Wyeth and Progenics start second Phase 3 trial of intravenous methylnaltrexone

Wyeth Pharmaceuticals, of Pennsylvania, USA and Progenics Pharmaceuticals, of New York, are to initiate a second global phase 3 clinical trials to evaluate intravenous methylnaltrexone for the treatment of post-operative ileus (POI).

POI is a temporary impairment of gastrointestinal (GI) function characterised by abdominal bloating and pain, nausea and vomiting, and an inability to pass gas or a stool. POI is a common response to abdominal surgical procedures, but can also occur after other types of surgery. POI can worsen when opioid analgesics, such as morphine, are given to relieve post-operative pain, potentially leading to delayed introduction of food, lengthened hospital stays and increased healthcare costs.

Methylnaltrexone is a mu-opioid receptor antagonist designed to reverse the peripheral side effects caused by opioids, particularly in the GI tract. It does not interfere with brain-centered pain relief.

The first phase 3 trial was initiated in September 2006. Similar to the first phase 3 POI trial, the second study will enrol approximately 500 patients who have undergone segmental colectomy surgery in a double-blind, randomized, placebo-controlled clinical trial at approximately 75-90 surgical centers worldwide.

The intravenous form of methylnaltrexone currently under investigation for the treatment of POI received Fast Track designation from the FDA in July 2006. Because many postoperative patients cannot tolerate oral medications, intravenous methylnaltrexone may represent an important therapeutic option. Methylnaltrexone is also being developed in other dosage forms, including subcutaneous and oral forms, as treatment for opioid-induced constipation.