ANAVEX2-73 for the treatment of genetic neurodevelopmental disorders
The present invention provides methods for treating a genetic neurodevelopmental disorder such as Rett syndrome, comprising administering to a subject in need thereof a liquid oral dosage formulation comprising a therapeutically effective amount of ANAVEX2-73.
1 . A method for treating Rett Syndrome in a subject in need thereof, the method comprising:
(a) evaluating the subject for the occurrence and/or severity of a symptom of Rett Syndrome consisting of repetitive hand movements, the evaluating comprising obtaining a baseline Rett Syndrome Behavior Questionnaire (RSBQ) score and/or a baseline Clinical Global Impressions-Improvement (CGI-I) score;
(b) daily administering to the subject a dosage formulation comprising a therapeutically effective amount of tetrahydro-N,N-dimethyl-2,2-diphenyl-3-furanmethanamine hydrochloride (ANAVEX2-73) for a period of at least about 1 week, wherein the dosage formulation is selected from a liquid oral dosage formulation, a topical formulation, a transmucosal formulation, a transdermal formulation, a buccal formulation, a sublingual formulation and a parenteral formulation;
(c) re-evaluating the subject for the occurrence and/or severity of the symptom evaluated in (a), the re-evaluating comprising obtaining a post-administration RSBQ score and/or a post-administration CGI-I score; and
(d) modifying the dosage of ANAVEX2-73 administered to the subject based upon the re-evaluations in (c), wherein
(i) improvement in the occurrence and/or severity of the symptom based upon (A) a comparison of the baseline RSBQ score and the post-administration RSBQ score and/or based upon (B) a comparison of the baseline CGI-I score and the post-administration CGI-I score indicates maintaining or reducing the amount of ANAVEX2-73 administered to the subject; and
(ii) absence of improvement in the occurrence and/or severity of the symptom based upon (A) a comparison of the baseline RSBQ score and the post-administration RSBQ score and/or based upon (B) a comparison of the baseline CGI-I score and the post-administration CGI-I score indicates increasing the dosage of ANAVEX2-73.
2 . The method of claim 1 , wherein the amount of ANAVEX2-73 is about 55 mg or less.
3 . The method of claim 2 , wherein the amount of ANAVEX2-73 is from about 0.2 mg to about 40 mg.
4 . The method of claim 2 , wherein the amount of ANAVEX2-73 is from about 0.2 mg to about 20 mg.
5 . The method of claim 2 , wherein the amount of ANAVEX2-73 is from about 0.2 mg to about 10 mg.
6 . The method of claim 2 , wherein the amount of ANAVEX2-73 is from about 0.2 mg to about 5 mg.
7 . The method of claim 2 , wherein the amount of ANAVEX2-73 is from about 0.2 mg to about 2 mg.
8 . The method of claim 2 , wherein the dosage formulation comprises ANAVEX2-73 at a concentration of about 0.2 mg/ml to about 8 mg/ml.
9 . The method of claim 1 , wherein the amount of ANAVEX2-73 is from about 0.2 mg to about 55 mg.
10 . The method of claim 1 , wherein the dosage formulation further comprises a pharmaceutically acceptable carrier.
11 . The method of claim 10 , wherein the dosage formulation is a topical formulation, a transmucosal formulation, a transdermal formulation, a buccal formulation, a sublingual formulation or a parenteral formulation, comprising about 0.2 mg to about 55 mg of ANAVEX2-73.
12 . The method of claim 10 , wherein the dosage formulation is administered in at least one dose of the liquid dosage formulation, at least once daily.
13 . The method of claim 1 , wherein the dosage formulation is a liquid oral dosage formulation comprising about 0.2 mg to about 55 mg of ANAVEX2-73, and at least one of a preservative and a flavoring agent.
14 . The method of claim 1 , wherein the dosage formulation is administered to the subject for a period of at least about 30 days.
15 . The method of claim 1 , wherein the modifying in step (d) is based upon (A) a comparison of the baseline RSBQ score and the post-administration RSBQ score.
