Trial of Linaclotide in Patients With Irritable Bowel Syndrome With Constipation (IBS-C)

Study Overview
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Brief Summary
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The purpose of this study is to determine the safety and efficacy of linaclotide administered to patients with Irritable Bowel Syndrome with Constipation (IBS-C).

Official Title
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A Phase 3, Randomized, Double-blind, Placebo-controlled, Parallel-group Trial of Linaclotide Administered Orally for 26 Weeks in Patients With Irritable Bowel Syndrome With Constipation

Conditions
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Irritable Bowel Syndrome With Constipation

Intervention / Treatment
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* Drug: Linaclotide or Matching Placebo


Participation Criteria
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Eligibility Criteria
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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 diagnosis of IBS-C Patient demonstrates continued IBS-C 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 a medical condition that may contribute to abdominal pain 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Linaclotide or Matching Placebo<br>* Linaclotide or Matching Placebo, administered orally, once daily, for the duration of the trial<br>|
| Experimental: 290 μg Linaclotide<br> | Drug: Linaclotide or Matching Placebo<br>* Linaclotide or Matching Placebo, administered orally, once daily, for the duration of the trial<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Abdominal Pain and Complete Spontaneous Bowel Movement (APC) Responder, 9 Out of 12 Weeks | A patient is considered to be a 9 out of 12 week APC responder if, for at least 9 out of the first 12 weeks of the treatment period, the patient had at least 3 CSBMs, had an increase of at least 1 CSBM from baseline, and had a decrease of at least 30 percent in their Abdominal Pain (AP) score from baseline during a particular week. The AP score assesses patient's worst 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. SBM is defined as a bowel movement that occurs in the absence of laxative, enema, or suppository use on either the calendar day of the bowel movement or the calendar day before the bowel movement. CSBM is defined as an SBM associated with a sense of complete evacuation. | Change from Baseline to Week 12 | 
| 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 | 
| 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 patient's worst 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 | 
| Abdominal Pain and Complete Spontaneous Bowel Movement (APC) Responder, 6 Out of 12 Weeks | A patient is considered to be a 6 out of 12 week APC responder if, for at least 6 out of the first 12 weeks of the treatment period, the patient had an increase of at least 1 CSBM from baseline, and had a decrease of at least 30 percent in their Abdominal Pain (AP) score from baseline during a particular week. The AP score assesses patient's worst 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. SBM is defined as a bowel movement that occurs in the absence of laxative, enema, or suppository use on either the calendar day of the bowel movement or the calendar day before the bowel movement. CSBM is defined as an SBM associated with a sense of complete evacuation. | Change from Baseline to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 12-Week Complete Spontaneous Bowel Movement (CSBM) Frequency | The change from baseline in 12-week CSBM frequency (i.e., weekly CSBM frequency over the first 12 weeks of the Treatment Period). | Change from Baseline to Week 12 | 
| 12-Week Spontaneous Bowl Movement (SBM) Frequency | The change from baseline in 12-week SBM frequency (i.e., weekly SBM frequency over the first 12 weeks of the Treatment Period). | Change from Baseline to Week 12 | 
| 12-Week Change in 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 | 
| 12-Week Change in 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 | 
| 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 | 
| 12-Week Change in Abdominal Discomfort | Abdominal discomfort 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 | 
| 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 | 
| 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 | 
| Abdominal Pain Responder for 6 Out of 12 Weeks | A patient is considered to be an AP responder if, for at least 6 out of the first 12 weeks of the treatment period, the patient had a decrease of at least 30 percent in their Abdominal Pain score from baseline during a particular week. | Change from Baseline to Week 12 | 
| 12-Week Percent of Abdominal Pain-free 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IBS