Trial of Linaclotide in Patients With Chronic Constipation

Chronic Constipation Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00730015
• Other study ID #: MCP-103-303
• Status: Completed
• Phase: Phase 3
• First received: August 5, 2008
• Last updated: December 19, 2012
• Start date: August 2008
• Est. completion date: October 2009

Study information

• Verified date: December 2012
• Source: Ironwood Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 643
• Est. completion date: October 2009
• Est. primary completion date: August 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Constipation
• Constipation

Intervention

Drug:
• Matching Placebo
Oral, once daily
• Linaclotide
Oral, once daily

Locations

Country	Name	City	State
United States	Ironwood Investigational Site	Albuquerque	New Mexico
United States	Ironwood Investigational Site	Anaheim	California
United States	Ironwood Investigational Site	Anderson	Indiana
United States	Ironwood Investigational Site	Anderson	South Carolina
United States	Ironwood Investigational Site	Annapolis	Maryland
United States	Ironwood Investigational Site	Asheboro	North Carolina
United States	Ironwood Investigational Site	Asheville	North Carolina
United States	Ironwood Investigational Site	Baltimore	Maryland
United States	Ironwood Investigational Site	Baton Rouge	Louisiana
United States	Ironwood Investigational Site	Beachwood	Ohio
United States	Ironwood Investigational Site	Beaumont	Texas
United States	Ironwood Investigational Site	Birmingham	Alabama
United States	Ironwood Investigational Site	Boynton Beach	Florida
United States	Ironwood Investigational Site	Bristol	Connecticut
United States	Ironwood Investigational Site	Bristol	Tennessee
United States	Ironwood Investigational Site	Cedar Knolls	New Jersey
United States	Ironwood Investigational Site	Chandler	Arizona
United States	Ironwood Investigational Site	Chapel Hill	North Carolina
United States	Ironwood Investigational Site	Charleston	South Carolina
United States	Ironwood Investigational Site	Charlotte	North Carolina
United States	Ironwood Investigational Site	Chattanooga	Tennessee
United States	Ironwood Investigational Site	Chesapeake	Virginia
United States	Ironwood Investigational Site	Chesterfield	Michigan
United States	Ironwood Investigational Site	Chula Vista	California
United States	Ironwood Investigational Site	Cincinnati	Ohio
United States	Ironwood Investigational Site	Cincinnati	Ohio
United States	Ironwood Investigational Site	Clive	Iowa
United States	Ironwood Investigational Site	Colorado Springs	Colorado
United States	Ironwood Investigational Site	Davenport	Iowa
United States	Ironwood Investigational Site	Dayton	Ohio
United States	Ironwood Investigational Site	El Paso	Texas
United States	Ironwood Investigational Site	Encinitas	California
United States	Ironwood Investigational Site	Garden Grove	California
United States	Ironwood Investigational Site	Germantown	Tennessee
United States	Ironwood Investigational Site	Greensboro	North Carolina
United States	Ironwood Investigational Site	Harrisburg	North Carolina
United States	Ironwood Investigational Site	Henderson	Nevada
United States	Ironwood Investigational Site	Hickory	North Carolina
United States	Ironwood Investigational Site	Hollywood	Florida
United States	Ironwood Investigational Site	Hollywood	Maryland
United States	Ironwood Investigational Site	Houston	Texas
United States	Ironwood Investigational Site	Huntsville	Alabama
United States	Ironwood Investigational Site	Inverness	Florida
United States	Ironwood Investigational Site	Irving	Texas
United States	Ironwood Investigational Site	Jackson	Mississippi
United States	Ironwood Investigational Site	Jacksonville	North Carolina
United States	Ironwood Investigational Site	Jacksonville	Florida
United States	Ironwood Investigational Site	Jefferson City	Missouri
United States	Ironwood Investigational Site	Kingsport	Tennessee
United States	Ironwood Investigational Site	LaCrosse	Wisconsin
United States	Ironwood Investigational Site	Laguna Hills	California
United States	Ironwood Investigational Site	Lancaster	Pennsylvania
United States	Ironwood Investigational Site	Lancaster	Pennsylvania
United States	Ironwood Investigational Site	Las Vegas	Nevada
United States	Ironwood Investigational Site	Laurel	Maryland
