Progenics Releases Positive Results of MNTX in Opioid-Induced Constipation

Progenics Pharmaceuticals has announced positive top-line results from a pivotal Phase III clinical trial of its investigational drug, methylnaltrexone (MNTX) for the treatment of opioid-induced constipation in patients with advanced medical illness (AMI).

MNTX induced laxation within four hours at more than four times the rate of placebo. On average, laxation occurred within roughly one hour in the MNTX-treated patients. These results were highly statistically significant, and the drug was generally well-tolerated. Most AMI patients are treated with opioids for pain and can experience debilitating constipation, a serious side effect that is not adequately addressed by current therapies, including laxatives or stool softeners. MNTX is a peripheral opioid receptor antagonist that is designed to treat the side effects of opioid therapy without interfering with pain relief.

The Phase III clinical trial was a double-blind, randomized, placebo-controlled study that enrolled AMI patients with opioid-induced constipation. Patients at 16 hospice centers in the U.S. were randomized to receive one of three blinded doses of study medication: placebo, MNTX 0.15 mg/kg or MNTX 0.3 mg/kg. All patients had a life expectancy of less than six months, no laxation for 48 hours despite the use of laxatives and stool softeners, and stable opioid therapy.

The primary endpoint of the study was whether a single subcutaneous dose of study medication induced laxation within four hours. Subsequently, all patients were eligible to receive MNTX in an open-label phase of the study over the next four weeks. Total accrual was 154 patients, approximately evenly divided among treatment groups.