A Randomized, Double-blind, Placebo-controlled Multicenter Study to Assess the Efficacy, Safety and Tolerability of Tegaserod 2 mg Bid vs Placebo in Patients With Chronic Constipation
Idiopathic or functional constipation is a common disorder, affecting up to 20% of the population depending on demographic factors, the sampling situation and the definitions used. Constipation is a symptom of many diseases and is a collective term, used by the patient to imply that stools are too hard, too infrequent or too difficult to pass. A recent survey conducted in Hong Kong showed a prevalence of 14% according to the Rome criteria. Based on an epidemiological study in US, there were 2.5 million annual physician visits for this problem. Exact epidemiological data however are lacking, mainly because of the difference between self-reported constipation and scientifically defined constipation.
Treatment of constipation is usually based on increased dietary fiber and supplementation with bulking agents, exercise, and habit training. However, often only partial relief is obtained, and the majority of patients use non-bulking laxatives on a regular basis without medical supervision. Chronic use of non-bulking laxatives is often inappropriate3, and may lead to side effects such as dependency and progressive tolerance, electrolyte imbalance, and, for the anthraquinones, melanosis coli. In addition, stimulant laxatives may damage the myenteric plexus4, resulting in cathartic colon5. A more appropriate approach to the therapy of constipation consists of physiologically stimulating intestinal motility.
Tegaserod, an aminoguanidine indole compound, is a representative of a new class of 5-HT4 agonists, with regard to both chemistry and pharmacology. Activation of 5-HT4 receptors triggers the release of neurotransmitters from the enteric nerves resulting in increased contractility and stimulation of the peristaltic reflex.
In animal models, tegaserod acts as a motility-enhancing agent, exerting activity throughout the gastrointestinal tract11. Tegaserod has also been shown to significantly accelerate bowel transit in healthy volunteers and in patients with constipation-predominant irritable bowel syndrome (C-IBS).
Based on the pharmacodynamic properties, tegaserod is a promotile compound suitable for the treatment associated with small and/or large bowel dysfunction e.g. constipation.
From phase III adequate and well-controlled studies in patients with C-IBS it has been shown that tegaserod was effective in relieving symptoms of C-IBS. The effect was seen as early as the first week of treatment with sustained effects over 12 weeks. Both tegaserod 4 mg/d (2 mg bid) and 12 mg/d (6 mg bid) significantly increased bowel frequency and decreased stool consistency. It is proposed to test both doses for the phase III program in chronic constipation.
The aim of this study is to demonstrate the effect of tegaserod on bowel habits in patients suffering from chronic idiopathic constipation.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
|Official Title:||A Randomized, Double-blind, Placebo-controlled Multicenter Study to Assess the Efficacy, Safety and Tolerability of Tegaserod 2 mg Bid vs Placebo in Patients With Chronic Constipation|
- the response for the first 4 weeks of double-blind treatment period using the criterion based on the daily diary assessment [ Time Frame: 4 Weeks ]
- Response rate throughout the 8 weeks of treatment [ Time Frame: 8 Weeks ]
- Evaluations of bowel habit [ Time Frame: 12 Weeks ]
- Patient' assessment of symptoms of constipation during the past week and Quality of life (QOL) assessment [ Time Frame: 12 Weeks ]
|Study Start Date:||December 2004|
|Study Completion Date:||February 2006|
|Queen Mary Hospital|
|Hong Kong, China|
|Principal Investigator:||Annie OO Chan, Dr||Department of Medicine, Queen Mary Hospital/ The University of Hong Kong|