A randomized study of lubiprostone for opioid-induced constipation in patients with chronic noncancer pain.

Abstract

OBJECTIVE:

To evaluate the efficacy and safety of oral lubiprostone for relieving symptoms of opioid-induced constipation (OIC) in patients with chronic noncancer pain.

DESIGN:

Prospective, randomized, double-blind, placebo-controlled trial.

SETTING:

Seventy-nine US and Canadian centers.

SUBJECTS:

Patients aged ≥ 18 years with OIC, defined as <3 spontaneous bowel movements (SBMs) per week.

METHODS:

Patients received lubiprostone 24 mcg or placebo twice daily for 12 weeks. The primary endpoint was change from baseline in SBM frequency at week 8.

RESULTS:

Among randomized patients (N=418; lubiprostone, N=210; placebo, N=208), most completed the study (lubiprostone, 67.1%; placebo, 69.7%). The safety and efficacy (intent-to-treat) populations included 414 (lubiprostone, N=208; placebo, N=206) and 413 (lubiprostone, N=209; placebo, N=204) patients, respectively. The mean (standard deviation) age was 50.4 (10.9) years; most patients were female (64.4%) and white (77.7%). Changes from baseline in SBM frequency rates were significantly higher at week 8 (P=0.005) and overall (P=0.004) in patients treated with lubiprostone compared with placebo. Pairwise comparisons showed significantly greater overall improvement for abdominal discomfort (P=0.047), straining (P<0.001), constipation severity (P=0.007), and stool consistency (P<0.001) with lubiprostone compared with placebo. Moreover, patients rated the effectiveness of lubiprostone as significantly (P<0.05) better than placebo for 11 of 12 weeks. The most common treatment-related adverse events (AEs) with lubiprostone and placebo were nausea (16.8% vs 5.8%, respectively), diarrhea (9.6% vs 2.9%), and abdominal distention (8.2% vs 2.4%). No lubiprostone-related serious AEs occurred.

CONCLUSION:

Lubiprostone effectively relieved OIC and associated signs and symptoms and was well tolerated in patients with chronic noncancer pain (http://clinicaltrials.gov/ct2/show/NCT00595946).

• Authors: Byron Cryer, Seymour Katz, Ricardo Vallejo, Anca Popescu, Ryuji Ueno
• Journal: Pain medicine (Malden, Mass.) (Pain Med) Vol. 15 Issue 11 Pg. 1825-34 (Nov 2014) ISSN: 1526-4637 [Electronic] England
• PMID: 24716835 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 The Authors. Pain Medicine published by Wiley Periodicals, Inc. on behalf of American Academy of Pain Medicine.

Chemical References

• Analgesics, Opioid
• Chloride Channel Agonists
• Lubiprostone
• Alprostadil

Topics

• Alprostadil (analogs & derivatives, therapeutic use)
• Analgesics, Opioid (adverse effects)
• Chloride Channel Agonists (therapeutic use)
• Chronic Pain (drug therapy)
• Constipation (chemically induced, drug therapy)
• Double-Blind Method
• Female
• Humans
• Lubiprostone
• Male
• Middle Aged