"The bottom line is that it seems that [methylnaltrexone] does reverse the constipating effect of the opioids in many patients," stated the study's lead investigator Jay Thomas, MD, clinical medical director, San Diego Hospice, San Diego, California.

It's well tolerated and has a predictable onset of action and may be a big addition to help decrease the number of laxatives that patients have to take and decrease side effects, Dr. Thomas said in a presentation on February 9^th.

"The side effects of opioids among patients who have advanced illness cause a lot of morbidity as well as a lot of cost to the system. The treatments we have now often don't work that well and patients need to take many of them," he explained.

Dr. Thomas and his team examined the results of 2 multicenter, randomized, double-blind, placebo-controlled trials that compared methylnaltrexone with placebo.

In their first trial, investigators assigned 301 patients to methylnaltrexone 0.15 or 0.30 mg/kg or to placebo. In the second trial, they assigned 133 patients to receive either methylnaltrexone 0.15mg/kg or placebo for 2 weeks. All patients had a life expectancy of less than 6 months, no laxation for 48 hours, and were receiving opioids along with stable doses of laxatives.

Researchers set their primary efficacy endpoint as laxation within 4 hours after a first dose of methylnaltrexone. In addition, they examined endpoints of laxation within 24 hours, laxation occurring within 4 hours of at least 2 of the first 4 doses of the trial medication.

Results showed that patients receiving methylnaltrexone experienced improved laxation (62% in the first study and 48.4% in the second study) within the first 4 hours of administration, the researchers reported.

They noted that the median time to laxation was significantly less for those in the methylnaltrexone group -- 70 minutes versus 24 hours for those in the placebo group (P < .0001).

Dr. Thomas said he anticipates that methylnaltrexone will be considered for marketing approval by the US Food and Drug Administration next year.


[Presentation title: Phase III Results From Two Multi-Center Randomized Double-Blind Placebo-Controlled Trials of Methylnaltrexone for Opioid-Induced Constipation (OIC) in Patients With Advanced Illness (AI). Abstract 137]

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