Study Shows Zelnorm Effective and Well Tolerated for Treating Chronic Constipation

Market Wire, 20050229

Zelnorm(R) (tegaserod maleate) was found significantly more effective than placebo in providing rapid and sustained relief from chronic constipation during 12 weeks of therapy based on a pivotal trial with 1,348 female and male patients. Furthermore, Zelnorm provided relief of several chronic constipation symptoms including abdominal discomfort or pain, bloating or distension, straining and stool consistency.

The new data, including findings that further support the safety and tolerability profile of Zelnorm were presented at the 34th Annual Digestive Disease Week Meeting. A submission to the U.S. Food and Drug Administration (FDA) for the drug's use in patients with chronic constipation is planned for the fourth quarter of 2003. Zelnorm is approved currently by the FDA for the short-term treatment of women with Irritable Bowel Syndrome (IBS) whose primary bowel symptom is constipation.

"If approved for use in chronic constipation, Zelnorm would be the first treatment not only to improve bowel frequency but also to provide relief of multiple symptoms to patients," said John Johanson, MD, MSC, lead investigator and clinical associate professor of medicine at the University of Illinois College of Medicine in Rockford. "This advance would be welcomed by the medical community because there is a need for additional therapies that are effective and well tolerated."

This study defined chronic constipation as symptoms for at least six months duration with less than three complete spontaneous bowel movements (CSBM) per week and straining, incomplete evacuation and/or hard stools. Ninety percent of the patients in the study were women who had constipation symptoms for an average of 19 years.

Zelnorm Provides Rapid and Sustained Relief Over Three Months

The study found that the response rate for Zelnorm taken twice a day (2 mg b.i.d. or 6 mg b.i.d.) was superior to placebo (p < 0.0001) in increasing the number of complete spontaneous bowel movements (CSBM). After four weeks, the 2 mg treated group had a 41.4% response rate, similar to the 6 mg treated group (43.2%), both of which were significantly better than the placebo group (24.9%) at four weeks. At 12 weeks the response rate for the 2 mg treatment group was 40.3%, while 44.8% of those receiving 6 mg responded, again both treatments were significantly better than the placebo group (26.9%). In addition, satisfaction with bowel habits improved and overall bothersomeness of symptoms decreased in patients receiving Zelnorm. Once the 12-week treatment period with Zelnorm was over, patient's symptoms returned within two weeks.

Data Provides Further Support of the Safety and Tolerability Profile of Zelnorm

The study also showed that Zelnorm was well tolerated in female and male patients over the duration of the study. While the most frequent adverse events reported during the study were headache and cold-like symptoms (nasopharyngitis), they occurred more often in placebo treated patients. Diarrhea was also reported as an adverse event and was generally mild or moderate in severity; of short duration (median < 2 days); occurred only once in the majority of patients; and had a low discontinuation rate ( < 1%). No clinically significant ECG changes were noted, including QTc interval (duration). Clinical and laboratory parameters examined showed no alterations in electrolytes or vitamin absorption. Overall, this study with more than 1,300 patients supports the safety and tolerability profile of this potential new therapeutic option for patients with chronic constipation.

Study Methods

This multicenter, double-blind, placebo-controlled study included patients randomly assigned to 2 mg (n=450) or 6 mg (n=451) doses of Zelnorm taken orally twice daily or placebo (n=447) for a period of 12 weeks. Successful response was defined as an increase of at least one CSBM per week compared to baseline and a minimum of seven days of treatment. Stool frequency and bowel habits for all participants were established during the two-week baseline period. The primary efficacy variable was the response during the first month of treatment. Secondary endpoints included response over three months and intensity of specific symptoms (bloating/distention, abdominal discomfort/pain, straining, stool consistency). Satisfaction with bowel habits and bothersomeness of overall symptoms also were assessed.

About Constipation

There are approximately 2.5 million constipation related visits to physicians each year. It is estimated that patients spend approximately $350-400 million annually on over-the-counter laxatives to help alleviate their constipation. Chronic constipation is a prevalent and bothersome disorder that can negatively impact patient's lives. Women are affected two to three times more often than men, and there are approximately four million people in the United States with chronic constipation.

About Zelnorm

The U.S. Food and Drug Administration approved Zelnorm on July 24, 2002 for the short-term treatment of women with IBS whose primary bowel symptom is constipation. The safety and effectiveness of Zelnorm in men have not been established. Zelnorm is the first agent in a new class of drugs that acts as an agonist at 5HT4 (serotonin type 4) receptor sites. By activating 5HT4 receptors, Zelnorm normalizes impaired motility in the GI tract, inhibits visceral sensitivity and stimulates intestinal secretion. Zelnorm is the first agent proven to provide women with relief of the abdominal discomfort or pain, bloating and constipation of IBS. The recommended dosage of Zelnorm is 6 mg taken orally twice daily before meals for four to six weeks. For those patients who respond to therapy at 4-6 weeks, an additional 4-6 week course can be considered.