Trial of Linaclotide Administered to Patients With Irritable Bowel Syndrome With Constipation

NCT00948818 | Completed Phase 3 Results

• 1 other identifier: LIN-MD-31
• Study Type: interventional
• Target: 803
• Locations: 2 countries
• Sites: 118

Brief Summary

The objective of this trial is to determine the efficacy and safety of linaclotide administered to patients with irritable bowel syndrome with constipation (IBS-C). The primary efficacy parameter is the percentage of patients in each treatment group that meet the protocol definition for Abdominal Pain and Complete Spontaneous Bowel Movement (APC) Responder.

Conditions

Irritable Bowel Syndrome Characterized by Constipation

Keywords

Irritable Bowel Syndrome; Constipation; Linaclotide

Outcome Measures

Primary Outcomes (4)

• Abdominal Pain and Complete Spontaneous Bowel Movement (APC) Responder, 9 Out of 12 Weeks

  A patient is considered to be an APC responder if, for at least 9 out of the 12 weeks of the treatment period, the patient had at least 3 CSBMs, experienced an increase of at least 1 CSBM from baseline, and experienced a decrease of at least 30 percent in their Abdominal Pain (AP) score from baseline during a particular week. The AP score assesses the worst of a patient's 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. A CSBM is defined as a spontaneous bowel movement, 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 the worst of a patient's 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 an APC responder if, for at least 6 of the 12 weeks of the treatment, the patient experienced an increase of at least 1 Complete Spontaneous Bowel Movement (CSBM) from baseline and experienced a decrease of at least 30 percent in their Abdominal Pain (AP)score during a particular week. The AP score assesses the worst of a patient's 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. A CSBM was defined as a Spontaneous Bowel Movement (SBM) that was associated with a sense of complete evacuation.

  Change from Baseline to Week 12

Secondary Outcomes (10)

• 12-Week Complete Spontaneous Bowel Movement (CSBM) Frequency Rate

  Change from Baseline to Week 12

• 12-Week Spontaneous Bowl Movement (SBM) Frequency Rate

  Change from Baseline to Week 12

• 12-Week Stool Consistency

  Change from Baseline to Week 12

• 12-Week Severity of Straining

  Change from Baseline to Week 12

• 12-Week Change in Abdominal Pain Score

  Change from Baseline to Week 12

Study Arms (2)

Linaclotide

EXPERIMENTAL

Linaclotide 290 micrograms

Drug: Linaclotide 290 micrograms

Placebo

PLACEBO COMPARATOR

Matching placebo

Drug: Matching placebo

Interventions

Linaclotide 290 micrograms DRUG

Oral, once daily each morning at least 30 minutes before breakfast for the duration of the study

Linaclotide

Matching placebo DRUG

Oral, once daily each morning at least 30 minutes before breakfast for the duration of the study

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient meets protocol criteria for IBS: reports abdominal discomfort or pain that has two or more of the following three features:
• Relieved with defecation
• Onset associated with a change in frequency of stool
• Onset associated with a change in form (appearance) of stool
• Patient reports \< 3 bowel movements (BMs) per week (in the absence of any laxative, suppository, or enema use during the preceding 24 hours) and reports straining, lumpy or hard stools, and/or sensation of incomplete evacuation during \> 25% of BMs
• Patient has successfully completed protocol procedures (with no clinically significant findings): physical exam, 12-lead ECG, or clinical laboratory tests (some patients may require a colonoscopy per American Gastroenterological Association (AGA) guidelines)
• Patient is compliant with Interactive Voice Response System (IVRS) for daily diary reporting of BM habits and IBS symptoms

You may not qualify if:

• Patient has history of loose or watery stools for \>25% of BMs
• Patient has a structural abnormality of the gastrointestinal (GI) tract or a history of a disease or condition that can affect GI motility
• Patient has any protocol-excluded or clinically significant medical or surgical history or concomitant medication use that could confound the study assessments

Sponsors & Collaborators

• Forest Laboratories: lead
• Ironwood Pharmaceuticals, Inc.: collaborator

Study Sites (118)

Forest Investigative Site 037

Birmingham, Alabama, 35209, United States

Location

Forest Investigative Site 036

Birmingham, Alabama, 35215, United States

Location

Forest Investigative Site 135

Hueytown, Alabama, 35023, United States

Location

Forest Investigative Site 014

Huntsville, Alabama, 35801, United States

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Forest Investigative Site 080

