Trial of Linaclotide in Patients With Chronic Constipation

December 19, 2012 updated by: Ironwood Pharmaceuticals, Inc.

A Phase 3, Randomized, Double-blind, Placebo-controlled, Parallel-group Trial of Linaclotide Administered Orally for 12 Weeks Followed by a 4-Week Randomized Withdrawal Period in Patients With Chronic Constipation

The objective of this trial is to determine the efficacy and safety of linaclotide administered to patients with chronic constipation (CC). The primary efficacy parameter is the percentage of patients in each dosing group that meet the protocol definition for Complete Spontaneous Bowel Movement (CSBM) Overall Responder.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

643

Phase

  • Phase 3

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

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35209
        • Ironwood Investigational Site
      • Huntsville, Alabama, United States, 35801
        • Ironwood Investigational Site
    • Arizona
      • Chandler, Arizona, United States, 85224
        • Ironwood Investigational Site
      • Phoenix, Arizona, United States, 85020
        • Ironwood Investigational Site
      • Tucson, Arizona, United States, 85715
        • Ironwood Investigational Site
      • Tuscon, Arizona, United States, 85710
        • Ironwood Investigational Site
    • Arkansas
      • Sherwood, Arkansas, United States, 72120
        • Ironwood Investigational Site
    • California
      • Anaheim, California, United States, 92801
        • Ironwood Investigational Site
      • Chula Vista, California, United States, 91910
        • Ironwood Investigational Site
      • Encinitas, California, United States, 92024
        • Ironwood Investigational Site
      • Garden Grove, California, United States, 92840
        • Ironwood Investigational Site
      • Laguna Hills, California, United States, 92653
        • Ironwood Investigational Site
      • Los Angeles, California, United States, 90045
        • Ironwood Investigational Site
      • Orange, California, United States, 92868
        • Ironwood Investigational Site
      • Sacramento, California, United States, 95830
        • Ironwood Investigational Site
      • San Carlos, California, United States, 94070
        • Ironwood Investigational Site
      • San Diego, California, United States, 92103
        • Ironwood Investigational Site
      • San Diego, California, United States, 92108
        • Ironwood Investigational Site
      • San Diego, California, United States, 92123
        • Ironwood Investigational Site
    • Colorado
      • Colorado Springs, Colorado, United States, 80904
        • Ironwood Investigational Site
    • Connecticut
      • Bristol, Connecticut, United States, 06010
        • Ironwood Investigational Site
    • Florida
      • Boynton Beach, Florida, United States, 33426
        • Ironwood Investigational Site
      • Hollywood, Florida, United States, 33021
        • Ironwood Investigational Site
      • Inverness, Florida, United States, 34452
        • Ironwood Investigational Site
      • Jacksonville, Florida, United States, 32256
        • Ironwood Investigational Site
      • Port Orange, Florida, United States, 32129
        • Ironwood Investigational Site
      • Tampa, Florida, United States, 33607
        • Ironwood Investigational Site
    • Georgia
      • Newnan, Georgia, United States, 30263
        • Ironwood Investigational Site
    • Illinois
      • Peoria, Illinois, United States, 61602
        • Ironwood Investigational Site
    • Indiana
      • Anderson, Indiana, United States, 46011
        • Ironwood Investigational Site
    • Iowa
      • Clive, Iowa, United States, 50325
        • Ironwood Investigational Site
      • Davenport, Iowa, United States, 52807
        • Ironwood Investigational Site
    • Kansas
      • Mission, Kansas, United States, 66202
        • Ironwood Investigational Site
      • Overland Park, Kansas, United States, 66215
        • Ironwood Investigational Site
      • Topeka, Kansas, United States, 66606
        • Ironwood Investigational Site
    • Louisiana
      • Baton Rouge, Louisiana, United States, 70809
        • Ironwood Investigational Site
      • Monroe, Louisiana, United States, 71201
        • Ironwood Investigational Site
      • Shreveport, Louisiana, United States, 71103
        • Ironwood Investigational Site
    • Maryland
      • Annapolis, Maryland, United States, 21401
        • Ironwood Investigational Site
      • Baltimore, Maryland, United States, 21215
        • Ironwood Investigational Site
      • Hollywood, Maryland, United States, 20636
        • Ironwood Investigational Site
      • Laurel, Maryland, United States, 20707
        • Ironwood Investigational Site
    • Michigan
      • Chesterfield, Michigan, United States, 48047
        • Ironwood Investigational Site
      • Traverse City, Michigan, United States, 49684
        • Ironwood Investigational Site
      • Troy, Michigan, United States, 48098
        • Ironwood Investigational Site
    • Mississippi
      • Jackson, Mississippi, United States, 39202
        • Ironwood Investigational Site
      • Tupelo, Mississippi, United States, 38801
        • Ironwood Investigational Site
    • Missouri
      • Jefferson City, Missouri, United States, 65109
        • Ironwood Investigational Site
    • Nevada
      • Henderson, Nevada, United States, 89104