United States	Ironwood Investigational Site	Levittown	Pennsylvania
United States	Ironwood Investigational Site	Longview	Texas
United States	Ironwood Investigational Site	Los Angeles	California
United States	Ironwood Investigational Site	Lynchburg	Virginia
United States	Ironwood Investigational Site	Marlton	New Jersey
United States	Ironwood Investigational Site	Milwaukee	Wisconsin
United States	Ironwood Investigational Site	Mineola	New York
United States	Ironwood Investigational Site	Mission	Kansas
United States	Ironwood Investigational Site	Monroe	Louisiana
United States	Ironwood Investigational Site	Nashville	Tennessee
United States	Ironwood Investigational Site	New Bern	North Carolina
United States	Ironwood Investigational Site	Newnan	Georgia
United States	Ironwood Investigational Site	Ocean	New Jersey
United States	Ironwood Investigational Site	Ogden	Utah
United States	Ironwood Investigational Site	Oklahoma City	Oklahoma
United States	Ironwood Investigational Site	Orange	California
United States	Ironwood Investigational Site	Overland Park	Kansas
United States	Ironwood Investigational Site	Peoria	Illinois
United States	Ironwood Investigational Site	Phoenix	Arizona
United States	Ironwood Investigational Site	Pittsburgh	Pennsylvania
United States	Ironwood Investigational Site	Pittsford	New York
United States	Ironwood Investigational Site	Port Orange	Florida
United States	Ironwood Investigational Site	Sacramento	California
United States	Ironwood Investigational Site	Salt Lake City	Utah
United States	Ironwood Investigational Site	San Antonio	Texas
United States	Ironwood Investigational Site	San Carlos	California
United States	Ironwood Investigational Site	San Diego	California
United States	Ironwood Investigational Site	San Diego	California
United States	Ironwood Investigational Site	San Diego	California
United States	Ironwood Investigational Site	Sellersville	Pennsylvania
United States	Ironwood Investigational Site	Sherwood	Arkansas
United States	Ironwood Investigational Site	Shreveport	Louisiana
United States	Ironwood Investigational Site	Simpsonville	South Carolina
United States	Ironwood Investigational Site	Spokane	Washington
United States	Ironwood Investigational Site	Statesville	North Carolina
United States	Ironwood Investigational Site	Summerville	North Carolina
United States	Ironwood Investigational Site	Sylvania	Ohio
United States	Ironwood Investigational Site	Tampa	Florida
United States	Ironwood Investigational Site	Topeka	Kansas
United States	Ironwood Investigational Site	Traverse City	Michigan
United States	Ironwood Investigational Site	Troy	Michigan
United States	Ironwood Investigational Site	Tucson	Arizona
United States	Ironwood Investigational Site	Tupelo	Mississippi
United States	Ironwood Investigational Site	Tuscon	Arizona
United States	Ironwood Investigational Site	Vancouver	Washington
United States	Ironwood Investigational Site	Wadsworth	Ohio
United States	Ironwood Investigational Site	Wilmington	North Carolina
United States	Ironwood Investigational Site	Winston Salem	North Carolina
United States	Ironwood Investigational Site	Yukon	Oklahoma
United States	Ironwood Investigational Site	Zanesville	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Ironwood Pharmaceuticals, Inc.	Forest Laboratories

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete Spontaneous Bowel Movement (CSBM) Overall Responder	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	No
Secondary	12-Week Complete Spontaneous Bowel Movement (CSBM) Frequency	The number of CSBMs per week.	Change from Baseline to Week 12	No
Secondary	12-Week Spontaneous Bowl Movement (SBM) Frequency	The number of SBMs per week.	Change from Baseline to Week 12	No
Secondary	12-week Change in Stool Consistency	The consistency of each BM was assessed using the 7-point Bristol Stool Form Scale: = 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	No
Secondary	12-week Change in Severity of Straining	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	No
Secondary	12-week Change in Abdominal Discomfort	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	No
Secondary	12-week Change in Bloating	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	No
Secondary	12-week Change in Constipation Severity	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	No