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

Irritable Bowel Syndrome Characterized by Constipation Clinical Trial

Official title:

A Phase 3b, Randomized, Double-blind, Placebo-controlled, Parallel-group Trial of Linaclotide 290 μg Administered Orally for 12 Weeks Followed by a 4-week Randomized Withdrawal Period in Patients With Irritable Bowel Syndrome With Constipation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03573908
• Other study ID #: MCP-103-312
• Status: Completed
• Phase: Phase 3
• Start date: June 20, 2018
• Est. completion date: April 10, 2019

Study information

• Verified date: November 2020
• Source: Ironwood Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 614
• Est. completion date: April 10, 2019
• Est. primary completion date: March 13, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

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

Related Conditions & MeSH terms

• Constipation
• Irritable Bowel Syndrome
• Irritable Bowel Syndrome Characterized by Constipation
• Syndrome

Intervention

Drug:
• Linaclotide
Oral capsule
• Placebo
Matching placebo oral capsule

Locations

Country	Name	City	State
United States	Alan A. Rosen, MD, PA	Baltimore	Maryland
United States	MW Clinical Research Center	Beaumont	Texas
United States	Boston Clinical Trials, Inc.	Boston	Massachusetts
United States	Bozeman Health Deaconess Hospital	Bozeman	Montana
United States	Connecticut Clinical Research Institute	Bristol	Connecticut
United States	Healthwise Medical Associates	Brooklyn	New York
United States	Carolina Digestive Health Associates	Charlotte	North Carolina
United States	ClinSearch, LLC	Chattanooga	Tennessee
United States	New River Valley Research Institute	Christiansburg	Virginia
United States	GW Research, Inc.	Chula Vista	California
United States	Hightop Medical Research Center	Cincinnati	Ohio
United States	New Horizons Clinical Research	Cincinnati	Ohio
United States	Remington Davis, Inc.	Columbus	Ohio
United States	Carolina Digestive Health Associates	Concord	North Carolina
United States	Clinical Research of South Florida	Coral Gables	Florida
United States	Kindred Medical Institute for Clinical Trials, LLC	Corona	California
United States	Partners In Clinical Research	Cumberland	Rhode Island
United States	Meridian Clinical Research	Dakota Dunes	South Dakota
United States	Dayton Gastroenterology, Inc.	Dayton	Ohio
United States	Hometown Urgent Care and Research	Dayton	Ohio
United States	Avail Clinical Research, LLC	DeLand	Florida
United States	Diagnamics, Inc.	Encinitas	California
United States	Lillestol Research	Fargo	North Dakota
United States	Cumberland Research Associates	Fayetteville	North Carolina
United States	Gastrointestinal Associates PA	Flowood	Mississippi
United States	MD Studies, Inc.	Fountain Valley	California
United States	Paragon Rx Clinical, Inc. - Garden Grove	Garden Grove	California
United States	Long Island Gastrointestinal Research Group, LLP	Great Neck	New York
United States	Mountain View Clinical Research, Inc.	Greer	South Carolina
United States	Meritus Center For Clinical Research	Hagerstown	Maryland
United States	Palmetto Research, LLC	Hialeah	Florida
United States	Peters Medical Research, LLC	High Point	North Carolina
United States	Southwest Clinical Trials	Houston	Texas
United States	Southwest Clinical Trials	Houston	Texas
United States	Clinical Research Associates	Huntsville	Alabama
United States	Nature Coast Clinical Research, LLC	Inverness	Florida
United States	The Chappel Group Research	Kissimmee	Florida
United States	New Phase Research & Development	Knoxville	Tennessee
United States	Grossmont Center For Clinical Research	La Mesa	California
United States	Clinical Research of South Nevada	Las Vegas	Nevada
United States	Blue Ridge Medical Research	Lynchburg	Virginia
United States	Great Lakes Gastroenterology Research, LLC	Mentor	Ohio
United States	Clinical Trials Management, LLC	Metairie	Louisiana
United States	Jesscan Medical Research	Miami	Florida
United States	New Horizon Research Center	Miami	Florida
United States	Well Pharma Medical Research Corporation	Miami	Florida
United States	San Marcus Research Clinic, Inc.	Miami Lakes	Florida
United States	Ocean Blue Medical Research Center, Inc.	Miami Springs	Florida
United States	Facey Medical Foundation	Mission Hills	California
United States	Delta Research Partners, LLC	Monroe	Louisiana
United States	Providence Clinical Research	North Hollywood	California
United States	Arkansas Gastroenterology	North Little Rock	Arkansas
United States	Advanced Research Institute	Ogden	Utah
United States	IPS Research Company	Oklahoma City	Oklahoma
United States	Ormond Medical Arts Pharmaceutical Research Center	Ormond Beach	Florida
United States	Elite Clinical Studies	Phoenix	Arizona
United States	Wake Research Associates, LLC	Raleigh	North Carolina
United States	St. Louis Center For Clinical Research	Saint Louis	Missouri
United States	Diagnostics Research Group	San Antonio	Texas
United States	Quality Research, Inc.	San Antonio	Texas
United States	Stone Oak, LLC dba Discovery Clinical Trials	San Antonio	Texas
United States	Precision Research Institute	San Diego	California
United States	Mount Vernon Clinical Research, LLC	Sandy Springs	Georgia
United States	Paragon Rx Clinical, Inc.- Santa Ana	Santa Ana	California
United States	Louisiana Research Center, LLC	Shreveport	Louisiana
United States	Precision Clinical Research	Sunrise	Florida
United States	Meridien Research - Tampa	Tampa	Florida
United States	Millennium Clinical Trials	Thousand Oaks	California
United States	Adobe Clinical Research, LLC	Tucson	Arizona
United States	Chase Medical Research, LLC	Waterbury	Connecticut
United States	MedVadis Research Corporation	Watertown	Massachusetts
United States	Palm Beach Research Center	West Palm Beach	Florida
United States	PMG Research of Wilmington	Wilmington	North Carolina
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	Research Institute of Central Florida, LLC	Winter Park	Florida
United States	Gastroenterology Associates of West Michigan	Wyoming	Michigan
United States	St. Joseph Heritage Healthcare	Yorba Linda	California

Sponsors (2)

Lead Sponsor	Collaborator
Ironwood Pharmaceuticals, Inc.	Allergan Sales, LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Change From Baseline in Abdominal Score (Abdominal Bloating, Abdominal Discomfort, and Abdominal Pain) Throughout the Treatment Period	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.	Baseline (14 days before randomization up to the time of randomization), Treatment Period (Weeks 1-12)
Secondary	Cumulative Distribution of Change From Baseline in 12-Week Abdominal Score	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).	Baseline (14 days before randomization up to the time of randomization), Treatment Period (Weeks 1-12)
Secondary	Percentage of 6/12 Week Abdominal Score Responders (Responder Rate)	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.	Baseline (14 days before randomization up to the time of randomization), Treatment Period (Weeks 1-12)
Secondary	Overall Change From Baseline in Abdominal Score (Abdominal Bloating, Abdominal Discomfort, and Abdominal Pain) Over Time in the Treatment Period	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.	Baseline (14 days before randomization up to the time of randomization), Weeks 1-12