Trial of Linaclotide in Patients With Irritable Bowel Syndrome With Constipation (IBS-C)

NCT02559206 | Completed Phase 2 Results

• 1 other identifier: MCP-103-204
• Study Type: interventional
• Target: 759
• Locations: 1 country
• Sites: 71

Brief Summary

The objectives of this study are to evaluate the safety, efficacy, and dose response of two delayed release formulations of linaclotide (DR; DR formulation 1 is DR1; DR formulation 2 is DR2) administered orally to patients with irritable bowel syndrome with constipation (IBS-C). Additional objectives include understanding how the two DR formulations compare with each other and with the FDA-approved 290 μg LINZESS® (the immediate release \[IR\] formulation of linaclotide).

Conditions

Irritable Bowel Syndrome With Constipation

Outcome Measures

Primary Outcomes (6)

• Change From Baseline in Weekly Abdominal Pain Score Over the 12-Week Treatment Period: DR1 or IR vs. Placebo

  Abdominal pain assessment was based on an 11-point numerical rating scale (0=No symptom; 10=Worst possible) assessing the symptom "at its worst in past 24 hours." A participant's weekly abdominal pain score is the average of the nonmissing abdominal pain scores reported by the participant during each week.

  Baseline, up to Week 12

• Change From Baseline in Weekly Abdominal Pain Score Over the 12-Week Treatment Period: DR2 or IR vs. Placebo

  Abdominal pain assessment was based on an 11-point numerical rating scale (0=No symptom; 10=Worst possible) assessing the symptom "at its worst in past 24 hours." A participant's weekly abdominal pain score is the average of the nonmissing abdominal pain scores reported by the participant during each week.

  Baseline, up to Week 12

• Change From Baseline in Weekly CSBM Frequency Rate Over the 12-Week Treatment Period: DR1 or IR vs. Placebo

  A participant's weekly CSBM frequency rate is the CSBM rate (CSBMs/week) calculated over that week.

  Baseline, up to Week 12

• Change From Baseline in Weekly CSBM Frequency Rate Over the 12-Week Treatment Period: DR2 or IR vs. Placebo

  A participant's weekly CSBM frequency rate is the CSBM rate (CSBMs/week) calculated over that week.

  Baseline, up to Week 12

• Number of 6/12 Week Abdominal Pain and Constipation (APC) +1 Responders Over the 12-Week Treatment Period: DR1 or IR vs. Placebo

  A 6/12 Week APC +1 Responder is a participant who meets the Weekly APC +1 Responder criteria for at least 6 out of the 12 weeks of the Treatment Period. * Weekly APC +1 Responder: A participant who meets the criteria to be a Weekly Abdominal Pain Responder and a Weekly CSBM +1 Responder. * Weekly Abdominal Pain Responder: A participant who has a decrease from baseline of ≥30% in the mean daily worst abdominal pain scores for that week. * Weekly CSBM +1 Responder: A participant who has an increase from baseline of ≥1 in the CSBM weekly rate for that week. A participant with \<4 days of completed eDiary data for that week is not considered a responder for that week.

  up to Week 12

• Number of 6/12 Week Abdominal Pain and Constipation (APC) +1 Responders Over the 12-Week Treatment Period: DR2 or IR vs. Placebo

  A 6/12 Week APC +1 Responder is a participant who meets the Weekly APC +1 Responder criteria for at least 6 out of the 12 weeks of the Treatment Period. * Weekly APC +1 Responder: A participant who meets the criteria to be a Weekly Abdominal Pain Responder and a Weekly CSBM +1 Responder. * Weekly Abdominal Pain Responder: A participant who has a decrease from baseline of ≥30% in the mean daily worst abdominal pain scores for that week. * Weekly CSBM +1 Responder: A participant who has an increase from baseline of ≥1 in the CSBM weekly rate for that week. A participant with \<4 days of completed eDiary data for that week is not considered a responder for that week.

  up to Week 12

Study Arms (8)

