A randomized, placebo-controlled trial of lubiprostone for opioid-induced constipation in chronic noncancer pain.

Abstract

OBJECTIVES:

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.

• Authors: M Mazen Jamal, Atoya B Adams, Jan-Peter Jansen, Lynn R Webster
• Journal: The American journal of gastroenterology (Am J Gastroenterol) Vol. 110 Issue 5 Pg. 725-32 (May 2015) ISSN: 1572-0241 [Electronic] United States
• PMID: 25916220 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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