in 10 hours, wherein the dissolution profile is determined using a USP type 2 (paddle) dissolution system at 50 rpm, at a temperature of 37±

0.5°

C., in 500 ml water.

15. A method of reducing the potential for an adverse effect while administering memantine to a human subject in need thereof, comprising:

orally administering to the human subject once per day a sustained release oral dosage form comprising 5-40 mg of memantine or a pharmaceutically acceptable salt thereof and a component that sustains release of the memantine or salt thereof,

wherein said sustained release memantine provides a change in plasma concentration as a function of time (dC/dT) in a defined time period of 0 to 6 hours after administration as measured in a single dose human PK study that is less than about 50% of the dC/dT provided by the same quantity of an immediate release form of memantine in said defined time period; and

wherein the subject has a condition selected from the group consisting of Alzheimer'"'"'s disease, dementia, Parkinson'"'"'s disease, and neuropathic pain.

16. The method of claim 15, wherein the dosage form comprises 12.5 to 40 mg of memantine or salt thereof.

17. The method of claim 15, wherein the dosage form comprises 25 to 40 mg of memantine or salt thereof.

18. The method of claim 15, wherein the dosage form has a memantine in vitro dissolution profile ranging between 0.1-20% in one hour, 5-30% in two hours, 40-80% in six hours, and 50 to 90% in 10 hours, wherein the dissolution profile is determined using a USP type 2 (paddle) dissolution system at 50 rpm, at a temperature of 37±

0.5°

C., in 500 ml water.