Clinical trial NCT00948818: Trial of Linaclotide Administered to Patients With Irritable Bowel Syndrome With Constipation
Official title: A Phase III, 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 Irritable Bowel Syndrome With Constipation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Irritable Bowel Syndrome Characterized by Constipation
Keywords: Irritable Bowel Syndrome
Constipation
Linaclotide
Lead sponsor: Forest Laboratories
Sponsor class: INDUSTRY
Collaborators: name: Ironwood Pharmaceuticals, Inc.
First posted: 2009-07-29
Enrollment: 803
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* Patient meets protocol criteria for IBS: reports abdominal discomfort or pain that has two or more of the following three features:

  1. Relieved with defecation
  2. Onset associated with a change in frequency of stool
  3. 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Abdominal Pain and Complete Spontaneous Bowel Movement (APC) Responder, 9 Out of 12 Weeks
timeFrame: Change from Baseline to Week 12
measure: Complete Spontaneous Bowel Movement (CSBM) 3+1 Responder, 9 Out of 12 Weeks
timeFrame: Change from Baseline to Week 12
measure: Abdominal Pain Responder, 9 Out of 12 Weeks
timeFrame: Change from Baseline to Week 12
measure: Abdominal Pain and Complete Spontaneous Bowel Movement (APC) Responder, 6 Out of 12 Weeks.
timeFrame: Change from Baseline to Week 12
Secondary outcomes:
measure: 12-Week Complete Spontaneous Bowel Movement (CSBM) Frequency Rate
timeFrame: Change from Baseline to Week 12
measure: 12-Week Spontaneous Bowl Movement (SBM) Frequency Rate
timeFrame: Change from Baseline to Week 12
measure: 12-Week Stool Consistency
timeFrame: Change from Baseline to Week 12
measure: 12-Week Severity of Straining
timeFrame: Change from Baseline to Week 12
measure: 12-Week Change in Abdominal Pain Score
timeFrame: Change from Baseline to Week 12
measure: 12-Week Change in Abdominal Discomfort
timeFrame: Change from Baseline to Week 12
measure: 12-Week Change in Bloating
timeFrame: Change from Baseline to Week 12
measure: Complete Spontaneous Bowl Movement (CSBM) Responder for 6 Weeks Out of 12 Weeks of Treatment
timeFrame: Change from Baseline to Week 12
measure: Abdominal Pain Responder for 6 Out of 12 Weeks
timeFrame: Change from Baseline to Week 12
measure: 12-Week Percent of Abdominal Pain-free (APF) Days
timeFrame: Change from Baseline to Week 12
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Forest Investigative Site 037
state: Alabama
city: Birmingham
country: United States
facility: Forest Investigative Site 036
state: Alabama
city: Hueytown
country: United States
facility: Forest Investigative Site 135
state: Alabama
city: Huntsville
country: United States
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state: Alabama
city: Chandler
country: United States
facility: Forest Investigative Site 080
state: Arizona
city: Mesa
country: United States
facility: Forest Investigative Site 053
state: Arizona
city: Peoria
country: United States
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state: Arizona
city: Phoenix
country: United States
facility: Forest Investigative Site 101
state: Arizona
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state: Arizona
city: Scottsdale
country: United States
facility: Forest Investigative Site 051
state: Arizona
city: Tucson
country: United States
facility: Forest Investigative Site 136
state: Arizona
city: Tucson
country: United States
facility: Forest Investigative Site 087
state: Arizona
city: Burbank
country: United States
facility: Forest Investigative Site 094
state: California
city: Encinitas
country: United States
facility: Forest Investigative Site 026
state: California
city: Foothill Ranch
country: United States
facility: Forest Investigative Site 096
state: California
city: Los Angeles
country: United States
facility: Forest Investigative Site 057
state: California
city: Mission Hills
country: United States
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state: California
city: Orange
country: United States
facility: Forest Investigative Site 005
state: California
city: Westlake Village
country: United States
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state: California
city: Boulder
country: United States
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state: Colorado
city: Colorado Springs
country: United States
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state: Colorado
city: Denver
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state: Colorado
city: Longmont
country: United States
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state: Colorado
city: Wheat Ridge
country: United States
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state: Colorado
city: Waterbury
country: United States
facility: Forest Investigative Site 058
state: Connecticut
city: Boca Raton
country: United States
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state: Florida
city: Bradenton
country: United States
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city: New Smyrna Beach
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city: Orlando
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city: Panama City
country: United States
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city: Pembroke Pines
country: United States
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city: St. Petersburg
country: United States
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city: Tampa
country: United States
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city: Trinity
country: United States
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city: Zephyrhills
country: United States
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state: Florida
city: Atlanta
country: United States
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state: Georgia
city: Atlanta
country: United States
facility: Forest Investigative Site 103
state: Georgia
city: Marietta
country: United States
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state: Georgia
city: Marietta
country: United States
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state: Georgia
city: Woodstock
country: United States
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city: Idaho Falls
country: United States
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state: Idaho
city: Rockford
country: United States
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state: Illinois
city: Evansville
country: United States
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state: Indiana
city: Iowa City
country: United States
