A Trial of Linaclotide 290 μg in Patients With Irritable Bowel Syndrome With Constipation (IBS-C)

Phase 3

Completed

• Conditions: Irritable Bowel Syndrome Characterized by Constipation
• Interventions: Drug: Linaclotide; Drug: Placebo

• Registration Number: NCT03573908
• Lead Sponsor: Ironwood Pharmaceuticals, Inc.

Brief Summary

To evaluate the efficacy on abdominal symptoms (abdominal bloating, abdominal discomfort, and abdominal pain) and safety of linaclotide 290 μg administered orally to patients with IBS-C.

Detailed Description

This study consists of a 12-week Treatment Period followed by 4-week Randomized Withdrawal (RW) Period.

Study Timeline

• Study First Submitted: 2018-06-18
• Study Start: 2018-06-20
• Study First Submitted QC: 2018-06-27
• Study First Posted: 2018-06-29
• Primary Completion: 2019-03-13
• Study Completion: 2019-04-10
• Disposition First Submitted: 2020-03-13
• Disposition First Submitted QC: 2020-03-13
• Disposition First Posted: 2020-03-17
• Results First Submitted: 2020-10-19
• Results First Submitted QC: 2020-10-19
• Status Verified: 2020-11
• Last Update Submitted: 2020-11-13
• Results First Posted: 2020-11-16
• Last Update Posted: 2020-12-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 614

Inclusion Criteria

• Patient has no clinically significant findings on a physical examination and clinical laboratory tests

• Female patients of childbearing potential must agree to use one of the following methods of birth control:

  1. Hormonal contraception
  2. Double-barrier birth control
  3. Maintenance of a monogamous relationship with a male partner who has been surgically sterilized by vasectomy

• Patient meets protocol criteria for diagnosis of IBS-C

• Patient demonstrates continued IBS-C symptoms through Pretreatment Period

• Patient maintains a minimum level of compliance with daily diary

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Exclusion Criteria

• 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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Linaclotide 290 µg	Placebo	Participants receive linaclotide 290 µg orally once daily for 12 weeks during the Treatment Period. At Week 12 participants are rerandomized to receive either linaclotide 290 µg or placebo for 4 weeks in the Randomized Withdrawal Period.
Placebo	Placebo	Participants receive placebo to linaclotide orally once daily for 12 weeks during the Treatment Period. At Week 12 participants are switched to receive linaclotide 290 µg for 4 weeks during the Randomized Withdrawal Period.
Linaclotide 290 µg	Linaclotide	Participants receive linaclotide 290 µg orally once daily for 12 weeks during the Treatment Period. At Week 12 participants are rerandomized to receive either linaclotide 290 µg or placebo for 4 weeks in the Randomized Withdrawal Period.
Placebo	Linaclotide	Participants receive placebo to linaclotide orally once daily for 12 weeks during the Treatment Period. At Week 12 participants are switched to receive linaclotide 290 µg for 4 weeks during the Randomized Withdrawal Period.

Primary Outcome Measures

Name	Time	Method
Overall Change From Baseline in Abdominal Score (Abdominal Bloating, Abdominal Discomfort, and Abdominal Pain) Throughout the Treatment Period	Baseline (14 days before randomization up to the time of randomization), Treatment Period (Weeks 1-12)	A participant's daily abdominal score was calculated as the average of daily e-diary abdominal pain, abdominal bloating and abdominal discomfort scores, each based on an 11-point scale of 0 (none) and 10 (worst possible). Baseline abdominal score was derived from the eDiary data collected daily in the Pretreatment Period, specifically the period of time from 14 days before randomization up to the time of randomization. The participant's abdominal score was averaged on a weekly basis, and each weekly change from baseline was calculated for the treatment period and used as the dependent variable in the mixed model with repeated measures (MMRM) model. MMRM results are based on a model with treatment, analysis week, region and treatment-by-week interaction as fixed effects and baseline as a covariate. An unstructured covariance structure was used to model intra-subject correlation with subjects as a random effect.

