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 objectives of this study are to evaluate the safety, efficacy, and dose response of two delayed release formulations of linaclotide (DR; DR formulation 1 is DR1; DR formulation 2 is DR2) administered orally to patients with irritable bowel syndrome with constipation (IBS-C). Additional objectives include understanding how the two DR formulations compare with each other and with the FDA-approved 290 μg LINZESS® (the immediate release [IR] formulation of linaclotide).

Official Title
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A Phase 2b, Randomized, Double-blind, Double-dummy, Placebo-controlled, Parallel-group, Dose-range-finding Study of Two Delayed Release Formulations of Linaclotide Administered Orally for 12 Weeks to 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
* Drug: Matching Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient has completed a colonoscopy according to the American Gastroenterological Association (AGA) criteria, with no clinically significant findings Patient has no clinically significant findings on a physical examination and clinical laboratory tests Patient meets protocol criteria for diagnosis of IBS-C Patient demonstrates continued IBS-C through Pretreatment Period Patient maintains a minimum level of compliance with daily diary 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 |
| --- | --- |
| Experimental: 30 μg linaclotide DR1 and placebo<br> | Drug: Linaclotide<br>* Oral, once daily<br>|
| Experimental: 100 μg linaclotide DR1 and placebo<br> | Drug: Linaclotide<br>* Oral, once daily<br>|
| Experimental: 300 μg linaclotide DR1 and placebo<br> | Drug: Linaclotide<br>* Oral, once daily<br>|
| Experimental: 30 μg linaclotide DR2 and placebo<br> | Drug: Linaclotide<br>* Oral, once daily<br>|
| Experimental: 100 μg linaclotide DR2 and placebo<br> | Drug: Linaclotide<br>* Oral, once daily<br>|
| Experimental: 300 μg linaclotide DR2 and placebo<br> | Drug: Linaclotide<br>* Oral, once daily<br>|
| Experimental: 290 μg linaclotide IR and placebo<br> | Drug: Linaclotide<br>* Oral, once daily<br>|
| Placebo Comparator: 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 |
| --- | --- | --- |
| Change From Baseline in Weekly Abdominal Pain Score Over the 12-Week Treatment Period: DR1 or IR vs. Placebo | Abdominal pain assessment was based on an 11-point numerical rating scale (0=No symptom; 10=Worst possible) assessing the symptom at its worst in past 24 hours. A participant's weekly abdominal pain score is the average of the nonmissing abdominal pain scores reported by the participant during each week. | Baseline, up to Week 12 | 
| Change From Baseline in Weekly Abdominal Pain Score Over the 12-Week Treatment Period: DR2 or IR vs. Placebo | Abdominal pain assessment was based on an 11-point numerical rating scale (0=No symptom; 10=Worst possible) assessing the symptom at its worst in past 24 hours. A participant's weekly abdominal pain score is the average of the nonmissing abdominal pain scores reported by the participant during each week. | Baseline, up to Week 12 | 
| Change From Baseline in Weekly CSBM Frequency Rate Over the 12-Week Treatment Period: DR1 or IR vs. Placebo | A participant's weekly CSBM frequency rate is the CSBM rate (CSBMs/week) calculated over that week. | Baseline, up to Week 12 | 
| Change From Baseline in Weekly CSBM Frequency Rate Over the 12-Week Treatment Period: DR2 or IR vs. Placebo | A participant's weekly CSBM frequency rate is the CSBM rate (CSBMs/week) calculated over that week. | Baseline, up to Week 12 | 
| Number of 6/12 Week Abdominal Pain and Constipation (APC) +1 Responders Over the 12-Week Treatment Period: DR1 or IR vs. Placebo | A 6/12 Week APC +1 Responder is a participant who meets the Weekly APC +1 Responder criteria for at least 6 out of the 12 weeks of the Treatment Period. Weekly APC +1 Responder: A participant who meets the criteria to be a Weekly Abdominal Pain Responder and a Weekly CSBM +1 Responder. Weekly Abdominal Pain Responder: A participant who has a decrease from baseline of ≥30% in the mean daily worst abdominal pain scores for that week. Weekly CSBM +1 Responder: A participant who has an increase from baseline of ≥1 in the CSBM weekly rate for that week. A participant with <4 days of completed eDiary data for that week is not considered a responder for that week. | up to Week 12 | 
| Number of 6/12 Week Abdominal Pain and Constipation (APC) +1 Responders Over the 12-Week Treatment Period: DR2 or IR vs. Placebo | A 6/12 Week APC +1 Responder is a participant who meets the Weekly APC +1 Responder criteria for at least 6 out of the 12 weeks of the Treatment Period. Weekly APC +1 Responder: A participant who meets the criteria to be a Weekly Abdominal Pain Responder and a Weekly CSBM +1 Responder. Weekly Abdominal Pain Responder: A participant who has a decrease from baseline of ≥30% in the mean daily worst abdominal pain scores for that week. Weekly CSBM +1 Responder: A participant who has an increase from baseline of ≥1 in the CSBM weekly rate for that week. A participant with <4 days of completed eDiary data for that week is not considered a responder for that week. | up to Week 12 |