Trial of Linaclotide in Patients With Chronic Constipation

Study Overview
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Brief Summary
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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 dosing group that meet the protocol definition for Complete Spontaneous Bowel Movement (CSBM) Overall Responder.

Official Title
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A Phase 3, 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 Chronic Constipation

Conditions
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Chronic Constipation

Intervention / Treatment
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* Drug: Matching Placebo
* Drug: Linaclotide


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 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

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 |
| --- | --- |
| Experimental: 145 μg linaclotide<br> | Drug: Linaclotide<br>* Oral, once daily<br>|
| Experimental: 290 μg linaclotide<br> | Drug: Linaclotide<br>* Oral, once daily<br>|
| Placebo Comparator: Matching Placebo<br> | Drug: Matching Placebo<br>* Oral, once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Spontaneous Bowel Movement (CSBM) Overall Responder | A 12-week CSBM Overall Responder 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 12-Week Complete Spontaneous Bowel Movement (CSBM) Frequency | The number of CSBMs per week. | Change from Baseline to Week 12 | 
| 12-Week Spontaneous Bowl Movement (SBM) Frequency | The number of SBMs per week. | Change from Baseline to Week 12 | 
| 12-week Change in 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 | 
| 12-week Change in Severity of Straining | Severity of 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 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 | 
| 12-week Change in 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 | 
| 12-week Change in 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 |