DEXMEDETOMIDINE TREATMENT REGIMENS
Disclosed herein are methods of administering dexmedetomidine or a pharmaceutically acceptable salt thereof to a human subject. The disclosed methods are particularly suitable for the treatment of agitation, especially when associated with neurodegenerative and/or neuropsychiatric diseases or disorders such as dementia and delirium.
1 . A method of treating agitation associated with dementia in patient in need thereof comprising administering a composition comprising dexmedetomidine or pharmaceutically acceptable salt thereof to the oral mucosa of the patient, wherein the oromucosal administration of the composition results in a C max from about 50 ng/L to about 300 ng/L and an AUC 0-inf from about 200 hr*ng/L to about 2200 hr*ng/L, and wherein the patient is at least about 65 years old.
2 . The method of claim 1 , wherein the C max is about 50 ng/L, about 60 ng/L, about 70 ng/L, about 80 ng/L, about 90 ng/L, about 100 ng/L, about 110 ng/L, about 120 ng/L, about 130 ng/L, about 140 ng/L, about 150 ng/L, about 160 ng/L, about 170 ng/L, about 180 ng/L, about 190 ng/L, about 200 ng/L, about 220 ng/L, about 240 ng/L, about 260 ng/L, about 280 ng/L, or about 300 ng/L.
3 . The method of claim 1 , wherein the C max is about 80% to about 125% of about 108 ng/L.
4 . The method of claim 1 , wherein the AUC 0-inf is about 200 hr*ng/L, 300 hr*ng/L, 400 hr*ng/L, about 450 hr*ng/L, about 500 hr*ng/L, about 550 hr*ng/L, about 600 hr*ng/L, about 650 hr*ng/L, about 700 hr*ng/L, about 750 hr*ng/L, about 800 hr*ng/L, about 850 hr*ng/L, about 900 hr*ng/L, about 950 hr*ng/L, about 1000 hr*ng/L, about 1050 hr*ng/L, about 1100 hr*ng/L, about 1150 hr*ng/L, about 1200 hr*ng/L, about 1250 hr*ng/L, about 1300 hr*ng/L, about 1350 hr*ng/L, about 1400 hr*ng/L, about 1450 hr*ng/L, or about 1500 hr*ng/L.
5 . The method of claim 1 , wherein the AUC 0-inf is about 80% to about 125% of about 985 hr*ng/L.
6 . (canceled)
7 . The method of claim 1 , wherein the administration to the oral mucosa is buccal or sublingual administration.
8 . The method of claim 1 , wherein the administration to the oral mucosa achieves a mean change in PEC or PAS score greater than −2 relative to baseline within 2 hours of administration.
9 . The method of claim 1 , wherein oral mucosa administration results in a 2-point or greater reduction in RASS score from the baseline value within 2 hours of administration.
10 . The method of claim 1 , wherein the administration to the oral mucosa achieves a mean change in Mod-CMAI score of greater than −7 relative to baseline within 2 hours of administration.
11 . The method of claim 1 , wherein the administration to the oral mucosa results in a CGI-I score improvement to about 1 (very much improved) or about a 2 (much improved) within 2 hours of administration.
12 . The method of claim 1 , wherein the administration to the oral mucosa results in Agitation-Calmness Evaluation Scale (ACES) score improvement to 2 (moderate agitation), 3 (mild agitation) or 4 (normal behavior) within 2 hours of administration.
13 . (canceled)
14 . The method of claim 1 , wherein the composition is a film a tablet, film, spray, gel or drops.
15 . The method claim 1 , wherein the composition is a film.
16 . The method of claim 1 , wherein dosage of dexmedetomidine or pharmaceutically acceptable salt thereof is about 30 μg to about 90 μg.
17 . The method of claim 1 , wherein dosage of dexmedetomidine or pharmaceutically acceptable salt thereof is about 30 μg.
18 . The method of claim 1 , wherein dosage of dexmedetomidine or pharmaceutically acceptable salt thereof is about 40 μg.
19 . The method of claim 1 , wherein dosage of dexmedetomidine or pharmaceutically acceptable salt thereof is about 60 μg.
20 . The method of claim 1 , wherein the patient is older than 80 years old.
21 . The method of claim 1 , wherein the patient is not significantly sedated within 60 minutes after administration.
22 . (canceled)
23 . (canceled)
24 . The method of claim 1 , wherein the dementia patient has Alzheimer's disease.