Chandler, Arizona, 85225, United States

Location

Forest Investigative Site 053

Mesa, Arizona, 85210, United States

Location

Forest Investigative Site 078

Peoria, Arizona, 85381, United States

Location

Forest Investigative Site 101

Phoenix, Arizona, 85012, United States

Location

Forest Investigative Site 128

Phoenix, Arizona, 85018, United States

Location

Forest Investigative Site 051

Scottsdale, Arizona, 85251, United States

Location

Forest Investigative Site 136

Tucson, Arizona, 85712, United States

Location

Forest Investigative Site 087

Tucson, Arizona, 85741, United States

Location

Forest Investigative Site 094

Burbank, California, 91505, United States

Location

Forest Investigative Site 026

Encinitas, California, 92024, United States

Location

Forest Investigative Site 096

Foothill Ranch, California, 92610, United States

Location

Forest Investigative Site 057

Los Angeles, California, 90036, United States

Location

Forest Investigative Site 097

Mission Hills, California, 91345, United States

Location

Forest Investigative Site 005

Orange, California, 92869, United States

Location

Forest Investigative Site 024

Westlake Village, California, 91361, United States

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Forest Investigative Site 021

Boulder, Colorado, 80304, United States

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Forest Investigative Site 019

Colorado Springs, Colorado, 80907, United States

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Forest Investigative Site 034

Denver, Colorado, 80205, United States

Location

Forest Investigative Site 074

Longmont, Colorado, 80501, United States

Location

Forest Investigative Site 010

Wheat Ridge, Colorado, 80033, United States

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Forest Investigative Site 058

Waterbury, Connecticut, 06708, United States

Location

Forest Investigative Site 042

Boca Raton, Florida, 33486, United States

Location

Forest Investigative Site 003

Bradenton, Florida, 34203, United States

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Forest Investigative Site 137

Brandon, Florida, 33511, United States

Location

Forest Investigative Site 070

Brooksville, Florida, 34613, United States

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Forest Investigative Site 018

Fort Myers, Florida, 33916, United States

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Forest Investigative Site 030

Jupiter, Florida, 33458, United States

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Forest Investigative Site 077

Kissimmee, Florida, 34741, United States

Location

Forest Investigative Site 133

Miami, Florida, 33126, United States

Location

Forest Investigative Site 031

Miami, Florida, 33143, United States

Location

Forest Investigative Site 129

New Smyrna Beach, Florida, 32168, United States

Location

Forest Investigative Site 108

Ocala, Florida, 34471, United States

Location

Forest Investigative Site 092

Orlando, Florida, 32806, United States

Location

Forest Investigative Site 038

Panama City, Florida, 32405, United States

Location

Forest Investigative Site 027

Pembroke Pines, Florida, 33024, United States

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Forest Investigative Site 045

St. Petersburg, Florida, 33709, United States

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Forest Investigative Site 015

Tampa, Florida, 33606, United States

Location

Forest Investigative Site 104

Trinity, Florida, 34655, United States

Location

Forest Investigative Site 068

Zephyrhills, Florida, 33542, United States

Location

Forest Investigative Site 032

Atlanta, Georgia, 30342, United States

Location

Forest Investigative Site 103

Atlanta, Georgia, 30342, United States

Location

Forest Investigative Site 033

Marietta, Georgia, 30060, United States

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Forest Investigative Site 020

Marietta, Georgia, 30067, United States

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Forest Investigative Site 040

Woodstock, Georgia, 30189, United States

Location

Forest Investigative Site 055

Idaho Falls, Idaho, 83404, United States

Location

Forest Investigative Site 043

Rockford, Illinois, 61107, United States

Location

Forest Investigative Site 047

Evansville, Indiana, 47714, United States

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Forest Investigative Site 046

Iowa City, Iowa, 52242, United States

Location

Forest Investigative Site 029

Arkansas City, Kansas, 67005, United States

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Forest Investigative Site 009

Newton, Kansas, 67114, United States

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Forest Investigative Site 023

Wichita, Kansas, 67205, United States

Location

Forest Investigative Site 093

Wichita, Kansas, 67207, United States

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Forest Investigative Site 067

Lexington, Kentucky, 40509, United States

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Forest Investigative Site 114

Madisonville, Kentucky, 42431, United States

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Forest Investigative Site 132

Baton Rouge, Louisiana, 70808, United States

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Forest Investigative Site 124

Shreveport, Louisiana, 71101, United States

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Forest Investigative Site 013

Chevy Chase, Maryland, 20815, United States

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Forest Investigative Site 006

Hagerstown, Maryland, 21742, United States

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Forest Investigative Site 073

Lutherville, Maryland, 21093, United States

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Forest Investigative Site 001

Boston, Massachusetts, 02135, United States

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Forest Investigative Site 125

Kalamazoo, Michigan, 49048, United States

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Forest Investigative Site 064

Chaska, Minnesota, 55318, United States

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Forest Investigative Site 004

St Louis, Missouri, 63128, United States

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Forest Investigative Site 085

Vineland, New Jersey, 08360, United States

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Forest Investigative Site 052