30 μg linaclotide DR1 and placebo

EXPERIMENTAL

Drug: Linaclotide

100 μg linaclotide DR1 and placebo

EXPERIMENTAL

Drug: Linaclotide

300 μg linaclotide DR1 and placebo

EXPERIMENTAL

Drug: Linaclotide

30 μg linaclotide DR2 and placebo

EXPERIMENTAL

Drug: Linaclotide

100 μg linaclotide DR2 and placebo

EXPERIMENTAL

Drug: Linaclotide

300 μg linaclotide DR2 and placebo

EXPERIMENTAL

Drug: Linaclotide

290 μg linaclotide IR and placebo

EXPERIMENTAL

Drug: Linaclotide

Placebo

PLACEBO COMPARATOR

Drug: Matching Placebo

Interventions

Linaclotide DRUG

Oral, once daily

100 μg linaclotide DR1 and placebo; 100 μg linaclotide DR2 and placebo; 290 μg linaclotide IR and placebo; 30 μg linaclotide DR1 and placebo; 30 μg linaclotide DR2 and placebo; 300 μg linaclotide DR1 and placebo; 300 μg linaclotide DR2 and placebo

Matching Placebo DRUG

Oral, once daily

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient has completed a colonoscopy 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 diagnosis of IBS-C
• Patient demonstrates continued IBS-C through Pretreatment Period
• Patient maintains a minimum level of compliance with daily diary

You may not qualify if:

• Patient has history of loose or watery stools
• Patient has symptoms of or been diagnosed with a medical condition that may contribute to abdominal pain
• 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

Sponsors & Collaborators

• Ironwood Pharmaceuticals, Inc.: lead
• Forest Laboratories: collaborator

Study Sites (71)

Ironwood Investigational Site

Huntsville, Alabama, 35801, United States

Location

Ironwood Investigational Site

Phoenix, Arizona, 85018, United States

Location

Ironwood Investigational Site

Tucson, Arizona, 85712, United States

Location

Ironwood Investigational Site

North Little Rock, Arkansas, 72117, United States

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Ironwood Investigational Site

Anaheim, California, 92801, United States

Location

Ironwood Investigational Site

Chula Vista, California, 91910, United States

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Ironwood Investigational Site

Garden Grove, California, 92843, United States

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Ironwood Investigational Site

La Mesa, California, 91942, United States

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Ironwood Investigational Site

Newport Beach, California, 92660, United States

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Ironwood Investigational Site

Orange, California, 92868, United States

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Ironwood Investigational Site

San Diego, California, 92108, United States

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Ironwood Investigational Site

Thousand Oaks, California, 91360, United States

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Ironwood Investigational Site

Colorado Springs, Colorado, 80904, United States

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Ironwood Investigational Site

Bristol, Connecticut, 06010, United States

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Ironwood Investigational Site

Waterbury, Connecticut, 06708, United States

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Ironwood Investigational Site

Hialeah, Florida, 33016, United States

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Ironwood Investigational Site

Kissimmee, Florida, 34744, United States

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Ironwood Investigational Site

Miami, Florida, 33015, United States

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Ironwood Investigational Site

Miami, Florida, 33135, United States

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Ironwood Investigational Site

Miami, Florida, 33165, United States

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Ironwood Investigational Site

Miami, Florida, 33175, United States

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Ironwood Investigational Site

Orlando, Florida, 32806, United States

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Ironwood Investigational Site

South Miami, Florida, 33143, United States

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Ironwood Investigational Site

Tampa, Florida, 33634, United States

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Ironwood Investigational Site

West Palm Beach, Florida, 33409, United States

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Ironwood Investigational Site

Atlanta, Georgia, 30328, United States

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Ironwood Investigational Site

Oakwood, Georgia, 30566, United States

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Ironwood Investigational Site

Sandy Springs, Georgia, 30328, United States

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Ironwood Investigational Site

Evansville, Indiana, 47714, United States

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Ironwood Investigational Site

Bastrop, Louisiana, 71220, United States

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Ironwood Investigational Site

Metairie, Louisiana, 70006, United States

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Ironwood Investigational Site

Shreveport, Louisiana, 71105, United States

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Ironwood Investigational Site

Baltimore, Maryland, 21215, United States

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Ironwood Investigational Site

