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Multicenter, 4-Week, Double-Blind, Randomized, Placebo-Controlled Trial of Lubiprostone, a Locally-Acting Type-2 Chloride Channel Activator, in Patients With Chronic Constipation

Johanson, John F., M.D.1; Morton, Dan, M.D.2; Geenen, Joseph, M.D.3; Ueno, Ryuji, M.D., Ph.D.4

American Journal of Gastroenterology: January 2008 - Volume 103 - Issue 1 - p 170–177
ORIGINAL CONTRIBUTIONS: FUNCTIONAL GI DISORDERS
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OBJECTIVES To assess the efficacy and safety of lubiprostone in adults with chronic constipation.

METHODS This multicenter, parallel-group, double-blind controlled trial enrolled 242 patients with constipation and randomized them to receive oral lubiprostone 24 mcg or placebo twice daily for 4 wk. The primary efficacy end point was the number of spontaneous bowel movements (SBMs; those occurring without use of constipation relieving medications) after 1 wk of double-blind treatment. Other evaluations included SBMs at weeks 2, 3, and 4; bowel movement (BM) characteristics (i.e., consistency and straining); constipation severity; abdominal bloating/discomfort; global treatment effectiveness ratings; and safety assessments.

RESULTS The 120 lubiprostone-treated patients reported a greater mean number of SBMs at week 1 compared with the 122 placebo-treated patients (5.69 vs 3.46, P= 0.0001), with a greater frequency of SBMs also reported at weeks 2, 3, and 4 (P≤ 0.002). Within 24 h of the first dose of study drug, 56.7% of those given lubiprostone reported a SBM compared with 36.9% of those given placebo (P= 0.0024); within 48 h, 80% and 60.7% of these patients reported a SBM (P= 0.0013), respectively. Stool consistency, straining, and constipation severity, as well as patient-reported assessments of treatment effectiveness, were significantly improved with lubiprostone compared with placebo at all weeks (P≤ 0.0003). The two most common treatment-related adverse events were nausea (31.7%) and headache (11.7%).

CONCLUSIONS In patients with chronic constipation, treatment with lubiprostone produces a BM in the majority of individuals within 24–48 h of initial dosing and improves the frequency as well as other characteristics associated with BMs with short-term (i.e., 4 wk) treatment. The most commonly reported adverse event was mild to moderate nausea, which resulted in treatment discontinuation in 5% of treated patients.

1University of Illinois College of Medicine, Rockford, Illinois; 2GANT Research, Ft. Worth, Texas; 3Gastroenterology Consultants, Ltd., Milwaukee, Wisconsin; and 4Sucampo Pharmaceuticals, Inc., Bethesda, Maryland

Reprint requests and correspondence: John F. Johanson, M.D., 593 Spring Creek Road, Rockford, Illinois 61114.

Received January 10, 2007; accepted July 18, 2007.

CONFLICT OF INTERESTGuarantor of the article: John Johanson, M.D., M.Sc.

Specific author contributions: The contract research organization (PRA International, Eatontown, NJ) collected all the data with central quality oversight. Sucampo Pharmaceuticals, Inc. analyzed and interpreted the study data and oversaw the writing of the study report. John Johanson, M.D., M.Sc. and coinvestigators were responsible for analysis and interpretation of the data and are the guarantors of the manuscript and its contents. Each author was involved in the development of the draft document and review of subsequent revisions. Dr. Ryuji Ueno provided scientific oversight into the study design and analysis. As an author, Dr. Ueno developed the manuscript draft and subsequent revisions. Editorial support in the preparation of the manuscript draft and subsequent revisions was provided by Takeda Pharmaceuticals North America, Inc. Editorial assistance was provided by Susan Ruffalo, PharmD of MedWrite, Inc. Newport Coast, California.

Financial support: This study was funded, designed, conducted, and supervised by the sponsor, Sucampo Pharmaceuticals, Inc., Bethesda, MD. It was performed in compliance with good clinical practice, including the archiving of essential documents.

Potential competing interests: Dr. Dan Morton reports no conflicts of interest. Dr. Joseph Geenen reports no conflicts of interest. Dr. Ryuji Ueno is an exmployee of Sucampo Pharmaceuticals, Inc. and a shareholder in this company. Dr. Johanson is on the speaker bureau of and is a consultant for Sucampo Pharmaceuticals and Takeda Pharmaceuticals North America, Inc. He has stock options in Sucampo Pharmaceuticals, Inc.

© The American College of Gastroenterology 2008. All Rights Reserved.
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