To print: Select File and then Print from your browser's menu --------------------------------------------------------------------------------------- Title: DDW: Zelmac (Tegaserod) Relieves Multiple Symptoms Of Irritable Bowel Syndrome URL: http://www.pslgroup.com/dg/1D355A.htm Doctor's Guide May 24, 2000
SAN DIEGO, CA -- May 24, 2000 -- Novartis Pharmaceuticals Corporation announced the results of five studies presented at Digestive Disease Week (DDW), which examine the role of Zelmac (tegaserod) in the treatment of multiple symptoms of irritable bowel syndrome (IBS). DDW is the combined annual meeting of the American Gastroenterological Association, American Association for the Study of Liver Diseases, American Society for Gastrointestinal Endoscopy and Society for the Surgery of the Alimentary Tract. Clinical studies presented at the meeting evaluated the efficacy and safety of Zelmac in IBS patients who suffer primarily from abdominal pain and constipation, its effect on overall GI transit and the use of the Subject's Global Assessment (SGA) of relief as an appropriate outcome measure in clinical trials of IBS. Preclinical studies further evaluated the effect of Zelmac on GI motility and gastric/colorectal sensitivity. "IBS is a complicated disorder that has a distressing impact on the lives of millions," said David Epstein, Chief Operating Officer, Novartis Pharmaceuticals Corporation. "This research supports the promising role Zelmac may have in treating IBS patients who suffer primarily from abdominal pain and constipation." Zelmac belongs to a new chemical class of compounds which selectively target and act on 5-HT(4) receptors present throughout the GI tract. These serotonin receptors are believed to potentially play a key role in pain perception and GI motility. By acting on the 5-HT(4) receptor pathway, Zelmac may reduce abdominal pain and may normalize altered GI function in IBS patients who suffer from abdominal pain and constipation as their primary symptoms. IBS is one of the most common gastrointestinal (GI) disorders of function, affecting up to 20 percent of the Western population. It is a chronic condition characterized by abdominal pain and symptoms associated with irregular bowel function, such as constipation, diarrhea or an alternating pattern between the two. To date, no medication has proven to be safe and effective in treating IBS patients who suffer from abdominal pain and constipation as their main symptoms. The safety and efficacy of Zelmac (4 and 12 mg/d) were tested in a 12-week double-blind, placebo controlled study of 881 patients who fulfilled the Rome criteria and two of three constipation criteria (< three bowel movements per week, hard stool or straining). Within one-week of starting treatment, patients in both treatment groups experienced a clinically relevant and statistically significant relief of symptoms. At endpoint, 47 percent of patients on 4 mg/d and 46 percent of patients on 12 mg/d compared with 35 percent on placebo experienced statistically significant relief of symptoms as measured by the Subject's Global Assessment (SGA) of relief. The SGA of relief is a global assessment that incorporates symptoms of abdominal pain, overall well being and altered bowel function. The effect was sustained throughout the duration of the study. Zelmac was found to be well tolerated with most side effects comparable to placebo. Diarrhea was the predominant adverse event reported more often in Zelmac treatment groups (7 percent at 4 mg/d; 10 percent at 12 mg/d and 3 percent on placebo). In most cases, the diarrhea occurred early, was transient, and resolved with continued therapy. Only 2.2 percent of patients discontinued Zelmac therapy due to diarrhea as compared to 0 percent on placebo. Researchers explored whether the Subject's Global Assessment (SGA), an assessment that incorporated the symptoms abdominal pain, overall well being and altered bowel function, was an effective way to measure globally the treatment effects of therapeutic agents in clinical trials of IBS. The primary outcome measure of the study was obtained weekly by patient self-assessment in two identical Phase III trials of Zelmac (one in the U.S.; one in Europe). Results from these trials support that SGA of relief is an appropriate measure of response in clinical trials of IBS. A positive response on the SGA of relief correlated with clinically relevant daily diary improvements in abdominal pain, bloating and bowel function. Preclinical studies have demonstrated that Zelmac may have promotile effects throughout the GI tract. A study was initiated to determine the effects of Zelmac on overall GI transit in healthy male subjects. In this study, 12 healthy male subjects received randomized treatment of oral Zelmac, intravenous Zelmac or placebo (6 mg tablets; 0.6 mg infusion). Overall GI transit was assessed using radioscintigraphy. Gastric emptying, small bowel transit and colonic transit times were also assessed. The study found that GI transit is accelerated following both oral and intravenous Zelmac therapy. The promotile effects were demonstrated throughout the entire GI tract, suggesting that Zelmac may have a potential therapeutic role in disorders of both the upper and lower GI tract. Researchers studied the effects of Zelmac on GI motility (gastric, small intestinal and colonic) in rats under normal and postoperative conditions (Zelmac doses of 0.3 mg; 1.0 mg; 3.0 mg). The study found that Zelmac significantly increased GI motility, with the lowest dose most effective in the stomach and small intestine and the highest dose most effective in stimulating colonic motility. These results suggest that Zelmac may have potential use in slow transit or postoperative motility disorders. Alterations of visceral sensitivity are commonly observed in GI disorders of function like IBS and functional dyspepsia. Researchers evaluated the dose-response effects of Zelmac on gastric and colorectal sensitivity in rats. In the study, Zelmac increased the pain threshold following colorectal distension, suggesting an antinociceptive (anti-pain) property. A new drug application (NDA) for Zelmac was submitted to the FDA on February 11 for the treatment of irritable bowel syndrome and was granted priority review. Similarly, a regulatory submission was filed with the European Medicine Evaluation Agency (EMEA) on February 16. Novartis is also assessing Zelmac as a potential treatment for other GI disorders of function such as gastroesophageal reflux disease (GERD) and functional dyspepsia. Novartis Pharmaceuticals Corporation researches, develops, manufactures and markets leading innovative prescription drugs used to treat a number of diseases and conditions, including gastroenterology, central nervous system disorders, organ transplantation, cardiovascular diseases, dermatological diseases, respiratory disorders, cancer and arthritis. The company's mission is to improve people's lives by pioneering novel healthcare solutions. Located in East Hanover, New Jersey, Novartis Pharmaceuticals Corporation is an affiliate of the Novartis Group, a world leader in healthcare with core businesses in pharmaceuticals, consumer health, generics, eye-care, and animal health. In 1999, the Group (including Agribusiness) achieved sales of USD 21.7 billion and invested more than USD 2.8 billion in R&D. Headquartered in Basel, Switzerland, Novartis employs about 82,400 people and operates in over 140 countries around the world. The Group recently announced plans to spin off its Crop Protection and Seeds sectors and to merge them with the agrochemicals business of AstraZeneca in the second half of 2000. Related Links: Zelmac (tegaserod) and Novartis Pharmaceuticals Corporation. --------------------------------------------------------------------------------------------- Copyright © 1999 P\S\L Consulting Group Inc. All rights reserved. Republication or redistribution of P\S\L content is expressly prohibited without the prior written consent of P\S\L. 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