Significant Symptom Relief Reported in Cilansetron Phase III Clinical Trial Patients
with Irritable Bowel Syndrome with Diarrhea Predominance (IBS-D)
Researchers Unveil Male-specific Efficacy Data on 5-HT3 Receptor Antagonist
New Orleans, LA, May 19, 2004 -- In a six-month study of both male and female IBS-D patients, treatment with cilansetron resulted in significant relief of abdominal pain/discomfort and abnormal bowel habits. Additionally, in a sub-group analysis of male patients, data shows significant treatment benefits among patients receiving cilansetron, including improvement in overall IBS symptoms, abdominal pain/discomfort and abnormal bowel habits. These study results were released during Digestive Disease Week (DDW) 2004, the annual international meeting for gastroenterologists, held May 15-20 in New Orleans, Louisiana.
5-HT3 antagonists inhibit 5-HT3 receptors, resulting in decreased GI motility, secretion, and sensation, thus improving symptoms of IBS. Current 5-HT3 therapy indicated for IBS is approved for women only.
“Men and women whose lives are disrupted due to the uncontrolled symptoms of IBS-D need a safe and effective treatment,” said Dr. Marc Bradette, Professor of Medicine, Laval University, Quebec City, Quebec. “The results of this study suggest that cilansetron has the potential to significantly relieve the overall symptoms of IBS-D, improving the quality of life for men and women who struggle with this disease on a daily basis.”
Study Details Cilansetron in IBS-D: Efficacy and Safety in a Six-Month Global Study In a Phase III study, 358 males and 434 females meeting the Rome criteria, the standard diagnostic measure for IBS, were randomized to receive cilansetron 2 mg TID or placebo for six months. An interactive voice response system was used to collect weekly data concerning relief of IBS symptoms, abdominal pain/discomfort, and abnormal bowel habits.
The primary efficacy parameter was the proportion of subjects who reported adequate relief of IBS symptoms in at least 50% of their weekly responses while receiving treatment.
After six months, 59% of patients receiving cilansetron reported overall adequate relief of IBS symptoms, while specifically 61% reported relief of abdominal pain/discomfort, and 64% reported relief of abnormal bowel habits.
The median exposure was 182 days and mean compliance was greater than 98%.
The most common adverse effect was constipation, which occurred in 12% of cilansetron patients; other adverse effects included headache, abdominal pain, nausea and nasopharyngitis.
The AE most frequently causing study withdrawal was constipation. No severe complications of constipation occurred. Three suspected cases of ischemic colitis events were reported; all resolved without complication.
Cilansetron Demonstrated Efficacy in Males with IBS-D A subset analysis of males was conducted in two double-blind, placebo-controlled studies, a 3-month U.S. study and a 6-month multinational study outside the U.S. Patients were selected based on the Rome criteria for IBS-D and randomized to receive cilansetron 2mg TID or placebo. For the first time, males showed statistically significant results favoring cilansetron over placebo in all the primary, main, and key secondary parameters except for adequate relief of IBS symptoms in the 6-month multinational study, which showed a strong clinical trend favoring cilansetron over placebo.
The primary efficacy parameter was the proportion of subjects who reported adequate
relief of IBS symptoms in at least 50% of their responses to weekly diary questions.
Results from the two trials were similar and demonstrated significant treatment benefits of cilansetron in males with IBS-D.
In the U.S. study, 41% of those who took cilansetron reported adequate relief of IBS symptoms after three months (p<0.001).
In the longer, six-month multinational study, 55% of those who took cilansetron reported adequate relief of IBS symptoms (p=0.073).
The most common adverse event reported was constipation, which occurred among 8% of the cilansetron group in the U.S. study and among 7% in the multinational study.
No cases of ischemic colitis were seen in males in either study.
Appropriate Use Program
Solvay Pharmaceuticals will submit to the Food and Drug Administration (FDA) a comprehensive appropriate use plan. The company will work with physicians, regulatory advisors and advocates to develop a novel educational approach and plans to work closely with the FDA to ensure that cilansetron, if approved would only be used to treat the appropriate patient populations - those with IBS-D.
Drug and Study Status
If approved, cilansetron is expected to be the only 5-HT3 therapy available to treat IBS-D in both men and women throughout the world. Solvay Pharmaceuticals has completed three phase III efficacy studies. Solvay Pharmaceuticals submitted a new drug application for cilansetron in the United Kingdom on April 28, 2004, and plans to submit to the FDA in the United States in the second quarter of this year.
About IBS-D
As many as 30-45 million North American adults have symptoms of IBS, with approximately one-third from IBS-D. The common symptoms of IBS-D are diarrhea, abdominal pain/discomfort, and fecal urgency. IBS-D is a chronic condition that may require long-term therapy. Symptoms of IBS-D vary widely in occurrence and intensity among patients.
IBS has a significant negative impact on the quality of life for the many men and women who suffer from this condition, causing lost days of work and interfering with home-based, social and leisure activities.
About Solvay Pharmaceuticals, Inc. Solvay Pharmaceuticals is an internationally orientated organization, whose core activities consist of discovering, developing and manufacturing medicines for human use. It is active in the therapeutic areas of gastroenterology, cardiology, psychiatry and women’s health/men’s health. Solvay Pharmaceuticals’ global research and development centers are located in Hanover, Germany; Marietta, Ga., USA; Tokyo, Japan; and Weesp, The Netherlands. It is a member of the worldwide Solvay Group of chemical and pharmaceutical companies, headquartered in Brussels, Belgium.
About DDW
Digestive Disease Week (DDW) is the largest international gathering of physicians, researchers and academics in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery. Jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA), the American Society for Gastrointestinal Endoscopy (ASGE) and the Society for Surgery of the Alimentary Tract (SSAT), the meeting showcases approximately 5,000 abstracts and hundreds of lectures on the latest advances in GI research, medicine and technology.
Contacts: Gabrielle Braswell
Solvay Pharmaceuticals, Inc.
(770) 578-5637