Secondary Outcome Measures

Name	Time	Method
Overall Change From Baseline in Abdominal Score (Abdominal Bloating, Abdominal Discomfort, and Abdominal Pain) Over Time in the Treatment Period	Baseline (14 days before randomization up to the time of randomization), Weeks 1-12	A participant's daily abdominal score was calculated as the average of daily e-diary abdominal pain, abdominal bloating and abdominal discomfort scores, each based on an 11-point scale of 0 (none) and 10 (worst possible). Baseline abdominal score was derived from the eDiary data collected daily in the Pretreatment Period, specifically the period of time from 14 days before randomization up to the time of randomization. The participant's abdominal score was averaged on a weekly basis, and each weekly change from baseline was calculated for the treatment period and used as the dependent variable in the mixed model with repeated measures (MMRM) model. MMRM results are based on a model with treatment, analysis week, region and treatment-by-week interaction as fixed effects and baseline as a covariate. An unstructured covariance structure was used to model intra-subject correlation with subjects as a random effect.
Cumulative Distribution of Change From Baseline in 12-Week Abdominal Score	Baseline (14 days before randomization up to the time of randomization), Treatment Period (Weeks 1-12)	A participant's daily abdominal score was calculated as the average of daily e-diary abdominal pain, abdominal bloating and abdominal discomfort scores, each based on an 11-point scale of 0 (none) and 10 (worst possible). Baseline abdominal score was derived from the eDiary data collected daily in the Pretreatment Period, specifically the period of time from 14 days before randomization up to the time of randomization. The 12-week abdominal score was the average of the non-missing abdominal scores reported over the course of the treatment period. Change from baseline (BL) was calculated as the 12-week score minus the baseline score. The table presents the percentage of participants whose 12-week change from baseline was less than or equal to the threshold value of the score change (cumulative distribution of change).
Percentage of 6/12 Week Abdominal Score Responders (Responder Rate)	Baseline (14 days before randomization up to the time of randomization), Treatment Period (Weeks 1-12)	A 6/12 week abdominal score responder is a participant who meets the weekly abdominal score responder criteria for at least 6 out of the 12 weeks of the Treatment Period. For each week in the Treatment Period, a weekly abdominal score responder is a participant who has an improvement from baseline of at least 2 points (ie, a -2 point change from baseline) in the respective weekly abdominal score. If a participant did not have at least 4 completed eDiary entries for a particular Treatment Period week, the participant was not considered a responder for that week.; A participant's daily abdominal score was calculated as the average of daily e-diary abdominal pain, abdominal bloating and abdominal discomfort scores, each based on an 11-point scale of 0 (none) and 10 (worst possible). The participant's abdominal score was averaged on a weekly basis, and each weekly change from baseline was calculated for the treatment period.

Trial Locations

Locations (77)

Long Island Gastrointestinal Research Group, LLP; 🇺🇸 Great Neck, New York, United States

Meritus Center For Clinical Research; 🇺🇸 Hagerstown, Maryland, United States

Boston Clinical Trials, Inc.; 🇺🇸 Boston, Massachusetts, United States

Remington Davis, Inc.; 🇺🇸 Columbus, Ohio, United States

Well Pharma Medical Research Corporation; 🇺🇸 Miami, Florida, United States

New Horizon Research Center; 🇺🇸 Miami, Florida, United States

Precision Research Institute; 🇺🇸 San Diego, California, United States

Clinical Research of South Nevada; 🇺🇸 Las Vegas, Nevada, United States

Hightop Medical Research Center; 🇺🇸 Cincinnati, Ohio, United States

New Horizons Clinical Research; 🇺🇸 Cincinnati, Ohio, United States

Diagnostics Research Group; 🇺🇸 San Antonio, Texas, United States

Stone Oak, LLC dba Discovery Clinical Trials; 🇺🇸 San Antonio, Texas, United States

New River Valley Research Institute; 🇺🇸 Christiansburg, Virginia, United States

Delta Research Partners, LLC; 🇺🇸 Monroe, Louisiana, United States

Lillestol Research; 🇺🇸 Fargo, North Dakota, United States

Elite Clinical Studies; 🇺🇸 Phoenix, Arizona, United States

IPS Research Company; 🇺🇸 Oklahoma City, Oklahoma, United States

Advanced Research Institute; 🇺🇸 Ogden, Utah, United States

MW Clinical Research Center; 🇺🇸 Beaumont, Texas, United States

Meridian Clinical Research; 🇺🇸 Dakota Dunes, South Dakota, United States

Blue Ridge Medical Research; 🇺🇸 Lynchburg, Virginia, United States

New Phase Research & Development; 🇺🇸 Knoxville, Tennessee, United States

Quality Research, Inc.; 🇺🇸 San Antonio, Texas, United States

Partners In Clinical Research; 🇺🇸 Cumberland, Rhode Island, United States

Dayton Gastroenterology, Inc.; 🇺🇸 Dayton, Ohio, United States

Hometown Urgent Care and Research; 🇺🇸 Dayton, Ohio, United States

Great Lakes Gastroenterology Research, LLC; 🇺🇸 Mentor, Ohio, United States

Southwest Clinical Trials; 🇺🇸 Houston, Texas, United States

Paragon Rx Clinical, Inc.- Santa Ana; 🇺🇸 Santa Ana, California, United States

Clinical Research Associates; 🇺🇸 Huntsville, Alabama, United States

Grossmont Center For Clinical Research; 🇺🇸 La Mesa, California, United States

GW Research, Inc.; 🇺🇸 Chula Vista, California, United States

Arkansas Gastroenterology; 🇺🇸 North Little Rock, Arkansas, United States

Kindred Medical Institute for Clinical Trials, LLC; 🇺🇸 Corona, California, United States

