Efficacy of Eluxadoline in the Treatment of Irritable Bowel Syndrome With Diarrhea in Patients With Inadequate Control of Symptoms With Prior Loperamide Use

Irritable Bowel Syndrome With Diarrhea Clinical Trial

Official title:

A Phase 4 Multicenter, Multinational, Prospective, Randomized, Placebo-Controlled, Double-Blinded Parallel Group Study to Assess Efficacy of Eluxadoline in the Treatment of Irritable Bowel Syndrome With Diarrhea (IBS-D) in Patients Who Report Inadequate Control of IBS-D Symptoms With Prior Loperamide Use (RELIEF)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02959983
• Other study ID #: CMO-US-GI-0429
• Status: Completed
• Phase: Phase 4
• Start date: October 25, 2016
• Est. completion date: January 22, 2018

Study information

• Verified date: January 2019
• Source: Allergan
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will evaluate the efficacy and safety of eluxadoline 100 milligrams (mg) twice a day (BID) versus placebo for the treatment of patients with Irritable Bowel Syndrome with Diarrhea (IBS-D) who report that the use of loperamide in the prior 12 months failed to provide control of their IBS-D symptoms.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 346
• Est. completion date: January 22, 2018
• Est. primary completion date: January 22, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Has a diagnosis of IBS-D, defined by the Rome III criteria as loose (mushy) or watery stools =25% and hard or lumpy stools =25% of bowel movements.

• Has had a colonoscopy performed within 5 years prior to Screening if they are at least 50 years of age, OR if they meet any of the following alarm features:

1. Has documented weight loss within the past 6 months; or

2. Has nocturnal symptoms; or

3. Has a familial history of colon cancer; or

4. Has blood mixed with their stool (excluding any blood from hemorrhoids)

• Patient reports use of loperamide in the 12 months prior to Screening for IBS-D symptoms and that loperamide did not provide adequate control of IBS-D symptoms.

• Has not used any loperamide rescue medication within 14 days prior to randomization.

Exclusion Criteria:

• Has a diagnosis of Irritable Bowel Syndrome (IBS) with a subtype of constipation IBS, mixed IBS, or unsubtyped IBS.

• Has a history of inflammatory or immune-mediated gastrointestinal (GI) disorders including inflammatory bowel disease (i.e., Crohn's disease, ulcerative colitis), microscopic colitis, or celiac disease.

• Has a history of diverticulitis within 3 months prior to screening.

• Has a documented history of lactose intolerance.

• Has a documented history of bile-acid malabsorption.

• Has a history of chronic or severe constipation or intestinal obstruction, stricture, toxic megacolon, GI perforation, fecal impaction, gastric banding, bariatric surgery, adhesions.

• Has any of the following surgical history:

1. Cholecystectomy or previously documented agenesis of gallbladder; or

2. Any abdominal surgery within the 3 months prior to screening; or

3. Major gastric, hepatic, pancreatic, or intestinal surgery (appendectomy, hemorrhoidectomy, or polypectomy greater than 3 months post-surgery are allowed).

• Has a history of cholecystitis within 6 months before screening.

• Has a history of pancreatitis or structural diseases of the pancreas, including known or suspected pancreatic duct obstruction.

• Has a history of known or suspected biliary duct obstruction or sphincter of Oddi disease or dysfunction, excluding a history of gallstones.

• Has a history or current evidence of laxative abuse within 5 years prior to screening.

• Has documented evidence of cirrhosis.

• Has a history of cardiovascular events, including stroke, myocardial infarction, congestive heart failure, or transient ischemic attack within 6 months prior to screening.

• Has an unstable renal, hepatic, metabolic, or hematologic condition.

• Has a history of malignancy within 5 years before screening (except squamous and basal cell carcinomas and cervical carcinoma in situ).

• Has a history of human immunodeficiency virus infection.

• Has a history of Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision-defined substance dependency, excluding nicotine and caffeine, within 2 years prior to screening.

• Has a history of alcohol abuse, alcohol addiction, and alcoholism or drinks more than 3 alcoholic beverages per day.

• Has used aspirin or aspirin-containing medications (>325 mg of aspirin per day) or nonsteroidal anti-inflammatory drugs, when taken specifically for the symptoms of IBS, within 14 days of randomization.

• Has current (within 14 days of randomization) or expected use of any narcotic or opioid-containing agents, tramadol, docusate, enemas, GI preparations (including antacids containing aluminum or magnesium, antidiarrheal agents [except loperamide rescue medication after randomization]), antinausea agents, antispasmodic agents, bismuth, or prokinetic agents.

