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A Phase 3, International, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Efficacy and Safety Trial of Linaclotide Administered Orally for 12 Weeks to Patients With Irritable Bowel Syndrome With Constipation (IBS-C) (D5630C00001)

Primary Purpose

Irritable Bowel Syndrome With Constipation (IBS-C)

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Placebo

Linaclotide

About this trial

This is an interventional treatment trial for Irritable Bowel Syndrome With Constipation (IBS-C)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patient has signed an Informed Consent Form(ICF).
Patient Must not be pregnant or breastfeeding and agree to use birth control
Patient meets the colonoscopy requirements defined by the American Gastroenterological Association guidelines and no clinically-significant laboratory or physical examination findings;
Patient meets protocol-defined criteria for Irritable Bowel Syndrome with Constipation(IBS-C), including stool frequency, straining, stool consistency, abdominal pain, and abdominal discomfort criteria
Patient meets protocol-defined eDiary completion Compliance and agrees to refrain from making any new, major life-style changes that may affect IBS-C symptoms

Exclusion Criteria:

Recent history of mushy or watery stools
Various medical conditions, medical histories, or family medical histories that would not make the patient a good candidate for the study
Patient currently has both unexplained and clinically significant alarm symptoms or systemic signs of infection or colitis.
Surgery to the gastrointestinal tract
Usage of prohibited medications

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

controlled arm

treatment arm

Arm Description

Outcomes

Primary Outcome Measures

12-week Abdominal Pain/Abdominal Discomfort Weekly Responder

A 12-week Abdominal Pain/Abdominal Discomfort Responder is a patient who meets the Abdominal Pain/Abdominal Discomfort Weekly Responder criteria (i.e., an improvement of ≥30% from baseline in either the mean abdominal pain score or mean abdominal discomfort score for that week, with neither score worsening from baseline for that week) for at least 6 out of the 12 weeks of the Treatment Period. Abdominal pain at its worst (in the last 24 hours) was assessed daily by patients on an 11-point numerical rating scale (NRS) where 0 represents no abdominal pain and 10 represents very severe abdominal pain. Abdominal discomfort (in the last 24 hours) was assessed daily by patients on an 11-point NRS where 0 represents no abdominal discomfort and 10 represents very severe abdominal discomfort.

12-week Irritable Bowel Syndrome (IBS) Degree of Relief Responder

A 12-week IBS Degree of Relief Responder is a patient who meets the IBS Degree of Relief Weekly Responder criteria (i.e., response to the degree of relief of IBS symptoms question for that week was "Considerably relieved" or "Completely relieved") for at least 6 out of the 12 weeks of the Treatment Period. Degree of relief of IBS symptoms (in the last 7 days) was assessed weekly by patients on a 7-point balanced ordinal scale where 1 = Completely relieved, 4 = Unchanged, and 7 = As bad as I can imagine.

Secondary Outcome Measures

Change From Baseline in 12-week Complete Spontaneous Bowel Movement Frequency Rate

The change from baseline in 12-week CSBM frequency (i.e., average weekly CSBM frequency over the 12 weeks of the Treatment Period). A spontaneous bowel movement (SBM) is defined as a bowel movement without laxative use in the preceding 24 hours. A CSBM is defined as an SBM that is associated with a sense of complete evacuation.

Change From Baseline in 12-week Spontaneous Bowel Movement Frequency Rate

The change from baseline in 12-week SBM frequency (i.e., average weekly SBM frequency over the 12 weeks of the Treatment Period). SBM is defined as a bowel movement without laxative use in the preceding 24 hours.

Change From Baseline in 12-week Stool Consistency

The change from baseline in 12-week stool consistency (i.e., the average of the non-missing Bristol Stool Form Scale [BSFS] score from the SBMs occurring during the 12-week Treatment Period). Consistency of each bowel movement was assessed daily by patients using the 7-point BSFS (1=Separate hard lumps like nuts [difficult to pass] to 7=Watery, no solid pieces [entirely liquid]).

Change From Baseline in 12-week Severity of Straining

The change from baseline in 12-week severity of straining (i.e., the average of the non-missing straining scores from the SBMs occurring during the 12-week Treatment Period). Severity of straining was assessed daily by patients on a 5-point ordinal scale (1=Not at all to 5=An extreme amount).

Change From Baseline in 12-week Abdominal Bloating

The change from baseline in 12-week abdominal bloating (i.e., the average of the non-missing daily abdominal bloating scores reported during the 12-week Treatment Period). Abdominal bloating (in the last 24 hours) was assessed daily by patients on an 11-point NRS where 0 represents no abdominal bloating and 10 represents very severe abdominal bloating.

