Randomized, Double-blind, Dose-range-finding, Phase 2 Study of Linaclotide Administered to Patients With Irritable Bowel Syndrome With Constipation (IBS-C)

January 29, 2013 updated by: Ironwood Pharmaceuticals, Inc.

A Randomized, Multicenter, Double-blind, Placebo-controlled, Dose-range-finding, Parallel-design, Phase 2 Trial of Oral Linaclotide Acetate Administered to Patients With Irritable Bowel Syndrome With Constipation

The purpose of this study is to determine the safety, efficacy, and dose response of a range of oral doses of linaclotide administered to patients meeting criteria for IBS-C.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

420

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • British Columbia
      • Abbortsford, British Columbia, Canada
        • Microbia Investigational Site
    • Manitoba
      • Winnipeg, Manitoba, Canada
        • Microbia Investigational Site
    • Ontario
      • Guelph, Ontario, Canada
        • Microbia Investigational Site
      • Milton, Ontario, Canada
        • Microbia Investigational Site
      • Toronto, Ontario, Canada
        • Microbia Investigational Site
    • Saskatchewan
      • Saskatoon, Saskatchewan, Canada
        • Microbia Investigational Site
  • United States
    • Alabama
      • Huntsville, Alabama, United States, 35801
        • Microbia Investigational Site
    • Arizona
      • Chandler, Arizona, United States
        • Microbia Investigational Site
      • Tuscon, Arizona, United States
        • Microbia Investigational Site
    • Arkansas
      • Sherwood, Arkansas, United States
        • Microbia Investigational Site
    • California
      • Anaheim, California, United States
        • Microbia Investigational Site
      • Garden Grove, California, United States
        • Microbia Investigational Site
      • Sacramento, California, United States
        • Microbia Investigational Site
      • San Diego, California, United States
        • Microbia Investigational Site
    • Connecticut
      • Bristol, Connecticut, United States
        • Microbia Investigational Site
    • Florida
      • Boynton Beach, Florida, United States
        • Microbia Investigational Site
      • Dunedin, Florida, United States
        • Microbia Investigational Site
      • Largo, Florida, United States
        • Microbia Investigational Site
      • Ocala, Florida, United States
        • Microbia Investigational Site
      • Port Orange, Florida, United States
        • Microbia Investigational Site
      • Stuart, Florida, United States
        • Microbia Investigational Site
      • Tampa, Florida, United States, 33607
        • Microbia Investigational Site
    • Georgia
      • Stockbridge, Georgia, United States
        • Microbia Investigational Site
    • Illinois
      • Libertyville, Illinois, United States
        • Microbia Investigational Site
      • Peoria, Illinois, United States, 60601
        • Microbia Investigational Site
    • Iowa
      • Clive, Iowa, United States
        • Microbia Investigational Site
      • Davenport, Iowa, United States
        • Microbia Investigational Site
    • Kansas
      • Mission, Kansas, United States
        • Microbia Investigational Site
      • Shawnee, Kansas, United States
        • Microbia Investigational Site
    • Louisiana
      • Baton Rouge, Louisiana, United States
        • Microbia Investigational Site
      • Monroe, Louisiana, United States, 71201
        • Microbia Investigational Site
      • West Monroe, Louisiana, United States
        • Microbia Investigational Site
    • Maryland
      • Annapolis, Maryland, United States
        • Microbia Investigational Site
      • Silver Spring, Maryland, United States
        • Microbia Investigational Site
    • Massachusetts
      • Fall River, Massachusetts, United States
        • Microbia Investigational Site
    • Michigan
      • Ann Arbor, Michigan, United States
        • Microbia Investigational Site
    • Missouri
      • St. Louis, Missouri, United States
        • Microbia Investigational Site
    • Montana
      • Missoula, Montana, United States
        • Microbia Investigational Site
    • Nevada
      • Henderson, Nevada, United States
        • Microbia Investigational Site
      • Las Vegas, Nevada, United States
        • Microbia Investigational Site
    • New Jersey
      • Blackwood, New Jersey, United States
        • Microbia Investigational Site
    • New York
