This trial is designed to identify the dose or doses of methylnaltrexone to be taken forward into the phase III clinical studies that will evaluate the efficacy, safety and tolerability of oral methylnaltrexone for opioid-induced constipation in patients treated with opioids for chronic pain.
Opioid analgesics, such as morphine, are widely used to treat patients with moderate to severe pain. In addition to their ability to palliate pain via their interaction with the central nervous system, these medications also interact with opioid-specific receptors outside the brain and spinal cord, often resulting in constipation.
Methylnaltrexone is a peripheral mu opioid-receptor antagonist designed to reverse the effect of these medications on opioid receptors outside the central nervous system. Because methylnaltrexone acts outside of the central nervous system, it does not interfere with brain-centered pain relief.
More than 100 clinical sites in 21 countries are expected to participate in the randomized, double blind, placebo-controlled, parallel-group phase II trial, which will recruit approximately 200 to 400 patients.
The primary efficacy endpoint of the phase II study is the number of spontaneous bowel movements per week for six weeks in the methylnaltrexone and placebo groups compared to baseline. Completion of the study is expected to take less than a year and to be followed by phase III trials initiating in 2007.