Clinical trial NCT00730015: Trial of Linaclotide in Patients With Chronic Constipation
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Constipation
Lead sponsor: Ironwood Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Forest Laboratories
First posted: 2008-08-08
Enrollment: 643
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 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.


Eligibility criteria: 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

Primary outcomes:
measure: Complete Spontaneous Bowel Movement (CSBM) Overall Responder
timeFrame: Change from Baseline to Week 12
Secondary outcomes:
measure: 12-Week Complete Spontaneous Bowel Movement (CSBM) Frequency
timeFrame: Change from Baseline to Week 12
measure: 12-Week Spontaneous Bowl Movement (SBM) Frequency
timeFrame: Change from Baseline to Week 12
measure: 12-week Change in Stool Consistency
timeFrame: Change from Baseline to Week 12
measure: 12-week Change in Severity of Straining
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: 12-week Change in Constipation Severity
timeFrame: Change from Baseline to Week 12
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Ironwood Investigational Site
state: Alabama
city: Huntsville
country: United States
facility: Ironwood Investigational Site
state: Alabama
city: Chandler
country: United States
facility: Ironwood Investigational Site
state: Arizona
city: Phoenix
country: United States
facility: Ironwood Investigational Site
state: Arizona
city: Tucson
country: United States
facility: Ironwood Investigational Site
state: Arizona
city: Tuscon
country: United States
facility: Ironwood Investigational Site
state: Arizona
city: Sherwood
country: United States
facility: Ironwood Investigational Site
state: Arkansas
city: Anaheim
country: United States
facility: Ironwood Investigational Site
state: California
city: Chula Vista
country: United States
facility: Ironwood Investigational Site
state: California
city: Encinitas
country: United States
facility: Ironwood Investigational Site
state: California
city: Garden Grove
country: United States
facility: Ironwood Investigational Site
state: California
city: Laguna Hills
country: United States
facility: Ironwood Investigational Site
state: California
city: Los Angeles
country: United States
facility: Ironwood Investigational Site
state: California
city: Orange
country: United States
facility: Ironwood Investigational Site
state: California
city: Sacramento
country: United States
facility: Ironwood Investigational Site
state: California
city: San Carlos
country: United States
facility: Ironwood Investigational Site
state: California
city: San Diego
country: United States
facility: Ironwood Investigational Site
state: California
city: San Diego
country: United States
facility: Ironwood Investigational Site
state: California
city: San Diego
country: United States
facility: Ironwood Investigational Site
state: California
city: Colorado Springs
country: United States
facility: Ironwood Investigational Site
state: Colorado
city: Bristol
country: United States
facility: Ironwood Investigational Site
state: Connecticut
city: Boynton Beach
country: United States
facility: Ironwood Investigational Site
state: Florida
city: Hollywood
country: United States
facility: Ironwood Investigational Site
state: Florida
city: Inverness
country: United States
facility: Ironwood Investigational Site
state: Florida
city: Jacksonville
country: United States
facility: Ironwood Investigational Site
state: Florida
city: Port Orange
country: United States
facility: Ironwood Investigational Site
state: Florida
city: Tampa
country: United States
facility: Ironwood Investigational Site
state: Florida
city: Newnan
country: United States
facility: Ironwood Investigational Site
state: Georgia
city: Peoria
country: United States
facility: Ironwood Investigational Site
state: Illinois
city: Anderson
country: United States
facility: Ironwood Investigational Site
state: Indiana
city: Clive
country: United States
facility: Ironwood Investigational Site
state: Iowa
city: Davenport
country: United States
facility: Ironwood Investigational Site
state: Iowa
city: Mission
country: United States
facility: Ironwood Investigational Site
state: Kansas
city: Overland Park
country: United States
facility: Ironwood Investigational Site
state: Kansas
city: Topeka
country: United States
facility: Ironwood Investigational Site
state: Kansas
city: Baton Rouge
country: United States
facility: Ironwood Investigational Site
state: Louisiana
city: Monroe
country: United States
facility: Ironwood Investigational Site
state: Louisiana
city: Shreveport
country: United States
facility: Ironwood Investigational Site
state: Louisiana
city: Annapolis
country: United States
facility: Ironwood Investigational Site
state: Maryland
city: Baltimore
country: United States
facility: Ironwood Investigational Site
state: Maryland
city: Hollywood
country: United States
facility: Ironwood Investigational Site
state: Maryland
city: Laurel
country: United States
facility: Ironwood Investigational Site
state: Maryland
city: Chesterfield
country: United States
facility: Ironwood Investigational Site
state: Michigan
city: Traverse City
country: United States
facility: Ironwood Investigational Site
state: Michigan
city: Troy
country: United States
facility: Ironwood Investigational Site
state: Michigan
city: Jackson
country: United States
facility: Ironwood Investigational Site
state: Mississippi
city: Tupelo
country: United States
facility: Ironwood Investigational Site
state: Mississippi
city: Jefferson City
country: United States
facility: Ironwood Investigational Site
state: Missouri
city: Henderson
country: United States
facility: Ironwood Investigational Site
state: Nevada
city: Las Vegas
country: United States
facility: Ironwood Investigational Site
state: Nevada
city: Cedar Knolls
country: United States
facility: Ironwood Investigational Site
state: New Jersey
city: Marlton
country: United States
