TY - JOUR
T1 - Pharmacodynamic effects of a novel prokinetic 5-HT 4 receptor agonist, ATI-7505, in humans
AU - Camilleri, M.
AU - Vazquez-Roque, M. I.
AU - Burton, D.
AU - Ford, T.
AU - McKinzie, S.
AU - Zinsmeister, A. R.
AU - Druzgala, P.
PY - 2007/1
Y1 - 2007/1
N2 - ATI-7505, an investigational 5-HT 4 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) T 1/2, colonic geometric centre (GC) at 24 h and ascending colon (AC) emptying T 1/2. 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 T 1/2 (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 T 1/2 (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.
AB - ATI-7505, an investigational 5-HT 4 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) T 1/2, colonic geometric centre (GC) at 24 h and ascending colon (AC) emptying T 1/2. 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 T 1/2 (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 T 1/2 (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.
KW - 5-HT receptor
KW - ATI-7505
KW - Agonist
KW - Serotonin
UR - http://www.scopus.com/inward/record.url?scp=33845656047&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33845656047&partnerID=8YFLogxK
U2 - 10.1111/j.1365-2982.2006.00865.x
DO - 10.1111/j.1365-2982.2006.00865.x
M3 - Article
C2 - 17187586
AN - SCOPUS:33845656047
SN - 1350-1925
VL - 19
SP - 30
EP - 38
JO - Neurogastroenterology and Motility
JF - Neurogastroenterology and Motility
IS - 1
ER -