Chevy Chase, Maryland, 20815, United States

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Ironwood Investigational Site

Boston, Massachusetts, 02131, United States

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Ironwood Investigational Site

Watertown, Massachusetts, 02472, United States

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Ironwood Investigational Site

Chesterfield, Michigan, 48047, United States

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Ironwood Investigational Site

Wyoming, Michigan, 49519, United States

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Ironwood Investigational Site

Jackson, Mississippi, 39202, United States

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Ironwood Investigational Site

St Louis, Missouri, 63128-2197, United States

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Ironwood Investigational Site

Bozeman, Montana, 59718, United States

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Ironwood Investigational Site

Las Vegas, Nevada, 89119, United States

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Ironwood Investigational Site

Las Vegas, Nevada, 89121, United States

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Ironwood Investigational Site

Brooklyn, New York, 11206, United States

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Ironwood Investigational Site

Charlotte, North Carolina, 28210, United States

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Ironwood Investigational Site

Concord, North Carolina, 28025, United States

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Ironwood Investigational Site

Davidson, North Carolina, 28036, United States

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Ironwood Investigational Site

Fayetteville, North Carolina, 28304, United States

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Ironwood Investigational Site

Wilmington, North Carolina, 28401, United States

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Ironwood Investigational Site

Winston-Salem, North Carolina, 27103, United States

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Ironwood Investigational Site

Cincinnati, Ohio, 45219, United States

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Ironwood Investigational Site

Cincinnati, Ohio, 45224, United States

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Ironwood Investigational Site

Mentor, Ohio, 44060, United States

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Ironwood Investigational Site

Xenia, Ohio, 45385, United States

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Ironwood Investigational Site

Pittsburgh, Pennsylvania, 15206, United States

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Ironwood Investigational Site

Dakota Dunes, South Dakota, 57049, United States

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Ironwood Investigational Site

Bristol, Tennessee, 37620, United States

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Ironwood Investigational Site

Chattanooga, Tennessee, 37421, United States

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Ironwood Investigational Site

Knoxville, Tennessee, 37909, United States

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Ironwood Investigational Site

Arlington, Texas, 76012, United States

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Ironwood Investigational Site

Beaumont, Texas, 77001, United States

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Ironwood Investigational Site

El Paso, Texas, 79905, United States

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Ironwood Investigational Site

Houston, Texas, 77074, United States

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Ironwood Investigational Site

San Antonio, Texas, 78209, United States

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Ironwood Investigational Site

San Antonio, Texas, 78229, United States

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Ironwood Investigational Site

San Antonio, Texas, 78258, United States

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Ironwood Investigational Site

Ogden, Utah, 84405, United States

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Ironwood Investigational Site

Sandy City, Utah, 84094, United States

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Ironwood Investigational Site

Christiansburg, Virginia, 24073, United States

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Ironwood Investigational Site

Lynchburg, Virginia, 24502, United States

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Ironwood Investigational Site

La Crosse, Wisconsin, 54601, United States

Location

Related Publications (1)

• Chey WD, Sayuk GS, Bartolini W, Reasner DS, Fox SM, Bochenek W, Boinpally R, Shea E, Tripp K, Borgstein N. Randomized Trial of 2 Delayed-Release Formulations of Linaclotide in Patients With Irritable Bowel Syndrome With Constipation. Am J Gastroenterol. 2021 Feb 1;116(2):354-361. doi: 10.14309/ajg.0000000000000967.

  PMID: 33065589 DERIVED

MeSH Terms

Interventions

linaclotide

Results Point of Contact

• Title: Nick Omniewski, MPH
• Organization: Ironwood Pharmaceuticals, Inc.

nomniewski@ironwoodpharma.com

(617) 621-8454

Study Officials

• Paul Chamberlin, MD

  Ironwood Pharmaceuticals, Inc.

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 22, 2015
• First Posted: September 24, 2015
• Study Start: October 22, 2015
• Primary Completion: September 30, 2016
• Study Completion: September 30, 2016
• Last Updated: April 24, 2020
• Results First Posted: April 24, 2020

Record last verified: 2020-04

Locations

US (71)