NEW ORLEANS, May 19 /PRNewswire/ -- Results from the two largest multinational studies conducted in the research of chronic constipation demonstrated Zelnorm(R) (tegaserod maleate) was significantly more effective than placebo in relieving the multiple symptoms patients suffer most -- straining, stool consistency, bloating and abdominal discomfort/pain, as well as increasing the frequency of complete spontaneous bowel movements.
The drug’s effect was rapid, with the majority of the Zelnorm-treated patients experiencing a spontaneous bowel movement within the first 24 hours. The results from the randomized, double-blind, placebo-controlled trials with more than 2,600 patients, conducted in North and South America, Europe, South Africa and Australia, were reported today during Digestive Disease Week in New Orleans, Louisiana. These results were submitted to the U.S. FDA in the fourth quarter of 2003 in a supplemental new drug application for Zelnorm’s use in the treatment of chronic constipation.
“Physicians tend to define constipation as fewer than three bowel movements a week. However, research shows that patients’ primary concerns are associated with straining, hard stools, incomplete evacuation, bloating and abdominal discomfort,” says Satish Rao, M.D., Ph.D., professor of medicine and director of Neurogastroenterology and GI Motility, University of Iowa, Carver College of Medicine, Iowa City, Iowa. “The study results are promising for patients because Zelnorm is the first drug to show improvement in treating the multiple symptoms and also to increase bowel frequency.”
Constipation is the number one gastrointestinal (GI) complaint in the U.S. and affects nearly 15 percent of the population, or 43 million people. More than 4.5 million Americans suffer with the symptoms of constipation most of the time. The condition is treated most frequently by primary care physicians, accounts for more than 2.5 million annual visits to the doctor each year and leads to 92,000 hospitalizations.
Data from one of the studies incorporating a 13-month extension study showed Zelnorm to be generally safe and well tolerated. The study reinforces the long-term safety and tolerability data demonstrated in patients with Irritable Bowel Syndrome (IBS) with constipation.
Zelnorm Effective Throughout the Three Months of the Studies
The studies demonstrated that Zelnorm-treated patients experienced significantly more complete spontaneous bowel movements than placebo during 12 weeks. The response rate for the first four weeks of treatment (primary efficacy variable) was 42 percent in the group receiving 6 mg of Zelnorm -- significantly higher than the 26 percent in the placebo group. Over the 12-week period, the response rate for the 6 mg twice-a-day treated group was significantly superior to placebo (44 percent vs. 29 percent).
Significant weekly improvements were observed in Zelnorm-treated patients for stool frequency, consistency and straining compared to placebo. Zelnorm- treated patients also reported less bothersome constipation, abdominal pain/discomfort, bloating/distension, satisfaction with bowel habits and relief from constipation symptoms compared to placebo. Frequency of laxative use also was significantly lower in Zelnorm-treated patients.
Study Methods
To enroll in the multinational, randomized, double-blind, placebo-controlled studies, patients had to have had chronic constipation for at least six months. Symptoms were defined as less than three complete spontaneous bowel movements per week, accompanied by at least one of the following additional symptoms: straining, incomplete evacuation and/or hard/very hard stools. After a two-week baseline, patients were randomly assigned to 2 mg or 6 mg of Zelnorm, or placebo taken orally twice daily for 12 weeks. More than 2,600 patients (n=2,612) were randomized and 82.9 percent completed treatment.
Successful response was defined as an increase of at least one complete spontaneous bowel movement per week compared to the bowel movement frequency at baseline, and at least seven days of treatment. The primary efficacy variable was the response during the first four weeks of treatment. Secondary endpoints included response over 12 weeks and improvement in specific symptoms including straining, stool form, abdominal distension/bloating and abdominal discomfort/pain.
Zelnorm Long-Term Safety Demonstrated in Trial Lasting More Than A Year
Safety and tolerability assessments were based on physical examination, monitoring adverse events, serious adverse events, laboratory parameters, vital signs and electrocardiograms (ECGs). Out of 842 enrolled patients, 451 patients completed the long-term safety study (mean age 46 years, 87 percent women). The most common reasons for discontinuation were unsatisfactory therapeutic effect (19 percent), withdrawal of consent (11 percent) and adverse events (6 percent).