      • Great Neck, New York, United States, 11020
        • Microbia Investigational Site
      • Pittsford, New York, United States
        • Microbia Investigational Site
    • North Carolina
      • Asheville, North Carolina, United States
        • Microbia Investigational Site
      • Chapel Hill, North Carolina, United States
        • Microbia Investigational Site
      • Elkin, North Carolina, United States
        • Microbia Investigational Site
      • Greensboro, North Carolina, United States
        • Microbia Investigational Site
      • Harrisburg, North Carolina, United States
        • Microbia Investigational Site
      • Hickory, North Carolina, United States
        • Microbia Investigational Site
      • Raleigh, North Carolina, United States
        • Microbia Investigational Site
      • Statesville, North Carolina, United States
        • Microbia Investigational Site
      • Winston-Salem, North Carolina, United States
        • Microbia Investigational Site
    • Ohio
      • Cincinnati, Ohio, United States
        • Microbia Investigational Site
      • Cleveland, Ohio, United States
        • Microbia Investigational Site
      • Dayton, Ohio, United States
        • Microbia Investigational Site
      • Sylvania, Ohio, United States
        • Microbia Investigational Site
    • Oklahoma
      • Oklahoma City, Oklahoma, United States
        • Microbia Investigational Site
      • Tulsa, Oklahoma, United States
        • Microbia Investigational Site
      • Yukon, Oklahoma, United States
        • Microbia Investigational Site
    • Oregon
      • Medford, Oregon, United States
        • Microbia Investigational Site
    • Pennsylvania
      • Levittown, Pennsylvania, United States
        • Microbia Investigational Site
      • Pittsburgh, Pennsylvania, United States
        • Microbia Investigational Site
      • Reading, Pennsylvania, United States
        • Microbia Investigational Site
      • Sellersville, Pennsylvania, United States, 18960
        • Microbia Investigational Site
    • South Carolina
      • Anderson, South Carolina, United States
        • Microbia Investigational Site
      • Mt. Pleasant, South Carolina, United States
        • Microbia Investigational Site
      • Simpsonville, South Carolina, United States
        • Microbia Investigational Site
      • Summerville, South Carolina, United States
        • Microbia Investigational Site
    • Tennessee
      • Bristol, Tennessee, United States
        • Microbia Investigational Site
      • Germantown, Tennessee, United States
        • Microbia Investigational Site
      • Jackson, Tennessee, United States
        • Microbia Investigational Site
      • Kingsport, Tennessee, United States
        • Microbia Investigational Site
    • Texas
      • Beaumont, Texas, United States
        • Microbia Investigational Site
      • Corsicana, Texas, United States
        • Microbia Investigational Site
      • El Paso, Texas, United States
        • Microbia Investigational Site
      • San Antonio, Texas, United States
        • Microbia Investigational Site
    • Utah
      • Ogden, Utah, United States
        • Microbia Investigational Site
    • Virginia
      • Chesapeake, Virginia, United States
        • Microbia Investigational Site
      • Lynchburg, Virginia, United States
        • Microbia Investigational Site
      • Richmond, Virginia, United States
        • Microbia Investigational Site
    • Washington
      • Lakewood, Washington, United States
        • Microbia Investigational Site
      • Olympia, Washington, United States
        • Microbia Investigational Site
      • Vancouver, Washington, United States
        • Microbia Investigational Site
    • West Virginia
      • Charleston, West Virginia, United States
        • Microbia Investigational Site
    • Wisconsin
      • LaCrosse, Wisconsin, United States
        • Microbia Investigational Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Must not be pregnant or breastfeeding and agree to use birth control;
  • Completion of a negative colonoscopy as per American Gastroenterology Association (AGA) criteria and no clinically-significant laboratory or physical examination findings;
  • Meets protocol-defined criteria for IBS-C, including stool frequency, straining, stool consistency, abdominal pain, and abdominal discomfort criteria;
  • Demonstrates English fluency and has access to a touch-tone telephone.

