US2022288042A1PendingUtilityA1

Treatment of gastroparesis with triazaspiro[4.5]decanone

64
Assignee: TAKEDA PHARMACEUTICALS COPriority: May 12, 2017Filed: Jun 1, 2022Published: Sep 15, 2022
Est. expiryMay 12, 2037(~10.8 yrs left)· nominal 20-yr term from priority
Inventors:Emil Chuang
A61K 31/454A61P 1/00A61P 1/14A61K 31/435A61K 31/438
64
PatentIndex Score
0
Cited by
0
References
0
Claims

Abstract

Provided herein is a method of treating or alleviating one or more symptoms of a disorder, disease, or condition mediated by a dopamine D 2 or D 3 receptor with 3-((1-cyclohexyl-4-oxo-8-(4-oxo-4-phenylbutyl)-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoic acid or a pharmaceutically acceptable salt thereof. Also provided herein is a method of increasing the scrum prolactin level with 3-((1-cyclohexyl-4-oxo-8-(4-oxo-4-phenylbutyl)-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoic acid or a pharmaceutically acceptable salt thereof.

Claims

exact text as granted — not AI-modified
What is claimed is: 
     
         1 . A method of treating or alleviating one or more symptoms of gastroparesis in a subject, comprising administering to the subject a therapeutically effective amount of 3-((1-cyclohexyl-4-oxo-8-(4-oxo-4-phenylbutyl)-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoic acid or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate or hydrate thereof. 
     
     
         2 . A method of treating or alleviating one or more symptoms of a disorder, disease, or condition characterized by delayed gastric emptying in a subject, comprising administering to the subject a therapeutically effective amount of 3-((1-cyclohexyl-4-oxo-8-(4-oxo-4-phenylbutyl)-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoic acid or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate or hydrate thereof. 
     
     
         3 . The method of  claim 2 , wherein the disorder, disease, or condition is gastroparesis. 
     
     
         4 . The method of  claim 1  or  3 , wherein the gastroparesis is diabetic or idiopathic gastroparesis. 
     
     
         5 . The method of any one of  claims 1  to  4 , wherein the one or more symptoms are abdominal pain, belching, bloating, early satiety, epigastric pain or discomfort, excess gas, heartburn, loss of appetite, nausea, postprandial fullness, regurgitation, swollen abdomen, vomiting, or a combination thereof. 
     
     
         6 . The method of any one of  claims 1  to  5 , wherein the one or more symptoms are abdominal pain, bloating, early satiety, epigastric pain or discomfort, nausea, postprandial fullness, vomiting, or a combination thereof. 
     
     
         7 . The method of any one of  claims 1  to  6 , wherein the one or more symptoms are belching, bloating, heartburn, indigestion, nausea, regurgitation, vomiting, or a combination thereof. 
     
     
         8 . A method of increasing the serum prolactin concentration in a subject, comprising administering to the subject a therapeutically effective amount of 3-((1-cyclohexyl-4-oxo-8-(4-oxo-4-phenylbutyl)-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoic acid or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate or hydrate thereof. 
     
     
         9 . The method of  claim 8 , wherein the therapeutically effective amount of 3-((1-cyclohexyl-4-oxo-8-(4-oxo-4-phenylbutyl)-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoic acid is the amount sufficient to increase the serum prolactin level to a concentration ranging from about 10 to about 500 ng/mL. 
     
     
         10 . The method of  claim 8  or  9 , wherein the therapeutically effective amount of 3-((1-cyclohexyl-4-oxo-8-(4-oxo-4-phenylbutyl)-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoic acid is the amount sufficient to increase the serum prolactin level to a concentration ranging from about 50 to about 200 ng/mL. 
     
     
         11 . The method of any one of  claims 1  to  10 , wherein 3-((1-cyclohexyl-4-oxo-8-(4-oxo-4-phenylbutyl)-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoic acid is administered as a pharmaceutically acceptable salt, or a pharmaceutically acceptable solvate or hydrate thereof. 
     
     
         12 . The method of  claim 11 , wherein the pharmaceutically acceptable salt is a pharmaceutically acceptable salt of 3-((1-cyclohexyl-4-oxo-8-(4-oxo-4-phenylbutyl)-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoic acid and maleic acid, or a pharmaceutically acceptable solvate or hydrate thereof. 
     
     
         13 . The method of  claim 12 , wherein the molar ratio of the maleic acid to 3-((1-cyclohexyl-4-oxo-8-(4-oxo-4-phenylbutyl)-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoic acid is about 1. 
     
     
         14 . The method of any one of  claims 1  to  13 , wherein the therapeutically effective amount is ranging from about 1 to about 250 mg per day as measured in the amount of 3-((1-cyclohexyl-4-oxo-8-(4-oxo-4-phenylbutyl)-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoic acid or a maleate salt thereof. 
     
