Abstract| Volume 14, ISSUE 4, SUPPLEMENT , S62, April 2013

Efficacy and safety of subcutaneous methylnaltrexone in advanced illness patients with opioid-induced constipation: a responder analysis

      Opioid-induced constipation (OIC) is a distressing side effect of chronic opioid therapy, evidenced in up to 90% of advanced illness patients taking long-term opioids. Subcutaneous methylnaltrexone (MNTX) has been shown to be efficacious and safe in this patient population, although factors that determine optimal responsiveness have not been elucidated. The objective of this post-hoc analysis was to examine the influence of demographic and baseline characteristics on efficacy and tolerability of MNTX in advanced illness patients with OIC. Data were pooled from 2 randomized, double-blind, placebo (PBO)-controlled, Phase 3 studies (n=287) of MNTX (0.15 and 0.3 mg/kg). Subgroup analyses of the primary outcome measure, proportion of patients with a rescue-free bowel movement (RFBM) within 4 hours of first dose, were conducted for gender (female/male), age (<65/≥65 years), primary diagnosis (cancer/noncancer), and baseline morphine equivalent dose (<150/≥150 mg/d). Overall, 54.1% and 58.2% of patients treated with MNTX 0.15 and 0.3 mg/kg experienced a RFBM within 4 hours, versus 14.6% for PBO-treated patients (P<0.0001 for both doses vs. PBO). Responsiveness to MNTX was significantly greater than PBO in all subgroups (range of MNTX responses: 48.1%-73.3%, range of PBO responses: 10.2%-18.8%, P<0.0001 for nearly all comparisons). The largest differences from PBO were observed for noncancer patients taking MNTX 0.3 mg/kg (70.0% vs. 12.8%, P=0.0002) and for patients maintained on ≥150 mg/d oral morphine taking MNTX 0.3 mg/kg (73.3% vs. 16.7%, P<0.0001). Common adverse events were abdominal pain (pooled MNTX: 27.9%, PBO: 9.8%), flatulence (13.3%, 5.7%) and nausea (10.9%, 4.9%) Tolerability was generally comparable across subgroups. These findings demonstrate that in advanced illness patients with OIC, MNTX produces a rapid and robust laxation response that is consistent across gender, age, primary diagnosis, and baseline opioid use. MNTX 0.3 mg/kg may elicit particularly favorable responses in select subgroups. Development of abstract supported by Salix Pharmaceuticals, Inc.