Paragon Rx Clinical, Inc. - Garden Grove; 🇺🇸 Garden Grove, California, United States

Diagnamics, Inc.; 🇺🇸 Encinitas, California, United States

Providence Clinical Research; 🇺🇸 North Hollywood, California, United States

Facey Medical Foundation; 🇺🇸 Mission Hills, California, United States

Millennium Clinical Trials; 🇺🇸 Thousand Oaks, California, United States

St. Joseph Heritage Healthcare; 🇺🇸 Yorba Linda, California, United States

Chase Medical Research, LLC; 🇺🇸 Waterbury, Connecticut, United States

Avail Clinical Research, LLC; 🇺🇸 DeLand, Florida, United States

Clinical Research of South Florida; 🇺🇸 Coral Gables, Florida, United States

The Chappel Group Research; 🇺🇸 Kissimmee, Florida, United States

Nature Coast Clinical Research, LLC; 🇺🇸 Inverness, Florida, United States

San Marcus Research Clinic, Inc.; 🇺🇸 Miami Lakes, Florida, United States

Ocean Blue Medical Research Center, Inc.; 🇺🇸 Miami Springs, Florida, United States

Ormond Medical Arts Pharmaceutical Research Center; 🇺🇸 Ormond Beach, Florida, United States

Jesscan Medical Research; 🇺🇸 Miami, Florida, United States

Precision Clinical Research; 🇺🇸 Sunrise, Florida, United States

Palm Beach Research Center; 🇺🇸 West Palm Beach, Florida, United States

Mount Vernon Clinical Research, LLC; 🇺🇸 Sandy Springs, Georgia, United States

Clinical Trials Management, LLC; 🇺🇸 Metairie, Louisiana, United States

Bozeman Health Deaconess Hospital; 🇺🇸 Bozeman, Montana, United States

Alan A. Rosen, MD, PA; 🇺🇸 Baltimore, Maryland, United States

MedVadis Research Corporation; 🇺🇸 Watertown, Massachusetts, United States

St. Louis Center For Clinical Research; 🇺🇸 Saint Louis, Missouri, United States

Gastroenterology Associates of West Michigan; 🇺🇸 Wyoming, Michigan, United States

Healthwise Medical Associates; 🇺🇸 Brooklyn, New York, United States

Gastrointestinal Associates PA; 🇺🇸 Flowood, Mississippi, United States

Cumberland Research Associates; 🇺🇸 Fayetteville, North Carolina, United States

Carolina Digestive Health Associates; 🇺🇸 Concord, North Carolina, United States

MD Studies, Inc.; 🇺🇸 Fountain Valley, California, United States

Palmetto Research, LLC; 🇺🇸 Hialeah, Florida, United States

Peters Medical Research, LLC; 🇺🇸 High Point, North Carolina, United States

PMG Research of Wilmington; 🇺🇸 Wilmington, North Carolina, United States

Research Institute of Central Florida, LLC; 🇺🇸 Winter Park, Florida, United States

Wake Research Associates, LLC; 🇺🇸 Raleigh, North Carolina, United States

Connecticut Clinical Research Institute; 🇺🇸 Bristol, Connecticut, United States

Adobe Clinical Research, LLC; 🇺🇸 Tucson, Arizona, United States

Louisiana Research Center, LLC; 🇺🇸 Shreveport, Louisiana, United States

ClinSearch, LLC; 🇺🇸 Chattanooga, Tennessee, United States

Meridien Research - Tampa; 🇺🇸 Tampa, Florida, United States

Clinical Trials of America - North Carolina, LLC; 🇺🇸 Winston-Salem, North Carolina, United States

Lyndhurst Clinical Research; 🇺🇸 Winston-Salem, North Carolina, United States

PMG Research of Winston-Salem; 🇺🇸 Winston-Salem, North Carolina, United States

Mountain View Clinical Research, Inc.; 🇺🇸 Greer, South Carolina, United States