A Study of the Effect of Linaclotide on Abdominal Girth in Participants With IBS-C

• ClinicalTrials.gov Identifier: NCT02837783
• Recruitment Status: Terminated
• First Posted: July 20, 2016
• Last Update Posted: January 29, 2020
• Sponsor: Ironwood Pharmaceuticals, Inc.
• Collaborator: Manchester University NHS Foundation Trust
• Information provided by (Responsible Party): Ironwood Pharmaceuticals, Inc.

Study Description

Brief Summary:

The objective of this trial is to determine the effect of linaclotide on abdominal girth in irritable bowel syndrome with constipation (IBS-C) participants with the baseline symptoms of abdominal bloating and an increased abdominal girth.

Condition or disease	Intervention/treatment	Phase
Irritable Bowel Syndrome Characterized by Constipation	Drug: Linaclotide; Drug: Placebo	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: December 21, 2016
• Actual Primary Completion Date: October 31, 2018
• Actual Study Completion Date: October 31, 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: 290 μg linaclotide; Linaclotide Oral, once daily	Drug: Linaclotide; Oral, once daily
Placebo Comparator: Matching Placebo; Matching Placebo Oral, once daily	Drug: Placebo; Oral, one daily

Outcome Measures

Primary Outcome Measures :

1. Mean Change in Abdominal Girth (physical measure of bloating/distention) [ Time Frame: Randomisation (Visit 4) to End of Treatment (Day 28±2) ]
   Mean change in abdominal girth (as measured by AUC) determined by 24-hour abdominal inductance plethysmography (AIP) between the linaclotide and placebo groups.

Secondary Outcome Measures :

1. Change from Baseline in Abdominal Distension at Week 2 [ Time Frame: Baseline to Week 2 ]
   Mean change in abdominal girth (as measured by AUC) determined by 24-hour AIP, between the linaclotide and placebo groups.
2. Change from Baseline in Maximal Abdominal Distension at Week 4 [ Time Frame: Baseline to 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.
3. Change from Baseline of symptom severity (abdominal pain, discomfort, bloating, and distension) [ Time Frame: Baseline to End of Treatment (Day 28±2) ]
   Daily diary scores for each of the digestive symptoms and a composite score of these parameters will be averaged to obtain 'weekly' scores.
4. Change from Baseline in Digestive sensations (subjective bloating, abdominal discomfort, abdominal distension and abdominal pain) at Weeks 4 and 8 [ Time Frame: Baseline to Week 4, Baseline to Week 8 ]
   The mean change in each of the hourly measures of digestive sensations (as measured by AUC), between the linaclotide and placebo groups.
5. Change from Baseline of Bristol Stool Form Scale at Weeks 4 and 8 [ Time Frame: Baseline to Week 4, Baseline to Week 8 ]

   Daily diary BSFS scores will be recoded to represent discrepancies from a 'normal' stool type 4, daily average recoded BSFS scores for each subject will be computed. The following means will be calculated for each subject:

   • Baseline = mean (day -7 to day -1)
   • Week 1 = mean (day 1 to day 7)
   • Week 2 = mean (day 8 to day 14)
   • Week 3 = mean (day 15 to day 21)
   • Week 4 = mean (day 22 to day 28)

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United Kingdom

Peter Whorwell

Wythenshawe, Manchester, United Kingdom

Sponsors and Collaborators

Ironwood Pharmaceuticals, Inc.

Manchester University NHS Foundation Trust

Investigators

• Principal Investigator: Peter Whorwell; University Hospital of South Manchester

More Information

• Responsible Party: Ironwood Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT02837783
• Other Study ID Numbers: MCP-103-403
• First Posted: July 20, 2016
• Last Update Posted: January 29, 2020
• Last Verified: January 2020

Additional relevant MeSH terms:

Irritable Bowel Syndrome; Syndrome; Constipation; Disease; Pathologic Processes; Signs and Symptoms, Digestive; Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Linaclotide; Guanylyl Cyclase C Agonists; Enzyme Activators; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents