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


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


METHODS
Seventy-nine US and Canadian centers.


METHODS
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.


CONCLUSIONS
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).
Department of Internal Medicine, Digestive and Liver Diseases, University of Texas Southwestern Medical School, Dallas, Texas, USA; Gastroenterology and Hepatology, Veterans Affairs North Texas Health Care System, Dallas, Texas, USA.
Byron
B
Cryer
Seymour
S
Katz
Ricardo
R
Vallejo
Anca
A
Popescu
Ryuji
R
Ueno
D000527:Alprostadil / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000701:Analgesics, Opioid / Q000009:adverse effects*; D065101:Chloride Channel Agonists / Q000627:therapeutic use*; D059350:Chronic Pain / Q000188:drug therapy*; D003248:Constipation / Q000139:chemically induced* / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D000068238:Lubiprostone; D008297:Male; D008875:Middle Aged
D000701:Analgesics, Opioid; D065101:Chloride Channel Agonists; D000068238:Lubiprostone; D000527:Alprostadil
Bowel Movement; ClC-2; Opioid; Opioid-Induced Constipation; Placebo-Controlled Trial; Prostone