Trial of Linaclotide Administered to Patients With Irritable Bowel Syndrome With Constipation

Forest Laboratories803 enrolled

Overview

The objective of this trial is to determine the efficacy and safety of linaclotide administered to patients with irritable bowel syndrome with constipation (IBS-C). The primary efficacy parameter is the percentage of patients in each treatment group that meet the protocol definition for Abdominal Pain and Complete Spontaneous Bowel Movement (APC) Responder.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

803

Conditions

Irritable Bowel Syndrome Characterized by Constipation

Interventions

Linaclotide 290 microgramsDRUG

Oral, once daily each morning at least 30 minutes before breakfast for the duration of the study

Matching placeboDRUG

Oral, once daily each morning at least 30 minutes before breakfast for the duration of the study

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Patient meets protocol criteria for IBS: reports abdominal discomfort or pain that has two or more of the following three features: 1. Relieved with defecation 2. Onset associated with a change in frequency of stool 3. Onset associated with a change in form (appearance) of stool * Patient reports \< 3 bowel movements (BMs) per week (in the absence of any laxative, suppository, or enema use during the preceding 24 hours) and reports straining, lumpy or hard stools, and/or sensation of incomplete evacuation during \> 25% of BMs * Patient has successfully completed protocol procedures (with no clinically significant findings): physical exam, 12-lead ECG, or clinical laboratory tests (some patients may require a colonoscopy per American Gastroenterological Association (AGA) guidelines) * Patient is compliant with Interactive Voice Response System (IVRS) for daily diary reporting of BM habits and IBS symptoms Exclusion Criteria: * Patient has history of loose or watery stools for \>25% of BMs * Patient has a structural abnormality of the gastrointestinal (GI) tract or a history of a disease or condition that can affect GI motility * Patient has any protocol-excluded or clinically significant medical or surgical history or concomitant medication use that could confound the study assessments

Locations (118)

Outcomes

Primary Outcomes

Abdominal Pain and Complete Spontaneous Bowel Movement (APC) Responder, 9 Out of 12 Weeks

A patient is considered to be an APC responder if, for at least 9 out of the 12 weeks of the treatment period, the patient had at least 3 CSBMs, experienced an increase of at least 1 CSBM from baseline, and experienced a decrease of at least 30 percent in their Abdominal Pain (AP) score from baseline during a particular week. The AP score assesses the worst of a patient's AP in the past 24 hours using an 11-point scale (from 0-10), where 0 represents no AP and 10 represents very severe AP. A CSBM is defined as a spontaneous bowel movement, associated with a sense of complete evacuation.

Time frame: Change from Baseline to Week 12

Complete Spontaneous Bowel Movement (CSBM) 3+1 Responder, 9 Out of 12 Weeks

A patient is considered to be a CSBM 3+1 responder if, for at least 9 out of the 12 weeks of the treatment period, the patient had at least 3 CSBMs and experienced an increase of at least 1 CSBM from baseline during a particular week. 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.

Time frame: Change from Baseline to Week 12

Abdominal Pain Responder, 9 Out of 12 Weeks

A patient is considered to be an abdominal pain responder if, for at least 9 out of the 12 weeks of the treatment period, they experienced a decrease of at least 30 percent in the mean abdominal pain score from baseline during a particular week. The Abdominal Pain score assesses the worst of a patient's abdominal pain in the past 24 hours using an 11-point scale (from 0-10), where 0 represents no abdominal pain and 10 represents very severe abdominal pain.

Time frame: Change from Baseline to Week 12

Abdominal Pain and Complete Spontaneous Bowel Movement (APC) Responder, 6 Out of 12 Weeks.

A patient is considered an APC responder if, for at least 6 of the 12 weeks of the treatment, the patient experienced an increase of at least 1 Complete Spontaneous Bowel Movement (CSBM) from baseline and experienced a decrease of at least 30 percent in their Abdominal Pain (AP)score during a particular week. The AP score assesses the worst of a patient's AP in the past 24 hours using an 11-point scale (from 0-10), where 0 represents no AP and 10 represents very severe AP. A CSBM was defined as a Spontaneous Bowel Movement (SBM) that was associated with a sense of complete evacuation.

Data from ClinicalTrials.gov

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Forest Investigative Site 037

Birmingham, Alabama, United States

Forest Investigative Site 036

Birmingham, Alabama, United States

Forest Investigative Site 135

Hueytown, Alabama, United States

Forest Investigative Site 014

Huntsville, Alabama, United States

Forest Investigative Site 080

Chandler, Arizona, United States

Forest Investigative Site 053

Mesa, Arizona, United States

Forest Investigative Site 078

Peoria, Arizona, United States

Forest Investigative Site 101

Phoenix, Arizona, United States

Forest Investigative Site 128

Phoenix, Arizona, United States

Forest Investigative Site 051

Scottsdale, Arizona, United States

...and 108 more locations

Secondary Outcomes

12-Week Complete Spontaneous Bowel Movement (CSBM) Frequency Rate

The number of CSBMs per week.

Time frame: Change from Baseline to Week 12

12-Week Spontaneous Bowl Movement (SBM) Frequency Rate

The number of Spontaneous Bowl Movements experienced per week.

Time frame: Change from Baseline to Week 12

12-Week Stool Consistency

The consistency of each BM was assessed by patients using the 7-point Bristol Stool Form Scale (BSFS) from 1 to 7. 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 7. = watery, no solid pieces \[entirely liquid\]).

Time frame: Change from Baseline to Week 12

12-Week Severity of Straining

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.

Time frame: Change from Baseline to Week 12

12-Week Change in Abdominal Pain Score

Abdominal Pain at its worst (in the last 24 hours) is based on an 11-point scale where 0 represents no abdominal pain and 10 represents very severe abdominal pain.

Time frame: Change from Baseline to Week 12

12-Week Change in Abdominal Discomfort

Abdominal Discomfort is measured on an 11-point scale where a value of 0 is "none" and a value of 10 is "very severe."

Time frame: Change from Baseline to Week 12

12-Week Change in Bloating

Bloating was assessed on an 11-point scale where a value of 0 is "none" and a value of 10 is "very severe".

Time frame: Change from Baseline to Week 12

Complete Spontaneous Bowl Movement (CSBM) Responder for 6 Weeks Out of 12 Weeks of Treatment

A patient is considered to be a CSBM responder if, for at least 6 out of the 12 weeks of the treatment period, an increase of at least 1 CSBM per week from baseline was experienced.

Time frame: Change from Baseline to Week 12

Abdominal Pain Responder for 6 Out of 12 Weeks

A patient is considered to be an abdominal pain responder if, for at least 6 out of the 12 weeks of the treatment period, they experienced a decrease of 30 percent or more in the abdominal pain score from baseline. The Abdominal Pain score assesses the worst of a patient's abdominal pain in the past 24 hours using an 11-point scale (from 0-10), where 0 represents no abdominal pain and 10 represents very severe abdominal pain.

Time frame: Change from Baseline to Week 12

12-Week Percent of Abdominal Pain-free (APF) Days

Abdominal pain free (APF) days are those days where the patient reported a score of '0' for abdominal pain at its worst Abdominal Pain at its worst (in the last 24 hours) is based on an 11-point scale where 0 represents no abdominal pain and 10 represents very severe abdominal pain.

Time frame: Change from Baseline to Week 12