Clinical researchers in primary care and specialty gastroenterology practices worldwide have just started recruiting patients for the largest clinical trial to be conducted in Irritable Bowel Syndrome (IBS). The objective of the ZENSAA study is to assess the efficacy and safety of repeated treatment with the novel Novartis drug Zelmac (tegaserod), in female patients with IBS with constipation, who experience a positive response during initial treatment but whose symptoms recur after treatment is stopped.
The ZENSAA study seeks to enroll 2,500 women aged 18 - 65 years who suffer from IBS with constipation. The study will be conducted at 262 centers in 24 countries, including the United States, United Kingdom, Canada, Mexico, Germany, France, Italy, Spain, South Africa and New Zealand. Zelmac is currently available in more than 30 countries including Australia, Switzerland, Canada, the United States and Brazil.
IBS is a chronic, episodic condition characterized by abdominal pain and discomfort, bloating, and altered bowel function (constipation and/or diarrhea). The prevalence of IBS differs by country, however recent studies suggest that the disorder affects approximately 10-20 per cent of the Western population - up to 1 in 5 adults.
"IBS affects millions of women worldwide, and this study will examine the ability of Zelmac to relieve the multiple symptoms of IBS with constipation in a situation that closely duplicates actual clinical practice," said Joerg Reinhardt, Head of Development, Novartis Pharma AG. "The symptoms of IBS come and go, and vary in intensity throughout the course of the disease, having a very serious impact on patients' lifestyles."
This study is a prospective, randomized, double blind, parallel group, multicenter trial comparing Zelmac at 6 mg twice daily (b.i.d.) to placebo, in female patients with IBS with constipation. Primary efficacy variables are overall relief of IBS symptoms and overall relief of abdominal pain/discomfort. Efficacy will be measured by patient responses to several assessment questionnaires, recorded in electronic diaries. In addition, patients will be asked to record their abdominal discomfort or pain, bloating, constipation and bowel habits on a daily and weekly basis in the electronic diaries.
Secondary efficacy variables include the individual gastrointestinal (GI) symptoms of IBS such as pain/discomfort and bloating (daily) and constipation (weekly) and the time of onset of GI symptom relief. The study is designed to mirror clinical practice as closely as possible in the clinical trial setting.
In addition to the efficacy and safety assessments, the study will also evaluate the impact of Zelmac vs. placebo on patient quality of life. Patients will be asked to complete the Hospital Anxiety and Depression Scale (HADS), an Overall Satisfaction with Treatment questionnaire, and a Work-Productivity Activity Impairment for IBS questionnaire. The data from each, except HADS, will be used for secondary efficacy evaluation. Data from the HADS evaluation will be used for characterization of the study populations in each treatment period.
The study was designed in close collaboration with the Committee for Proprietary Medicinal Products of the European Health Authorities, to ensure the protocol meets the highest scientific standards and fulfills their requirements. In addition, the study will provide important insight into the time-course of IBS, and a more thorough understanding of the disease in general.
Until recently, the cause of IBS has been poorly understood and under-estimated. However, in recent years, new research has yielded a better understanding of IBS and its causes. People who have abdominal pain and discomfort, bloating and constipation associated with IBS may have altered sensitivity and altered motility of their lower GI tract. This may be due to the way their lower GI tract reacts to changes in serotonin (5HT), a naturally occurring chemical in their body that regulates motility and perception of pain and discomfort in the intestinal system.
Zelmac is the first in a new class of medicines, known as serotonin-4 receptor agonists (5HT4 agonists) developed especially for the treatment of the multiple symptoms associated with IBS with constipation. By activating 5HT4 receptors in the gastrointestinal tract, Zelmac normalizes impaired motility and reduces sensitivity of the intestinal tract. In clinical studies, significantly more patients experienced a general relief of symptoms when treated with Zelmac, such as a decrease in abdominal pain, bloating and constipation. In most patients, the onset of relief occurred within just one week. The medicine was well tolerated and showed a profile of side effects similar to that of placebo. Zelmac was discovered and developed by Novartis and is known as Zelnorm in the United States and Canada.