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 037
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Birmingham, Alabama, United States
Forest Investigative Site 036
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Birmingham, Alabama, United States
Forest Investigative Site 135
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Hueytown, Alabama, United States
Forest Investigative Site 014
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Huntsville, Alabama, United States
Forest Investigative Site 080
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Chandler, Arizona, United States
Forest Investigative Site 053
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Mesa, Arizona, United States
Forest Investigative Site 078
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Peoria, Arizona, United States
Forest Investigative Site 101
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Phoenix, Arizona, United States
Forest Investigative Site 128
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Phoenix, Arizona, United States
Forest Investigative Site 051
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Scottsdale, Arizona, United States
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Forest Investigative Site 037
🇺🇸Birmingham, Alabama, United States