16 . The method of claim 1 , wherein the modifying in step (d) is based upon (B) a comparison of the baseline CGI-I score and the post-administration CGI-I score.
17 . The method of claim 1 , wherein the modifying in step (d) is based upon (A) a comparison of the baseline RSBQ score and the post-administration RSBQ score and (B) a comparison of the baseline CGI-I score and the post-administration CGI-I score.
18 . A method for treating Rett Syndrome in a subject in need thereof, the method comprising:
(a) evaluating the subject for the occurrence and/or severity of a symptom of Rett Syndrome consisting of repetitive hand movements, the evaluating comprising obtaining a baseline Rett Syndrome Behavior Questionnaire (RSBQ) score and/or a baseline Clinical Global Impressions-Improvement (CGI-I) score;
(b) measuring the level of plasma glutamate in the subject to determine a baseline plasma glutamate level in the subject;
(c) daily administering to the subject a dosage formulation comprising a therapeutically effective amount of tetrahydro-N,N-dimethyl-2,2-diphenyl-3-furanmethanamine hydrochloride (ANAVEX2-73) for a period of at least about 1 week, wherein the dosage formulation is selected from a liquid oral dosage formulation, a topical formulation, a transmucosal formulation, a transdermal formulation, a buccal formulation, a sublingual formulation and a parenteral formulation;
(d) re-evaluating the subject for the occurrence and/or severity of the symptom evaluated in (a), the re-evaluating comprising obtaining a post-administration RSBQ score and/or a post-administration CGI-I score; and/or re-measuring the level of plasma glutamate in the subject to determine a second glutamate level and comparing the second glutamate level to the baseline glutamate level; and
(e) modifying the dosage of ANAVEX2-73 administered to the subject based upon the re-evaluation and re-measuring in (d), wherein
(i) improvement in the occurrence and/or severity of the symptom based upon (A) a comparison of the baseline RSBQ score and the post-administration RSBQ score and/or based upon (B) a comparison of the baseline CGI-I score and the post-administration CGI-I score and/or (C) a second glutamate level less than the baseline glutamate level indicates maintaining or reducing the amount of ANAVEX2-73 administered to the subject; and
(ii) absence of improvement in the occurrence and/or severity of the symptom based upon (A) a comparison of the baseline RSBQ score and the post-administration RSBQ score and/or (B) a comparison of the baseline CGI-I score and the post-administration CGI-I score and/or (C) a second glutamate level about the same or higher than the baseline glutamate level indicates optionally increasing the dosage of ANAVEX2-73.
19 . The method of claim 18 , wherein the modifying in step (e) is based upon (A) a comparison of the baseline RSBQ score and the post-administration RSBQ score.
20 . The method of claim 18 , wherein the modifying in step (e) is based upon (B) a comparison of the baseline CGI-I score and the post-administration CGI-I score.
21 . The method of claim 18 , wherein the modifying in step (e) is based upon (C) a second glutamate level less than the baseline glutamate level.
22 . The method of claim 18 , wherein the modifying in step (e) is based upon (A) a comparison of the baseline RSBQ score and the post-administration RSBQ score and (B) a comparison of the baseline CGI-I score and the post-administration CGI-I score.
23 . The method of claim 18 , wherein the modifying in step (e) is based upon (A) a comparison of the baseline RSBQ score and the post-administration RSBQ score and (C) a second glutamate level less than the baseline glutamate level.
24 . The method of claim 18 , wherein the modifying in step (e) is based upon (B) a comparison of the baseline CGI-I score and the post-administration CGI-I score and (C) a second glutamate level less than the baseline glutamate level.
25 . The method of claim 18 , wherein the modifying in step (e) is based upon (A) a comparison of the baseline RSBQ score and the post-administration RSBQ score and (B) a comparison of the baseline CGI-I score and the post-administration CGI-I score and (C) a second glutamate level less than the baseline glutamate level.