Pharmaceutical formulations of amyloid inhibiting compounds

• US 20060257480A1
• Filed: 04/12/2006
• Published: 11/16/2006
• Est. Priority Date: 04/12/2005
• Status: Abandoned Application

• Current Assignee: Bellus Health (Interational) Limited
• Original Assignee: Bellus Health (Interational) Limited
• Inventors: Garceau, Denis, Laurin, Julie
• Application Number:
  US11/402,277
• Publication Number:
  US 20060257480A1
• Time in Patent Office: Days
• US Class Current: 424/468
• CPC Class Codes: A61K 31/185 Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids hydroxamic acids A61K31/16; peroxy acids A61K31/327
• CPC Class Codes: A61K 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
• CPC Class Codes: A61K 9/2009 Inorganic compounds
• CPC Class Codes: A61K 9/2018 Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2086 Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat active cores with a complete drug-free outer coat A61K9/28
• CPC Class Codes: A61K 9/209 containing drug in at least two layers or in the core and in at least one outer layer
• CPC Class Codes: A61K 9/2846 Poly(meth)acrylates
• CPC Class Codes: A61K 9/2886 having two or more different drug-free coatings; Tablets of the type inert core-drug layer-inactive layer of the type active core-drug layer-inactive layer A61K9/209
• CPC Class Codes: A61K 9/485 Inorganic compounds
• CPC Class Codes: A61K 9/5047 Cellulose ethers containing no ester groups, e.g. hydroxypropyl methylcellulose
• 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 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

Therapeutic formulations and methods for inhibiting amyloid deposition in a subject, whatever its clinical setting, are described. Therapeutic formulations and methods for preventing or treating amyloidosis and/or amyloid-related disease are also described.

Claims

1. A method of lessening gastrointestinal side effects in a human patient which occur from orally administering an active agent which is 3-amino-1-propanesulfonic acid or a pharmaceutically acceptable salt thereof, comprising administering said agent according to a schedule wherein an initial dose is administered and the dose is increased over time to a higher dose, wherein the method is effective to treat or prevent Alzheimer'"'"'s disease and/or Cerebral Amyloid Angiopathy (CAA).

2. The method of claim 1, wherein the 3-amino-1-propanesulfonic acid or a pharmaceutically acceptable salt thereof, is administered in an initial dose for one month followed by an increased dose the second month, which is optionally maintained throughout the treatment, or is followed by an increased dose for the third month which is maintained throughout the treatment.

3. The method of claim 1, wherein the patient is administered 50 mg B.I.D. doses in the first month and 100 mg B.I.D. doses in the second and followings months of treatment.

4. The method of claim 1, wherein the patient is administered 50 mg B.I.D. doses in the first month, 100 mg B.I.D. doses in the second month and 150 mg B.I.D. doses in the third and following months of treatment.

5. The method of claim 1, wherein the method is for treating and/or preventing Alzheimer'"'"'s disease.

6. The method of claim 1, wherein the method is for treating and/or preventing Cerebral Amyloid Angiopathy (CAA).

8. A method of claim 5, wherein said agent is administered in a formulation which, when administered to a mild to moderate Alzheimer'"'"'s disease patient:

in a dose of 50 mg BID of the active agent, achieves a mean plasma concentration profile of the active agent having a mean AUC_∞

of about 1396 ng·

h/mL±

20%, and a mean Cmax of about 310 ng/mL±

20%;

or

in a dose of 100 mg BID of the active agent, achieves a mean plasma concentration profile of the active agent having a mean AUC_∞

of about 2569 ng·

h/mL±

20%, and a mean Cmax of about 618 ng/mL±

20%;

or

in a dose of 150 mg BID of the active agent, achieves a mean plasma concentration profile of the active agent having a mean AUC_∞

of about 3418 ng·

h/mL±

20%, and a mean Cmax of about 624 ng/mL±

20%.

9. A method of claim 5, wherein said agent is administered in a formulation which, when administered to a mild to moderate Alzheimer'"'"'s disease patient for 12 weeks:

in a dose of 50 mg BID of the active agent, achieves a mean plasma concentration profile of the active agent having a mean AUC_ss of about 1975 ng·

h/mL±

20%, and a mean Cmax of about 451 ng/mL±

20%;

or

in a dose of 100 mg BID of the active agent, achieves a mean plasma concentration profile of the active agent having a mean AUC_ss of about 2590 ng·

h/mL±

20%, and a mean Cmax of about 538 ng/mL±

20%;

or

in a dose of 150 mg BID of the active agent, achieves a mean plasma concentration profile of the active agent having a mean AUC_ss of about 3570 ng·

h/mL±

20%, and a mean Cmax of about 639 ng/mL±

20%.

10. A method of claim 6, wherein said agent is administered in a formulation which, when administered to a Cerebral Amyloid Angiopathy (CAA) patient:

in a dose of 50 mg BID of the active agent, achieves a mean plasma concentration profile of the active agent having a mean AUC_∞

of about 1643 ng·

h/mL±

20%, and a mean Cmax of about 346 ng/mL±

20%;

or

in a dose of 100 mg BID of the active agent, achieves a mean plasma concentration profile of the active agent having a mean AUC_∞

of about 2777 ng·

h/mL±

20%, and a mean Cmax of about 552 ng/mL±

20%;

or

in a dose of 150 mg BID of the active agent, achieves a mean plasma concentration profile of the active agent having a mean AUC_∞

of about 3689 ng·

h/mL±

20%, and a mean Cmax of about 857 ng/mL±

20%.

11. A method of claim 6, wherein said agent is administered in a formulation which, when administered to a Cerebral Amyloid Angiopathy (CAA) patient for 12 weeks:

in a dose of 50 mg BID of the active agent, achieves a mean plasma concentration profile of the active agent having a mean AUC_ss of about 947 ng·

h/mL±

20%, and a mean Cmax of about 171 ng/mL±

20%;

or

in a dose of 100 mg BID of the active agent, achieves a mean plasma concentration profile of the active agent having a mean AUC_ss of about 3703 ng·

h/mL±

20%, and a mean Cmax of about 806 ng/mL±

20%;

or

in a dose of 150 mg BID of the active agent, achieves a mean plasma concentration profile of the active agent having a mean AUC_ss of about 6753 ng·

h/mL±

20%, and a mean Cmax of about 1031 ng/mL±

20%.

12. A method of claim 1, wherein said active agent is in a formulation effective for osmotic release, pulsatile release, sustained release, controlled release, extended release or delayed release of the active agent.

7. A method for lowering the level of Aβ

₄₂ in the cerebrospinal fluid of a patient which comprises orally administering to the patient a formulation comprising an active agent which is 3-amino-1-propanesulfonic acid or a pharmaceutically acceptable salt thereof.