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

Irritable Bowel Syndrome Characterized by Constipation Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00948818
• Other study ID #: LIN-MD-31
• Status: Completed
• Phase: Phase 3
• First received: July 28, 2009
• Last updated: December 19, 2012
• Start date: July 2009
• Est. completion date: August 2010

Study information

• Verified date: December 2012
• Source: Forest Laboratories
• 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 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 803
• Est. completion date: August 2010
• Est. primary completion date: July 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

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

• Constipation
• Irritable Bowel Syndrome
• Irritable Bowel Syndrome Characterized by Constipation
• Syndrome

Intervention

Drug:
• Linaclotide 290 micrograms
Oral, once daily each morning at least 30 minutes before breakfast for the duration of the study
• Matching 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 107	Hamilton	Ontario
Canada	Forest Investigative Site 112	New Market	Ontario
Canada	Forest Investigative Site 106	Ottawa	Ontario
Canada	Forest Investigative Site 115	Sarnia	Ontario
Canada	Forest Investigative Site 113	Sudbury	Ontario
Canada	Forest Investigative Site 008	Toronto	Ontario
Canada	Forest Investigative Site 116	Toronto	Ontario
United States	Forest Investigative Site 052	Albuquerque	New Mexico
United States	Forest Investigative Site 029	Arkansas City	Kansas
United States	Forest Investigative Site 032	Atlanta	Georgia
United States	Forest Investigative Site 103	Atlanta	Georgia
United States	Forest Investigative Site 099	Austin	Texas
United States	Forest Investigative Site 132	Baton Rouge	Louisiana
United States	Forest Investigative Site 049	Bellevue	Washington
United States	Forest Investigative Site 036	Birmingham	Alabama
United States	Forest Investigative Site 037	Birmingham	Alabama
United States	Forest Investigative Site 042	Boca Raton	Florida
United States	Forest Investigative Site 122	Boone	North Carolina
United States	Forest Investigative Site 001	Boston	Massachusetts
United States	Forest Investigative Site 021	Boulder	Colorado
United States	Forest Investigative Site 003	Bradenton	Florida
United States	Forest Investigative Site 137	Brandon	Florida
United States	Forest Investigative Site 035	Brooklyn	New York
United States	Forest Investigative Site 070	Brooksville	Florida
United States	Forest Investigative Site 094	Burbank	California
United States	Forest Investigative Site 080	Chandler	Arizona
United States	Forest Investigative Site 054	Charlottesville	Virginia
United States	Forest Investigative Site 064	Chaska	Minnesota
United States	Forest Investigative Site 013	Chevy Chase	Maryland
United States	Forest Investigative Site 061	Christianburg	Virginia
United States	Forest Investigative Site 028	Cincinnati	Ohio
United States	Forest Investigative Site 044	Cleveland	Ohio
United States	Forest Investigative Site 019	Colorado Springs	Colorado
United States	Forest Investigative Site 123	Columbus	Ohio
United States	Forest Investigative Site 002	Dallas	Texas
United States	Forest Investigative Site 130	Dayton	Ohio
United States	Forest Investigative Site 034	Denver	Colorado
United States	Forest Investigative Site 026	Encinitas	California
United States	Forest Investigative Site 047	Evansville	Indiana
United States	Forest Investigative Site 072	Fayetteville	North Carolina
United States	Forest Investigative Site 096	Foothill Ranch	California
United States	Forest Investigative Site 018	Ft. Myers	Florida
United States	Forest Investigative Site 011	Great Neck	New York
United States	Forest Investigative Site 017	Great Neck	New York
United States	Forest Investigative Site 016	Greensboro	North Carolina
United States	Forest Investigative Site 121	Greenville	South Carolina
United States	Forest Investigative Site 069	Greer	South Carolina
United States	Forest Investigative Site 131	Greer	South Carolina
United States	Forest Investigative Site 006	Hagerstown	Maryland
United States	Forest Investigative Site 119	Hickory	North Carolina
United States	Forest Investigative Site 041	Houston	Texas
United States	Forest Investigative Site 110	Houston	Texas
United States	Forest Investigative Site 135	Hueytown	Alabama
United States	Forest Investigative Site 014	Huntsville	Alabama
United States	Forest Investigative Site 055	Idaho Falls	Idaho
United States	Forest Investigative Site 046	Iowa City	Iowa
United States	Forest Investigative Site 030	Jupiter	Florida
United States	Forest Investigative Site 125	Kalamazoo	Michigan
United States	Forest Investigative Site 077	Kissimmee	Florida
United States	Forest Investigative Site 063	Lake Jackson	Texas
United States	Forest Investigative Site 098	Lakewood	Washington
United States	Forest Investigative Site 067	Lexington	Kentucky
United States	Forest Investigative Site 074	Longmont	Colorado
United States	Forest Investigative Site 057	Los Angeles	California
United States	Forest Investigative Site 073	Lutherville	Maryland
United States	Forest Investigative Site 114	Madisonville	Kentucky
United States	Forest Investigative Site 020	Marietta	Georgia
United States	Forest Investigative Site 033	Marietta	Georgia
United States	Forest Investigative Site 053	Mesa	Arizona
United States	Forest Investigative Site 031	Miami	Florida