facility: Ironwood Investigational Site
state: New Jersey
city: Ocean
country: United States
facility: Ironwood Investigational Site
state: New Jersey
city: Albuquerque
country: United States
facility: Ironwood Investigational Site
state: New Mexico
city: Mineola
country: United States
facility: Ironwood Investigational Site
state: New York
city: Pittsford
country: United States
facility: Ironwood Investigational Site
state: New York
city: Asheboro
country: United States
facility: Ironwood Investigational Site
state: North Carolina
city: Asheville
country: United States
facility: Ironwood Investigational Site
state: North Carolina
city: Chapel Hill
country: United States
facility: Ironwood Investigational Site
state: North Carolina
city: Charlotte
country: United States
facility: Ironwood Investigational Site
state: North Carolina
city: Greensboro
country: United States
facility: Ironwood Investigational Site
state: North Carolina
city: Harrisburg
country: United States
facility: Ironwood Investigational Site
state: North Carolina
city: Hickory
country: United States
facility: Ironwood Investigational Site
state: North Carolina
city: Jacksonville
country: United States
facility: Ironwood Investigational Site
state: North Carolina
city: New Bern
country: United States
facility: Ironwood Investigational Site
state: North Carolina
city: Statesville
country: United States
facility: Ironwood Investigational Site
state: North Carolina
city: Summerville
country: United States
facility: Ironwood Investigational Site
state: North Carolina
city: Wilmington
country: United States
facility: Ironwood Investigational Site
state: North Carolina
city: Winston Salem
country: United States
facility: Ironwood Investigational Site
state: North Carolina
city: Beachwood
country: United States
facility: Ironwood Investigational Site
state: Ohio
city: Cincinnati
country: United States
facility: Ironwood Investigational Site
state: Ohio
city: Cincinnati
country: United States
facility: Ironwood Investigational Site
state: Ohio
city: Dayton
country: United States
facility: Ironwood Investigational Site
state: Ohio
city: Sylvania
country: United States
facility: Ironwood Investigational Site
state: Ohio
city: Wadsworth
country: United States
facility: Ironwood Investigational Site
state: Ohio
city: Zanesville
country: United States
facility: Ironwood Investigational Site
state: Ohio
city: Oklahoma City
country: United States
facility: Ironwood Investigational Site
state: Oklahoma
city: Yukon
country: United States
facility: Ironwood Investigational Site
state: Oklahoma
city: Lancaster
country: United States
facility: Ironwood Investigational Site
state: Pennsylvania
city: Lancaster
country: United States
facility: Ironwood Investigational Site
state: Pennsylvania
city: Levittown
country: United States
facility: Ironwood Investigational Site
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Ironwood Investigational Site
state: Pennsylvania
city: Sellersville
country: United States
facility: Ironwood Investigational Site
state: Pennsylvania
city: Anderson
country: United States
facility: Ironwood Investigational Site
state: South Carolina
city: Charleston
country: United States
facility: Ironwood Investigational Site
state: South Carolina
city: Simpsonville
country: United States
facility: Ironwood Investigational Site
state: South Carolina
city: Bristol
country: United States
facility: Ironwood Investigational Site
state: Tennessee
city: Chattanooga
country: United States
facility: Ironwood Investigational Site
state: Tennessee
city: Germantown
country: United States
facility: Ironwood Investigational Site
state: Tennessee
city: Kingsport
country: United States
facility: Ironwood Investigational Site
state: Tennessee
city: Nashville
country: United States
facility: Ironwood Investigational Site
state: Tennessee
city: Beaumont
country: United States
facility: Ironwood Investigational Site
state: Texas
city: El Paso
country: United States
facility: Ironwood Investigational Site
state: Texas
city: Houston
country: United States
facility: Ironwood Investigational Site
state: Texas
city: Irving
country: United States
facility: Ironwood Investigational Site
state: Texas
city: Longview
country: United States
facility: Ironwood Investigational Site
state: Texas
city: San Antonio
country: United States
facility: Ironwood Investigational Site
state: Texas
city: Ogden
country: United States
facility: Ironwood Investigational Site
state: Utah
city: Salt Lake City
country: United States
facility: Ironwood Investigational Site
state: Utah
city: Chesapeake
country: United States
facility: Ironwood Investigational Site
state: Virginia
city: Lynchburg
country: United States
facility: Ironwood Investigational Site
state: Virginia
city: Spokane
country: United States
facility: Ironwood Investigational Site
state: Washington
city: Vancouver
country: United States
facility: Ironwood Investigational Site
state: Washington
city: LaCrosse
country: United States
facility: Ironwood Investigational Site
state: Wisconsin
city: Milwaukee
country: United States
facility: Ironwood Investigational Site
state: Wisconsin
Study officials:
affiliation: Ironwood Pharmaceuticals, Inc.
name: Jeffrey M. Johnston, MD, FACP
role: STUDY_CHAIR
References:
citation: Chang L, Lembo AJ, Lavins BJ, Shiff SJ, Hao X, Chickering JG, Jia XD, Currie MG, Kurtz CB, Johnston JM. The impact of abdominal pain on global measures in patients with chronic idiopathic constipation, before and after treatment with linaclotide: a pooled analysis of two randomised, double-blind, placebo-controlled, phase 3 trials. Aliment Pharmacol Ther. 2014 Dec;40(11-12):1302-12. doi: 10.1111/apt.12985. Epub 2014 Oct 13.
citation: Lembo AJ, Schneier HA, Shiff SJ, Kurtz CB, MacDougall JE, Jia XD, Shao JZ, Lavins BJ, Currie MG, Fitch DA, Jeglinski BI, Eng P, Fox SM, Johnston JM. Two randomized trials of linaclotide for chronic constipation. N Engl J Med. 2011 Aug 11;365(6):527-36. doi: 10.1056/NEJMoa1010863.