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

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)

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.

Study Overview

• Status: Completed
• Conditions: Irritable Bowel Syndrome With Diarrhea
• Intervention / Treatment: Drug: Eluxadoline; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 346
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Calgary, Canada, T2N 1N4
    • University of Calgary
  • Nova Scotia, Canada, B4V 3N2
    • Viable Clinical Research Corp.
  • Quebec, Canada, G1W4R4
    • Centre de reserche St Louis
  • Quebec, Canada, H9R 3J1
    • Dynamik Research Inc
  • Ontario
    • Corunna, Ontario, Canada, N0N 1G0
      • Corunna Medical Research Centre
    • Etobicoke, Ontario, Canada, 7LM 4Y1
      • Manna Research
    • Newmarket, Ontario, Canada, L3Y 5G8
      • SKDS Research Inc
• United States
  • Alabama
    • Huntsville, Alabama, United States, 35801
      • Clinical Research Associates, LLC
    • Saraland, Alabama, United States, 36571
      • The Center for Clinical Trials
  • Arizona
    • Phoenix, Arizona, United States, 85018
      • Elite Clinical Studies
  • Arkansas
    • North Little Rock, Arkansas, United States, 72117
      • Arkansas Gastroenterology
  • California
    • Carmichael, California, United States, 95608
      • MED Investigations
    • Chula Vista, California, United States, 91910
      • GW Research Inc
    • Encinitas, California, United States, 92024
      • Diagnamics Inc
    • Irvine, California, United States, 92606
      • Behavioral Research Specialists, LLC
    • North Hollywood, California, United States, 91606
      • Providence Clinical Research
    • Sherman Oaks, California, United States, 91403
      • Shahram Jacobs MD INC.
    • Thousand Oaks, California, United States, 91360
      • Westlake Medical Research
    • Upland, California, United States, 91786
      • Upland Clinical Research
    • Westminster, California, United States, 92683
      • Advanced RX Clinicial Research Group, Inc.
  • Connecticut
    • Bristol, Connecticut, United States, 06010
      • Connecticut Clinical Research Foundation
    • Hamden, Connecticut, United States, 06518
      • Medical Research Center of Connecticut, LLC
  • Florida
    • Clearwater, Florida, United States, 33756
      • Innovative Research Of West Florida, Inc.
    • Coral Springs, Florida, United States, 33065
      • Digestive Care of N. Broward
    • Homestead, Florida, United States, 33030
      • Homestead Medical Research
    • Jacksonville, Florida, United States, 32256
      • Clinical Neuroscience Solutions Inc.
    • Jupiter, Florida, United States, 33458
      • Health Awareness, Inc.
    • Lauderdale Lakes, Florida, United States, 33319
      • Precision Clinical Research LLC
    • Miami, Florida, United States, 33143
      • Well Pharma Medical Research, Corp.
    • Miami, Florida, United States, 33126
      • Pharmax Research Clinic Inc.
    • Miami Springs, Florida, United States, 33166
      • Ocean Blue Medical Research Center, Inc
    • North Bay Village, Florida, United States, 33141
      • Bravo Health Care Center
    • Orlando, Florida, United States, 32801
      • Clinical Neuroscience Solutions Inc.
    • Tampa, Florida, United States, 33634
      • Meridien Research
    • Tampa, Florida, United States, 33603
      • Clinical Research of West Florida Inc.
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University School of Medicine
    • Buford, Georgia, United States, 30518
      • RNA America, LLC
  • Illinois
    • Chicago, Illinois, United States, 606611
      • Northwestern University Feinbery School of Medicine
    • Evergreen Park, Illinois, United States, 60805
      • Pharmakon Inc
  • Indiana
    • Brownsburg, Indiana, United States, 46112
      • Investigators Research
    • Evansville, Indiana, United States, 47714
      • Radiant Research, Inc.
    • Evansville, Indiana, United States, 47725
      • Clinical Research Advantage Inc/Radiant Research Inc.
  • Kansas
    • Shawnee Mission, Kansas, United States, 66218
      • Gtc Research
  • Maryland
    • Annapolis, Maryland, United States, 21401
      • Investigative Clinical Research
    • Chevy Chase, Maryland, United States, 20815
      • MGG Group Co. Inc. Chevy Chase Clinical Research
  • Massachusetts
    • Watertown, Massachusetts, United States, 02472
      • MedVadis Research Corporation
  • Michigan
    • Chesterfield, Michigan, United States, 48047
      • Clinical Research Insititute of Michigan LLC
    • Wyoming, Michigan, United States, 49519
      • Gastroenterology Associates of Western Michigan, PLC
