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

Phase 3

Completed

Conditions: Irritable Bowel Syndrome Characterized by Constipation

Interventions: Drug: Linaclotide 290 micrograms
Drug: Matching placebo

Registration Number: NCT00948818

Lead Sponsor: Forest Laboratories

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 803

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

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Linaclotide	Linaclotide 290 micrograms	Linaclotide 290 micrograms
Placebo	Matching placebo	Matching placebo

Primary Outcome Measures

Name	Time	Method
Abdominal Pain and Complete Spontaneous Bowel Movement (APC) Responder, 9 Out of 12 Weeks	Change from Baseline to Week 12	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.
Complete Spontaneous Bowel Movement (CSBM) 3+1 Responder, 9 Out of 12 Weeks	Change from Baseline to Week 12	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.
Abdominal Pain Responder, 9 Out of 12 Weeks	Change from Baseline to Week 12	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.
Abdominal Pain and Complete Spontaneous Bowel Movement (APC) Responder, 6 Out of 12 Weeks.	Change from Baseline to Week 12	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.

Secondary Outcome Measures

Name	Time	Method
12-Week Complete Spontaneous Bowel Movement (CSBM) Frequency Rate	Change from Baseline to Week 12	The number of CSBMs per week.
12-Week Spontaneous Bowl Movement (SBM) Frequency Rate	Change from Baseline to Week 12	The number of Spontaneous Bowl Movements experienced per week.
12-Week Stool Consistency	Change from Baseline to Week 12	The consistency of each BM was assessed by patients using the 7-point Bristol Stool Form Scale (BSFS) from 1 to 7. 1. = separate hard lumps like nuts \[difficult to pass\] 2. = sausage shaped but lumpy 3. = like a sausage but with cracks on surface 4. = like a sausage or snake, smooth and soft 5. = soft blobs with clear-cut edges \[passed easily\] 6. = fluffy pieces with ragged edges, a mushy stool 7. = watery, no solid pieces \[entirely liquid\]).
12-Week Severity of Straining	Change from Baseline to Week 12	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.
12-Week Change in Abdominal Pain Score	Change from Baseline to Week 12	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.
12-Week Change in Abdominal Discomfort	Change from Baseline to Week 12	Abdominal Discomfort is measured on an 11-point scale where a value of 0 is "none" and a value of 10 is "very severe."
12-Week Change in Bloating	Change from Baseline to Week 12	Bloating was assessed on an 11-point scale where a value of 0 is "none" and a value of 10 is "very severe".
Complete Spontaneous Bowl Movement (CSBM) Responder for 6 Weeks Out of 12 Weeks of Treatment	Change from Baseline to Week 12	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.
Abdominal Pain Responder for 6 Out of 12 Weeks	Change from Baseline to Week 12	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.
12-Week Percent of Abdominal Pain-free (APF) Days	Change from Baseline to Week 12	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.

