Progenics Pharmaceuticals, Inc. (Nasdaq:PGNX) announced the initiation of an international 700-patient, phase 3 trial of oral methylnaltrexone in patients with chronic, non-cancer pain who are experiencing constipation as a result of their opioid-pain management regimens. The goal of the study is to evaluate the safety and efficacy of oral methylnaltrexone to treat opioid-induced constipation (OIC) in this patient setting.
"An oral formulation of methylnaltrexone, if successfully tested and approved, would be an important addition to the RELISTOR® franchise," said Paul J. Maddon, M.D., Ph.D., Progenics' Founder, Chief Executive and Chief Science Officer. "We have been pleased in the testing of this formulation to date. We look forward to confirming these results in this phase 3 clinical trial."
The phase 3 study will evaluate the oral formulation of methylnaltrexone that was tested in a formulation optimization clinical trial and reported on by Progenics on March 12, 2010. That trial examined the safety and activity of different dose levels of a tablet formulation of oral methylnaltrexone in subjects with chronic, non-cancer pain with a history of OIC receiving various opioid treatment regimens.
Phase 3 Study Design for Oral Methylnaltrexone
The phase 3 study is an international, randomized, double-blind, placebo-controlled trial and plans to enroll approximately 700 chronic, non-cancer pain patients experiencing OIC. Patients will be randomized to receive either placebo or one of three doses of oral methylnaltrexone. Following a two-week screening period, study participants will, on a blinded basis, receive oral methylnaltrexone or placebo once daily for four weeks, then continue, on a blinded basis, to receive oral methylnaltrexone or placebo on an as needed basis for eight additional weeks. The primary efficacy endpoint of the study is the proportion of subjects with a rescue-free bowel movement (RFBM) within four hours of receiving oral methylnaltrexone during the four-week blinded period.
The methylnaltrexone tablets to be used in this phase 3 trial were produced and supplied by Progenics' former collaboration partner Wyeth* under the provisions of the termination of the collaboration between the two companies.
About Chronic Pain and OIC
Approximately 10 million patients a year in the U.S. are prescribed opioids for 30 days or more to manage their pain. In a multinational Internet-based survey of 322 patients with chronic pain taking daily oral opioids and laxatives, 81% of patients reported experiencing constipation while using their current opioid regimen, and 45% reported less than 3 bowel movements per week. Opioids are considered to be effective analgesics for the management of moderate-to-severe chronic pain, and one of the most common side effects of opioids is constipation.
About Methylnaltrexone
Methylnaltrexone selectively displaces opioids from the mu-opioid receptors outside the CNS, including those located in the gastrointestinal tract, thereby decreasing their constipating effects. Because of its chemical structure, methylnaltrexone has not been shown to affect the opioid-mediated analgesic effects on the CNS.
About RELISTOR
RELISTOR (methylnaltrexone bromide or methylnaltrexone) subcutaneous injection is approved in the United States for the treatment of OIC in patients with advanced illness who are receiving palliative care, when response to laxative therapy has not been sufficient. The use of RELISTOR beyond four months has not been studied. The drug is also approved for use in over 50 countries worldwide, including the European Union, Canada, Australia and Brazil. Applications in additional countries are pending.
Important Safety Information for RELISTOR
- RELISTOR is contraindicated in patients with known or suspected mechanical gastrointestinal obstruction
- If severe or persistent diarrhea occurs during treatment, advise patients to discontinue therapy with RELISTOR and consult their physician
- Rare cases of gastrointestinal (GI) perforation have been reported in advanced illness patients. Use of RELISTOR with caution in patients with known or suspected lesions of the GI tract
- Use of RELISTOR has not been studied in patients with peritoneal catheters
- The most common adverse reactions reported with RELISTOR compared with placebo in clinical trials were abdominal pain (28.5% vs. 9.8%), flatulence (13.3% vs. 5.7%), nausea (11.5% vs. 4.9%), dizziness (7.3% vs. 2.4%), diarrhea (5.5% vs. 2.4%), and hyperhidrosis (6.7% vs. 6.5%)
- Safety and efficacy of RELISTOR have not been established in pediatric patients
RELISTOR is indicated for the treatment of opioid-induced constipation (OIC) in patients with advanced illness who are receiving palliative care, when response to laxative therapy has not been sufficient. Use of RELISTOR beyond 4 months has not been studied.
Source:
Progenics Pharmaceuticals, Inc.