In a pivotal phase III trial, more than 70% of seriously ill patients with opioid-induced constipation responded to the investigational agent methylnaltrexone (MNTX) by the end of the first week of treatment. Neil Slatkin, MD, DABPN, reported the results at Digestive Disease Week (DDW) 2006 (abstract 686e).
LOS ANGELES-In a pivotal phase III trial, more than 70% of seriously ill patients with opioid-induced constipation responded to the investigational agent methylnaltrexone (MNTX) by the end of the first week of treatment. Neil Slatkin, MD, DABPN, reported the results at Digestive Disease Week (DDW) 2006 (abstract 686e).
Nearly half of the study patients experienced laxation within 4 hours of receiving their first dose of the drug, said Dr. Slatkin, director, Department of Supportive Care, Pain and Palliative Medicine, City of Hope, Duarte, California. He presented the research at a late-breaking abstract session.
"In order to provide the most compassionate care possible, health care professionals want to focus on aggressive pain management without the worry of opioid-induced bowel dysfunction," he said. "These data are encouraging for patients living with advanced illnesses who must take opioids to control their pain."
More than 50% of cancer patients admitted to palliative care units experience opioid-induced bowel dysfunction, which includes constipation that is not adequately addressed by current therapies such as laxatives or stool softeners, Dr. Slatkin commented.
Methylnaltrexone is a peripheral opioid-receptor antagonist designed to rapidly block the effect of opioid painkillers on opioid receptors outside the central nervous system. Since methylnaltrexone does not cross the blood-brain barrier, it does not interfere with brain-centered pain relief, according to the developers of the agent Wyeth Pharmaceuticals and Progenics Pharmaceuticals, Inc.
In the double-blind, placebo-controlled trial, 133 patients with advanced illness residing in nursing homes, hospice, and palliative care centers across the United States, were randomized to receive either methylnaltrexone (0.15 mg/kg subcutaneously) or placebo every other day for 2 weeks.
All of the patients experienced opioid-induced constipation, despite the use of laxatives and stool softeners, Dr. Slatkin said. No rescue laxatives were allowed within 4 hours of dosing.
By day 8, a blinded dose escalation was permitted (methylnaltrexone 0.30 mg/kg or placebo) if a patient did not have at least three bowel movements during the previous week that were not associated with rescue therapy. This dosing regimen was continued through the remaining week of the trial (dosing on days 9, 11, and 13).
The study results showed that 48.4% of patients experienced laxation within 4 hours of receiving the first dose of methylnaltrexone, more than three times the rate seen in patients treated with placebo (15.5%, P < .0001), Dr. Slatkin reported.
Slightly more than half of the patients in the study (51.6%) experienced laxation within 4 hours of receiving at least two of the first four methylnaltrexone doses, compared with 8.5% receiving placebo (P < .0001). For the responding patients, the median time to laxation was 30 minutes, with no reports of diminished pain relief or systemic opioid withdrawal due to the study medication.
Methylnaltrexone was well tolerated, Dr. Slatkin said, with transient abdominal cramping and flatulence the most commonly reported adverse events.
He concluded: "MNTX can reverse constipation due to opioids in patients with advanced illness when given every other day for a 2-week period. The drug has the potential to meet a significant unmet medical need."