Digestive Diseases and Sciences

, Volume 55, Issue 4, pp 1090–1097 | Cite as

Efficacy and Safety of Lubiprostone in Patients with Chronic Constipation

  • Charles F. BarishEmail author
  • Douglas Drossman
  • John F. Johanson
  • Ryuji Ueno
Original Article



The aim of this study is to assess the efficacy and safety of lubiprostone in adults with chronic constipation.


This multicenter, parallel-group trial enrolled 237 patients with chronic constipation and randomized them to 4 weeks of double-blind treatment with oral lubiprostone 24 mcg or placebo twice daily. The primary efficacy endpoint was the number of spontaneous bowel movements (SBMs) after 1 week of treatment. Secondary evaluations included SBMs at weeks 2, 3, and 4; percentage of patients with a SBM within 24 h of first study dose; stool consistency; degree of straining; constipation severity; abdominal bloating and discomfort; global treatment effectiveness; and safety assessments.


Lubiprostone-treated patients experienced greater mean numbers of SBMs at week 1 compared with placebo (5.89 versus 3.99, P = 0.0001), with significantly greater percentages having SBMs within 24 h of the first dose (61.3% versus 31.4%, P < 0.0001). At each assessment, SBM frequency and percentages of full responders (≥4 SBM per week) were significantly greater among lubiprostone-treated patients compared with placebo (P ≤ 0.0171). Lubiprostone-treated patients reported significant improvements in stool consistency, straining, and constipation severity at all weeks, and in abdominal bloating at week 1. Patient assessments of treatment effectiveness were significantly greater with lubiprostone compared with placebo at all weeks (P < 0.0004). Gastrointestinal-related disorders were the most common adverse events in both treatment groups.


In patients with chronic constipation, lubiprostone produced a bowel movement in the majority of individuals within 24 h of initial dosing, with sustained improvement in frequency as well as other constipation symptoms over 4 weeks of treatment.


Lubiprostone Chronic constipation Stool frequency Bowel movement 



Writing and editorial support for this manuscript was provided by Brian G. Shearer, PhD, Takeda Pharmaceuticals North American, Deerfield, IL and Susan Ruffalo, PharmD, MedWrite, Inc., Newport Coast, California.


  1. 1.
    Brandt LJ, Prather CM, Quigley EMM, et al. Systematic review on the management of chronic constipation in north america. Am J Gastroenterol. 2005;100:S5–S22.CrossRefPubMedGoogle Scholar
  2. 2.
    Stewart W, Liberman J, Sandler RS, et al. Epidemiology of constipation (epoc) study in the United States: relation of clinical subtypes to sociodemographic features. Am J Gastroenterol. 1999;94:3530–3540.CrossRefPubMedGoogle Scholar
  3. 3.
    Higgins PD, Johanson JF. Epidemiology of constipation in North America: a systematic review. Am J Gastroenterol. 2004;99:750–759.CrossRefPubMedGoogle Scholar
  4. 4.
    Talley NJ, Lasch KL, Baum CL. A gap in our understanding: chronic constipation and its comorbid conditions. Clin Gastroenterol Hepatol. 2009;7(1):9–19.CrossRefPubMedGoogle Scholar
  5. 5.
    Johanson JF. Geographic distribution of constipation in the United States. Am J Gastroenterol. 1998;93:188–191.CrossRefPubMedGoogle Scholar
  6. 6.
    Johanson JF, Kralstein J. Chronic constipation: a survey of the patient perspective. Aliment Pharmacol Ther. 2007;25:599–608.PubMedGoogle Scholar
  7. 7.
    Johanson JF, Gargano MA, Holland PC, et al. Phase III study of lubiprostone, a chloride channel-2 (clc-2) activator for the treatment of constipation: safety and primary efficacy. Am J Gastroenterol. 2005;100(Suppl 9):S328–S329.Google Scholar
  8. 8.
    Johanson JF, Morton D, Geenen J, Ueno R. Multicenter, four-week, double-blind, randomized, placebo-controlled trial of lubiprostone, a locally-acting type-2 chloride channel activator in patients with chronic constipation. Am J Gastroenterol. 2008;103:170–177.CrossRefPubMedGoogle Scholar
  9. 9.
    Johanson JF, Ueno R. Lubiprostone, a locally acting chloride channel activator, in adult patients with chronic constipation: a double-blind, placebo-controlled, dose-ranging study to evaluate efficacy and safety. Aliment Pharmacol Ther. 2007;25:1351–1361.PubMedCrossRefGoogle Scholar
  10. 10.
    Drost J, Harris LA. Diagnosis and management of chronic constipation. JAAPA. 2006;19:24–29.PubMedGoogle Scholar
  11. 11.
    Camilleri M, Bharaucha AE, Ueno R, et al. Effect of a selective chloride channel activator, lubiprostone, on gastrointestinal transit, gastric sensory, and motor functions in healthy volunteers. Am J Physiol Gastrointest Liver Physiol. 2006;290:G942–G947.CrossRefPubMedGoogle Scholar
  12. 12.
    Cuppoletti J, Malinowska DH, Tewari KP, et al. Spi-0211 activates t84 cell chloride transport and recombinant human clc-2 chloride currents. Am J Physiol Cell Physiol. 2004;287:C1173–C1183.CrossRefPubMedGoogle Scholar
  13. 13.
    Ueno R, Osama H, Habe T, et al. Oral spi-0211 increases intestinal fluid secretion and chloride concentration without altering serum electrolyte levels (abstract). Gastroenterology. 2004;126:298.Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Charles F. Barish
    • 1
    Email author
  • Douglas Drossman
    • 2
  • John F. Johanson
    • 3
  • Ryuji Ueno
    • 4
  1. 1.Wake GastroenterologyWake Research AssociatesRaleighUSA
  2. 2.University of North Carolina Center for Functional GI and Mobility DisordersUniversity of North Carolina at Chapel HillChapel HillUSA
  3. 3.University of Illinois College of MedicineRockfordUSA
  4. 4.Sucampo Pharma Americas Inc.BethesdaUSA

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