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state: Iowa
city: Arkansas City
country: United States
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state: Kansas
city: Newton
country: United States
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city: Wichita
country: United States
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city: Wichita
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state: Kansas
city: Lexington
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state: Kentucky
city: Madisonville
country: United States
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state: Kentucky
city: Baton Rouge
country: United States
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state: Louisiana
city: Shreveport
country: United States
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state: Louisiana
city: Chevy Chase
country: United States
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state: Maryland
city: Hagerstown
country: United States
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state: Maryland
city: Lutherville
country: United States
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state: Maryland
city: Boston
country: United States
facility: Forest Investigative Site 001
state: Massachusetts
city: Kalamazoo
country: United States
facility: Forest Investigative Site 125
state: Michigan
city: Chaska
country: United States
facility: Forest Investigative Site 064
state: Minnesota
city: St. Louis
country: United States
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state: Missouri
city: Vineland
country: United States
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state: New Jersey
city: Albuquerque
country: United States
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state: New Mexico
city: Brooklyn
country: United States
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state: New York
city: Great Neck
country: United States
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state: New York
city: Great Neck
country: United States
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state: New York
city: Setauket
country: United States
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state: New York
city: Boone
country: United States
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state: North Carolina
city: Fayetteville
country: United States
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city: Greensboro
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city: Hickory
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state: North Carolina
city: Raleigh
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city: Wilmington
country: United States
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state: North Carolina
city: Winston-Salem
country: United States
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state: North Carolina
city: Cincinnati
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state: Ohio
city: Cleveland
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state: Ohio
city: Columbus
country: United States
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state: Ohio
city: Dayton
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state: Ohio
city: Oklahoma City
country: United States
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state: Oklahoma
city: Tulsa
country: United States
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state: Oklahoma
city: Pittsburgh
country: United States
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state: Pennsylvania
city: Greenville
country: United States
facility: Forest Investigative Site 121
state: South Carolina
city: Greer
country: United States
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state: South Carolina
city: Greer
country: United States
facility: Forest Investigative Site 131
state: South Carolina
city: Nashville
country: United States
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state: Tennessee
city: Austin
country: United States
facility: Forest Investigative Site 099
state: Texas
city: Dallas
country: United States
facility: Forest Investigative Site 002
state: Texas
city: Houston
country: United States
facility: Forest Investigative Site 041
state: Texas
city: Houston
country: United States
facility: Forest Investigative Site 110
state: Texas
city: Lake Jackson
country: United States
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state: Texas
city: San Antonio
country: United States
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state: Texas
city: San Antonio
country: United States
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state: Texas
city: Salt Lake City
country: United States
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state: Utah
city: Salt Lake City
country: United States
facility: Forest Investigative Site 091
state: Utah
city: Salt Lake City
country: United States
facility: Forest Investigative Site 100
state: Utah
city: Charlottesville
country: United States
facility: Forest Investigative Site 054
state: Virginia
city: Christianburg
country: United States
facility: Forest Investigative Site 061
state: Virginia
city: Newport News
country: United States
facility: Forest Investigative Site 007
state: Virginia
city: Norfolk
country: United States
facility: Forest Investigative Site 060
state: Virginia
city: Norfolk
country: United States
facility: Forest Investigative Site 075
state: Virginia
city: Richmond
country: United States
facility: Forest Investigative Site 050
state: Virginia
city: Bellevue
country: United States
facility: Forest Investigative Site 049
state: Washington
city: Lakewood
country: United States
facility: Forest Investigative Site 098
state: Washington
city: Wenatchee
country: United States
facility: Forest Investigative Site 066
state: Washington
city: Milwaukee
country: United States
facility: Forest Investigative Site 083
state: Wisconsin
city: Hamilton
country: Canada
facility: Forest Investigative Site 107
state: Ontario
city: New Market
country: Canada
facility: Forest Investigative Site 112
state: Ontario
city: Ottawa
country: Canada
facility: Forest Investigative Site 106
state: Ontario
city: Sarnia
country: Canada
facility: Forest Investigative Site 115
state: Ontario
city: Sudbury
country: Canada
facility: Forest Investigative Site 113
state: Ontario
city: Toronto
country: Canada
facility: Forest Investigative Site 008
state: Ontario
city: Toronto
country: Canada
facility: Forest Investigative Site 116
state: Ontario
Study officials:
affiliation: Forest Research Institute, a subsidiary of Forest Laboratories Inc.
name: Paul F.C. Eng, PhD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.