• Has current (within 28 days of randomization) use of rifaximin or other antibiotics (with the exception of topical antibiotics or a 1-day course with an antibiotic). Expected use of rifaximin or other antibiotics during the course of the study that is known at the time of randomization.

• Has an elective surgery planned or expects to need elective surgery at any time during the study.

Related Conditions & MeSH terms

• Diarrhea
• Irritable Bowel Syndrome
• Irritable Bowel Syndrome With Diarrhea
• Syndrome

Intervention

Drug:
• Eluxadoline
Eluxadoline 100 mg oral tablets BID with food.
• Placebo
Placebo matching eluxadoline oral tablets BID with food.

Locations

Country	Name	City	State
Canada	University of Calgary	Calgary
Canada	Corunna Medical Research Centre	Corunna	Ontario
Canada	Manna Research	Etobicoke	Ontario
Canada	SKDS Research Inc	Newmarket	Ontario
Canada	Viable Clinical Research Corp.	Nova Scotia
Canada	Centre de reserche St Louis	Quebec
Canada	Dynamik Research Inc	Quebec
United States	Investigative Clinical Research	Annapolis	Maryland
United States	Emory University School of Medicine	Atlanta	Georgia
United States	Premier Family Physicians	Austin	Texas
United States	Clinical Inquest Center Ltd	Beavercreek	Ohio
United States	The Center for Clinical Trials	Biloxi	Mississippi
United States	Connecticut Clinical Research Foundation	Bristol	Connecticut
United States	Drug Trials Brooklyn	Brooklyn	New York
United States	NY Scientific	Brooklyn	New York
United States	Investigators Research	Brownsburg	Indiana
United States	RNA America, LLC	Buford	Georgia
United States	Med Investigations	Carmichael	California
United States	Family Medicine Associate of Texas	Carrollton	Texas
United States	Charlotte Gastroenterology & Hepatology, PLLC	Charlotte	North Carolina
United States	WR-ClinSearch, LLC	Chattanooga	Tennessee
United States	Clinical Research Insititute of Michigan LLC	Chesterfield	Michigan
United States	MGG Group Co. Inc. Chevy Chase Clinical Research	Chevy Chase	Maryland
United States	Northwestern University Feinbery School of Medicine	Chicago	Illinois
United States	GW Research Inc	Chula Vista	California
United States	Hometown Urgent Care and Research	Cincinnati	Ohio
United States	Innovative Research of West Florida, Inc.	Clearwater	Florida
United States	Buckeye Health and Research	Columbus	Ohio
United States	Hometown Urgent Care and Research	Columbus	Ohio
United States	Digestive Care of N. Broward	Coral Springs	Florida
United States	Partners in Clinical Research	Cumberland	Rhode Island
United States	Diagnamics Inc	Encinitas	California
United States	Clinical Research Advantage Inc/Radiant Research Inc.	Evansville	Indiana
United States	Radiant Research, Inc.	Evansville	Indiana
United States	Pharmakon Inc	Evergreen Park	Illinois
United States	Gastroenterology Associates of Northern Virginia	Fairfax	Virginia
United States	Long Island Gastrointestinal Group LLP	Great Neck	New York
United States	Medical Research Center of Connecticut, LLC	Hamden	Connecticut
United States	Peters Medical Research LLC	High Point	North Carolina
United States	Homestead Medical Research	Homestead	Florida
United States	Hometown Urgent Care and Research	Huber Heights	Ohio
United States	Clinical Research Associates, LLC	Huntsville	Alabama
United States	Behavioral Research Specialists, LLC	Irvine	California
United States	Clinical Neuroscience Solutions Inc.	Jacksonville	Florida
United States	Health Awareness, Inc.	Jupiter	Florida
United States	IMA Medical Research, PC	Kew Gardens	New York
United States	New Phase Research & Development	Knoxville	Tennessee
United States	Advanced Biomedical Research of America	Las Vegas	Nevada
United States	Precision Clinical Research LLC	Lauderdale Lakes	Florida
United States	North State Clincial Research PLLC	Lenoir	North Carolina
United States	Women's Clinic of Lincoln, P.C.	Lincoln	Nebraska
United States	Blue Ridge Medical Research	Lynchburg	Virginia
United States	CNS Healthcare	Memphis	Tennessee
United States	Pharmax Research Clinic Inc.	Miami	Florida
United States	Well Pharma Medical Research, Corp.	Miami	Florida
United States	Ocean Blue Medical Research Center, Inc	Miami Springs	Florida
United States	Central Sooner Research	Norman	Oklahoma
United States	Bravo Health Care Center	North Bay Village	Florida
United States	Providence Clinical Research	North Hollywood	California
United States	Arkansas Gastroenterology	North Little Rock	Arkansas
United States	Advanced Research Institute - Ogden	Ogden	Utah
United States	Quality Clinical Research Inc.	Omaha	Nebraska
United States	Clinical Neuroscience Solutions Inc.	Orlando	Florida
United States	Elite Clinical Studies	Phoenix	Arizona
United States	Wake Research Associates LLC	Raleigh	North Carolina
United States	Advanced Research Institute	Reno	Nevada
United States	The Oregon Center for Clinical Investigations, INC.	Salem	Oregon
United States	Wasatch Clinical Research, LLC	Salt Lake City	Utah
United States	Discovery Clinical Trials - Stone Oak	San Antonio	Texas
United States	Health Texas Research Institute	San Antonio	Texas
United States	Multi-Phase Trials LLC	San Antonio	Texas
United States	The Center for Clinical Trials	Saraland	Alabama
United States	Gtc Research	Shawnee Mission	Kansas
United States	Shahram Jacobs MD INC.	Sherman Oaks	California
United States	Carl Meisner Medical Clinic	Sugar Land	Texas
United States	Clinical Research of West Florida Inc.	Tampa	Florida
United States	Meridien Research	Tampa	Florida
United States	Westlake Medical Research	Thousand Oaks	California
United States	Upland Clinical Research	Upland	California
United States	MedVadis Research Corporation	Watertown	Massachusetts
United States	Advanced RX Clinicial Research Group, Inc.	Westminster	California
United States	Trial Management Associates, LLC	Wilmington	North Carolina
United States	Gastroenterology Associates of Western Michigan, PLC	Wyoming	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
Allergan