  • Mississippi
    • Biloxi, Mississippi, United States, 39531
      • The Center for Clinical Trials
  • Nebraska
    • Lincoln, Nebraska, United States, 68510
      • Women's Clinic of Lincoln, P.C.
    • Omaha, Nebraska, United States, 68114
      • Quality Clinical Research Inc.
  • Nevada
    • Las Vegas, Nevada, United States, 89123
      • Advanced Biomedical Research of America
    • Reno, Nevada, United States, 89511
      • Advanced Research Institute
  • New York
    • Brooklyn, New York, United States, 11235
      • NY Scientific
    • Brooklyn, New York, United States, 11230
      • Drug Trials Brooklyn
    • Great Neck, New York, United States, 11023
      • Long Island Gastrointestinal Group LLP
    • Kew Gardens, New York, United States, 11415
      • IMA Medical Research, PC
  • North Carolina
    • Charlotte, North Carolina, United States, 28207
      • Charlotte Gastroenterology & Hepatology, PLLC
    • High Point, North Carolina, United States, 27265
      • Peters Medical Research LLC
    • Lenoir, North Carolina, United States, 28645
      • North State Clincial Research PLLC
    • Raleigh, North Carolina, United States, 27612
      • Wake Research Associates Llc
    • Wilmington, North Carolina, United States, 28403
      • Trial Management Associates, LLC
  • Ohio
    • Beavercreek, Ohio, United States, 45431
      • Clinical Inquest Center Ltd
    • Cincinnati, Ohio, United States, 45215
      • Hometown Urgent Care and Research
    • Columbus, Ohio, United States, 43214
      • Hometown Urgent Care and Research
    • Columbus, Ohio, United States, 43207
      • Buckeye Health and Research
    • Huber Heights, Ohio, United States, 45424
      • Hometown Urgent Care and Research
  • Oklahoma
    • Norman, Oklahoma, United States, 73071
      • Central Sooner Research
  • Oregon
    • Salem, Oregon, United States, 97301
      • The Oregon Center for Clinical Investigations, INC.
  • Rhode Island
    • Cumberland, Rhode Island, United States, 02864
      • Partners in Clinical Research
  • Tennessee
    • Chattanooga, Tennessee, United States, 37421
      • WR-ClinSearch, LLC
    • Knoxville, Tennessee, United States, 37909
      • New Phase Research & Development
    • Memphis, Tennessee, United States, 38119
      • CNS Healthcare
  • Texas
    • Austin, Texas, United States, 78735
      • Premier Family Physicians
    • Carrollton, Texas, United States, 75010
      • Family Medicine Associate of Texas
    • San Antonio, Texas, United States, 78217
      • Multi-Phase Trials LLC
    • San Antonio, Texas, United States, 78228
      • Health Texas Research Institute
    • San Antonio, Texas, United States, 78258
      • Discovery Clinical Trials - Stone Oak
    • Sugar Land, Texas, United States, 77478
      • Carl Meisner Medical Clinic
  • Utah
    • Ogden, Utah, United States, 84405
      • Advanced Research Institute - Ogden
    • Salt Lake City, Utah, United States, 84107
      • Wasatch Clinical Research, LLC
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Gastroenterology Associates of Northern Virginia
    • Lynchburg, Virginia, United States, 24502
      • Blue Ridge Medical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Eluxadoline; Eluxadoline 100 mg oral tablets twice daily (BID) with food for 12 weeks.	Drug: Eluxadoline; Eluxadoline 100 mg oral tablets BID with food.; Other Names: VIBERZI™
PLACEBO_COMPARATOR: Placebo; Placebo matching eluxadoline oral tablets BID with food for 12 weeks.	Drug: Placebo; Placebo matching eluxadoline oral tablets BID with food.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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)
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

Collaborators and Investigators

• Sponsor: Allergan

Publications and helpful links

Helpful Links

• More Information

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 25, 2016
• Primary Completion (ACTUAL): January 22, 2018
• Study Completion (ACTUAL): January 22, 2018

Study Registration Dates

• First Submitted: November 7, 2016
• First Submitted That Met QC Criteria: November 7, 2016
• First Posted (ESTIMATE): November 9, 2016

Study Record Updates

• Last Update Posted (ACTUAL): February 15, 2019
• Last Update Submitted That Met QC Criteria: January 22, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Disease; Signs and Symptoms, Digestive; Gastrointestinal Diseases; Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Syndrome; Irritable Bowel Syndrome; Diarrhea; Gastrointestinal Agents; Eluxadoline
• Other Study ID Numbers: CMO-US-GI-0429

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No