     
         15 . The method of  claim 14 , wherein the therapeutically effective amount is ranging from about 5 to 200 mg per day as measured in the amount of 3-((1-cyclohexyl-4-oxo-8-(4-oxo-4-phenylbutyl)-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoic acid or a maleate salt thereof. 
     
     
         16 . The method of  claim 14 , wherein the therapeutically effective amount is about 10, about 25, about 50, or about 100 mg per day as measured in the amount of 3-((1-cyclohexyl-4-oxo-8-(4-oxo-4-phenylbutyl)-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoic acid or a maleate salt thereof. 
     
     
         17 . The method of any one of  claims 1  to  16 , wherein the therapeutically effective amount is the amount sufficient to provide an arithmetic mean AUC ∞  of 3-((1-cyclohexyl-4-oxo-8-(4-oxo-4-phenylbutyl)-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoic acid ranging from about 1 to about 500 ng·hr/mL. 
     
     
         18 . The method of  claim 17 , wherein the therapeutically effective amount is the amount sufficient to provide an arithmetic mean AUC ∞  of 3-((1-cyclohexyl-4-oxo-8-(4-oxo-4-phenylbutyl)-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoic acid ranging from about 10 to about 200 ng·hr/mL. 
     
     
         19 . The method of any one of  claims 1  to  18 , wherein the therapeutically effective amount is the amount sufficient to provide an arithmetic mean peak plasma concentration (C max ) of 3-((1-cyclohexyl-4-oxo-8-(4-oxo-4-phenylbutyl)-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoic acid ranging from about 1 to about 500 ng/mL. 
     
     
         20 . The method of  claim 19 , wherein the therapeutically effective amount is the amount sufficient to provide an arithmetic mean peak plasma concentration (C max ) of 3-((1-cyclohexyl-4-oxo-8-(4-oxo-4-phenylbutyl)-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoic acid ranging from about 5 to about 50 ng/mL. 
     
     
         21 . The method of any one of  claims 1  to  20 , wherein the therapeutically effective amount is the amount sufficient to provide an average steady-state plasma concentration of 3-((1-cyclohexyl-4-oxo-8-(4-oxo-4-phenylbutyl)-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoic acid ranging from about 1 to about 500 ng/mL. 
     
     
         22 . The method of  claim 21 , wherein the therapeutically effective amount is the amount sufficient to provide an average steady-state plasma concentration of 3-((1-cyclohexyl-4-oxo-8-(4-oxo-4-phenylbutyl)-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoic acid ranging from about 5 to about 100 ng/mL. 
     
     
         23 . The method of any one of  claims 1  to  22 , wherein the therapeutically effective amount is the amount sufficient to provide an average trough plasma concentration of 3-((1-cyclohexyl-4-oxo-8-(4-oxo-4-phenylbutyl)-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoic acid ranging from about 0.01 to about 50 ng/mL. 
     
     
         24 . The method of  claim 23 , wherein the therapeutically effective amount is the amount sufficient to provide an average trough plasma concentration of 3-((1-cyclohexyl-4-oxo-8-(4-oxo-4-phenylbutyl)-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoic acid ranging from about 0.2 to about 10 ng/mL. 
     
     
         25 . The method of any one of  claims 1  to  24 , wherein 3-((1-cyclohexyl-4-oxo-8-(4-oxo-4-phenylbutyl)-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoic acid is administered orally or parenterally. 
     
     
         26 . The method of any one of  claims 1  to  25 , wherein 3-((1-cyclohexyl-4-oxo-8-(4-oxo-4-phenylbutyl)-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoic acid is administered under fasted conditions. 
     
     
         27 . The method of any one of  claims 1  to  26 , wherein 3-((1-cyclohexyl-4-oxo-8-(4-oxo-4-phenylbutyl)-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoic acid is administered without a food. 
     
     
         28 . The method of any one of  claims 1  to  27 , wherein 3-((1-cyclohexyl-4-oxo-8-(4-oxo-4-phenylbutyl)-1,3,8-tri azaspiro[4.5]decan-3-yl)methyl)benzoic acid is administered at least 30 minutes before a meal. 
     
     
         29 . The method of any one of  claims 1  to  25 , wherein 3-((1-cyclohexyl-4-oxo-8-(4-oxo-4-phenylbutyl)-1,3,8-tri azaspiro[4.5]decan-3-yl)methyl)benzoic acid is administered at least 1 hour after a meal.

Join the waitlist — get patent alerts

Track US2022288042A1 — get alerts on status changes and closely related new filings.

We store only your email — no account needed. See our privacy policy.