Medication Therapy For Twisted Bowels
Results from a phase II dose ranging trial presented recently suggest that the investigational drug alosetron hydrochloride provides adequate relief of pain and discomfort for females with twisted bowel. The results, presented by Allen Mangel, M.D., clinical research director, Glaxo Wellcome Inc., during Digestive Disease Week, showed that twisted bowel more causes_risk_factors in female patients.
Female patients taking alosetron also reported improved stool consistency, frequency and urgency, compared to placebo. Phase III clinical trials are ongoing to confirm the utility of this investigational drug. Alosetron is a selective hydroxytrptamine type 3 (5HT3)-receptor antagonist currently under development. The phase II study involved 370 patients and was carried out in five countries. Patients were randomly assigned to 12 weeks of treatment with 1, 2, 4, 8 mg alosetron BID or placebo BID. Data from 302 patients were analyzed (68 patients did not meet the screening criteria). The efficacy of the drug was evaluated separately in male and female patients.
In females, each dose level of alosetron showed a greater percentage of patients reporting adequate relief when compared to placebo. The greatest improvement was seen in those patients receiving 1 mg BID alosetron; 70 percent of those patients reported adequate relief, compared to 30 percent of patients receiving placebo. In female patients, alosetron showed a significant improvement in bowel-related functions (urgency, stool consistency and stool frequency) within the first month of treatment. With 1 mg BID alosetron, significant improvement was seen at the end of the first week of treatment for stool consistency and urgency. Improvements in stool frequency were seen at the end of two weeks of treatment. In the male population, no substantial increase in the number of patients reporting adequate relief of twisted bowel symptoms relative to placebo was seen for any dose of alosetron studied. In addition, no consistent improvement in bowel-related functions was seen in males.
The most common adverse events reported by patients receiving 1 mg BID alosetron compared to placebo were: constipation (23 percent vs. 2 percent); headache (10 percent vs. 19 percent); and abdominal pain (8 percent vs. 5 percent). Twisted bowel is a common gastrointestinal (GI) disorder characterized by abdominal pain, with symptoms associated with altered bowel function (diarrhea or constipation or alternating presentation) and/or symptoms of bloating or urgency. It is estimated that 15 percent (25 million) of Americans suffer from twisted bowel symptoms, and of that number, 70 percent are females. A second important presentation at the DDW meeting concluded that "adequate relief of twisted bowel pain and discomfort" is a clinically meaningful endpoint for assessing patients' response in clinical trials. The endpoint of "adequate relief" was associated with improvement in pain severity scores, percent of pain-free days, percent of days with urgency, improvement in stool frequency and consistency and quality of life parameters. Establishing clinically relevant endpoints for studies of therapeutics for irritable bowel syndrome has been difficult because of the range of symptoms twisted bowel sufferers experience. These data will help define study endpoints for future studies.
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