Lubiprostone to Treat Non-Cancer Pain and Opioid-Induced Constipation

Orlando—Patients with chronic non-cancer pain and opioid-induced constipation (OIC) who took lubiprostone twice daily did not have an affect on opioid-induced analgesia and had an improvement in signs and symptoms of OIC, according to a 36-week, open-label extension of a phase 3 trial.

At months 6, 7, and 8, patients had a statistically significant increase in opioid usage, but the authors noted the change was not clinically significant.

Results were presented at the AAPM meeting. The poster was titled Lubiprostone Does Not Affect Analgesia in OIC Patients.

In April, lubiprostone became the only FDA-approved oral medication to treat OIC in patients with chronic non-cancer pain, although its effectiveness in patients taking methadone and other diphenylheptane opioids has not been established. Lubiprostone is also approved to treat chronic idiopathic constipation and irritable bowel syndrome with constipation in adult women.

Patients enrolled in this study had completed 1 of 2 previous 12-week OIC treatment trials, in which they received placebo or 24 mcg of lubiprostone twice daily. The authors defined OIC as <3 spontaneous bowel movements (SBMs) per week during the screening period and at least 1 of the following symptoms during at least 25% of the SBMs: hard to very hard stools, sensation of incomplete evacuation, or moderate to very severe straining. They considered an SBM as any bowel movement with the exception of those occurring within 24 hours of patients receiving rescue medication.

Exclusion criteria included newly diagnosed impaired renal function or unexplained and/or clinically significant weight loss, which the authors defined as more than 5% in the 90 days before screening.

Of the 439 patients in the study, 59.9% were female and 83.8% were white. The mean age was 49.8 years, and the mean SBMs per week was 1.4. Patients recorded bowel movements daily and underwent pain assessments monthly using the Brief Pain Inventory short form (BPI-SF). The BPI-SF scores were highest at month 5 for pain interference, pain severity, and worst pain.

For the first 5 months of treatment, the mean opioid use of patients was similar to at baseline. However, compared with their use at baseline, patients had significant increases in opioid use at month 6 (2.6%; P=.013), month 7 (3.5%; P=.031), and month 8 (3.6%; P=.035).

From months 1 to 9, the reliance on rescue medications decreased from 33.0% to 18.6% of patients. Patients received the rescue medication (bisacodyl suppository or saline enema) after not having a bowel movement for 3 days and after consulting with an investigator.

The authors found that 24.6% of patients had a treatment-related adverse event, with the most common being nausea (5.0%) and diarrhea (4.6%). There were no drug-related serious adverse events during the study, while 5 patients discontinued the study because of nausea and diarrhea.

Throughout the study, the frequency of SBMs increased each month (P<.001). Compared with at baseline, patients had a significant improvement each month in straining, stool consistency, constipation severity, abdominal bloating, abdominal discomfort, and bowel habit (P<.001 in each instance).

This study was sponsored by Takeda Pharmaceuticals, Inc. and Sucampo Pharma Americas, LLC.