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

Aliment Pharmacol Ther. 2010 Nov;32(9):1102-12. doi: 10.1111/j.1365-2036.2010.04456.x. Epub 2010 Sep 22.

Abstract

Background: Velusetrag is an orally active 5-HT(4) receptor agonist of potential benefit in treating chronic idiopathic constipation.

Aim: To evaluate the efficacy, safety and tolerability of velusetrag in chronic idiopathic constipation.

Methods: After a 2-week baseline period, patients [<3 spontaneous bowel movements (SBM)/week] received placebo or velusetrag (15, 30 or 50 mg) daily for 4 weeks in a randomized, double-blind design, followed by a 1-week follow-up period. The primary endpoint was the change from baseline in weekly SBM frequency averaged over the 4-week treatment period.

Results: Patients receiving velusetrag (15, 30 and 50 mg) achieved statistically and clinically significant increases in weekly SBM frequency relative to those receiving placebo. Mean increases were 3.6, 3.3 and 3.5 SBM/week respectively, compared with 1.4 SBM/week for placebo (P < 0.0001). Statistically significant increases in the weekly frequency of complete SBM (CSBM) were also reported (mean increases of 2.3, 1.8 and 2.3 for 15, 30 and 50 mg velusetrag respectively, compared with 0.6 for placebo). Common adverse events associated with velusetrag were diarrhoea, headache, nausea and vomiting, generally occurring during the initial days of dosing.

Conclusion: Velusetrag was efficacious and well tolerated in patients with chronic idiopathic constipation (ClinicalTrials.gov identifier NCT00391820).

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Azabicyclo Compounds / therapeutic use*
  • Chronic Disease
  • Constipation / drug therapy*
  • Defecation / drug effects*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Gastrointestinal Agents / therapeutic use*
  • Humans
  • Male
  • Middle Aged
  • Serotonin 5-HT4 Receptor Agonists / therapeutic use*
  • Statistics as Topic
  • Treatment Outcome

Substances

  • Azabicyclo Compounds
  • Gastrointestinal Agents
  • Serotonin 5-HT4 Receptor Agonists
  • TD-5108

Associated data

  • ClinicalTrials.gov/NCT00391820