(451) Efficacy and safety of methylnaltrexone for opioid-induced constipation in patients with chronic noncancer pain: a placebo crossover analysis

Abstract

In patients with chronic noncancer pain, efficacy of subcutaneous methylnaltrexone (MNTX) for treatment of opioid-induced constipation (OIC) was examined in a 4-week, randomized, controlled trial (RCT), followed by an 8-week open-label extension. To examine the reproducibility of findings from the RCT, data from placebo (PBO)-treated patients who crossed over to open-label MNTX were analyzed. Adults with <3 rescue-free bowel movements (RFBMs; bowel movement[s] occurring without any laxative in the prior 24 hours) per week, and taking ≥50 mg oral morphine equivalent/day, were randomized to receive MNTX 12 mg or PBO for 4 weeks followed by open-label MNTX (prn) for 8 weeks. Patients were evaluated during both phases according to: 1) RFBMs within 4 hours of the first dose, 2) percentage of injections resulting in any RFBM within 4 hours, and 3) percentage of patients experiencing ≥3 RFBMs/week and 1 RFBM increase over baseline. Patients (n=134, median morphine equivalent dose: 150 mg/day) experienced approximately 1 RFBM/week at baseline. Under PBO conditions, 10% of patients experienced a RFBM within 4 hours of first dose, and 9% of all PBO injections resulted in any RFBM within 4 hours. By contrast, during open-label MNTX, these percentages were 46% and 35%. When expressed according to percentage of patients experiencing ≥3 RFBMs/week and 1 RFBM increase over baseline, weekly values ranged from 35-41% during PBO treatment; at Week 5 during open-label MNTX, this percentage increased to >70% and remained relatively stable throughout the extension phase. Most common adverse events during MNTX treatment were abdominal pain (9.7% vs. 1.5% for PBO) and nausea (5.2% vs. 6.7%). Findings during PBO treatment further establish the nature of OIC and support that little or no gastrointestinal tolerance develops over time. Findings under open-label conditions establish the reproducibility and durability of MNTX for treatment of OIC. Supported by Salix Pharmaceuticals, Inc. In patients with chronic noncancer pain, efficacy of subcutaneous methylnaltrexone (MNTX) for treatment of opioid-induced constipation (OIC) was examined in a 4-week, randomized, controlled trial (RCT), followed by an 8-week open-label extension. To examine the reproducibility of findings from the RCT, data from placebo (PBO)-treated patients who crossed over to open-label MNTX were analyzed. Adults with <3 rescue-free bowel movements (RFBMs; bowel movement[s] occurring without any laxative in the prior 24 hours) per week, and taking ≥50 mg oral morphine equivalent/day, were randomized to receive MNTX 12 mg or PBO for 4 weeks followed by open-label MNTX (prn) for 8 weeks. Patients were evaluated during both phases according to: 1) RFBMs within 4 hours of the first dose, 2) percentage of injections resulting in any RFBM within 4 hours, and 3) percentage of patients experiencing ≥3 RFBMs/week and 1 RFBM increase over baseline. Patients (n=134, median morphine equivalent dose: 150 mg/day) experienced approximately 1 RFBM/week at baseline. Under PBO conditions, 10% of patients experienced a RFBM within 4 hours of first dose, and 9% of all PBO injections resulted in any RFBM within 4 hours. By contrast, during open-label MNTX, these percentages were 46% and 35%. When expressed according to percentage of patients experiencing ≥3 RFBMs/week and 1 RFBM increase over baseline, weekly values ranged from 35-41% during PBO treatment; at Week 5 during open-label MNTX, this percentage increased to >70% and remained relatively stable throughout the extension phase. Most common adverse events during MNTX treatment were abdominal pain (9.7% vs. 1.5% for PBO) and nausea (5.2% vs. 6.7%). Findings during PBO treatment further establish the nature of OIC and support that little or no gastrointestinal tolerance develops over time. Findings under open-label conditions establish the reproducibility and durability of MNTX for treatment of OIC. Supported by Salix Pharmaceuticals, Inc.