        • Ironwood Investigational Site
      • Las Vegas, Nevada, United States, 89128
        • Ironwood Investigational Site
    • New Jersey
      • Cedar Knolls, New Jersey, United States, 07927
        • Ironwood Investigational Site
      • Marlton, New Jersey, United States, 08053
        • Ironwood Investigational Site
      • Ocean, New Jersey, United States, 07712
        • Ironwood Investigational Site
    • New Mexico
      • Albuquerque, New Mexico, United States, 87108
        • Ironwood Investigational Site
    • New York
      • Mineola, New York, United States, 11501
        • Ironwood Investigational Site
      • Pittsford, New York, United States, 14534
        • Ironwood Investigational Site
    • North Carolina
      • Asheboro, North Carolina, United States, 27203
        • Ironwood Investigational Site
      • Asheville, North Carolina, United States, 28801
        • Ironwood Investigational Site
      • Chapel Hill, North Carolina, United States, 27599
        • Ironwood Investigational Site
      • Charlotte, North Carolina, United States, 28211
        • Ironwood Investigational Site
      • Greensboro, North Carolina, United States, 27408
        • Ironwood Investigational Site
      • Harrisburg, North Carolina, United States, 28075
        • Ironwood Investigational Site
      • Hickory, North Carolina, United States, 28602
        • Ironwood Investigational Site
      • Jacksonville, North Carolina, United States, 28546
        • Ironwood Investigational Site
      • New Bern, North Carolina, United States, 28562
        • Ironwood Investigational Site
      • Statesville, North Carolina, United States, 28625
        • Ironwood Investigational Site
      • Summerville, North Carolina, United States, 29485
        • Ironwood Investigational Site
      • Wilmington, North Carolina, United States, 28401
        • Ironwood Investigational Site
      • Winston Salem, North Carolina, United States, 27103
        • Ironwood Investigational Site
    • Ohio
      • Beachwood, Ohio, United States, 44122
        • Ironwood Investigational Site
      • Cincinnati, Ohio, United States, 45224
        • Ironwood Investigational Site
      • Cincinnati, Ohio, United States, 45242
        • Ironwood Investigational Site
      • Dayton, Ohio, United States, 45440
        • Ironwood Investigational Site
      • Sylvania, Ohio, United States, 43560
        • Ironwood Investigational Site
      • Wadsworth, Ohio, United States, 44281
        • Ironwood Investigational Site
      • Zanesville, Ohio, United States, 43701
        • Ironwood Investigational Site
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73116
        • Ironwood Investigational Site
      • Yukon, Oklahoma, United States, 73099
        • Ironwood Investigational Site
    • Pennsylvania
      • Lancaster, Pennsylvania, United States, 17604
        • Ironwood Investigational Site
      • Lancaster, Pennsylvania, United States, 19606
        • Ironwood Investigational Site
      • Levittown, Pennsylvania, United States, 19056
        • Ironwood Investigational Site
      • Pittsburgh, Pennsylvania, United States, 15213
        • Ironwood Investigational Site
      • Sellersville, Pennsylvania, United States, 18960
        • Ironwood Investigational Site
    • South Carolina
      • Anderson, South Carolina, United States, 29621
        • Ironwood Investigational Site
      • Charleston, South Carolina, United States, 29414
        • Ironwood Investigational Site
      • Simpsonville, South Carolina, United States, 29681
        • Ironwood Investigational Site
    • Tennessee
      • Bristol, Tennessee, United States, 37620
        • Ironwood Investigational Site
      • Chattanooga, Tennessee, United States, 37421
        • Ironwood Investigational Site
      • Germantown, Tennessee, United States, 38138
        • Ironwood Investigational Site
      • Kingsport, Tennessee, United States, 37660
        • Ironwood Investigational Site
      • Nashville, Tennessee, United States, 37203
        • Ironwood Investigational Site
    • Texas
      • Beaumont, Texas, United States, 77701
        • Ironwood Investigational Site
      • El Paso, Texas, United States, 79905
        • Ironwood Investigational Site
      • Houston, Texas, United States, 77024
        • Ironwood Investigational Site
      • Irving, Texas, United States, 75061
        • Ironwood Investigational Site
      • Longview, Texas, United States, 75605
        • Ironwood Investigational Site
      • San Antonio, Texas, United States, 78229
        • Ironwood Investigational Site
    • Utah
      • Ogden, Utah, United States, 84405
        • Ironwood Investigational Site
      • Salt Lake City, Utah, United States, 84107
        • Ironwood Investigational Site
    • Virginia
      • Chesapeake, Virginia, United States, 23320
        • Ironwood Investigational Site
      • Lynchburg, Virginia, United States, 24502
        • Ironwood Investigational Site
    • Washington
      • Spokane, Washington, United States, 99208
        • Ironwood Investigational Site
      • Vancouver, Washington, United States, 98664
        • Ironwood Investigational Site
    • Wisconsin
      • LaCrosse, Wisconsin, United States, 54601
        • Ironwood Investigational Site
      • Milwaukee, Wisconsin, United States, 53215
        • Ironwood 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:

