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

Byron Cryer, Seymour Katz, Ricardo Vallejo, Anca Popescu, Ryuji Ueno

Research output: Contribution to journalArticle

60 Citations (Scopus)

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 24mcg 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).

Original languageEnglish (US)
Pages (from-to)1825-1834
Number of pages10
JournalPain Medicine (United States)
Volume15
Issue number11
DOIs
StatePublished - Nov 1 2014

Fingerprint

Constipation
Chronic Pain
Opioid Analgesics
Placebos
Lubiprostone
Safety
Nausea
Signs and Symptoms
Diarrhea

Keywords

  • Bowel Movement
  • ClC-2
  • Opioid
  • Opioid-Induced Constipation
  • Placebo-Controlled Trial
  • Prostone

ASJC Scopus subject areas

  • Clinical Neurology
  • Anesthesiology and Pain Medicine

Cite this

A randomized study of lubiprostone for opioid-induced constipation in patients with chronic noncancer pain. / Cryer, Byron; Katz, Seymour; Vallejo, Ricardo; Popescu, Anca; Ueno, Ryuji.

In: Pain Medicine (United States), Vol. 15, No. 11, 01.11.2014, p. 1825-1834.

Research output: Contribution to journalArticle

Cryer, Byron ; Katz, Seymour ; Vallejo, Ricardo ; Popescu, Anca ; Ueno, Ryuji. / A randomized study of lubiprostone for opioid-induced constipation in patients with chronic noncancer pain. In: Pain Medicine (United States). 2014 ; Vol. 15, No. 11. pp. 1825-1834.
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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 24mcg 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).",
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AU - Ueno, Ryuji

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N2 - 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 24mcg 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).

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