Phase III, Randomized, Double-Blind, Placebo-Controlled, Trial of Linaclotide Administered to Patients With Chronic Constipation

Chronic Constipation Clinical Trial

Official title:

A Phase III, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Trial of Linaclotide Administered Orally for 12 Weeks in Patients With Chronic Constipation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00765882
• Other study ID #: LIN-MD-01
• Status: Completed
• Phase: Phase 3
• First received: October 1, 2008
• Last updated: December 19, 2012
• Start date: September 2008
• Est. completion date: August 2009

Study information

• Verified date: December 2012
• Source: Forest Laboratories
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationCanada: Health Canada
• 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 treatment group that meet the protocol definition for Complete Spontaneous Bowel Movement (CSBM) Overall Responder

Recruitment information / eligibility

• Status: Completed
• Enrollment: 633
• Est. completion date: August 2009
• Est. primary completion date: July 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: 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:
• Linaclotide 290 micrograms
Oral, once daily each morning at least 30 minutes before breakfast for the duration of the study
• Linaclotide 145 micrograms
Oral, once daily each morning at least 30 minutes before breakfast for the duration of the study
• Placebo
Oral, once daily each morning at least 30 minutes before breakfast for the duration of the study

Locations

Country	Name	City	State
Canada	Forest Investigative Site	Hamilton	Ontario
Canada	Forest Investigative Site	Newmarket	Ontario
Canada	Forest Investigative Site	Ottawa	Ontario
Canada	Forest Investigative Site 1	Sarnia	Ontario
Canada	Forest Investigative Site 2	Sarnia	Ontario
Canada	Forest Investigative Site	Sudbury	Ontario
Canada	Forest Investigative Site	Toronto	Ontario
Canada	Forest Investigative Site	Vancouver	British Columbia
United States	Forest Investigative Site	Akron	Ohio
United States	Forest Investigative Site	Albuquerque	New Mexico
United States	Forest Investigative Site	Arkansas City	Kansas
United States	Forest Investigative Site	Atlanta	Georgia
United States	Forest Investigative Site	Austin	Texas
United States	Forest Investigative Site	Bellevue	Washington
United States	Forest Investigative Site	Bensalem	Pennsylvania
United States	Forest Investigative Site	Birmingham	Alabama
United States	Forest Investigative Site	Birmingham	Alabama
United States	Forest Investigative Site	Bismark	North Dakota
United States	Forest Investigative Site	Boca Raton	Florida
United States	Forest Investigative Site	Boston	Massachusetts
United States	Forest Investigative Site	Boulder	Colorado
United States	Forest Investigative Site	Bradenton	Florida
United States	Forest Investigative Site	Brooklyn	New York
United States	Forest Investigative Site	Brooksville	Florida
United States	Forest Investigative Site	Burbank	California
United States	Forest Investigative Site	Chandler	Arizona
United States	Forest Investigative Site	Charlottesville	Virginia
United States	Forest Investigative Site	Chaska	Minnesota
United States	Forest Investigative Site	Chevy Chase	Maryland
United States	Forest Investigative Site	Christianburg	Virginia
United States	Forest Investigative Site	Cincinnati	Ohio
United States	Forest Investigative Site	Cleveland	Ohio
United States	Forest Investigative Site	Colorado Springs	Colorado
United States	Forest Investigative Site	Dallas	Texas
United States	Forest Investigative Sites	Denver	Colorado
United States	Forest Investigative Site	Elkhart	Indiana
United States	Forest Investigative Site	Encinitas	California
United States	Forest Investigative Site	Evansville	Indiana
United States	Forest Investigative Site	Fayetteville	North Carolina
United States	Forest Investigative Site	Foothill Ranch	California
United States	Forest Investigative Site	Ft. Myers	Florida
United States	Forest Investigative Site	Great Neck	New York
United States	Forest Investigative Site	Great Neck	New York
United States	Forest Investigative Site	Greensboro	North Carolina
United States	Forest Investigative Site	Greenville	South Carolina
United States	Forest Investigative Site	Greer	South Carolina
United States	Forest Investigative Site	Hagerstown	Maryland
United States	Forest Investigative Site	Hickory	North Carolina