  • Patient has completed a colonoscopy according to the AGA criteria, with no clinically significant findings
  • Patient has successfully completed protocol procedures (with no clinically significant findings): physical exam, 12-lead ECG, or clinical laboratory tests
  • Patient meets protocol criteria for CC: reports < 3 bowel movements per week and reports straining, lumpy or hard stools, and/or sensation of incomplete evacuation during > 25% of BMs
  • Patient demonstrates continued chronic constipation through Pretreatment Period
  • Patient is compliant with IVRS

Exclusion Criteria:

  • Patient has history of loose or watery stools
  • Patient has symptoms of or been diagnosed with Irritable Bowel Syndrome (IBS)
  • Patient has a structural abnormality of the gastrointestinal (GI) tract or a disease or condition that can affect GI motility
  • Patient has any protocol-excluded or clinically significant medical or surgical history that could confound the study assessments

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
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
PLACEBO_COMPARATOR: Matching Placebo
Drug: Matching Placebo
Oral, once daily
EXPERIMENTAL: 145 μg linaclotide
Drug: Linaclotide
Oral, once daily
EXPERIMENTAL: 290 μg linaclotide
Drug: Linaclotide
Oral, once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Complete Spontaneous Bowel Movement (CSBM) Overall Responder
Time Frame: Change from Baseline to Week 12

A 12-week CSBM Overall Responder was defined as a patient who for at least 9 of the 12 weeks of the treatment period had a CSBM weekly frequency rate that was 3 or greater and increased by 1 or more from baseline. A CSBM was defined as a spontaneous bowel movement (SBM) that was associated with a sense of complete evacuation.

An SBM was defined as a bowel movement (BM) that occurred in the absence of laxative, enema, or suppository use on either the calendar day of the BM or the calendar day before the BM.
Change from Baseline to Week 12

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
12-Week Complete Spontaneous Bowel Movement (CSBM) Frequency
Time Frame: Change from Baseline to Week 12
The number of CSBMs per week.
Change from Baseline to Week 12
12-Week Spontaneous Bowl Movement (SBM) Frequency
Time Frame: Change from Baseline to Week 12
The number of SBMs per week.
Change from Baseline to Week 12
12-week Change in Stool Consistency
Time Frame: Change from Baseline to Week 12

The consistency of each BM was assessed using the 7-point Bristol Stool Form Scale:

  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
  7. = watery, no solid pieces [entirely liquid]
Change from Baseline to Week 12
12-week Change in Severity of Straining
Time Frame: Change from Baseline to Week 12
Severity of Straining is measured on a 5-point scale, where a value of 1 is "not at all" and a value of 5 is "an extreme amount".
Change from Baseline to Week 12
12-week Change in Abdominal Discomfort
Time Frame: Change from Baseline to Week 12
Abdominal discomfort is based on a 5-point scale where a value of l is "none" and a value of 5 is "very severe."
Change from Baseline to Week 12
12-week Change in Bloating
Time Frame: Change from Baseline to Week 12
Bloating was based on a 5-point scale where a value of l is "none" and a value of 5 is "very severe".
Change from Baseline to Week 12
12-week Change in Constipation Severity
Time Frame: Change from Baseline to Week 12
Constipation severity was based on a 5-point ordinal scale where a value of l is "none" and a value of 5 is "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.

Collaborators

Forest Laboratories

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

August 1, 2008

Primary Completion (ACTUAL)

August 1, 2009

Study Completion (ACTUAL)

October 1, 2009

Study Registration Dates

First Submitted

August 5, 2008

First Submitted That Met QC Criteria

August 5, 2008

First Posted (ESTIMATE)

August 8, 2008

Study Record Updates

Last Update Posted (ESTIMATE)

January 30, 2013

Last Update Submitted That Met QC Criteria

December 19, 2012

Last Verified

December 1, 2012

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MCP-103-303

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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