A randomized, placebo-controlled trial of lubiprostone for opioid-induced constipation in chronic noncancer pain.
OBJECTIVE
This multicenter, phase 3 trial evaluated oral lubiprostone for constipation associated with non-methadone opioids in patients with chronic noncancer-related pain.


METHODS
Adults with opioid-induced constipation (OIC; <3 spontaneous bowel movements [SBMs] per week) were randomized 1:1 to double-blind lubiprostone 24 μg or placebo twice daily for 12 weeks. The primary end point was the overall SBM response rate. Responders had at least moderate response (≥1 SBM improvement over baseline frequency) in all treatment weeks with available observed data, as well as full response (≥3 SBMs per week) for at least 9 of the 12 treatment weeks.


RESULTS
In total, 431 patients were randomized; 212 each received lubiprostone and placebo, and 7 were not treated. Overall, the SBM response rate was significantly higher for patients treated with lubiprostone vs. placebo (27.1 vs. 18.9%, respectively; P=0.030). Overall mean change from baseline in SBM frequency was significantly greater with lubiprostone vs. placebo (3.2 vs. 2.4, respectively; P=0.001). The median time to first SBM was significantly shorter with lubiprostone vs. placebo (23.5 vs. 37.7 h, respectively; P=0.004). Compared with placebo, the patients treated with lubiprostone exhibited significant improvements in straining (P=0.004), stool consistency (P<0.001), and constipation severity (P=0.010). No significant differences were observed in quality-of-life measures or the use of rescue medication; however, the percentage of patients who used rescue medication was consistently lower in the lubiprostone group than in the placebo group at months 1 (34.9 vs. 37.7%), 2 (23.4 vs. 26.6%), and 3 (20.5 vs. 22.0%). Adverse events (AEs) >5% were diarrhea, nausea, vomiting, and abdominal pain (lubiprostone: 11.3, 9.9, 4.2, and 7.1%, respectively; placebo, 3.8, 4.7, 5.2, and 0%, respectively). None of the serious AEs (lubiprostone, 3.3%; placebo, 2.8%) were related to lubiprostone.


CONCLUSIONS
Lubiprostone significantly improved symptoms of OIC and was well tolerated in patients with chronic noncancer pain.
1] Department of Internal Medicine, Long Beach VA Medical Center, Long Beach, California, USA [2] Department of Medicine, UCI College of Medicine, Irvine, California, USA.
M Mazen
MM
Jamal
AB Clinical Trials, Las Vegas, Nevada, USA.
Atoya B
AB
Adams
SZ Schmerzzentrum Berlin GmbH, Berlin, Germany.
Jan-Peter
JP
Jansen
PRA Health Sciences, Salt Lake City, Utah, USA.
Lynn R
LR
Webster
D000328:Adult; D000527:Alprostadil / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000701:Analgesics, Opioid / Q000009:adverse effects*; D065101:Chloride Channel Agonists / Q000009:adverse effects / Q000627:therapeutic use*; D059350:Chronic Pain / Q000188:drug therapy; D003248:Constipation / Q000139:chemically induced / Q000188:drug therapy*; D003672:Defecation; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D000068238:Lubiprostone; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D013997:Time Factors
D000701:Analgesics, Opioid; D065101:Chloride Channel Agonists; D000068238:Lubiprostone; D000527:Alprostadil