PHARMACEUTICAL COMPOSITION FOR THE TREATMENT OF ALZHEIMER'S DISEASE OR DEMENTIA
This invention relates to the use of compounds which are agonists of the muscarinic M 1 receptor and M 4 receptor, their salts and pharmaceutical compositions containing them in therapy of the human body. In particular, the invention is directed to compounds, which are useful in the treatment of diseases mediated by the muscarinic M 1 /M 4 receptors, including neurodegenerative disorders (i.e. Alzheimer's disease) and neuropsychiatric disorders (Schizophrenia).
1 . A pharmaceutical composition comprising the compound ethyl 3-(3-oxo-2,8-diazaspiro[4.5]dec-8-yl)-8-azabicyclo[3.2.1]octane-8-carboxylate, or a pharmaceutically acceptable salt thereof, for use in the treatment of Alzheimer's Disease or dementia; wherein the load dose of the compound or pharmaceutically acceptable salt thereof is between 5 to 25 mg.
2 . The pharmaceutical composition for use according to claim 1 , wherein the compound ethyl 3-(3-oxo-2,8-diazaspiro[4.5]dec-8-yl)-8-azabicyclo[3.2.1]octane-8-carboxylate is:
or a pharmaceutically acceptable salt thereof.
3 . The pharmaceutical composition for use according to claim 1 , wherein the compound ethyl 3-(3-oxo-2,8-diazaspiro[4.5]dec-8-yl)-8-azabicyclo[3.2.1]octane-8-carboxylate is:
or a pharmaceutically acceptable salt thereof.
4 . The pharmaceutical composition for use according to any one of claims 1 to 3 , wherein the compound ethyl 3-(3-oxo-2,8-diazaspiro[4.5]dec-8-yl)-8-azabicyclo[3.2.1]octane-8-carboxylate is present as a hydrochloride salt.
5 . The pharmaceutical composition for use according to any one of claims 1 to 4 , wherein the load dose of the compound ethyl 3-(3-oxo-2,8-diazaspiro[4.5]dec-8-yl)-8-azabicyclo[3.2.1]octane-8-carboxylate or pharmaceutically acceptable salt thereof is 5 mg.
6 . The pharmaceutical composition for use according to any one of claims 1 to 4 , wherein the load dose of the compound ethyl 3-(3-oxo-2,8-diazaspiro[4.5]dec-8-yl)-8-azabicyclo[3.2.1]octane-8-carboxylate or pharmaceutically acceptable salt thereof is 15 mg.
7 . The pharmaceutical composition for use according to any one of claims 1 to 4 , wherein the load dose of the compound ethyl 3-(3-oxo-2,8-diazaspiro[4.5]dec-8-yl)-8-azabicyclo[3.2.1]octane-8-carboxylate or pharmaceutically acceptable salt thereof is 25 mg.
8 . The composition for use according to any one of claims 1 to 7 , which is co-administered with a standard of care cholinesterase inhibitor.
9 . The composition for use according to claim 8 , wherein the standard of care cholinesterase inhibitor is Donepezil, wherein the load dose of Donepezil is 10 mg.
10 . The pharmaceutical composition for use according to any one of claims 1 to 9 , further comprising one or more pharmaceutically acceptable carriers or excipients.
11 . The pharmaceutical composition for use according to any one of claims 1 to 10 , which is in the form of a tablet.
12 . The pharmaceutical composition for use according to any one of claims 1 to 11 , which is suitable for oral administration.
13 . The pharmaceutical composition for use according to any one of claims 1 to 12 , wherein the compound ethyl 3-(3-oxo-2,8-diazaspiro[4.5]dec-8-yl)-8-azabicyclo[3.2.1]octane-8-carboxylate, or a pharmaceutically acceptable salt thereof is administered at a daily dose of 5 to 25 mg.
14 . The pharmaceutical composition for use according to claim 13 , wherein the daily dose is 15 mg.
15 . The pharmaceutical composition for use according to any one of claims 1 to 14 , which is for use in the treatment of Alzheimer's Disease.
16 . The pharmaceutical composition for use according to any one of claims 1 to 15 , which is for use in the treatment of dementia.
17 . The pharmaceutical composition for use according to claim 16 , wherein the dementia is dementia with Lewy bodies.