Efficacy and Safety of Lubiprostone in Patients With Irritable Bowel Syndrome With Constipation

Phase 3, 12-Week, Multicenter, Double-Blind, Randomized, Efficacy and Safety Study of Lubiprostone for the Treatment of Irritable Bowel Syndrome With Constipation

The primary purpose of this study is to evaluate the efficacy and safety of administration of lubiprostone in patients with irritable bowel syndrome with constipation.

Study Overview

• Status: Completed
• Conditions: Irritable Bowel Syndrome With Constipation
• Intervention / Treatment: Drug: Placebo; Drug: Lubiprostone

• Study Type: Interventional
• Enrollment (Actual): 590
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 18 years of age and older
• Stable fiber therapy
• Normal colonoscopy/sigmoidoscopy
• Able to refrain from use of medications known to treat or associated with constipation symptoms
• Experiences abdominal discomfort/pain associated with bowel movements
• Reports decreased bowel movement frequency and/or other symptoms associated with constipation

Exclusion Criteria:

• Diarrhea-predominant or alternating (diarrhea and constipation cycling) irritable bowel syndrome (IBS), or constipation other than that associated with IBS
• Open gastrointestinal or abdominal surgery prior to IBS onset
• Organic bowel disorder, mechanical bowel obstruction, pseudo-obstruction, unexplained weight loss or rectal bleeding
• Uncontrolled cardiovascular, liver or lung disease, neurologic or psychiatric disorder, other systemic disease, or abnormal laboratory tests per investigator discretion
• If female, is currently pregnant or nursing, or plans to become pregnant or nurse during the clinical study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lubiprostone; 8 mcg capsule twice daily (BID)	Drug: Lubiprostone
Placebo Comparator: Placebo; Matching placebo capsule twice daily (BID)	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Responder Rate	Monthly responder: >=Moderately relieved symptoms 4 weeks/month or Significantly relieved >= 2 weeks/month IF: Rescue med use did not increase during the month; AND did not discontinue during the month for lack of efficacy; AND no Moderately worse or Significantly worse response in month. Overall responder: responder for at least 2/3 months	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Month 1 Spontaneous Bowel Movement (SBM) Frequency Rates Change From Baseline	SBMs are any bowel movement not associated with rescue medication use.	Change from baseline for month 1
Month 1 Stool Consistency Change From Baseline	0 = Very loose (watery), 1 = Loose, 2 = Normal, 3 = Hard, 4 = Very hard (little balls)	Change from baseline for month 1
Month 1 Bowel Straining Change From Baseline	0 = Absent,1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe	Change from baseline for month 1
Month 1 Constipation Severity Change From Baseline	0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe	Change from baseline at 28 days
Month 1 Symptom Relief	Significantly worse = -3; Moderately worse = -2; A little bit worse = -1; Unchanged = 0; A little bit relieved=1; Moderately relieved=2; Significantly relieved = 3	Change from baseline for month 1
Quality of Life Change From Baseline	Irritable Bowel Syndrome Quality of Life (IBS-QOL) questionnaire included 34 questions with 5 possible responses yielding the following sub-categories: dysphoria, interference with activity, body image, health worry, food avoidance, social reaction, sexual, and relationship Results range from 34 (low) to 100 (high); meaningful clinical improvement=14 point increase	Change from baseline at 12 weeks
Month 2 Responder Rate	Monthly responder: >=Moderately relieved symptoms 4 weeks/month or Significantly relieved >= 2 weeks/month IF: Rescue med use did not increase during the month; AND did not discontinue during the month for lack of efficacy; AND no Moderately worse or Significantly worse response in month.	month 2 (28 days)
Month 3 Responder Rate	Symptoms >= Moderately relieved for 4 weeks/month or Significantly relieved for >=2 weeks/month AND: Rescue medication use does not increase during the month as compared to baseline;; No discontinuation during the month due to lack of efficacy;AND; No ratings during the month of Moderately worse or Significantly worse.	month 3 (28 days)
Month 1 Responder Rate	Symptoms >= Moderately relieved for 4 weeks/month or Significantly relieved for >=2 weeks/month AND: Rescue medication use does not increase during the month as compared to baseline;; No discontinuation during the month due to lack of efficacy;AND; No ratings during the month of Moderately worse or Significantly worse.	month 1 (28 days)
Month 2 Abdominal Bloating Change From Baseline	0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe	Change from baseline for month 2
Month 3 Abdominal Bloating Change From Baseline	0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe	Change from baseline for month 3
Month 2 Spontaneous Bowel Movement Frequency Rates Change From Baseline	Any bowel movement not associated with rescue medication use	Change from baseline for month 2
Month 3 Spontaneous Bowel Movement Frequency Rates Change From Baseline	Any bowel movement not associated with rescue medication use	Change from baseline for month 3
Month 2 Stool Consistency Change From Baseline	0 = Very loose (watery), 1 = Loose, 2 = Normal, 3 = Hard, 4 = Very hard (little balls)	Change from baseline for month 2
Month 3 Stool Consistency Change From Baseline	0 = Very loose (watery), 1 = Loose, 2 = Normal, 3 = Hard, 4 = Very hard (little balls)	Change from baseline for month 3
Month 2 Bowel Straining Change From Baseline	0 = Absent,1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe	Change from baseline for month 2
Month 3 Bowel Straining Change From Baseline	0 = Absent,1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe	Change from baseline for month 3
Month 2 Constipation Severity Change From Baseline	0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe	Change from baseline for month 2
Month 3 Constipation Severity Change From Baseline	0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe	Change from baseline for month 3
Month 2 Symptom Relief	Significantly worse = -3; Moderately worse = -2; A little bit worse = -1; Unchanged = 0; A little bit relieved=1; Moderately relieved=2; Significantly relieved = 3	Change from baseline for month 2
Month 3 Symptom Relief	Significantly worse = -3; Moderately worse = -2; A little bit worse = -1; Unchanged = 0; A little bit relieved=1; Moderately relieved=2; Significantly relieved = 3	Change from baseline for month 3
Month 1 Abdominal Bloating Change From Baseline	0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe	Change from baseline for month 1
Month 1 Bowel Movement Frequency Rates Change From Baseline		Change from baseline for month 1
Month 2 Bowel Movement Frequency Rates Change From Baseline		Change from baseline for month 2
Month 3 Bowel Movement Frequency Rates Change From Baseline		Change from baseline for month 3
Month 1 Abdominal Pain Change From Baseline	0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe	Change from baseline for month 1
Month 2 Abdominal Pain Change From Baseline	0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe	Change from baseline for month 2
Month 3 Abdominal Pain Change From Baseline	0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe	Change from baseline for month 3

