A Study of the Effect of Linaclotide on Abdominal Girth in Participants With Irritable Bowel Syndrome With Constipation (IBS-C)

Study Overview
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Brief Summary
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The objective of this trial is to determine the effect of linaclotide on abdominal girth in IBS-C participants with the baseline symptoms of abdominal bloating and an increased abdominal girth.

Official Title
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A Phase 4, Single-centre, Randomised, Double-blind, Placebo-controlled, Parallel-group, Fixed-dose Study of the Effect of Linaclotide on Abdominal Girth in Participants With Irritable Bowel Syndrome With Constipation

Conditions
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Irritable Bowel Syndrome Characterized by Constipation

Intervention / Treatment
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* Drug: Linaclotide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: • Patient meets protocol criteria for diagnosis of IBS-C, abdominal pain, abdominal bloating and abdominal girth Exclusion Criteria: Patient has history of loose or watery stools Patient has both clinically significant findings and unexplained clinically significant alarm symptoms Patient has symptoms of or been diagnosed with a medical condition that may contribute to abdominal pain 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: 290 μg linaclotide<br>Linaclotide Oral, once daily | Drug: Linaclotide<br>* Oral, once daily<br>|
| Placebo Comparator: Matching Placebo<br>Matching Placebo Oral, once daily | Drug: Placebo<br>* Oral, one daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Abdominal Girth at Week 4 | Mean change in abdominal girth (physical measure of bloating/distension) as measured by area under the curve (AUC), determined by 24-hour abdominal inductance plesthymography (AIP; with hourly averages). The AUC was calculated using the Trapezoidal method from the first reliable hour of measurement to last measurement (bedtime). The AUC for each participant was then individually standardized by dividing the total AUC over the period by that patient's number of hours of measurement included in the AUC. (Therefore, the time element was removed from the standardized AUC, and the unit of measure for this outcome is centimeters [cm]). | Baseline, Week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Abdominal Girth at Week 2 | Mean change in abdominal girth (physical measure of bloating/distention) as measured by AUC, determined by 24-hour AIP (with hourly averages). The AUC was calculated using the Trapezoidal method from the first reliable hour of measurement to last measurement (bedtime). The AUC for each participant was then individually standardized by dividing the total AUC over the period by that patient's number of hours of measurement included in the AUC. (Therefore, the time element was removed from the standardized AUC, and the unit of measure for this outcome is centimeters [cm]). | Baseline, Week 2 | 
| Percent Change From Baseline in Maximal Abdominal Girth at Week 4 | The maximum change in girth from the first hour, over the period from the 2nd hour to bedtime. The percentage change in maximum distension from baseline to 4 weeks will also be calculated. | Baseline, Week 4 | 
| Change From Baseline of Symptom Severity (Abdominal Pain, Discomfort, Bloating, and Distension) at Week 1 | Symptom severity was assessed daily on an 11-point numerical rating scale (NRS) from 0 to 10, where 0 represents no symptoms and 10 represents very severe symptoms. Participants rated their abdominal pain, discomfort, bloating, and distension at its worst over the last 24 hours. Weekly average scores were calculated individually for abdominal pain, discomfort, bloating, distension. The abdominal score was calculated as the weekly average from the daily scores of the individual items of pain, discomfort, bloating combined. The abdominal score plus distension was calculated as the weekly average from the daily scores of the individual items of pain, discomfort, bloating and distension combined. | Baseline, Week 1 | 
| Change From Baseline of Symptom Severity (Abdominal Pain, Discomfort, Bloating, and Distension) at Week 2 | Symptom severity was assessed daily on an 11-point NRS from 0 to 10, where 0 represents no symptoms and 10 represents very severe symptoms. Participants rated their abdominal pain, discomfort, bloating, and distension at its worst over the last 24 hours. Weekly average scores were calculated individually for abdominal pain, discomfort, bloating, distension. The abdominal score was calculated as the weekly average from the daily scores of the individual items of pain, discomfort, bloating combined. The abdominal score plus distension was calculated as the weekly average from the daily scores of the individual items of pain, discomfort, bloating and distension combined. | Baseline, Week 2 | 
| Change From Baseline of Symptom Severity (Abdominal Pain, Discomfort, Bloating, and Distension) at Week 3 | Symptom severity was assessed daily on an 11-point NRS from 0 to 10, where 0 represents no symptoms and 10 represents very severe symptoms. Participants rated their abdominal pain, discomfort, bloating, and distension at its worst over the last 24 hours. Weekly average scores were calculated individually for abdominal pain, discomfort, bloating, distension. The abdominal score was calculated as the weekly average from the daily scores of the individual items of pain, discomfort, bloating combined. The abdominal score plus distension was calculated as the weekly average from the daily scores of the individual items of pain, discomfort, bloating and distension combined. | Baseline, Week 3 | 
| Change From Baseline of Symptom Severity (Abdominal Pain, Discomfort, Bloating, and Distension) at Week 4 | Symptom severity was assessed daily on an 11-point NRS from 0 to 10, where 0 represents no symptoms and 10 represents very severe symptoms. Participants rated their abdominal pain, discomfort, bloating, and distension at its worst over the last 24 hours. Weekly average scores were calculated individually for abdominal pain, discomfort, bloating, distension. The abdominal score was calculated as the weekly average from the daily scores of the individual items of pain, discomfort, bloating combined. The abdominal score plus distension was calculated as the weekly average from the daily scores of the individual items of pain, discomfort, bloating and distension combined. | Baseline, Week 4 | 
| Change From Baseline in Digestive Sensations (Subjective Bloating, Abdominal Discomfort, Abdominal Distension and Abdominal Pain) at Week 2 | A digestive sensations questionnaire was used to record abdominal pain, discomfort, bloating, and distension symptoms on an hourly basis (waking hours only) during the 24 hours the participants are fitted with the AIP belt, using an 11-point NRS, with 0=no symptomatic sensations and 10=most severe symptomatic sensations. Daily diary scores for each of the digestive symptoms was averaged to obtain 'weekly' scores. | Baseline, Week 2 | 
| Change From Baseline in Digestive Sensations (Subjective Bloating, Abdominal Discomfort, Abdominal Distension and Abdominal Pain) at Week 4 | A digestive sensations questionnaire was used to record abdominal pain, discomfort, bloating, and distension on an hourly basis (waking hours only) during the 24 hours the participants are fitted with the AIP belt, using an 11-point NRS, with 0=no symptomatic sensations and 10=most severe symptomatic sensations. Daily diary scores for each of the digestive symptoms was averaged to obtain 'weekly' scores. | Baseline, Week 4 | 
| Change From Baseline in Bristol Stool Form Scale (BSFS) Over Time | Daily stool consistency analyses were performed using the 7-point Bristol Stool Form Scale (BSFS), whereby a score of 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; and 7 = watery, no solid pieces (entirely liquid). Daily average recorded BSFS scores for each participant were computed for each week. | Baseline, Week 1, Week 2, Week 3, Week 4 |