Lubiprostone and Opioid-Induced Bowel Dysfunction

Phoenix—A randomized phase 3, multicenter, double-blind, placebo-controlled study of patients with opioid-induced bowel dysfunction (OBD) who took lubiprostone had a statistically significant higher spontaneous bowel movement (SBM) response rate compared with those who took placebo. The lubiprostone group also had a significantly lower median time to first SBM, and the drug was well tolerated.

Results were presented during a poster session at the AAPM meeting. The poster was titled Lubiprostone Improves OBD without Affecting Opioid Analgesia.

Patients who take opioids for an extended period typically have gastrointestinal (GI) side effects, including OBD. However, there are no FDA-approved oral treatments for OBD in noncancer, chronic pain patients.

In this study, 447 adults with OBD were randomized in a 1:1 ratio to receive 24 mcg of lubiprostone (n=221) or placebo (n=226) twice daily for 24 weeks. Lubiprostone, an oral locally acting chloride channel activator, has been shown in previous trials to counteract the adverse GI side effects associated with opioids. The drug also enhances secretion of chloride-rich intestinal fluid without altering serum electrolyte levels and counteracts the effect of morphine on slowed transit without interference with the analgesic effect, according to the authors.

The intent-to-treat population included 439 patients (220 in the placebo group and 219 in the lubiprostone group) who had a mean age of approximately 52 years. Approximately 37% of patients in each group were male, and mean days in treatment were 77.3 in the placebo group and 74.0 in the lubiprostone group.

The overall SBM response rate (the primary end point) was 26.9% in the lubiprostone group and 18.6% in the placebo group (P=.035). The authors defined overall SBM response rate as the proportion of patients with ≥3 SBMs per week for ≥9 weeks and ≥1 additional SBM over the mean baseline SBM frequency during every treatment week with observed data.

In addition, the median time to first SBM was 23.8 hours (95% confidence interval [CI], 21.2-28.5 hours) in the lubiprostone group and 38.2 hours (95% CI, 27.0-41.8 hours) in the placebo group (P=.013).

The authors assessed the durability of the analgesia during treatment using the Brief Pain Inventory (Short Form) and the mean group changes in morphine equivalent daily dose (MEDD) of opioid therapy throughout the study.

After 1, 2, or 3 months of treatment and at the end of the study, there was no significant difference in the mean pain interference, pain severity, or worst pain scores and no significant difference in the mean change from baseline in MEDD of opioid therapy between the groups. The authors noted “these results suggest lubiprostone does not interfere with the analgesic effect of opioids.”

The most common treatment-related adverse events were diarrhea, nausea, abdominal pain, flatulence, vomiting, and abdominal distension. The rates were higher in the lubiprostone group for all of the adverse events with the exception of abdominal distension, which was 0.9% of patients in each group.

Diarrhea was the most common adverse event, and it occurred in <10% of patients in each group. Further, 91.7% of the 21 patients who took lubiprostone and had diarrhea reported having diarrhea of mild-to-moderate severity. None of the lubiprostone-related adverse events were considered serious, according to the authors.

This study was sponsored by Takeda Pharmaceutical Company Limited and Sucampo Pharmaceuticals, Inc.