NEW YORK (Reuters Health) - The experimental drug linaclotide can relieve some cases of chronic constipation, but the majority of patients showed no significant benefit, according to the results of two studies published in the August 11th New England Journal of Medicine.
More than 21 percent of the volunteers showed improvement if they took the drug. Among patients given a placebo, the rate was no higher than six percent.
But the chief author, Dr. Anthony Lembo, of Beth Israel Deaconess Medical Center in Boston, said the satisfaction rate among patients was much higher.
Over 40 percent of the volunteers in both studies said they were quite satisfied or very satisfied with the way their treatment improved their bowel habits. The rate was no higher than 23 percent among volunteers who got a placebo.
There were side effects. Diarrhea led more than one in 25 of the linaclotide recipients to stop taking the drug. Just one in 200 placebo patients stopped their treatment.
The drug is being developed by Ironwood Pharmaceuticals and Forest Research Institute, which paid for the studies and helped design the tests. The two companies announced yesterday that they have submitted a new drug application to the U.S. Food and Drug Administration for linaclotide.
Up to one in five people suffers from chronic constipation, according to the authors of the study, which means they have fewer than three bowel movements per week, often with pain, excessive straining, a feeling of blockage, or very hard stools. Doctors usually recommend adding fluid, dietary fiber and exercise before turning to laxatives.
“Chronic constipation can dramatically negatively affect one’s quality of life,” said Dr. David Schwartz, director of the Inflammatory Bowel Disease Center at Vanderbilt University Medical Center, who was not involved in the study.
“If these results hold up in future longer-term trials, linaclotide potentially offers an effective and safe option for patients with chronic constipation, especially those individuals that do not respond to laxatives,” Schwartz told Reuters Health.
The pair of studies reported in the Journal involved 1,272 volunteers at more than 200 clinical centers in Canada. They were divided more or less evenly into three groups who received 145 micrograms of linaclotide, twice that dose, or a placebo pill, all taken at least 30 minutes before breakfast.
At the beginning of the trial, all reported having fewer than three bowel movements per week. They took the treatment for 12 weeks.
In one of the two trials, half the patients had their treatment switched between linaclotide and placebo at the end of the 12-week period.
The drug was considered to be effective if it produced at least three bowel movements per week and an increase of one bowel movement per week from baseline for at least nine out of 12 weeks. Patients used an interactive voice-response system to log their progress.
In neither trial was the higher dose more effective than the lower dose.
“For each trial, scores for constipation relief, treatment satisfaction, and treatment continuation were also significantly greater in the linaclotide groups than in the placebo group,” the researchers said.
Patients who were switched to placebo lost the improvements they had experienced with the drug.
Lembo told Reuters Health that the crossover part of the study was designed to see if there was a “rebound effect” among patients who were suddenly taken off the drug.
“You clearly don’t see that. When you stop the drug, they’re not worse than when they started,” he said.
“If it works, it’s clear it works,” Lembo said. “It happens pretty quickly, within a week, and you pretty much reach a plateau.”
SOURCE: bit.ly/qR26Th New England Journal of Medicine, August 11, 2011.