Collaborators and Investigators

• Sponsor: Sucampo Pharma Americas, LLC
• Collaborators: Takeda
• Investigators: Study Director: Medical Director, MD, Sucampo Pharmaceuticals, Inc.

Publications and helpful links

General Publications

• Drossman DA, Chey WD, Johanson JF, Fass R, Scott C, Panas R, Ueno R. Clinical trial: lubiprostone in patients with constipation-associated irritable bowel syndrome--results of two randomized, placebo-controlled studies. Aliment Pharmacol Ther. 2009 Feb 1;29(3):329-41. doi: 10.1111/j.1365-2036.2008.03881.x. Epub 2008 Nov 4.

Study record dates

Study Major Dates

• Study Start: May 1, 2005
• Study Completion (Actual): July 1, 2006

Study Registration Dates

• First Submitted: September 21, 2006
• First Submitted That Met QC Criteria: September 21, 2006
• First Posted (Estimate): September 25, 2006

Study Record Updates

• Last Update Posted (Actual): November 15, 2019
• Last Update Submitted That Met QC Criteria: November 4, 2019
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Disease; Signs and Symptoms, Digestive; Gastrointestinal Diseases; Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Syndrome; Irritable Bowel Syndrome; Constipation; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Chloride Channel Agonists; Lubiprostone
• Other Study ID Numbers: 0211SIB-0431

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No