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."