Post-hoc analysis of phase III clinical study results finds lubiprostone doesn't interfere with the analgesic effect of opioids in chronic non-cancer pain patients with opioid-induced constipation.
While the efficacy of Takeda Pharmaceutical’s Amitiza (lubiprostone) in opioid-induced constipation (OIC) among chronic non-cancer pain patients has already been demonstrated in clinical trials that factored into its April 2013 indication approval by the US Food and Drug Administration, some concerns remain about the drug’s potential to interfere with the analgesic effect of opioids in those patients.
To provide an evidence-based answer to that question, researchers from Tufts University School of Dental Medicine and Harvard Medical School in Boston, MA, and Takeda subsidiary Sucampo in Bethesda, MD, and Zug, Switzerland, presented their “Lubiprostone for Treatment of Opioid-Induced Constipation Does Not Interfere with Opioid Analgesic Effects in Patients with Non-Cancer Pain” poster at PAINWeek 2013.
For their post-hoc analysis, the researchers reviewed data pooled from three double-blind, phase III clinical studies involving adults with chronic non-cancer pain and OIC who were on a stable opioid dose and had less than three spontaneous bowel movements per week. Within those trials, 1,300 patients were randomly assigned to receive either 24 mcg of the oral chloride channel activator lubiprostone twice a day (n=659) or twice-daily placebo (n=641) for 12 weeks.
The investigators assessed possible analgesic interference with patient-reported Brief Pain Inventory-Short Form (BPI-SF) scores on pain severity and pain interference with daily activities, as well as mean changes from baseline measures of morphine-equivalent daily dose (MEDD) converted from opioid doses. According to the study authors, baseline BPI-SF scores and MEDD were comparable in the lubiprostone and placebo groups.
Examining mean changes from baseline in BPI-SF scores between the two groups, the poster authors found that across the three clinical studies, the scores “were similar for patients treated with lubiprostone and placebo at nearly all time points” of one, two, and three months, but “changes in pain interference were significantly greater with placebo at month two in one study, while changes in pain severity were significantly greater with lubiprostone at month 3 in another study.”
While tracking mean changes from baseline in MEDD, the researchers found that in the pooled lubiprostone and placebo patients, the MEDD changes “ranged from -14.1 to 0.0 in the lubiprostone group and -2.3 and -0.1 in the placebo group” at month three, while in each of the three individual studies, the changes “ranged from -42.8 to 2.3 in the lubiprostone group and -6.2 to 0.6 in the placebo group.”
Based on their analysis of the pooled and individual study findings, the poster authors concluded that twice-daily “oral lubiprostone 24 mcg for the treatment of OIC does not interfere with the analgesic effect of opioids in adult patients with chronic non-cancer pain and OIC.”
Inspecting potential safety issues associated with lubiprostone treatment, the investigators found that “similar percentages of patients reported one or more treatment-emergency adverse events.” However, compared to patients in the placebo group, significantly more patients in the lubiprostone group reported one or more treatment-related adverse events — the most frequent of which were nausea (77 lubiprostone patients versus 30 placebo patients), diarrhea (51 lubiprostone versus 12 placebo), and abdominal pain (28 versus 8). Still, the poster authors noted that the OIC drug “did not increase the occurrence of abnormalities in liver function tests or other laboratory values,” and so they concluded that it “was not associated with any unexpected safety issues.”