Change From Baseline in 12-week Abdominal Pain

The change from baseline in 12-week abdominal pain (i.e., the average of the non-missing daily abdominal pain scores reported during the 12-week Treatment Period). Abdominal pain at its worst (in the last 24 hours) was assessed daily by patients on an 11-point NRS where 0 represents no abdominal pain and 10 represents very severe abdominal pain.

Change From Baseline in 12-week Abdominal Discomfort

The change from baseline in 12-week abdominal discomfort (i.e., the average of the non-missing daily abdominal discomfort scores reported during the 12-week Treatment Period). Abdominal discomfort (in the last 24 hours) was assessed daily by patients on an 11-point NRS where 0 represents no abdominal discomfort and 10 represents very severe abdominal discomfort.

Full Information

NCT ID

NCT01880424

First Posted

June 12, 2013

Last Updated

August 4, 2016

Sponsor

AstraZeneca

Collaborators

Ironwood Pharmaceuticals, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT01880424

Brief Title

A Phase 3, International, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Efficacy and Safety Trial of Linaclotide Administered Orally for 12 Weeks to Patients With Irritable Bowel Syndrome With Constipation (IBS-C)

Acronym

D5630C00001

Official Title

Study Type

Interventional

2. Study Status

Record Verification Date

August 2016

Overall Recruitment Status

Completed

Study Start Date

July 2013 (undefined)

Primary Completion Date

May 2015 (Actual)

Study Completion Date

May 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

AstraZeneca

Collaborators

Ironwood Pharmaceuticals, Inc.

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

This clinical trial is an international, multicenter, randomized, double-blind, placebo-controlled, parallel-group trial comparing one dose of linaclotide to placebo. Approximately 800 patients with a diagnosis of IBS-C (modified Rome III criteria) will be randomized at up to 60 trial centers in China, Australia, and New Zealand. The trial will consist of up to 21 days of screening, 14 to 21 days of pre-treatment, 12 weeks of double-blind treatment, and 2 weeks of follow-up. At the end of the Pre-treatment Period, patients meeting the entry criteria for this trial will be randomized to one of two double-blind treatment groups: 290 ug linaclotide, or placebo (1:1).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Irritable Bowel Syndrome With Constipation (IBS-C)

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

1722 (Actual)

8. Arms, Groups, and Interventions

Arm Title

controlled arm

Arm Type

Placebo Comparator

Arm Title

treatment arm

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

matching Placebo Capsules, Oral, once daily

Intervention Type

Drug

Intervention Name(s)

Linaclotide

Intervention Description

Linaclotide 290 ug Capsules, Oral, once daily

Primary Outcome Measure Information:

Title

12-week Abdominal Pain/Abdominal Discomfort Weekly Responder

Description

Time Frame

Baseline and Weeks 1-12 during the Treatment Period

Title

12-week Irritable Bowel Syndrome (IBS) Degree of Relief Responder

Description

Time Frame

Baseline and Weeks 1-12 during the Treatment Period

Secondary Outcome Measure Information:

Title

Change From Baseline in 12-week Complete Spontaneous Bowel Movement Frequency Rate

Description

Time Frame

Baseline and 12-week Treatment Period

Title

Change From Baseline in 12-week Spontaneous Bowel Movement Frequency Rate

Description

Time Frame

Baseline and 12-week Treatment Period

Title

Change From Baseline in 12-week Stool Consistency

Description

Time Frame

Baseline and 12-week Treatment Period

Title

Change From Baseline in 12-week Severity of Straining

Description

Time Frame

Baseline and 12-week Treatment Period

Title

Change From Baseline in 12-week Abdominal Bloating

Description

Time Frame

Baseline and 12-week Treatment Period

Title

Change From Baseline in 12-week Abdominal Pain

Description

Time Frame

Baseline and 12-week Treatment Period

Title

Change From Baseline in 12-week Abdominal Discomfort

Description

Time Frame

Baseline and 12-week Treatment Period

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patient has signed an Informed Consent Form(ICF). Patient Must not be pregnant or breastfeeding and agree to use birth control Patient meets the colonoscopy requirements defined by the American Gastroenterological Association guidelines and no clinically-significant laboratory or physical examination findings; Patient meets protocol-defined criteria for Irritable Bowel Syndrome with Constipation(IBS-C), including stool frequency, straining, stool consistency, abdominal pain, and abdominal discomfort criteria Patient meets protocol-defined eDiary completion Compliance and agrees to refrain from making any new, major life-style changes that may affect IBS-C symptoms Exclusion Criteria: Recent history of mushy or watery stools Various medical conditions, medical histories, or family medical histories that would not make the patient a good candidate for the study Patient currently has both unexplained and clinically significant alarm symptoms or systemic signs of infection or colitis. Surgery to the gastrointestinal tract Usage of prohibited medications

Overall Study Officials: