Trial of Linaclotide in Patients With Irritable Bowel Syndrome With Constipation (IBS-C)

A Phase 3, Randomized, Double-blind, Placebo-controlled, Parallel-group Trial of Linaclotide Administered Orally for 26 Weeks in Patients With Irritable Bowel Syndrome With Constipation

The purpose of this study is to determine the safety and efficacy of linaclotide administered to patients with Irritable Bowel Syndrome with Constipation (IBS-C).

Study Overview

• Status: Completed
• Conditions: Irritable Bowel Syndrome With Constipation
• Intervention / Treatment: Drug: Linaclotide or Matching Placebo

• Study Type: Interventional
• Enrollment (Actual): 805
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35209
      • Ironwood Investigational Site
    • Huntsville, Alabama, United States, 35801
      • Ironwood Investigational Site
  • Arizona
    • Phoenix, Arizona, United States, 85014
      • Ironwood Investigational Site
    • Tempe, Arizona, United States, 85282
      • Ironwood Investigational Site
    • Tucson, Arizona, United States, 85710
      • Ironwood Investigational Site
    • Tucson, Arizona, United States, 85741
      • 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
    • Orange, California, United States, 92868
      • 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, 06011
      • 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, 32205
      • Ironwood Investigational Site
    • Jacksonville, Florida, United States, 32207
      • Ironwood Investigational Site
    • Lauderdale Lakes, Florida, United States, 33319
      • Ironwood Investigational Site
    • Miami, Florida, United States, 33156
      • Ironwood Investigational Site
    • Pinellas Park, Florida, United States, 33782
      • 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
    • Metairie, Louisiana, United States, 70006
      • 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
  • Minnesota
    • Plymouth, Minnesota, United States, 55446
      • 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
  • New Jersey
    • Marlton, New Jersey, United States, 08053
      • 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
    • Charlotte, North Carolina, United States, 28209
      • Ironwood Investigational Site
    • Greensboro, North Carolina, United States, 27408
      • Ironwood Investigational Site
    • Greensboro, North Carolina, United States, 27401
      • Ironwood Investigational Site
    • Harrisburg, North Carolina, United States, 28075
      • Ironwood Investigational Site
    • Hickory, North Carolina, United States, 28602
      • Ironwood Investigational Site
    • Huntersville, North Carolina, United States, 28078
      • Ironwood Investigational Site
    • New Bern, North Carolina, United States, 28562
      • Ironwood Investigational Site
    • Statesville, North Carolina, United States, 28625
      • 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
    • Mentor, Ohio, United States, 44060
      • Ironwood Investigational Site
    • Sylvania, Ohio, United States, 43560
      • Ironwood Investigational Site
    • Wadsworth, Ohio, United States, 44281
      • 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
    • Levittown, Pennsylvania, United States, 19056
      • Ironwood Investigational Site
    • Reading, Pennsylvania, United States, 19606
      • Ironwood Investigational Site
    • Sellersville, Pennsylvania, United States, 18960
      • Ironwood Investigational Site
    • Washington, Pennsylvania, United States, 15301
      • 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, 29581
      • Ironwood Investigational Site
    • Summerville, South Carolina, United States, 29485
      • Ironwood Investigational Site
  • Tennessee
    • Bristol, Tennessee, United States, 37620
      • Ironwood Investigational Site
    • Chattanooga, Tennessee, United States, 37404
      • Ironwood Investigational Site
    • Germantown, Tennessee, United States, 38183
      • 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
    • Fort Worth, Texas, United States, 76104
      • 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
    • Sugarland, Texas, United States, 77479
      • 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
    • La Crosse, Wisconsin, United States, 54601
      • Ironwood Investigational Site
    • Milwaukee, Wisconsin, United States, 53215
      • Ironwood Investigational Site

Participation Criteria

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 diagnosis of IBS-C
• Patient demonstrates continued IBS-C 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 a medical condition that may contribute to abdominal pain
• 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

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Linaclotide or Matching Placebo; Linaclotide or Matching Placebo, administered orally, once daily, for the duration of the trial
Experimental: 290 μg Linaclotide	Drug: Linaclotide or Matching Placebo; Linaclotide or Matching Placebo, administered orally, once daily, for the duration of the trial