Albuquerque, New Mexico, 87106, United States

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Forest Investigative Site 035

Brooklyn, New York, 11214, United States

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Forest Investigative Site 017

Great Neck, New York, 11021, United States

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Forest Investigative Site 011

Great Neck, New York, 11023, United States

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Forest Investigative Site 134

Setauket, New York, 11733, United States

Location

Forest Investigative Site 122

Boone, North Carolina, 28607, United States

Location

Forest Investigative Site 072

Fayetteville, North Carolina, 28304, United States

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Forest Investigative Site 016

Greensboro, North Carolina, 27403, United States

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Forest Investigative Site 119

Hickory, North Carolina, 28601, United States

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Forest Investigative Site 088

Raleigh, North Carolina, 27612, United States

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Forest Investigative Site 056

Wilmington, North Carolina, 28401, United States

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Forest Investigative Site 065

Winston-Salem, North Carolina, 27103, United States

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Forest Investigative Site 028

Cincinnati, Ohio, 45219, United States

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Forest Investigative Site 044

Cleveland, Ohio, 44122, United States

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Forest Investigative Site 123

Columbus, Ohio, 43215, United States

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Forest Investigative Site 130

Dayton, Ohio, 45432, United States

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Forest Investigative Site 082

Oklahoma City, Oklahoma, 73104, United States

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Forest Investigative Site 102

Tulsa, Oklahoma, 74135, United States

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Forest Investigative Site 039

Pittsburgh, Pennsylvania, 15206, United States

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Forest Investigative Site 121

Greenville, South Carolina, 29615, United States

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Forest Investigative Site 069

Greer, South Carolina, 29651, United States

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Forest Investigative Site 131

Greer, South Carolina, 29651, United States

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Forest Investigative Site 025

Nashville, Tennessee, 37205, United States

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Forest Investigative Site 099

Austin, Texas, 78705, United States

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Forest Investigative Site 002

Dallas, Texas, 75234, United States

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Forest Investigative Site 041

Houston, Texas, 77090, United States

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Forest Investigative Site 110

Houston, Texas, 77090, United States

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Forest Investigative Site 063

Lake Jackson, Texas, 77566, United States

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Forest Investigative Site 095

San Antonio, Texas, 78209, United States

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Forest Investigative Site 076

San Antonio, Texas, 78229, United States

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Forest Investigative Site 089

Salt Lake City, Utah, 84102, United States

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Forest Investigative Site 091

Salt Lake City, Utah, 84132, United States

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Forest Investigative Site 100

Salt Lake City, Utah, 84148, United States

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Forest Investigative Site 054

Charlottesville, Virginia, 22911, United States

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Forest Investigative Site 061

Christianburg, Virginia, 24073, United States

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Forest Investigative Site 007

Newport News, Virginia, 23606, United States

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Forest Investigative Site 060

Norfolk, Virginia, 23502, United States

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Forest Investigative Site 075

Norfolk, Virginia, 23507, United States

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Forest Investigative Site 050

Richmond, Virginia, 23294, United States

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Forest Investigative Site 049

Bellevue, Washington, 98402, United States

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Forest Investigative Site 098

Lakewood, Washington, 98499, United States

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Forest Investigative Site 066

Wenatchee, Washington, 98801, United States

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Forest Investigative Site 083

Milwaukee, Wisconsin, 53209, United States

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Forest Investigative Site 113

Greater Sudbury, Ontario, P3E 1H5, Canada

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Forest Investigative Site 107

Hamilton, Ontario, L8N 4A6, Canada

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Forest Investigative Site 112

Newmarket, Ontario, L3Y 7V1, Canada

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Forest Investigative Site 106

Ottawa, Ontario, K2C 3R2, Canada

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Forest Investigative Site 115

Sarnia, Ontario, N7T 4X3, Canada

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Forest Investigative Site 008

Toronto, Ontario, M3N 2V7, Canada

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Forest Investigative Site 116

Toronto, Ontario, M4S 1Y2, Canada

Location

Related Publications (2)

• 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.

  PMID: 24075889 DERIVED

• 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.

  PMID: 23116208 DERIVED

MeSH Terms

Conditions

Irritable Bowel Syndrome; Constipation

Condition Hierarchy (Ancestors)

Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Paul F.C. Eng Ph.D Director, Clinical Development
• Organization: Forest Research Institute

Paul.Eng@frx.com

201-427-8071

Study Officials

• Paul F.C. Eng, PhD

  Forest Research Institute, a subsidiary of Forest Laboratories Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 28, 2009
• First Posted: July 29, 2009
• Study Start: July 1, 2009
• Primary Completion: July 1, 2010
• Study Completion: August 1, 2010
• Last Updated: January 30, 2013
• Results First Posted: January 30, 2013

Record last verified: 2012-12

Locations

CA (7); US (111)