Trial Locations

Locations (118): Forest Investigative Site 057
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Los Angeles, California, United States
Forest Investigative Site 032
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Atlanta, Georgia, United States
Forest Investigative Site 001
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Boston, Massachusetts, United States
Forest Investigative Site 044
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Cleveland, Ohio, United States
Forest Investigative Site 113
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Sudbury, Ontario, Canada
Forest Investigative Site 094
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Burbank, California, United States
Forest Investigative Site 026
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Encinitas, California, United States
Forest Investigative Site 005
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Orange, California, United States
Forest Investigative Site 053
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Mesa, Arizona, United States
Forest Investigative Site 097
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Mission Hills, California, United States
Forest Investigative Site 074
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Longmont, Colorado, United States
Forest Investigative Site 018
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Ft. Myers, Florida, United States
Forest Investigative Site 096
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Foothill Ranch, California, United States
Forest Investigative Site 080
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Chandler, Arizona, United States
Forest Investigative Site 078
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Peoria, Arizona, United States
Forest Investigative Site 108
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Ocala, Florida, United States
Forest Investigative Site 014
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Huntsville, Alabama, United States
Forest Investigative Site 051
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Scottsdale, Arizona, United States
Forest Investigative Site 042
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Boca Raton, Florida, United States
Forest Investigative Site 058
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Waterbury, Connecticut, United States
Forest Investigative Site 070
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Brooksville, Florida, United States
Forest Investigative Site 068
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Zephyrhills, Florida, United States
Forest Investigative Site 029
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Arkansas City, Kansas, United States
Forest Investigative Site 125
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Kalamazoo, Michigan, United States
Forest Investigative Site 006
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Hagerstown, Maryland, United States
Forest Investigative Site 104
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Trinity, Florida, United States
Forest Investigative Site 033
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Marietta, Georgia, United States
Forest Investigative Site 046
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Iowa City, Iowa, United States
Forest Investigative Site 073
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Lutherville, Maryland, United States
Forest Investigative Site 047
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Evansville, Indiana, United States
Forest Investigative Site 134
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Setauket, New York, United States
Forest Investigative Site 124
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Shreveport, Louisiana, United States
Forest Investigative Site 009
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Newton, Kansas, United States
Forest Investigative Site 093
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Wichita, Kansas, United States
Forest Investigative Site 023
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Wichita, Kansas, United States
Forest Investigative Site 037
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Birmingham, Alabama, United States
Forest Investigative Site 036
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Birmingham, Alabama, United States
Forest Investigative Site 128
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Phoenix, Arizona, United States
Forest Investigative Site 101
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Phoenix, Arizona, United States
Forest Investigative Site 034
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Denver, Colorado, United States
Forest Investigative Site 133
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Miami, Florida, United States
Forest Investigative Site 031
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Miami, Florida, United States
Forest Investigative Site 028
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Cincinnati, Ohio, United States
Forest Investigative Site 082
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Oklahoma City, Oklahoma, United States
Forest Investigative Site 025
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Nashville, Tennessee, United States
Forest Investigative Site 041
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Houston, Texas, United States
Forest Investigative Site 110
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Houston, Texas, United States
Forest Investigative Site 095
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San Antonio, Texas, United States
Forest Investigative Site 076
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San Antonio, Texas, United States
Forest Investigative Site 089
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Salt Lake City, Utah, United States
Forest Investigative Site 091
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Salt Lake City, Utah, United States
Forest Investigative Site 100
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Salt Lake City, Utah, United States
Forest Investigative Site 115
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Sarnia, Ontario, Canada
Forest Investigative Site 135
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Hueytown, Alabama, United States
Forest Investigative Site 077
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Kissimmee, Florida, United States
Forest Investigative Site 136
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Tucson, Arizona, United States
Forest Investigative Site 024
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Westlake Village, California, United States
Forest Investigative Site 087
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Tucson, Arizona, United States
Forest Investigative Site 021
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Boulder, Colorado, United States
Forest Investigative Site 019
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Colorado Springs, Colorado, United States
Forest Investigative Site 010
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Wheat Ridge, Colorado, United States
Forest Investigative Site 030
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Jupiter, Florida, United States
Forest Investigative Site 003
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Bradenton, Florida, United States
Forest Investigative Site 129
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New Smyrna Beach, Florida, United States
Forest Investigative Site 027
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Pembroke Pines, Florida, United States
Forest Investigative Site 040
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Woodstock, Georgia, United States
Forest Investigative Site 103
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Atlanta, Georgia, United States
Forest Investigative Site 015
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Tampa, Florida, United States
Forest Investigative Site 085
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Vineland, New Jersey, United States
Forest Investigative Site 043
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Rockford, Illinois, United States
Forest Investigative Site 064
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Chaska, Minnesota, United States
Forest Investigative Site 137
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Brandon, Florida, United States
Forest Investigative Site 045
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St. Petersburg, Florida, United States
Forest Investigative Site 038
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Panama City, Florida, United States
Forest Investigative Site 020
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Marietta, Georgia, United States
Forest Investigative Site 055
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Idaho Falls, Idaho, United States
Forest Investigative Site 013
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Chevy Chase, Maryland, United States
Forest Investigative Site 132
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Baton Rouge, Louisiana, United States
Forest Investigative Site 067
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Lexington, Kentucky, United States
Forest Investigative Site 004
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St. Louis, Missouri, United States
Forest Investigative Site 011
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Great Neck, New York, United States
Forest Investigative Site 035
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Brooklyn, New York, United States
Forest Investigative Site 052
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Albuquerque, New Mexico, United States
Forest Investigative Site 017
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Great Neck, New York, United States
Forest Investigative Site 122
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Boone, North Carolina, United States
Forest Investigative Site 016
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Greensboro, North Carolina, United States
Forest Investigative Site 088
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Raleigh, North Carolina, United States
Forest Investigative Site 072
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Fayetteville, North Carolina, United States
Forest Investigative Site 119
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Hickory, North Carolina, United States
Forest Investigative Site 056
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Wilmington, North Carolina, United States
Forest Investigative Site 065
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Winston-Salem, North Carolina, United States
Forest Investigative Site 123
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Columbus, Ohio, United States
Forest Investigative Site 130
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Dayton, Ohio, United States
Forest Investigative Site 039
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Pittsburgh, Pennsylvania, United States
Forest Investigative Site 102
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Tulsa, Oklahoma, United States
Forest Investigative Site 131
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Greer, South Carolina, United States
Forest Investigative Site 121
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Greenville, South Carolina, United States
Forest Investigative Site 069
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Greer, South Carolina, United States
Forest Investigative Site 002
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Dallas, Texas, United States
Forest Investigative Site 099
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Austin, Texas, United States
Forest Investigative Site 063
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Lake Jackson, Texas, United States
Forest Investigative Site 054
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Charlottesville, Virginia, United States
Forest Investigative Site 060
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Norfolk, Virginia, United States
Forest Investigative Site 050
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Richmond, Virginia, United States
Forest Investigative Site 007
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Newport News, Virginia, United States
Forest Investigative Site 075
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Norfolk, Virginia, United States
Forest Investigative Site 061
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Christianburg, Virginia, United States
Forest Investigative Site 049
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Bellevue, Washington, United States
Forest Investigative Site 098
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Lakewood, Washington, United States
Forest Investigative Site 112
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New Market, Ontario, Canada
Forest Investigative Site 107
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Hamilton, Ontario, Canada
Forest Investigative Site 066
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Wenatchee, Washington, United States
Forest Investigative Site 083
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Milwaukee, Wisconsin, United States
Forest Investigative Site 106
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Ottawa, Ontario, Canada
Forest Investigative Site 116
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Toronto, Ontario, Canada
Forest Investigative Site 008
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Toronto, Ontario, Canada
Forest Investigative Site 092
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Orlando, Florida, United States
Forest Investigative Site 114
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Madisonville, Kentucky, United States