In a 3-month extension study of the methylnaltrexone phase III MNTX-302 trial, the investigational agent continued to produce laxation in patients with advanced illness being treated with opioids for pain
ST. GALLEN, Switzerland-In a 3-month extension study of the methylnaltrexone phase III MNTX-302 trial, the investigational agent continued to produce laxation in patients with advanced illness being treated with opioids for pain. Neal E. Slatkin, MD, DABPM, of City of Hope National Medical Center, presented the results at the 2007 symposium of the Multinational Association of Supportive Care in Cancer (MASCC) (abstract P-234).
MNTX-302 included 133 patients with advanced illness requiring opioid painkillers who had opioid-induced constipation (OIC) and were receiving stable doses of laxatives. OIC was defined as fewer than three bowel movements per week or no bowel movements for at least 48 hours. Patients received either placebo or methylnaltrexone 0.15 mg/kg subcutaneously every other day for 2 weeks.
The results showed significant improvements in laxation with methylnaltrexone after a single dose and over the 2 weeks of treatment, with no evidence of opioid withdrawal or clinically meaningful changes in pain scores.
A total of 82 patients who completed the placebo-controlled MNTX-302 study went on to participate in the open-label extension study. For the 42 patients from MNTX-302 who continued methylnaltrexone, the mean laxation response rates (laxation within 4 hours) were 45.5% during the first month, 57.7% in the second month, and 57.3% in the third month. For the 40 placebo patients who crossed over to methylnaltrexone for the extension study, laxation response rates were 48.3%, 47.6%, and 52.1%, respectively, in the first, second, and third months.
Consistent with previous studies, the authors said, subcutaneous methylnaltrexone was generally well tolerated in the extension study. The most common adverse event was abdominal pain, typically mild to moderate in severity.
Methylnaltrexone is a peripherally acting muopioid receptor antagonist designed to treat OIC without interfering with pain relief (see box). Currently, there is no approved agent that specifically targets the underlying cause of OIC to relieve constipation in this patient population.
In March 2007, Progenics, which is developing the agent with Wyeth Pharmaceuticals, submitted a New Drug Application for subcutaneous methylnaltrexone. FDA has set a date of January 30, 2008, to complete its review.
Progenics also announced positive preliminary results of a phase I clinical study of a new oral formulation of methylnaltrexone, conducted by Wyeth. The trial is a double-blind, randomized single-dose crossover pharmacokinetic/pharmacodynamic study in subjects receiving methadone, an opioid used to treat addiction.According to the companies, a substantial majority of patients experienced a bowel movement after receiving the higher of two doses of oral methylnaltrexone. The formulation was generally well tolerated. Based on these findings, the companies plan to conduct further clinical testing of new oral formulations.