Phase III study results show patients with chronic non-cancer pain and opioid-induced constipation (OIC) experienced improvements in spontaneous bowel movement frequency and other symptoms of OIC.
Constipation is a common and often severe side effect of the opioid therapy patients take for chronic non-cancer pain. Opioid-induced constipation (OIC) can compromise a patient’s quality of life and reduce the effectiveness of pain management. Although OTC stool softeners and bulk laxatives are commonly prescribed as therapy for the prevention and management of OIC, their usefulness may be limited by poor efficacy and adverse effects. There is also little data to support the efficacy and safety of these OTC options. The CIC-2 chloride channel activator lubiprostone, which is approved for the treatment of OIC in adults, may offer a more effective option for these patients.
According to results from a phase III, multicenter, randomized, placebo-controlled study presented presented at the American Pain Society’s 32nd Annual Scientific Meeting, held May 8-13, 2013, in New Orleans, LA, patients with OIC who were treated with twice-daily oral lubiprostone 24 mcg reported significant improvements in spontaneous bowel movement (SBM) and other symptoms associated with OIC compared to patients who received placebo.
For the study, 438 patients with chronic non-cancer pain who had been on a stable dose of opioids for at least 30 days prior to study enrollment (patients continued receiving opioid treatment during this study), and who reported having fewer than three SBMs per week during a three-week screening period (SBM defined here as any bowel movement that did not occur within 24 hours after use of rescue medication), were randomized to receive either placebo (n=217) or twice-daily lubiprostone 24 mcg (n=221) for 12 weeks.
The primary efficacy endpoint was change from baseline in SBM frequency at week 8 in patients who did reduce their dose of study medication prior to week 8. Secondary endpoints were overall change from baseline in SBM frequency, percentage of patients with a first SBM within 24 and 48 hours of receiving the first dose of study medication, and change from baseline in other symptoms of OIC, including straining, stool consistency, and severity of constipation.
The researchers also monitored adverse events in both study groups and used the Brief Pain Inventory short form (BPI-SF) to measure effectiveness of ongoing pain therapy.
The authors reported that the mean increase in SBM frequency “was significantly greater with lubiprostone vs. placebo at week 8 (P=.0188) and overall (P=.0047).” They also reported that higher percentages of patients treated with lubiprostone vs. placebo reported their first SBM within 24 hours (40.3% vs. 30.0%) and 48 hours (62.4% vs. 53.5%), but only the 24-hour scores reached statistical significance. They also found significant improvements in constipation severity, stool consistency, abdominal discomfort, and straining in patients treated with lubiprostone compared to patients who received placebo.
The most commonly reported adverse events with lubiprostone and placebo were nausea (16% vs. 6%), diarrhea (10% vs. 3%), and abdominal distension (8% vs. 2%).
Mean changes in morphine equivalent daily dose and in BPI-SF scores were similar in both study groups at all times, “except for significantly less pain interference at month 2 with lubiprostone.”
Based on these results, the study authors concluded that lubiprostone “was well-tolerated and improved SBM frequency and associated symptoms of OIC without altering analgesic response in patients treated chronically with opioids for non-cancer pain.”