United States	Forest Investigative Site	Houston	Texas
United States	Forest Investigative Site	Huntsville	Alabama
United States	Forest Investigative Site	Idaho Falls	Idaho
United States	Forest Investigative Site	Indianapolis	Indiana
United States	Forest Investigative Site	Indianapolis	Indiana
United States	Forest Investigative Site	Iowa City	Iowa
United States	Forest Investigative Site	Jupiter	Florida
United States	Forest Investigative Site	Kissimmee	Florida
United States	Forest Investigative Site	Lake Jackson	Texas
United States	Forest Investigative Site	Lakewood	Washington
United States	Forest Investigative Site	Lexington	Kentucky
United States	Forest Investigative Site	Longmont	Colorado
United States	Forest Investigative Site	Los Angeles	California
United States	Forest Investigative Site	Lutherville	Maryland
United States	Forest Investigative Site	Madisonville	Kentucky
United States	Forest Investigative Site	Marietta	Georgia
United States	Forest Investigative Site	Marietta	Georgia
United States	Forest Investigative Site	Mesa	Arizona
United States	Forest Investigative Site	Miami	Florida
United States	Forest Investigative Site	Milwaukee	Wisconsin
United States	Forest Investigative Site	Nashville	Tennessee
United States	Forest Investigative Site	Newport News	Virginia
United States	Forest Investigative Site	Newton	Kansas
United States	Forest Investigative Site	Norfolk	Virginia
United States	Forest Investigative Site	Norfolk	Virginia
United States	Forest Investigative Site	Ocala	Florida
United States	Forest Investigative Site	Oklahoma City	Oklahoma
United States	Forest Investigative Site	Orange	California
United States	Forest Investigative Site	Orlando	Florida
United States	Forest Investigative Site	Panama City	Florida
United States	Forest Investigative Site	Pembroke Pines	Florida
United States	Forest Investigative Site	Peoria	Arizona
United States	Forest Investigative Site	Phoenix	Arizona
United States	Forest Investigative Site	Pittsburgh	Pennsylvania
United States	Forest Investigative Site	Raleigh	North Carolina
United States	Forest Investigative Site	Richmond	Virginia
United States	Forest Investigative Site	Rockford	Illinois
United States	Forest Investigative Site	Salt Lake City	Utah
United States	Forest Investigative Site	San Antonio	Texas
United States	Forest Investigative Site	San Antonio	Texas
United States	Forest Investigative Site	Scottsdale	Arizona
United States	Forest Investigative Site	St. Louis	Missouri
United States	Forest Investigative Site	St. Louis	Missouri
United States	Forest Investigative Site	St. Petersburg	Florida
United States	Forest Investigative Site	Stockbridge	Georgia
United States	Forest Investigative Site	Tampa	Florida
United States	Forest Investigative Site	Trinity	Florida
United States	Forest Investigative Site	Tucson	Arizona
United States	Forest Investigative Site	Tulsa	Oklahoma
United States	Forest Investigative Site	Vineland	New Jersey
United States	Forest Investigative Site	Waterbury	Connecticut
United States	Forest Investigative Site	Wenatchee	Washington
United States	Forest Investigative Site	Westlake Village	California
United States	Forest Investigative Site	Wheat Ridge	Colorado
United States	Forest Investigative Site	Wichita	Kansas
United States	Forest Investigative Site	Wichita	Kansas
United States	Forest Investigative Site	Wilmington	North Carolina
United States	Forest Investigative Site	Winston-Salem	North Carolina
United States	Forest Investigative Site	Woodstock	Georgia
United States	Forest Investigative Site	Zephyrhills	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Forest Laboratories	Ironwood Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete Spontaneous Bowel Movement (CSBM) Overall Responder	A 12-week CSBM overall responders 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 Rate	The number of CSBMs per week.	Change from Baseline to Week 12	No
Secondary	12-Week Spontaneous Bowel Movement (SBM) Frequency Rate	A patient's 12-week spontaneous bowel movement (SBM) frequency rate was the number of SBMs per week calculated over the 12-weeks of the treatment period.	Change from Baseline to Week 12	No
Secondary	12-Week 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 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	No
Secondary	12-Week 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 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 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