Trial of Linaclotide in Patients With Chronic Idiopathic Constipation

Ironwood Pharmaceuticals, Inc.1,223 enrolled

Overview

The objective of this trial was to determine the efficacy and safety of linaclotide 72 ug administered once daily to patients with chronic idiopathic constipation (CIC). The primary efficacy parameter is the percentage of participants in each dosing group that meet the protocol definition for complete spontaneous bowel movement (CSBM) Overall Responder.

The trial also included a 145 ug linaclotide treatment arm (an FDA-approved dose for CIC) as an established positive control to validate the study design.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

1,223

Conditions

Chronic Idiopathic Constipation

Interventions

LinaclotideDRUG

Matching PlaceboDRUG

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Patient has completed a colonoscopy if one is needed 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 CIC: reports \< 3 bowel movements (BMs) per week and reports one or more of the following during ≥ 25% of BMs: straining, lumpy or hard stools, sensation of incomplete evacuation during the 3 months before the diagnosis with the onset at least 6 months before the diagnosis * Patient is compliant with daily interactive voice response system (IVRS) calls * Patient reports an average of \< 3 complete spontaneous BMs (CSBMs) and ≤ 6 SBMs per week by the IVRS over the 14 calendar days before the Randomization Visit and the calendar day of Randomization. Exclusion Criteria: * Patient has history of loose or watery stools * Patient has symptoms of or been diagnosed with irritable bowel syndrome (IBS) * 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 * Patient has Bristol Stool Form Scale score of 7 during Pretreatment period.

Locations (95)

Outcomes

Primary Outcomes

Percentage of 12-Week CSBM Overall Responders

A 12-week CSBM Overall Responder is a participant who was a CSBM Weekly Responder for at least 9 of the 12 weeks of the Treatment Period. A CSBM Weekly Responder is a participant who had a CSBM weekly frequency rate that was 3 or greater and increased by 1 or more from baseline, and completed ≥ 4 IVRS calls for the specified week. A CSBM is defined as an SBM that is associated with a sense of complete evacuation. An SBM is 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: Week 12

Secondary Outcomes

Change From Baseline in 12-Week CSBM Frequency Rate

A participant's 12-week CSBM Frequency Rate is the CSBM rate (CSBMs/week) calculated over the 12 weeks of the Treatment Period. A CSBM is defined as an SBM that is associated with a sense of complete evacuation. An SBM is defined as a 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: Baseline, Week 1 to Week 12

Change From Baseline in 12-Week SBM Frequency Rate

A participant's 12-week SBM Frequency Rate is the SBM rate (SBMs/week) calculated over the 12-weeks of the Treatment Period. An SBM is defined as a 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: Baseline, Week 1 to Week 12

Change From Baseline in 12-Week Stool Consistency Score

Stool consistency was measured daily using the 7-point ordinal Bristol Stool Form Scale (BSFS; 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 \[entirely liquid\]). The participant's BSFS score for the Treatment Period is the average of the non-missing BSFS scores from the SBMs reported by the participant during the 12-week Treatment Period.

Data from ClinicalTrials.gov

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Ironwood Investigational Site

Huntsville, Alabama, United States

Ironwood Investigational Site

Phoenix, Arizona, United States

Ironwood Investigational Site

Tucson, Arizona, United States

Ironwood Investigational Site

North Little Rock, Arkansas, United States

Ironwood Investigational Site

Anaheim, California, United States

Ironwood Investigational Site

Chula Vista, California, United States

Ironwood Investigational Site

Garden Grove, California, United States

Ironwood Investigational Site

La Mesa, California, United States

Ironwood Investigational Site

North Hollywood, California, United States

Ironwood Investigational Site

Orange, California, United States

...and 85 more locations

Time frame: Baseline, Week 1 to Week 12

Change From Baseline in 12-Week Straining Score

Straining was measured daily using a 5-point ordinal scale (1 = not at all; 2 = a little bit; 3 = a moderate amount; 4 = a great deal; 5 = an extreme amount). The participant's straining score for the Treatment Period is the average of the non-missing straining scores from the SBMs reported by the participant during the 12-week Treatment Period.

Time frame: Baseline, Week 1 to Week 12

Percentage of 12-Week CSBM Overall Responders (>1 SBM/Week Subpopulation)

A 12-week CSBM Overall Responder is a participant who was a CSBM Weekly Responder for at least 9 of the 12 weeks of the Treatment Period. A CSBM Weekly Responder is a participant who had a CSBM weekly frequency rate that was 3 or greater and increased by 1 or more from baseline, and completed ≥4 IVRS calls for the specified week. A CSBM is defined as an SBM that is associated with a sense of complete evacuation. An SBM is defined as a 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: Week 12

Percentage of Month 1 CSBM Responders

A Month 1 CSBM Responder is a participant who is a CSBM weekly responder for at least 3 of the 4 weeks of Month 1 of the Treatment Period. A CSBM weekly responder is a participant who had a CSBM weekly frequency rate that was 3 or greater and increased by 1 or more from baseline based on a minimum of 4 complete IVRS calls for that week. A CSBM is defined as an SBM that is associated with a sense of complete evacuation. An SBM is defined as a 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: Month 1

Percentage of Month 2 CSBM Responders

A Month 2 CSBM Responder is a participant who is a CSBM weekly responder for at least 3 of the 4 weeks of Month 2 of the Treatment Period. A CSBM weekly responder is a participant who had a CSBM weekly frequency rate that was 3 or greater and increased by 1 or more from baseline based on a minimum of 4 complete IVRS calls for that week. A CSBM is defined as an SBM that is associated with a sense of complete evacuation. An SBM is defined as a 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: Month 2

Percentage of Month 3 CSBM Responders

A Month 3 CSBM Responder is a participant who is a CSBM weekly responder for at least 3 of the 4 weeks of Month 3 of the Treatment Period. A CSBM weekly responder is a participant who had a CSBM weekly frequency rate that was 3 or greater and increased by 1 or more from baseline based on a minimum of 4 complete IVRS calls for that week. A CSBM is defined as an SBM that is associated with a sense of complete evacuation. An SBM is defined as a 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: Month 3

Change From Baseline in 12-Week Abdominal Bloating

Abdominal bloating was measured daily using an 11-point NRS (0 = none; 10 = very severe). The participant's abdominal bloating score for the Treatment Period is the average of the non-missing daily participant assessments of abdominal bloating scores reported during the 12-week Treatment Period.

Time frame: Baseline, Week 1 to Week 12

Change From Baseline in 12-Week Abdominal Discomfort

Abdominal discomfort was measured daily using an 11-point NRS (0 = none; 10 = very severe). The participant's abdominal discomfort score for the Treatment Period is the average of the non-missing daily participant assessments of abdominal discomfort scores reported during the 12-week Treatment Period.

Time frame: Baseline, Week 1 to Week 12