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

Phase 4

Completed

Conditions: Irritable Bowel Syndrome With Diarrhea

Interventions: Drug: Placebo
Drug: Eluxadoline

Registration Number: NCT02959983

Lead Sponsor: Allergan

Brief 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 346

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo matching eluxadoline oral tablets BID with food for 12 weeks.
Eluxadoline	Eluxadoline	Eluxadoline 100 mg oral tablets twice daily (BID) with food for 12 weeks.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Who Were Composite Responders Based on Improvements From Baseline in Daily Worst Abdominal Pain And Daily Stool Consistency Scores	Baseline, Weeks 1 to 12	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).

Secondary Outcome Measures

Name	Time	Method
Percentage of Pain Responders	Baseline, Weeks 1 to 12 and 4-week intervals (Weeks 1 to 4, Weeks 5 to 8 and Weeks 9 to 12)	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.
Percentage of Monthly Composite Responders	Weeks 1 to 4, 5 to 8, and 9 to 12	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).
Percentage of Stool Consistency Responders	Weeks 1 to 12 and 4-week intervals (Weeks 1 to 4, Weeks 5 to 8 and Weeks 9 to 12)	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.

Trial Locations

Locations (79): Emory University School of Medicine
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Atlanta, Georgia, United States
Gtc Research
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Shawnee Mission, Kansas, United States
Pharmax Research Clinic Inc.
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Miami, Florida, United States
Well Pharma Medical Research, Corp.
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Miami, Florida, United States
Discovery Clinical Trials - Stone Oak
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San Antonio, Texas, United States
Wasatch Clinical Research, LLC
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Salt Lake City, Utah, United States
GW Research Inc
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Chula Vista, California, United States
Diagnamics Inc
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Encinitas, California, United States
Shahram Jacobs MD INC.
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Sherman Oaks, California, United States
Elite Clinical Studies
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Phoenix, Arizona, United States
Providence Clinical Research
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North Hollywood, California, United States
Connecticut Clinical Research Foundation
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Bristol, Connecticut, United States
Digestive Care of N. Broward
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Coral Springs, Florida, United States
Innovative Research of West Florida, Inc.
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Clearwater, Florida, United States
Upland Clinical Research
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Upland, California, United States
Advanced Biomedical Research of America
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Las Vegas, Nevada, United States
Trial Management Associates, LLC
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Wilmington, North Carolina, United States
Hometown Urgent Care and Research
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Huber Heights, Ohio, United States
Clinical Research Advantage Inc/Radiant Research Inc.
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Evansville, Indiana, United States
MGG Group Co. Inc. Chevy Chase Clinical Research
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Chevy Chase, Maryland, United States
Buckeye Health and Research
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Columbus, Ohio, United States
Wake Research Associates LLC
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Raleigh, North Carolina, United States
Advanced Research Institute - Ogden
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Ogden, Utah, United States
Health Texas Research Institute
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San Antonio, Texas, United States
Clinical Inquest Center Ltd
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Beavercreek, Ohio, United States
Corunna Medical Research Centre
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Corunna, Ontario, Canada
Viable Clinical Research Corp.
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Nova Scotia, Canada
Multi-Phase Trials LLC
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San Antonio, Texas, United States
Family Medicine Associate of Texas
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Carrollton, Texas, United States
Gastroenterology Associates of Northern Virginia
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Fairfax, Virginia, United States
SKDS Research Inc
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Newmarket, Ontario, Canada
Dynamik Research Inc
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Quebec, Canada
Centre de reserche St Louis
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Quebec, Canada
Quality Clinical Research Inc.
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Omaha, Nebraska, United States
Central Sooner Research
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Norman, Oklahoma, United States
Blue Ridge Medical Research
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Lynchburg, Virginia, United States
Clinical Research Associates, LLC
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Huntsville, Alabama, United States
Arkansas Gastroenterology
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North Little Rock, Arkansas, United States
Med Investigations
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Carmichael, California, United States
The Center for Clinical Trials
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Biloxi, Mississippi, United States
Medical Research Center of Connecticut, LLC
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Hamden, Connecticut, United States
Homestead Medical Research
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Homestead, Florida, United States
Precision Clinical Research LLC
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Lauderdale Lakes, Florida, United States
Bravo Health Care Center
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North Bay Village, Florida, United States
Northwestern University Feinbery School of Medicine
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Chicago, Illinois, United States
Pharmakon Inc
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Evergreen Park, Illinois, United States
Investigators Research
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Brownsburg, Indiana, United States
Investigative Clinical Research
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Annapolis, Maryland, United States
Women's Clinic of Lincoln, P.C.
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Lincoln, Nebraska, United States
Gastroenterology Associates of Western Michigan, PLC
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Wyoming, Michigan, United States
NY Scientific
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Brooklyn, New York, United States
North State Clincial Research PLLC
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Lenoir, North Carolina, United States
IMA Medical Research, PC
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Kew Gardens, New York, United States
New Phase Research & Development
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Knoxville, Tennessee, United States
University of Calgary
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Calgary, Canada
Clinical Research Insititute of Michigan LLC
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Chesterfield, Michigan, United States
Westlake Medical Research
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Thousand Oaks, California, United States
Advanced RX Clinicial Research Group, Inc.
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Westminster, California, United States
Ocean Blue Medical Research Center, Inc
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Miami Springs, Florida, United States
Radiant Research, Inc.
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Evansville, Indiana, United States
Advanced Research Institute
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Reno, Nevada, United States
Behavioral Research Specialists, LLC
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Irvine, California, United States
Health Awareness, Inc.
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Jupiter, Florida, United States
RNA America, LLC
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Buford, Georgia, United States
Peters Medical Research LLC
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High Point, North Carolina, United States
The Oregon Center for Clinical Investigations, INC.
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Salem, Oregon, United States
Drug Trials Brooklyn
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Brooklyn, New York, United States
Charlotte Gastroenterology & Hepatology, PLLC
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Charlotte, North Carolina, United States
Long Island Gastrointestinal Group LLP
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Great Neck, New York, United States
Manna Research
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Etobicoke, Ontario, Canada
Partners in Clinical Research
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Cumberland, Rhode Island, United States
WR-ClinSearch, LLC
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Chattanooga, Tennessee, United States
Carl Meisner Medical Clinic
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Sugar Land, Texas, United States
CNS Healthcare
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Memphis, Tennessee, United States
Premier Family Physicians
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Austin, Texas, United States
Clinical Neuroscience Solutions Inc.
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Orlando, Florida, United States
Clinical Research of West Florida Inc.
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Tampa, Florida, United States
Meridien Research
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Tampa, Florida, United States
MedVadis Research Corporation
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Watertown, Massachusetts, United States