Pharmacodynamic effects of a novel prokinetic 5-HT4receptor agonist, ATI-7505, in humans

Camilleri, M., Vazquez-Roque, M.I., Burton, D., Ford, T. , McKinzie, S., Zinsmeister, A.R. and Druzgala, P. (2007) Pharmacodynamic effects of a novel prokinetic 5-HT4receptor agonist, ATI-7505, in humans. Neurogastroenterology and Motility, 19(1), pp. 30-38. (doi: 10.1111/j.1365-2982.2006.00865.x) (PMID:17187586)

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Abstract

ATI-7505, an investigational 5-HT4 receptor agonist, was designed to have similar activity as cisapride without the cardiac adverse effects, i.e. without QT prolongation. In addition, ATI-7505 is not metabolized by CYP450. The aim of the study was to assess the effect of ATI-7505 on gastrointestinal (GI) and colonic transit in healthy humans. A randomized, parallel-group, double-blind, placebo-controlled study evaluated effects of 9-day treatment with ATI-7505 (3, 10 or 20 mg t.i.d.) on scintigraphic GI and colonic transit in healthy volunteers (12 per group). Primary endpoints were gastric-emptying (GE) T1/2, colonic geometric centre (GC) at 24 h and ascending colon (AC) emptying T1/2. Daily stool diaries were kept. Analysis of covariance assessed overall treatment group differences, followed by post hoc unadjusted pairwise comparisons. There were borderline overall treatment effects (decrease) on GE T1/2 (P = 0.154); the 20 mg t.i.d. of ATI-7505-accelerated GE vs placebo (P = 0.038). ATI-7505 increased colonic transit (GC24, P = 0.031) with fastest transit at 10 mg t.i.d. vs placebo (P = 0.065). ATI-7505 accelerated AC emptying T1/2 (overall P = 0.075) with 10 mg dose vs placebo (P = 0.042). There was looser stool (Bristol stool form scale, overall P = 0.056) with the 10 and 20 mg t.i.d. doses. No safety issues were identified. ATI-7505 accelerates overall colonic transit and tends to accelerate GE and AC emptying and loosen stool consistency.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Ford, Thomas
Authors: Camilleri, M., Vazquez-Roque, M.I., Burton, D., Ford, T., McKinzie, S., Zinsmeister, A.R., and Druzgala, P.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Neurogastroenterology and Motility
Publisher:Wiley
ISSN:1350-1925
ISSN (Online):1365-2982
Published Online:13 December 2006

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