Compositions for the treatment of CNS-related conditions

• US 8,338,485 B2
• Filed: 06/28/2012
• Issued: 12/25/2012
• 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:
  US13/536,588
• Publication Number:
  US 20120264782A1
• Time in Patent Office: 180 Days
• Field of Search: 514/597, 514/766, 424/400
• US Class Current: 514/597
• 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 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61K 9/1635 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/1652 Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin homeopathic globules A61K9/1623
• CPC Class Codes: A61K 9/20 Pills, tablets, discs, rods A61K9/0004, A61K9/0007, A61K9/0056, A61K9/0065 take precedence; for reconstitution of a drink A61K9/0095
• CPC Class Codes: A61K 9/2009 Inorganic compounds
• CPC Class Codes: A61K 9/2013 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2059 Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
• CPC Class Codes: A61K 9/2813 Inorganic compounds
• CPC Class Codes: A61K 9/282 Organic compounds, e.g. fats
• 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 9/7061 Polyacrylates
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/20 : Hypnotics; Sedatives
• 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
• CPC Class Codes: A61P 29/00 : Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: Y02A 50/30 : Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The invention provides compositions comprising extended release memantine in combination with immediate release donepezil to a subject. Memantine in an extended release form containing 22.5 to 30 mg memantine or a pharmaceutically acceptable salt thereof in combination with donepezil achieves particular pharmacokinetic criteria such as change in plasma concentration of memantine over time and ratio of maximum memantine plasma concentration to mean memantine plasma concentration.

Claims

1. A solid pharmaceutical composition in a unit dosage form for oral administration comprising:

(a) an extended release formulation of 22.5 to 30 mg memantine or 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 concentration of memantine as a function of time (dC/dT) that is;

(1) 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-Tmax of the immediate release form of memantine; and

(2) 2.1 ng/ml/hr or less, determined in a time period of 0 to 4 hours; and

wherein dC/dT is measured in a single-dose human PK study; and

(b) a therapeutically effective amount of immediate release donepezil.

2. The composition of claim 1, wherein the dC/dT of 2.1 ng/ml/hr or less is determined in a time period of 2 to 4 hours.

3. The composition of claim 1, comprising 25 mg to 30 mg memantine or a pharmaceutically acceptable salt thereof.

4. The composition of claim 3, wherein the dC/dT of 2.1 ng/ml/hr or less is determined in a time period of 2 to 4 hours.

5. The composition of claim 1, comprising 25 mg to 28 mg memantine or a pharmaceutically acceptable salt thereof.

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

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

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

9. A solid pharmaceutical composition in a unit dosage form for oral administration comprising:

(a) an extended release formulation of 22.5 to 30 mg memantine or 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 concentration of memantine as a function of time (dC/dT) that is;

(1) 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

(2) 2.1 ng/ml/hr or less, determined in a time period of 0 to 4 hours; and

wherein dC/dT is measured in a single-dose human PK study; and

(b) a therapeutically effective amount of immediate release donepezil.

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

11. The composition of claim 9, comprising 25 mg to 30 mg memantine or a pharmaceutically acceptable salt thereof.

12. The composition of claim 11, wherein the dC/dT of 2.1 ng/ml/hr or less is determined in a time period of 2 to 4 hours.

13. The composition of claim 9, comprising 25 mg to 28 mg memantine or a pharmaceutically acceptable salt thereof.

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 to 4 hours.

15. The composition of claim 9, comprising 28 mg memantine or a pharmaceutically acceptable salt thereof.

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 to 4 hours.