United States	Forest Investigative Site 133	Miami	Florida
United States	Forest Investigative Site 083	Milwaukee	Wisconsin
United States	Forest Investigative Site 097	Mission Hills	California
United States	Forest Investigative Site 025	Nashville	Tennessee
United States	Forest Investigative Site 129	New Smyrna Beach	Florida
United States	Forest Investigative Site 007	Newport News	Virginia
United States	Forest Investigative Site 009	Newton	Kansas
United States	Forest Investigative Site 060	Norfolk	Virginia
United States	Forest Investigative Site 075	Norfolk	Virginia
United States	Forest Investigative Site 108	Ocala	Florida
United States	Forest Investigative Site 082	Oklahoma City	Oklahoma
United States	Forest Investigative Site 005	Orange	California
United States	Forest Investigative Site 092	Orlando	Florida
United States	Forest Investigative Site 038	Panama City	Florida
United States	Forest Investigative Site 027	Pembroke Pines	Florida
United States	Forest Investigative Site 078	Peoria	Arizona
United States	Forest Investigative Site 101	Phoenix	Arizona
United States	Forest Investigative Site 128	Phoenix	Arizona
United States	Forest Investigative Site 039	Pittsburgh	Pennsylvania
United States	Forest Investigative Site 088	Raleigh	North Carolina
United States	Forest Investigative Site 050	Richmond	Virginia
United States	Forest Investigative Site 043	Rockford	Illinois
United States	Forest Investigative Site 089	Salt Lake City	Utah
United States	Forest Investigative Site 091	Salt Lake City	Utah
United States	Forest Investigative Site 100	Salt Lake City	Utah
United States	Forest Investigative Site 076	San Antonio	Texas
United States	Forest Investigative Site 095	San Antonio	Texas
United States	Forest Investigative Site 051	Scottsdale	Arizona
United States	Forest Investigative Site 134	Setauket	New York
United States	Forest Investigative Site 124	Shreveport	Louisiana
United States	Forest Investigative Site 004	St. Louis	Missouri
United States	Forest Investigative Site 045	St. Petersburg	Florida
United States	Forest Investigative Site 015	Tampa	Florida
United States	Forest Investigative Site 104	Trinity	Florida
United States	Forest Investigative Site 087	Tucson	Arizona
United States	Forest Investigative Site 136	Tucson	Arizona
United States	Forest Investigative Site 102	Tulsa	Oklahoma
United States	Forest Investigative Site 085	Vineland	New Jersey
United States	Forest Investigative Site 058	Waterbury	Connecticut
United States	Forest Investigative Site 066	Wenatchee	Washington
United States	Forest Investigative Site 024	Westlake Village	California
United States	Forest Investigative Site 010	Wheat Ridge	Colorado
United States	Forest Investigative Site 023	Wichita	Kansas
United States	Forest Investigative Site 093	Wichita	Kansas
United States	Forest Investigative Site 056	Wilmington	North Carolina
United States	Forest Investigative Site 065	Winston-Salem	North Carolina
United States	Forest Investigative Site 040	Woodstock	Georgia
United States	Forest Investigative Site 068	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	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	No
Primary	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	No
Primary	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	No
Primary	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	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 Bowl Movement (SBM) Frequency Rate	The number of Spontaneous Bowl Movements experienced per week.	Change from Baseline to Week 12	No
Secondary	12-Week Stool Consistency	The consistency of each BM was assessed by patients using the 7-point Bristol Stool Form Scale (BSFS) from 1 to 7.; = 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 Change in Abdominal Pain Score	Abdominal Pain at its worst (in the last 24 hours) is based on an 11-point scale where 0 represents no abdominal pain and 10 represents very severe abdominal pain.	Change from Baseline to Week 12	No
Secondary	12-Week Change in Abdominal Discomfort	Abdominal Discomfort is measured on an 11-point scale where a value of 0 is "none" and a value of 10 is "very severe."	Change from Baseline to Week 12	No
Secondary	12-Week Change in Bloating	Bloating was assessed on an 11-point scale where a value of 0 is "none" and a value of 10 is "very severe".	Change from Baseline to Week 12	No
Secondary	Complete Spontaneous Bowl Movement (CSBM) Responder for 6 Weeks Out of 12 Weeks of Treatment	A patient is considered to be a CSBM responder if, for at least 6 out of the 12 weeks of the treatment period, an increase of at least 1 CSBM per week from baseline was experienced.	Change from Baseline to Week 12	No
Secondary	Abdominal Pain Responder for 6 Out of 12 Weeks	A patient is considered to be an abdominal pain responder if, for at least 6 out of the 12 weeks of the treatment period, they experienced a decrease of 30 percent or more in the abdominal pain score from baseline.; 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	No
Secondary	12-Week Percent of Abdominal Pain-free (APF) Days	Abdominal pain free (APF) days are those days where the patient reported a score of '0' for abdominal pain at its worst; Abdominal Pain at its worst (in the last 24 hours) is based on an 11-point scale where 0 represents no abdominal pain and 10 represents very severe abdominal pain.	Change from Baseline to Week 12	No