LAS VEGAS, NV—Oral methylnaltrexone is generally safe and well tolerated across 12 weeks of therapy in patients with chronic, non-cancer pain and a history of opioid-induced constipation, a study presented at PAINWeek 2012 has found.
Methylnaltrexone is a peripherally acting, selective mu-opioid receptor antagonist, approved as a subcutaneous injection for the treatment of opioid-induced constipation in patients with advanced illness when response to laxatives is inadequate. Opioid-induced constipation is an adverse effect and limiting factor in obtaining adequate analgesia.
Neal Slatkin, MD, from Hospice of the Valley and El Camino Hospital, San Jose, CA, and colleagues conducted a Phase 3, multicenter, double-blind, placebo-controlled, parallel-group study evaluating the safety, efficacy, and tolerability of oral methylnaltrexone, including potential effects of methylnaltrexone on centrally mediated opioid activity. A total of 804 patients received placebo or oral methylnaltrexone (150 mg, 300 mg, or 450 mg), assigned 1:1:1:1, for 12 weeks (4 weeks daily dosing, followed by 8 weeks PRN dosing). Patients needed to be taking ≥50 mg oral morphine equivalents for ≥14 days to take part in the study.
The primary endpoint was average percentage of doses per patient resulting in a rescue-free bowel movement (RFBM) within 4 hours of all doses during the once-daily dosing period. The following safety parameters were evaluated: treatment-emergent adverse events, changes from baseline in total Objective Opioid Withdrawal Scale scores, total Subjective Opioid Withdrawal Scale score, and changes from baseline in pain intensity scores, assessed on an 11-point numeric rating scale.
The incidence of adverse events was similar between the oral methylnaltrexone groups and placebo; the most frequent adverse events (≥5%; the majority of which were mild or moderate) were: abdominal pain, nausea, and diarrhea. Also, the methylnaltrexone groups experienced little or no change from baseline in the Objective Opioid Withdrawal Scale score; this was not a statistically significant difference from placebo. The Subjective Opioid Withdrawal Scale scores were found to be similar.
RFBMs within 4 hours of dosing and RFBMs per week were statistically significant for the 300 mg and 45 0mg groups compared with placebo (P<0.01). Throughout the study, there were minimal changes from baseline in pain intensity scores regardless of the treatment group.
The lack of effects on opioid withdrawal scores and analgesia are consistent with the peripheral mechanism of action of oral methylnaltrexone. Oral methylnaltrexone appeared safe and was generally well tolerated by patients with chronic non-cancer pain across the 12 weeks of therapy, concluded Dr. Slatkin and colleagues.