News from American College of Gastroenterology (ACG) 2004
Cilansetron Improves Health Related Quality of Life in Multinational Phase III Clinical Trial Patients with Irritable Bowel Syndrome with Diarrhea Predominance (IBS-D)
Researchers Also Unveil Additional Efficacy Data on 5-HT3 Receptor Antagonist in U.S. Population
Orlando, Fla. (November 1, 2004) - In a sub-sample analysis of IBS-D subjects that completed a Phase III, 6-month, multinational trial, treatment with cilansetron resulted in significant improvement of health related quality of life (HRQOL) in both men and women. The largest improvements were observed for the interference with activity, food avoidance, and dysphoria. Also presented, was additional efficacy data from a Phase III U.S. study, further demonstrating the significant treatment benefits among subjects who received cilansetron, including improvement in overall IBS symptoms, abdominal pain/discomfort and abnormal bowel habits. These data were presented this week during the annual meeting for the American College of Gastroenterology (ACG).
Cilansetron is an investigational 5-HT3 receptor antagonist, being studied for the treatment of irritable bowel syndrome with diarrhea predominance (IBS-D) in men and women. 5-HT3 antagonists inhibit 5-HT3 receptors, resulting in decreased GI motility, secretion, and pain sensation, thus improving symptoms of IBS. Current 5-HT3 therapy indicated for IBS is approved for women only.
“Irritable Bowel Syndrome is a leading cause of worker absenteeism and can have a significant negative impact on an individual’s daily activities,” said Dr. Kevin Olden, Professor of Medicine, Division of Gastroenterology, University of South Alabama, Mobile, Alabama. “Effective symptom control is critical to improving quality of life for the men and women who struggle with this condition on a daily basis.”
Study Details
Efficacy of cilansetron compared to placebo on HRQOL
In a Phase III, 6-month, multinational study, subjects (ages 18-84) meeting the Rome criteria for IBS-D, were randomized to receive cilansetron 2 mg three times daily (TID) or placebo. A subgroup of 157 male and 181 female subjects completed an IBS-QOL survey, a validated 34-item condition-specific, quality-of-life measure consisting of eight subscales (interference with daily activity, body image, health worry, food avoidance, social reaction, sexual, relationship, and dysphoria), at day 1 of randomization and after 6 months of treatment.
Subjects showed total improvements of 17.7 for cilansetron vs. 9.6 for placebo in HRQOL scores (p<0.005)
Lower scores at baseline at day 1 and after 6 months of treatment indicated lower HRQOL. Higher scores after 6 months of treatment indicated a higher HRQOL
Results for cilansetron were statistically significant from placebo (p<0.005) for all subscales except the sexual subscale (p=0.169)
The sexual subscale showed the highest score at baseline and treatment reflects a trend in favor of cilansetron
Cilansetron in IBS-D: Efficacy and Safety in a Three-Month US Study In a Phase III study, 205 males and 487 females meeting the Rome criteria for IBS-D were randomized to receive cilansetron 2 mg TID or placebo for three 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 on at least 50% of their weekly responses while receiving treatment
After three months, 49% of subjects (male and female) receiving cilansetron reported overall adequate relief of IBS symptoms versus 28% of subjects receiving placebo (p< 0.001), while specifically 52% receiving cilansetron versus 37% who received placebo (p<0.001) reported relief of abdominal pain/discomfort, and 51% in the cilansetron group versus 26% in the placebo group (p<0.001) reported relief of abnormal bowel habits
The most common adverse effect was constipation, which occurred in 19% of subjects receiving cilansetron versus 4% in the placebo group; other adverse effects included headache and abdominal pain
No severe complications of constipation occurred. There was one suspected case of ischemic colitis which was transient and resolved without complication within 9 days.
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. A new drug application (NDA) was submitted to the FDA in the United States on June 30, 2004, and a registration dossier to the MHRA in the UK on April 28, 2004. The product has been assigned priority review by the FDA in the United States.
Appropriate Use Program
Solvay Pharmaceuticals’ NDA submission in both the US and the UK includes a comprehensive appropriate use program based on collaboration with physicians, pharmacists, patients, and risk minimization experts. The cilansetron Appropriate Use Program (AUP) features an array of educational tools and specific promotional strategies that the company intends to discuss with the FDA.
About IBS
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, Inc. (www.solvaypharmaceuticals-us.com) of Marietta, Georgia (USA), is a research-driven pharmaceutical company that seeks to fulfil unmet medical needs in the therapeutic areas of cardiology, gastroenterology, mental health, women’s health and a select group of specialized markets including men’s health. It is a part of the global Solvay Pharmaceuticals organization whose core activities consist of discovering, developing, and manufacturing medicines for human use. Solvay Pharmaceuticals, Inc. is a subsidiary corporation of the worldwide Solvay Group of chemical and pharmaceutical companies headquartered in Brussels, Belgium.
About ACG The ACG was formed in 1932 to advance the scientific study and medical treatment of disorders of the gastrointestinal tract. The College promotes the highest standards in medical education and is guided by its commitment to meeting the needs of clinical gastroenterology practitioners.
Contacts:
Gabrielle Braswell
Solvay Pharmaceuticals, Inc.
(770) 578-5637
Kelly Tyler
Ketchum
(202) 835-7279
During ACG (201) 892-3345