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Who Were Composite Responders Based on Improvements From Baseline in Daily Worst Abdominal Pain And Daily Stool Consistency Scores	Percentage of primary composite responders is defined as the percentage of participants who meet both of the following daily composite criteria for at least 50% of the days with diary entry: 1)Worst Abdominal Pain (WAP) score improved by =40% compared to Baseline. The participant records their WAP score in the past 24 hours each day in a daily patient diary where: 0=no pain to 10=worst imaginable pain. 2) Bristol Stool Score (BSS) <5; or the absence of a bowel movement if accompanied by =40% improvement in WAP compared to Baseline. The participant records their stool consistency each day in a daily patient diary using the BSS on a scale from 1 (hard stool) to 7 (watery stool).	Baseline, Weeks 1 to 12
Secondary	Percentage of Stool Consistency Responders	Percentage of stool consistency responders is defined as the percentage of participants who meet the daily stool consistency response criteria: BSS <5; or the absence of a bowel movement if accompanied by =40% improvement in WAP compared to Baseline for =50% of days with daily patient diary entries over a certain time period. The participant records their stool consistency each day in a daily patient diary using the BSS on a scale from 1 (hard stool) to 7 (watery stool). A participant must have had a minimum of 20 days of diary entries over any 4-week interval.	Weeks 1 to 12 and 4-week intervals (Weeks 1 to 4, Weeks 5 to 8 and Weeks 9 to 12)
Secondary	Percentage of Pain Responders	Percentage of pain responders is defined as the percentage of participants who meet the daily pain response criteria: WAP score improved by =40% compared to Baseline for =50% of days with diary entries over a certain time period. The participant records their WAP score in the past 24 hours each day in a daily diary where: 0=no pain to 10=worst imaginable pain. A participant must have had a minimum of 20 days of diary entries over any 4-week interval.	Baseline, Weeks 1 to 12 and 4-week intervals (Weeks 1 to 4, Weeks 5 to 8 and Weeks 9 to 12)
Secondary	Percentage of Monthly Composite Responders	Percentage of monthly composite responders is defined as the percentage of participants who meet the daily composite response criteria for at least 50% of days with diary entry for a minimum of 20 days during each 4-week interval (weeks 1 to 4, 5 to 8, and 9 to 12). Composite response includes both of the following criteria: 1) WAP score improved by =40% compared to Baseline. The participant records their WAP score in the past 24 hours each day in a daily patient diary where: 0=no pain to 10=worst imaginable pain. 2) BSS <5; or the absence of a bowel movement if accompanied by =40% improvement in WAP compared to Baseline. The participant records their stool consistency each day in a daily patient diary using the BSS on a scale from 1 (hard stool) to 7 (watery stool).	Weeks 1 to 4, 5 to 8, and 9 to 12

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