GASTROINTESTINAL TRANSIT OF SDZ HTF919 IN PATIENTS WITH CONSTIPATION

Irritable bowel syndrome is a common disorder affecting up to 20% of the population. Constipation is a predominant symptom in many of these patients. These patients often fail therapy with current treatment options including fiber and laxatives. A prokinetic with colonic effects could be of major clinical benefit. SDZ HTF 919 is a new aminoguanidine-indole acting as a partial 5HT4 agonist with potent gastrointestinal stimulatory effects in animals and healthy human subjects. Initial studies show colonic transit time in healthy subjects is decreased, indicating its likely usefulness in the treatment of constipation. Our hypothesis is that SDZ HTF 919 is a safe and effective therapeutic agent in the treatment of constipation with prominent prokinetic effects resulting in decreased right colon transit time. The aim of this study is to evaluate the safety and efficacy of SDZ HTF 919 in the treatment of constipation predominant irritable bowel syndrome and to determine the effects of the drug on gastrointestinal transit. The study focused on understanding the mechanism of action of a new 5HT4 agonist in the context of patients with constipation-predominant irritable bowel syndrome. There were no significant adverse effects noted throughout the study. The experimental portions of the study were completed without complications. The data are currently being analyzed both by Mayo investigators as well as the statistical department of Novartis, and we do not anticipate needing to study any further patients on this protocl. The position of the Mayo GI Motility Group in the field was enhanced by this study which portrayed our ability to perform these pharmacodynamic exercises.