Treatment of cataplexy

Patent metadata

Field	Value
Publication number	US-2025059135-A1
Application number	US-202418935803-A
Country	US
Kind code	A1
Filing date	Nov 4, 2024
Priority date	Mar 13, 2013
Publication date	Feb 20, 2025
Grant date	—

Abstract

The present invention relates to a method of treating cataplexy in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of certain carbamate compounds.

First claim

1 . A method of treating cataplexy in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of Formula (I):

or a pharmaceutically acceptable salt or ester thereof;
wherein R is a member selected from the group consisting of hydrogen, lower alkyl of 1 to 8 carbon atoms, halogen selected from F, Cl, Br and I, alkoxy containing 1 to 3 carbon atoms, nitro, hydroxy, trifluoromethyl, and thioalkoxy containing 1 to 3 carbon atoms;
x is an integer of 0 to 3, with the proviso that R may be the same or different when x is 2 or 3;
R 1 and R 2 are independently selected from the group consisting of hydrogen, lower alkyl of 1 to 8 carbon atoms, aryl, arylalkyl, cycloalkyl of 3 to 7 carbon atoms; or
R 1 and R 2 can be joined to form a 5 to 7-membered heterocycle substituted with a member selected from the group consisting of hydrogen, alkyl, and aryl groups, wherein the heterocycle can comprise 1 to 2 nitrogen atoms and 0 to 1 oxygen atom, wherein the nitrogen atoms are not directly connected with each other or with the oxygen atom;
wherein the number of cataplectic events is decreased at least about 20% or more per week.

2 . The method of claim 1 , wherein x=0.

3 . The method of claim 1 , wherein R 1 and R 2 are hydrogen and x=0.

4 . The method of claim 1 , wherein the compound of Formula I is an enantiomer of Formula I substantially free of other enantiomers or an enantiomeric mixture wherein one enantiomer of Formula I predominates.

5 . The method of claim 4 , wherein the enantiomer of Formula I predominates to the extent of about 98% or greater.

6 . The method of claim 4 , wherein the enantiomer of Formula I is an enantiomer of Formula Ia:

or a pharmaceutically acceptable salt or ester thereof.

7 . The method of claim 6 , wherein the enantiomer of Formula Ia is the (R) or (D) enantiomer.

8 . The method of claim 6 , wherein the enantiomer of Formula Ia is the (S) or (L) enantiomer.

9 . The method of claim 6 , wherein the enantiomer of Formula Ia predominates to the extent of about 98% or greater.

10 . The method of claim 4 , wherein the enantiomer of Formula I substantially free of other enantiomers is the compound of Formula Ib or an enantiomeric mixture wherein the compound of Formula Ib predominates:

or a pharmaceutically acceptable salt or ester thereof.

11 . The method of claim 10 , wherein the compound of Formula Ib predominates to the extent of about 90% or greater.

12 . The method of claim 10 , wherein the compound of Formula Ib predominates to the extent of about 98% or greater.

13 . The method of claim 1 , wherein the cataplexy is associated with narcolepsy.

14 . The method of claim 1 , wherein the cataplexy is secondary to a condition that lowers hypocretin levels in the subject.

15 . The method of claim 14 , wherein the condition is selected from the group consisting of brain tumor, astrocytomas, glioblastoma, glioma, subependynoma, craniopharyngioma, arterio-venous malformations, ischemic events, multiple sclerosis, head injury, brain surgery, paraneoplastic syndromes, Neimann-Pick type C disease, and encephalitis.

16 . The method of claim 1 , wherein the therapeutically effective amount of the compound of Formula I is from about 0.01 mg/kg/dose to about 150 mg/kg/dose.

17 . The method of claim 1 , wherein the therapeutically effective amount of the compound of Formula I is from about 1 mg/day to about 7000 mg/day.

18 . The method of claim 1 , wherein the compound of Formula I is administered orally.

19 . The method of claim 1 , wherein the compound of Formula I is administered in the form of a capsule or tablet.

20 . The method of claim 1 , wherein the compound of Formula I is administered in the form of a capsule at a dose of about 150 mg to about 300 mg without any excipients.

21 . The method of claim 1 , wherein the number of cataplectic events is decreased at least about 30% per week.

22 . The method of claim 1 , wherein the number of cataplectic events is decreased at least about 40% per week.

23 . The method of claim 1 , wherein the number of cataplectic events is decreased at least about 50% per week.

24 . The method of claim 1 , wherein the number of cataplectic events is decreased at least about 60% per week.

25 . The method of claim 1 , wherein the number of cataplectic events is decreased at least about 70% per week.

26 . The method of claim 1 , wherein the number of cataplectic events is decreased at least about 80% per week.

Assignees

• Axsome Malta Ltd
• Sk Biopharmaceuticals Co Ltd

Inventors

• Khayrallah Moise A
• Bream Gary
• Butts Stephen E

Classifications

• A61K9/20

  Pills, tablets, {discs, rods (A61K9/0004, A61K9/0007, A61K9/0056, A61K9/0065 take precedence; for reconstitution of a drink A61K9/0095)} · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61K31/325

  Carbamic acids; Thiocarbamic acids; Anhydrides or salts thereof (thiurams A61K31/145) · CPC title

• A61K9/0053

  Mouth and digestive tract, i.e. intraoral and peroral administration · CPC title

• A61K31/27 Primary

  of carbamic or thiocarbamic acids, meprobamate, carbachol, neostigmine · CPC title