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Abdominal Pain and Complete Spontaneous Bowel Movement (APC) Responder, 9 Out of 12 Weeks	A patient is considered to be a 9 out of 12 week APC responder if, for at least 9 out of the first 12 weeks of the treatment period, the patient had at least 3 CSBMs, had an increase of at least 1 CSBM from baseline, and had a decrease of at least 30 percent in their Abdominal Pain (AP) score from baseline during a particular week. The AP score assesses patient's worst AP in the past 24 hours using an 11-point scale (from 0-10), where 0 represents no AP and 10 represents very severe AP. SBM is defined as a bowel movement that occurs in the absence of laxative, enema, or suppository use on either the calendar day of the bowel movement or the calendar day before the bowel movement. CSBM is defined as an SBM associated with a sense of complete evacuation.	Change from Baseline to Week 12
Complete Spontaneous Bowel Movement (CSBM) 3+1 Responder, 9 Out of 12 Weeks	A patient is considered to be a CSBM 3+1 responder if, for at least 9 out of the 12 weeks of the treatment period, the patient had at least 3 CSBMs and experienced an increase of at least 1 CSBM from baseline during a particular week. 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
Abdominal Pain Responder, 9 Out of 12 Weeks	A patient is considered to be an abdominal pain responder if, for at least 9 out of the 12 weeks of the treatment period, they experienced a decrease of at least 30 percent in the mean abdominal pain score from baseline during a particular week. The Abdominal Pain score assesses patient's worst abdominal pain in the past 24 hours using an 11-point scale (from 0-10), where 0 represents no abdominal pain and 10 represents very severe abdominal pain.	Change from Baseline to Week 12
Abdominal Pain and Complete Spontaneous Bowel Movement (APC) Responder, 6 Out of 12 Weeks	A patient is considered to be a 6 out of 12 week APC responder if, for at least 6 out of the first 12 weeks of the treatment period, the patient had an increase of at least 1 CSBM from baseline, and had a decrease of at least 30 percent in their Abdominal Pain (AP) score from baseline during a particular week. The AP score assesses patient's worst AP in the past 24 hours using an 11-point scale (from 0-10), where 0 represents no AP and 10 represents very severe AP. SBM is defined as a bowel movement that occurs in the absence of laxative, enema, or suppository use on either the calendar day of the bowel movement or the calendar day before the bowel movement. CSBM is defined as an SBM associated with a sense of complete evacuation.	Change from Baseline to Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
12-Week Complete Spontaneous Bowel Movement (CSBM) Frequency	The change from baseline in 12-week CSBM frequency (i.e., weekly CSBM frequency over the first 12 weeks of the Treatment Period).	Change from Baseline to Week 12
12-Week Spontaneous Bowl Movement (SBM) Frequency	The change from baseline in 12-week SBM frequency (i.e., weekly SBM frequency over the first 12 weeks of the Treatment Period).	Change from Baseline to Week 12
12-Week Change in Stool Consistency	The consistency of each BM was assessed by patients using the 7-point Bristol Stool Form Scale (BSFS) from 1 to 7.; = separate hard lumps like nuts [difficult to pass]; = sausage shaped but lumpy; = like a sausage but with cracks on surface; = like a sausage or snake, smooth and soft; = soft blobs with clear-cut edges [passed easily]; = fluffy pieces with ragged edges, a mushy stool; = watery, no solid pieces [entirely liquid]).	Change from Baseline to Week 12
12-Week Change in Severity of Straining	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 Pain Score	Abdominal Pain at its worst (in the last 24 hours) is based on an 11-point scale where 0 represents no abdominal pain and 10 represents very severe abdominal pain.	Change from Baseline to Week 12
12-Week Change in Abdominal Discomfort	Abdominal discomfort was assessed on an 11-point scale where a value of 0 is "none" and a value of 10 is "very severe".	Change from Baseline to Week 12
12-Week Change in Bloating	Bloating was assessed on an 11-point scale where a value of 0 is "none" and a value of 10 is "very severe".	Change from Baseline to Week 12
Complete Spontaneous Bowl Movement (CSBM) Responder for 6 Weeks Out of 12 Weeks of Treatment	A patient is considered to be a CSBM responder if, for at least 6 out of the 12 weeks of the treatment period, an increase of at least 1 CSBM per week from baseline was experienced.	Change from Baseline to Week 12
Abdominal Pain Responder for 6 Out of 12 Weeks	A patient is considered to be an AP responder if, for at least 6 out of the first 12 weeks of the treatment period, the patient had a decrease of at least 30 percent in their Abdominal Pain score from baseline during a particular week.	Change from Baseline to Week 12
12-Week Percent of Abdominal Pain-free Days	Abdominal pain free (APF) days are those days where the patient reported a score of '0' for abdominal pain at its worst. Abdominal Pain at its worst (in the last 24 hours) is based on an 11-point scale where 0 represents no abdominal pain and 10 represents very severe abdominal pain.	Change from Baseline to Week 12

Collaborators and Investigators

• Sponsor: Ironwood Pharmaceuticals, Inc.
• Collaborators: Forest Laboratories

Publications and helpful links

General Publications

• Rao SS, Quigley EM, Shiff SJ, Lavins BJ, Kurtz CB, MacDougall JE, Currie MG, Johnston JM. Effect of linaclotide on severe abdominal symptoms in patients with irritable bowel syndrome with constipation. Clin Gastroenterol Hepatol. 2014 Apr;12(4):616-23. doi: 10.1016/j.cgh.2013.09.022. Epub 2013 Sep 25.
• Quigley EM, Tack J, Chey WD, Rao SS, Fortea J, Falques M, Diaz C, Shiff SJ, Currie MG, Johnston JM. Randomised clinical trials: linaclotide phase 3 studies in IBS-C - a prespecified further analysis based on European Medicines Agency-specified endpoints. Aliment Pharmacol Ther. 2013 Jan;37(1):49-61. doi: 10.1111/apt.12123. Epub 2012 Nov 1.

Study record dates

Study Major Dates

• Study Start: July 1, 2009
• Primary Completion (Actual): September 1, 2010
• Study Completion (Actual): September 1, 2010

Study Registration Dates

• First Submitted: July 12, 2009
• First Submitted That Met QC Criteria: July 13, 2009
• First Posted (Estimate): July 14, 2009

Study Record Updates

• Last Update Posted (Estimate): November 5, 2013
• Last Update Submitted That Met QC Criteria: October 9, 2013
• Last Verified: October 1, 2013

More Information

Terms related to this study

• Keywords: IBS
• 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; Gastrointestinal Agents; Guanylyl Cyclase C Agonists; Enzyme Activators; Linaclotide
• Other Study ID Numbers: MCP-103-302