Treatment of Mild and Moderate Alzheimer's Disease
The present invention relates to methods of treatment using [3-(4-{2-butyl-1-[4-(4-chloro-phenoxy)-phenyl]-1H-imidazol-4-yl}-phenoxy)-propyl]-diethyl amine (“COMPOUND I”) or a pharmaceutically acceptable salt thereof. In various embodiments, the methods of treatment include treatment of mild-to-moderate dementia of Alzheimer's type, diabetes, insomnia, and other indications. The present invention also relates to pharmaceutical compositions comprising COMPOUND I or a pharmaceutically acceptable salt thereof.
1 - 12 . (canceled)
13 . A method of treating Alzheimer's disease comprising administering to a subject in need thereof an amount of [3-(4-{2-butyl-1-[4-(4-chloro-phenoxy)-phenyl]-1H-imidazol-4-yl}-phenoxy)-propyl]-diethyl amine or a pharmaceutically acceptable salt thereof between 1 mg/5 kg of the subject's body weight per day and 1 mg/50 kg of the subject's body weight per day.
14 . (canceled)
15 . A method for inhibiting the interaction of the receptor for advanced glycation end products (RAGE) with a RAGE ligand in subjects with mild-to-moderate Alzheimer's disease, comprising administering to a subject in need thereof an amount less than 20 mg per day of [3-(4-{2-butyl-1-[4-(4-chloro-phenoxy)-phenyl]-1H-imidazol-4-yl}-phenoxy)-propyl]-diethyl amine or a pharmaceutically acceptable salt thereof.
16 - 23 . (canceled)
24 . A method for treating diabetes comprising administering to a subject in need thereof an amount less than 20 mg per day of [3-(4-{2-butyl-1-[4-(4-chloro-phenoxy)-phenyl]-1H-imidazol-4-yl}-phenoxy)-propyl]-diethyl amine or a pharmaceutically acceptable salt thereof.
25 . The method of claim 24 , wherein the [3-(4-{2-butyl-1-[4-(4-chloro-phenoxy)-phenyl]-1H-imidazol-4-yl}-phenoxy)-propyl]-diethyl amine is administered in a dose ranging from about 1 to about 20 mg per day.
26 - 29 . (canceled)
30 . A method for inhibiting the reduction of glucose metabolism associated with the regression of subjects with mild-to-moderate Alzheimer's disease, comprising administering to a subject in need thereof an amount less than 20 mg per day of [3-(4-{2-butyl-1-[4-(4-chloro-phenoxy)-phenyl]-1H-imidazol-4-yl}-phenoxy)-propyl]-diethyl amine or a pharmaceutically acceptable salt thereof.
31 - 34 . (canceled)
35 . The method of claim 24 , wherein treatment of diabetes comprises lowering blood glucose levels in the subject.
36 - 39 . (canceled)
40 . The method of claim 35 , wherein the subject is suffering from mild-to-moderate Alzheimer's Disease.
41 . The method of claim 35 , wherein the subject's blood glucose levels are reduced by at least 5 mg/dl.
42 . The method of claim 35 , wherein the subject's naïve glucose level is greater than 100 mg/dl.
43 . A method of treating insomnia comprising administering to a subject in need thereof an amount less than 20 mg per day of [3-(4-{2-butyl-1-[4-(4-chloro-phenoxy)-phenyl]-1H-imidazol-4-yl}-phenoxy)-propyl]-diethyl amine or a pharmaceutically acceptable salt thereof.
44 - 47 . (canceled)
48 . A method of treating insomnia in a subject with mild-to-moderate Alzheimer's disease comprising administering to a subject in need thereof an amount less than 20 mg per day of [3-(4-{2-butyl-1-[4-(4-chloro-phenoxy)-phenyl]-1H-imidazol-4-yl}-phenoxy)-propyl]-diethyl amine or a pharmaceutically acceptable salt thereof.
49 - 52 . (canceled)
53 . The method of claim 43 , wherein treatment of insomnia comprises decreasing sleep onset latency in the subject.
54 - 57 . (canceled)
58 . The method of claim 48 , wherein treatment of insomnia comprises decreasing sleep onset latency in the subject.
59 - 62 . (canceled)
63 . A method of reducing the frequency of adverse events in a subject with mild-to-moderate Alzheimer's disease comprising administering to a subject in need thereof an amount less than 20 mg per day of [3-(4-{2-butyl-1-[4-(4-chloro-phenoxy)-phenyl]-1H-imidazol-4-yl}-phenoxy)-propyl]-diethyl amine or a pharmaceutically acceptable salt thereof.
64 - 68 . (canceled)
69 . A method of reducing HbA1C levels in a subject in need thereof comprising administering an amount less than 20 mg per day of [3-(4-{2-butyl-1-[4-(4-chloro-phenoxy)-phenyl]-1H-imidazol-4-yl}-phenoxy)-propyl]-diethyl amine or a pharmaceutically acceptable salt thereof.
70 . (canceled)
71 . (canceled)
72 . The method of claim 69 , wherein the administration of [3-(4-{2-butyl-1-[4-(4-chloro-phenoxy)-phenyl]-1H-imidazol-4-yl}-phenoxy)-propyl]-diethyl amine or a pharmaceutically acceptable salt thereof reduces the amount of HbA1C in the subject in need thereof by at least 0.1 of a percentage point.
73 . The method of claim 69 , wherein the administration of [3-(4-{2-butyl-1-[4-(4-chloro-phenoxy)-phenyl]-1H-imidazol-4-yl}-phenoxy)-propyl]-diethyl amine or a pharmaceutically acceptable salt thereof reduces the amount of HbA1C in the subject in need thereof to less than 7%.
74 - 76 . (canceled)
77 . A pharmaceutical composition comprising between 1 mg and 20 mg of [3-(4-{2-butyl-1-[4-(4-chloro-phenoxy)-phenyl]-1H-imidazol-4-yl}-phenoxy)-propyl]-diethyl amine or a pharmaceutically acceptable salt thereof; and an acetylcholinesterase inhibitor (AChEI).
78 . The pharmaceutical composition of claim 77 , wherein the AChEI is chosen from the group comprising donepezil hydrochloride, galantamine hydrochloride, rivastigmine tartrate, and tacrine hydrochloride.
79 - 82 . (canceled)
83 . A pharmaceutical composition comprising between 1 mg and 20 mg of [3-(4-{2-butyl-1-[4-(4-chloro-phenoxy)-phenyl]-1H-imidazol-4-yl}-phenoxy)-propyl]-diethyl amine or a pharmaceutically acceptable salt thereof, and memantine hydrochloride.