May 28, 2008 -- Results only now reported from a 12-week clinical trial that ended nine years ago suggest that a new drug, Resolor, helps people with chronic constipation.
Meanwhile, promising findings suggest that a new form of naltrexone, a drug used to block the narcotic effects of opioids in addicts, may relieve the terrible constipation that afflicts patients who need opioids to control their pain.
The Resolor results appeared only after Johnson & Johnson, which developed the drug, licensed it to the Belgian firm Movetis NV.
Late or not, the results may be good news to the estimated 15% of Americans who suffer the straining, bloating, and abdominal discomfort of chronic constipation.
Resolor "significantly increased the number of spontaneous, complete bowel movements, reduced the severity of symptoms, and improved the disease-related quality of life in patients with severe chronic constipation," report Mayo Clinic researcher Michael Camilleri, MD, and his Movetis colleagues.
Nearly half of the patients receiving Resolor, but only a fourth of the patients receiving an inactive placebo, averaged at least one complete bowel movement per week.
None of the patients showed signs of heart problems. That's good news, but there's reason to need more safety data, says Arthur J. Moss, MD, of the University of Rochester in New York. Moss' editorial accompanies the Camilleri report in the May 29 issue of The New England Journal of Medicine.
Resolor is in the same drug family as Propulsid and Zelnorm, both of which were taken off the market because they caused dangerous heart problems in some patients. Zelnorm returned to the market with a dire warning on its label, but was then voluntarily removed from the market by the manufacturer.
"It is not clear why clinical trials with [Resolor] were temporarily suspended around 2001 or why it took so long to bring this study to publication," Moss notes. "We simply do not know whether the drug will [cause serious heart problems] in a small fraction of vulnerable subjects with a non-life-threatening gastrointestinal disorder."
Moss says more complete data will be needed before the drug should be brought to market as a treatment for chronic constipation.
Constipation Help for Pain Sufferers
Opioid drugs are a huge boon in offering pain relief to patients with severe pain. But they cause their own form of suffering -- constipation that often cannot be relieved by laxatives. This problem often means patients have to cut back on opioid use, sometimes with a terrible increase in pain.
The drug naltrexone blocks opioid drugs from attaching to receptors, thus blocking their painkilling effects. Relistor is a form of naltrexone that has limited ability to enter the brain. The idea is to block the unwanted side effects of opioids, such as constipation, without blocking their painkilling effects.
In a clinical trial supported by Progenics, which is developing Relistor in collaboration with Wyeth, 133 patients with advanced illness and terminal disease who had been on opioids for two or more weeks received under-the-skin injections of Relistor or an inactive placebo.
Nearly half the Relistor-treated patients had a bowel movement within four hours of the first dose, compared with 15% of the placebo group. Time to bowel movement was significantly shorter for Relistor patients than placebo patients.
Importantly, none of the patients showed signs of opioid withdrawal or had changes in their pain scores.
Relistor "may represent an important therapeutic option for patients with advanced illness who are suffering from opioid-induced constipation," conclude Jay Thomas, MD, PhD, of San Diego Hospice and the Institute for Palliative Medicine, San Diego, and colleagues.
In an editorial accompanying the Thomas report in the May 29 issue of The New England Journal of Medicine, Harvard researchers Charles Berde, MD, PhD, and Samuel Nurko, MD, MPH, commend the Thomas team on its work.
However, Berde and Nurko wonder why only half of patients responded. Their hypothesis is that the constipating effects of opioids stem not only from opioid action in the gut, but also in the brain, which Relistor cannot reach.
"Future studies in a larger number of patients may help to delineate predictors of the success or failure of [Relistor] in specific subgroups of patients, and may guide decisions about increasing or decreasing the dose for various patients," they suggest.
Relistor was approved by the FDA in April 2008 for the treatment of opioid-induced constipation in patients with late-stage, advanced illness who are receiving opioids on a continuous basis to help alleviate their pain.