Exclusion Criteria:

  • Recent history of mushy or watery stools;
  • Various medical conditions, medical histories, or family medical histories that would not make the patient a good candidate for the study;
  • Clinically-significant alarm symptoms;
  • Secondary causes of constipation or evacuation disorders;
  • Surgery to the gastrointestinal tract;
  • Usage of prohibited medications.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Matching Placebo
Drug: Matching placebo
Oral, once daily
Active Comparator: 72 ug linaclotide acetate
Drug: Linaclotide Acetate
Oral, once daily
Active Comparator: 145 ug linaclotide acetate
Drug: Linaclotide Acetate
Oral, once daily
Active Comparator: 290 ug linaclotide acetate
Drug: Linaclotide Acetate
Oral, once daily
Active Comparator: 579 ug linaclotide acetate
Drug: Linaclotide Acetate
Oral, once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline in the Weekly Normalized Complete Spontaneous Bowel Movement (CSBM) Rate During Weeks 1 Through 12 of the Treatment Period
Time Frame: Change from Baseline to Week 12

The change in the weekly normalized CSBM Rate during Weeks 1 through 12 of the Treatment Period from the weekly normalized CSBM Rate obtained during the Pretreatment Period.

The CSBM rate was normalized based on the number of CSBMs occurring in that week, adjusting for differences in the duration of the week and black-out periods (time not covered due to a missed IVRS call) versus 7x24 hours.
Change from Baseline to Week 12

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
CSBM 75% Responder for the Treatment Period (Based on the Normalized Rate)
Time Frame: Change from Baseline to Week 12
For each week of the Treatment and Posttreatment Periods, a patient was considered a CSBM Responder if for that week the patient 1) completed ≥ 4 days of IVRS questions, 2) had a CSBM rate of ≥ 3 for the week, and 3) had an increase in CSBM rate of ≥ 1 from the baseline weekly CSBM rate.
Change from Baseline to Week 12
Change From Baseline in the Weekly Normalized SBM Rate for the Treatment Period
Time Frame: Change from Baseline to Week 12
SBMs were measured daily during the treatment period by patient calls to the IVRS.
Change from Baseline to Week 12
Change From Baseline in Stool Consistency (7-point Ordinal BSFS) for the Treatment Period
Time Frame: Change from Baseline to Week 12
Stool consistency analyses were performed using the 7-point Bristol Stool Form Scale (BSFS), whereby a score of 1 = separate hard lumps like nuts (difficult to pass); 2 = sausage shaped but lumpy; 3 = like a sausage but with cracks on surface; 4 = like a sausage or snake, smooth and soft; 5 = soft blobs with clear-cut edges (passed easily); 6 = fluffy pieces with ragged edges, a mushy stool; and 7 = watery, no solid pieces (entirely liquid).
Change from Baseline to Week 12
Change From Baseline in Straining (5-point Ordinal Scale) for the Treatment Period
Time Frame: Change from Baseline to Week 12
Straining was assessed using a 5-point ordinal scale, whereby a score of 1 = not at all, 2 = a little bit, 3 = a moderate amount, 4 = a great deal, and 5 = an extreme amount.
Change from Baseline to Week 12
Change From Baseline in Degree of Relief of Irritable Bowel Syndrome (IBS) Symptoms (7-point Balanced Scale) for the Treatment Period
Time Frame: Change from Baseline to Week 12
Patients provided a weekly assessment of Degree of Relief of IBS Symptoms using a 7-point balanced scale (1=completely relieved, 2=considerably relieved, 3=somewhat relieved, 4=unchanged, 5=somewhat worse, 6=considerably worse, 7=as bad as I can imagine).
Change from Baseline to Week 12
Change From Baseline in Abdominal Pain (5-point Ordinal Scale) for the Treatment Period
Time Frame: Change from Baseline to Week 12
During the study, patients provided their self assessment of abdominal pain using a 5-point ordinal scale (1=none, 2=mild, 3=moderate, 4=severe, 5=very severe
Change from Baseline to Week 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ironwood Pharmaceuticals, Inc.

Investigators

  • Study Director: Microbia Medical Director, MD, Microbia, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2007

Primary Completion (Actual)

February 1, 2008

Study Completion (Actual)

April 1, 2008

Study Registration Dates

First Submitted

April 13, 2007

First Submitted That Met QC Criteria

April 13, 2007

First Posted (Estimate)

April 16, 2007

Study Record Updates

Last Update Posted (Estimate)

February 4, 2013

Last Update Submitted That Met QC Criteria

January 29, 2013

Last Verified

January 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MCP-103-202

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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