HONOLULU — Lubiprostone, an investigational drug with a novel mechanism of action, performed well for the treatment of chronic constipation in a pivotal phase III clinical trial, John F. Johanson, M.D., reported at the annual meeting of the American College of Gastroenterology.
Lubiprostone is a functional fatty acid that selectively activates the GI type-2 chloride channels. Lubiprostone enhances intestinal fluid secretion without altering serum electrolyte levels, explained Dr. Johanson, a gastroenterologist in private practice in Rockford, Ill.
He reported on 237 patients with a history of chronic idiopathic constipation of at least 6 months duration who participated in a double-blind multicenter trial in which they were randomized to 4 weeks of lubiprostone at 24 mcg b.i.d. or placebo taken with food and water. Overall, 90% of the patients were women, and two-thirds were below age 50 years.
Lubiprostone acted fast: 61% of treated patients experienced a spontaneous bowel movement within 24 hours after their first dose, compared with 31% of controls. Within 48 hours, 79% of patients on lubiprostone and 66% on placebo had experienced a spontaneous bowel movement without rescue medication. After 1 week, 72% of patients in the lubiprostone group were categorized as full responders, meaning they had four or more spontaneous bowel movements per week, compared with 49% in the placebo group, a difference that held up through the remainder of the trial.
Mild nausea was the most frequent adverse event associated with lubiprostone; it was reported by 21% of patients, compared with 4% on placebo. Adverse events led 15 patients in the lubiprostone arm and 1 on placebo to drop out of the study. Six patients discontinued lubiprostone because of nausea, four due to dyspnea, and three because of abdominal pain.
Dr. Johanson also presented the results of a 24-week multicenter open-label study involving 306 lubiprostone-treated patients. Only 54% completed the full 24 weeks. By then, 20% had quit due to adverse events, of which nausea, followed by headache, was the most common, and 16% had dropped out due to lack of efficacy.
Patient self-assessed constipation severity on a 0–4 scale averaged 3.05—categorized as severe—at baseline and improved steadily by a mean of 1.19 points at week 4 and by 1.83 points at week 18. Significant improvements in self-rated abdominal bloating and discomfort were also noted.
Dr. Johanson, who serves as a consultant to Sucampo Pharmaceuticals, told FAMILY PRACTICE NEWS that the company expects to receive a decision from the Food and Drug Administration this winter on its application to market lubiprostone.
In animal studies, lubiprostone has been shown to stimulate the recovery of ischemic colonic and ileal mucosa.
Phase III clinical trials of lubiprostone for the treatment of patients with irritable bowel syndrome are ongoing.