Effect of atilmotin on gastrointestinal transit in healthy subjects: a randomized, placebo‐controlled study

Abstract

We studied effects of i.v. atilmotin (BAX-ACC-1638, a novel motilin agonist, circulating t(1/2) < 10 min) on gastrointestinal transit in humans using a randomized, parallel-group, dose-response double-blind study of i.v. atilmotin, 6, 30, 60 microg or vehicle (placebo) given 2 min after standardized breakfast, lunch and dinner. The breakfast meal contained (99m)Tc-eggs and (111)In-milk. Full gastrointestinal transit was measured by scintigraphy. Primary endpoints were % gastric emptying (GE) at 30 min, GE t(1/2), colonic filling (CF) at 6 h, and geometric centre of colonic transit at 24 h. Analysis included adjustment for age, gender and body mass index, with Bonferroni correction applied for multiple comparisons. A significant treatment effect of atilmotin was detected for GE (%) at 30 min for solids and liquids (P < 0.01 for both). There were no significant effects on CF or CT and no significant adverse clinical events. Thus, atilmotin accelerates GE of solids and liquids in healthy humans. These data suggest that, at the doses tested, atilmotin should be considered for treatment of stomach motility disorders.

Can the Intestinal Dysmotility of Critical Illness be Differentiated from Postoperative Ileus?

“…A separate prokinetic agent, atilmotin, has been shown to increase gastric migratory motor complexes (MMC) during phase 3 activity in dogs. In healthy humans, however, this agent failed at the tested dose to stimulate transit in the small intestine or colon [65]. Because of its short half life, higher doses may be necessary to stimulate activity at all levels, which may limit its clinical usefulness.…”

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“…Thus far, the motilin receptor agonists tested have had no significant effects on colonic filling or colonic transit [71].…”

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“…has been shown to accelerate gastric emptying of liquids and solids in healthy subjects without significant effects on colonic transit. 16 It is not yet known whether atilmotin has significant effects on symptoms in patients with gastroparesis.…”