Clinical trial: the efficacy and tolerability of velusetrag, a selective 5‐HT4 agonist with high intrinsic activity, in chronic idiopathic constipation – a 4‐week, randomized, double‐blind, placebo‐controlled, dose–response study

  title={Clinical trial: the efficacy and tolerability of velusetrag, a selective 5‐HT4 agonist with high intrinsic activity, in chronic idiopathic constipation – a 4‐week, randomized, double‐blind, placebo‐controlled, dose–response study},
  author={Michael R Goldberg and Y.‐P. Li and John F. Johanson and A W Mangel and Michael M. Kitt and David T. Beattie and Kathryn E. Kersey and Oranee Daniels},
  journal={Alimentary Pharmacology \& Therapeutics},
Aliment Pharmacol Ther 2010; 32: 1102–1112 

Systematic review with meta‐analysis: highly selective 5‐HT4 agonists (prucalopride, velusetrag or naronapride) in chronic constipation

Highly selective 5‐HT4 agonists have been suggested for the treatment of chronic constipation and have shown promising results in animals and humans.

Defining a responder in treatment trials for chronic idiopathic constipation

This study demonstrated a significant increase in average number of weekly spontaneous bowel movements from baseline with velusetrag compared with placebo, after 4 weeks of therapy, and utilised less stringent primary endpoints than other recent treatment trials in CIC, although the authors justify adequately why these were not used.

Velusetrag accelerates gastric emptying in subjects with gastroparesis: a multicentre, double‐blind, randomised, placebo‐controlled, phase 2 study

Velusetrag—a potent, selective, pan‐gastrointestinal 5‐hydroxytryptamine type 4 receptor agonist—is under investigation for treatment of GI motility disorders including gastroparesis.

New treatment options for chronic constipation: mechanisms, efficacy and safety.

  • M. Camilleri
  • Medicine, Biology
    Canadian journal of gastroenterology = Journal canadien de gastroenterologie
  • 2011
The present review has several objectives, the first of which is to review the pharmacology and selectivity of serotonergic agents to contrast the older serotonergic agents (which were withdrawn

Aspects of functional constipation : a trial of an opioid antagonist as a treatment and an investigation of the colonic microbiota associated with the illness

Differences in the colonic microbiota in FC warrant further investigation to see how it is implicated in the pathophysiology of FC and cannot be recommended in this group of patients.

Efficacy and Safety of Prucalopride in Chronic Constipation: An Integrated Analysis of Six Randomized, Controlled Clinical Trials

The integrated analysis demonstrates the efficacy and safety of prucalopride in the treatment of CC in men and women.

Current and future therapies for chronic constipation.

  • J. Tack
  • Medicine, Biology
    Best practice & research. Clinical gastroenterology
  • 2011

YH12852, a Potent and Selective Receptor Agonist of 5‐hydroxytryptamine, Increased Gastrointestinal Motility in Healthy Volunteers and Patients With Functional Constipation

YH12852 was safe and well‐tolerated up to 3 mg and showed nearly dose proportional PKs, and can be developed as an effective treatment option for GI motility disorders, including functional constipation.



Clinical trial: the efficacy, impact on quality of life, and safety and tolerability of prucalopride in severe chronic constipation – a 12‐week, randomized, double‐blind, placebo‐controlled study

This study focuses on the treatment of chronic constipation in women with a history of diarrhea and its role in the quality of life.

Lubiprostone, a locally acting chloride channel activator, in adult patients with chronic constipation: a double‐blind, placebo‐controlled, dose‐ranging study to evaluate efficacy and safety

Lubiprostone, a locally acting type‐2 chloride channel activator, induces intestinal fluid secretion in mice and results in down-regulation of prolactin and polypeptide A in the gut.

Prucalopride, a systemic enterokinetic, for the treatment of constipation

An alternative therapeutic approach is to target serotonin‐4 receptors, which are involved in initiating peristalsis, and it is shown that these receptors are activated by laxatives but are not involved in causing constipation.

Tegaserod, a 5‐HT4 receptor partial agonist, accelerates gastric emptying and gastrointestinal transit in healthy male subjects

Serotonin and its type‐4 (5‐hydroxytryptamine4) receptor play a major role in the physiology of the gastrointestinal tract and the effect of intravenous and/or oral tegaserod on gastric emptying, small bowel transit and colonic transit in humans is studied.

Effect of tegaserod in chronic constipation: a randomized, double-blind, controlled trial.

  • J. JohansonA. Wald B. Nault
  • Medicine
    Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
  • 2004

Tegaserod for the Treatment of Chronic Constipation: A Randomized, Double-Blind, Placebo-Controlled Multinational Study

Tegaserod was efficacious in relieving symptoms of chronic constipation and was well tolerated and significant improvements were also seen in stool form and in global assessment of bowel habits and constipation.

Effect of a novel prokinetic drug, R093877, on gastrointestinal transit in healthy volunteers

R093877 is well tolerated by healthy subjects and has a marked and consistent effect on stool frequency and consistency, and upper gut and colonic transit, and it holds promise for patients with large bowel symptoms or slow gut transit.

Prucalopride Is Effective in Patients with Severe Chronic Constipation in Whom Laxatives Fail to Provide Adequate Relief

Once-daily prucalopride 4 mg for 4 weeks is effective and well tolerated in patients with severe CC, and improves whole gut transit, reducing straining, softening stools and reducing time to first bowel movement.

Efficacy of linaclotide for patients with chronic constipation.

Linaclotide therapy was associated with few adverse events and produced rapid and sustained improvement of bowel habits, abdominal symptoms, global relief, and quality of life in patients with chronic constipation.

A randomised controlled trial assessing the efficacy and safety of repeated tegaserod therapy in women with irritable bowel syndrome with constipation

Tegaserod provides rapid and sustained relief of IBS-C symptoms both during first and repeated treatment and produced greater satisfaction, work productivity, and improved quality of life than placebo (p<0.05).