The most common adverse event with Zelnorm (6 mg) was diarrhea (10 percent), but it rarely led to discontinuation of the study (one percent). Typically, diarrhea was transient, lasting three to four days, and generally resolved without rescue medication or interruption of treatment. No clinically relevant changes were seen in other safety parameters evaluated, including vital signs or ECGs.
About Zelnorm
Zelnorm is the first agent proven to provide women with relief of the abdominal discomfort or pain, bloating and constipation of IBS, and it is the first in a novel class of drugs that act as an agonist at 5HT4 (serotonin type 4) receptors. Zelnorm mimics the natural effects of serotonin by activating 5HT4 receptors, which normalizes impaired motility in the GI tract, inhibits visceral sensitivity and stimulates intestinal secretion.
In IBS with constipation clinical trials, tolerability to Zelnorm was similar to placebo. The only adverse events reported significantly more often with Zelnorm than with placebo were headache (15 vs. 12 percent) and diarrhea (nine vs. four percent). The majority of patients reporting diarrhea had a single episode and in most cases, diarrhea occurred in the first week of treatment. Typically, diarrhea resolved with continued therapy. Serious consequences of diarrhea, including hypovolemia, hypotension, and syncope, have been reported in the clinical studies (0.04 percent) and during marketed use of Zelnorm. In some cases, these complications have required hospitalization for rehydration.
Zelnorm was developed by Novartis, and is known internationally as Zelmac. It is approved in more than 55 countries for IBS with constipation. Approximately three million patients worldwide have been treated with Zelnorm for IBS with constipation. Zelnorm also is approved for use in chronic constipation in Mexico and Latin America. Zelnorm is being studied as a potential treatment for other important gastrointestinal disorders, including gastroesophageal reflux disease (GERD) and dyspepsia.
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), DDW takes place May 15-20, 2004 in New Orleans, Louisiana. The meeting showcases approximately 5,000 abstracts and hundreds of lectures on the latest advances in GI research, medicine and technology.
Forward-looking Statement
This release contains certain forward-looking statements relating to the Company’s business, which can be identified by the use of forward-looking terminology such as “significantly more effective,” “promising,” “potential,” or similar expressions, or by discussions of strategy, plans or intentions. Such forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause actual results with Zelnorm to be materially different from any future results, performance or achievements expressed or implied by such statements. Specifically, there are no guarantees that the data described above will result in the commercial success of Zelnorm. Any such success can be affected by, among other things, uncertainties relating to product development, future clinical trial results, adverse regulatory actions or delays, government regulation generally, the ability to obtain or maintain patent or other proprietary intellectual property protection, competition in general and other risks and factors referred to in the Company’s current Form 20-F on file with the Securities and Exchange Commission of the United States.
About Novartis
Novartis Pharmaceuticals Corporation researches, develops, manufacturers and markets leading innovative prescription drugs used to treat a number of diseases and conditions, including 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 Novartis AG , a world leader in pharmaceuticals and consumer health. In 2003, the Novartis Group’s businesses achieved sales of USD 24.9 billion and a net income of USD 5.0 billion. The Group invested approximately USD 3.8 billion in R&D. Headquartered in Basel, Switzerland, Novartis Group companies employ about 78,500 people and operate in over 140 countries around the world. For further information please consult http://www.novartis.com/.
Editor’s Note: Full prescribing information available at http://www.zelnorm.com/ or by contacting Carrie Callahan of Novartis Pharmaceuticals Corporation at (862) 778-7065 or via e-mail at carrie.callahan@pharma.novartis.com.
Contacts: Carrie Callahan John McInerney Novartis Pharmaceuticals Corp. Ruder Finn (862) 778-7065 (516) 606-3516 carrie.callahan@pharma.novartis.commcinerneyj@ruderfinn.com Nicole Iorillo Ruder Finn (917) 375-7714 iorillon@ruderfinn.com
Novartis Pharmaceuticals Corporation
CONTACT: Carrie Callahan of Novartis Pharmaceuticals Corp.,+1-862-778-7065, carrie.callahan@pharma.novartis.com; or John McInerney,+1-516-606-3516, mcinerneyj@ruderfinn.com, or Nicole Iorillo, +1-917-375-7714,iorillon@ruderfinn.com, both of Ruder Finn, for Novartis PharmaceuticalsCorp.