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Second Phase III Trial Initiated of Methylnaltrexone in Opioid-Induced Constipation
The new phase 3 trial is a double-blind, randomized, placebo-controlled study that will measure the ability of MNTX to induce laxation within four hours in patients with AMI and opioid-induced constipation. In addition, the study will evaluate the ability of MNTX to restore patients to a normal bowel schedule of three or more laxations per week. Patients will receive study medication every-other day for two weeks at hospice centers across the United States and Canada. Thereafter, they will be eligible to enter an MNTX open-label extension study for an additional three months.
"The majority of patients who receive opioid pain therapy in the last months of life suffer from debilitating constipation," said Robert J. Israel, M.D., Progenics' Senior Vice President, Medical Affairs. "Treatment of opioid-induced constipation in this population is a major unmet medical need. This phase 3 study is intended to provide pivotal clinical evidence of the efficacy and safety of MNTX and to confirm the positive results that we observed in patients with advanced medical illness in phase 2 clinical trials."
In Progenics' other ongoing phase 3 trial of MNTX, AMI patients with opioid-induced constipation are being treated with single doses of MNTX or placebo. The Company believes that the results from these two ongoing MNTX pivotal studies will form the basis for a New Drug Application that it plans to file with the U.S. Food and Drug Administration.
Opioids are widely used to lessen suffering in advanced cancer and other terminal diseases. To relieve pain, narcotic medications such as morphine activate opioid receptors located in the central nervous system - the brain and spinal cord. Opioids, however, also react with receptors outside of the central nervous system, resulting in side effects which may be debilitating, including constipation, nausea, vomiting, urinary retention and severe itching. MNTX is designed to work by blocking peripheral opioid receptors whose activation causes these side effects. As MNTX does not cross the blood-brain barrier, it does not interfere with brain-centered pain relief.
Advanced medical illness
More than one-million deaths occur each year in the U.S. from AMI, including patients with cancer, AIDS, sickle-cell disease and other painful terminal illnesses. The majority of those treated with opioids for pain suffer debilitating constipation. Last year, the Company reported positive results from a phase 2 study in AMI, which showed subcutaneous MNTX induced laxation in approximately 60% of patients in a median time of one hour. In that study, MNTX restored AMI patients to normal bowel status of greater than three bowel movements per week, on average. MNTX was well tolerated, with no serious side effects reported, no opioid withdrawal, and no change in pain score. The most frequent side effects observed were mild prequels to laxation: flatulence and transient abdominal cramping.
Of the 40-million surgeries that occur in the U.S. each year, more than four-million patients are at high risk for developing ileus, a serious paralysis of the gastrointestinal tract. Ileus is a major factor in increasing hospital stay, as patients are typically not discharged until bowel and urinary functions are restored. A phase 2 study of intravenous MNTX in post-operative ileus is currently underway and will enroll 60 colectomy patients. The study is expected to be completed in the first half of 2004.
Chronic pain afflicts 25-million Americans. Approximately four-million of these patients receive opioids on a daily basis, and many experience constipation. Progenics is testing a tablet formulation of MNTX in a phase 1 study to characterize the tolerability and pharmacokinetics of oral MNTX at three dosage levels. The Company expects to initiate phase 2 studies of oral MNTX during 2004 in chronic pain patients who experience opioid-induced constipation.
Source: Progenics Pharmaceuticals, Inc.