Velusetrag

None US:Investigational New Drug N-((1R,3r,5S)-8-{(2R)-2-hydroxy-3-[(methanesulfonyl)(methyl)amino]propyl}-8-azabicyclo[3.2.1]octan-3-yl)-2-oxo-1-(propan-2-yl)-1H-quinoline-3-carboxamide 866933-46-2866933-51-9 (hydrochloride) 53297466 8425 28527582 J4VNV64ARB D09693 ChEMBL2087337 Interactive image CC(C)n1c(=O)c(C(=O)N[C@H]2C[C@H]3CC[C@@H](C2)N3C[C@@H](O)CN(C)S(C)(=O)=O)cc2ccccc21 InChI=1S/C25H36N4O5S/c1-16(2)29-23-8-6-5-7-17(23)11-22(25(29)32)24(31)26-18-12-19-9-10-20(13-18)28(19)15-21(30)14-27(3)35(4,33)34/h5-8,11,16,18-21,30H,9-10,12-15H2,1-4H3,(H,26,31)/t18-,19+,20-,21-/m0/s1Key:HXLOHDZQBKCUCR-WOZUAGRISA-N Velusetrag(INN,USAN; previously known asTD-5108) is an experimental drug candidate for the treatment of gastric neuromuscular disorders includinggastroparesis, and lower gastrointestinal motility disorders including chronic idiopathicconstipationandirritable bowel syndrome.It is apotent,selective, highefficacy5-HT4receptorserotoninagonistbeing developed by Theravance Biopharmaand Alfa Wassermann.Velusetrag demonstrates less selectivity for other serotonin receptors, such as 5-HT2and 5-HT3, to earlier generation 5-HT agonists likecisaprideandtegaserod. In a large clinical trial in patients with chronic idiopathic constipation (n=401), velusetrag statistically and clinically improved the frequency and consistency of complete spontaneous bowel movements (CSBMs) compared to placebo. Doses of 15 and 30 mg were well tolerated compared to placebo. Velusetrag showed accelerated intestinal and colonic transit after single dosing and accelerated gastric emptying after multiple dosing in healthy volunteer subjects.In addition, velusetrag showed accelerated gastric emptying in patients with diabetic or idiopathic gastroparesis.The proportion of patients who experienced at least a 20% improvement is gastric emptying ranged from 20% to 52% for velusetrag dosed patients and 5% for placebo patients. On December 6, 2016, Theravance Biopharma announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to velusetrag for the treatment of symptoms associated with diabetic and idiopathic Gastroparesis. As of May 10, 2017, Velusetrag is being studied, at doses of 5, 15 and 30 mg over a 12-week treatment period, for symptomatic improvement in patients with diabetic or idiopathic gastroparesis in the DIGEST study.