Clinical trial NCT02959983: Efficacy of Eluxadoline in the Treatment of Irritable Bowel Syndrome With Diarrhea in Patients With Inadequate Control of Symptoms With Prior Loperamide Use
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Irritable Bowel Syndrome With Diarrhea
Lead sponsor: Allergan
Sponsor class: INDUSTRY
First posted: 2016-11-09
Enrollment: 346
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants Who Were Composite Responders Based on Improvements From Baseline in Daily Worst Abdominal Pain And Daily Stool Consistency Scores
timeFrame: Baseline, Weeks 1 to 12
Secondary outcomes:
measure: Percentage of Stool Consistency Responders
timeFrame: Weeks 1 to 12 and 4-week intervals (Weeks 1 to 4, Weeks 5 to 8 and Weeks 9 to 12)
measure: Percentage of Pain Responders
timeFrame: Baseline, Weeks 1 to 12 and 4-week intervals (Weeks 1 to 4, Weeks 5 to 8 and Weeks 9 to 12)
measure: Percentage of Monthly Composite Responders
timeFrame: Weeks 1 to 4, 5 to 8, and 9 to 12
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Clinical Research Associates, LLC
state: Alabama
city: Saraland
country: United States
facility: The Center for Clinical Trials
state: Alabama
city: Phoenix
country: United States
facility: Elite Clinical Studies
state: Arizona
city: North Little Rock
country: United States
facility: Arkansas Gastroenterology
state: Arkansas
city: Carmichael
country: United States
facility: Med Investigations
state: California
city: Chula Vista
country: United States
facility: GW Research Inc
state: California
city: Encinitas
country: United States
facility: Diagnamics Inc
state: California
city: Irvine
country: United States
facility: Behavioral Research Specialists, LLC
state: California
city: North Hollywood
country: United States
facility: Providence Clinical Research
state: California
city: Sherman Oaks
country: United States
facility: Shahram Jacobs MD INC.
state: California
city: Thousand Oaks
country: United States
facility: Westlake Medical Research
state: California
city: Upland
country: United States
facility: Upland Clinical Research
state: California
city: Westminster
country: United States
facility: Advanced RX Clinicial Research Group, Inc.
state: California
city: Bristol
country: United States
facility: Connecticut Clinical Research Foundation
state: Connecticut
city: Hamden
country: United States
facility: Medical Research Center of Connecticut, LLC
state: Connecticut
city: Clearwater
country: United States
facility: Innovative Research of West Florida, Inc.
state: Florida
city: Coral Springs
country: United States
facility: Digestive Care of N. Broward
state: Florida
city: Homestead
country: United States
facility: Homestead Medical Research
state: Florida
city: Jacksonville
country: United States
facility: Clinical Neuroscience Solutions Inc.
state: Florida
city: Jupiter
country: United States
facility: Health Awareness, Inc.
state: Florida
city: Lauderdale Lakes
country: United States
facility: Precision Clinical Research LLC
state: Florida
city: Miami Springs
country: United States
facility: Ocean Blue Medical Research Center, Inc
state: Florida
city: Miami
country: United States
facility: Pharmax Research Clinic Inc.
state: Florida
city: Miami
country: United States
facility: Well Pharma Medical Research, Corp.
state: Florida
city: North Bay Village
country: United States
facility: Bravo Health Care Center
state: Florida
city: Orlando
country: United States
facility: Clinical Neuroscience Solutions Inc.
state: Florida
city: Tampa
country: United States
facility: Clinical Research of West Florida Inc.
state: Florida
city: Tampa
country: United States
facility: Meridien Research
state: Florida
city: Atlanta
country: United States
facility: Emory University School of Medicine
state: Georgia
city: Buford
country: United States
facility: RNA America, LLC
state: Georgia
city: Chicago
country: United States
facility: Northwestern University Feinbery School of Medicine
state: Illinois
city: Evergreen Park
country: United States
facility: Pharmakon Inc
state: Illinois
city: Brownsburg
country: United States
facility: Investigators Research
state: Indiana
city: Evansville
country: United States
facility: Radiant Research, Inc.
state: Indiana
city: Evansville
country: United States
facility: Clinical Research Advantage Inc/Radiant Research Inc.
state: Indiana
city: Shawnee Mission
country: United States
facility: Gtc Research
state: Kansas
city: Annapolis
country: United States
facility: Investigative Clinical Research
state: Maryland
city: Chevy Chase
country: United States
facility: MGG Group Co. Inc. Chevy Chase Clinical Research
state: Maryland
city: Watertown
country: United States
facility: MedVadis Research Corporation
state: Massachusetts
city: Chesterfield
country: United States
facility: Clinical Research Insititute of Michigan LLC
state: Michigan
city: Wyoming
country: United States
facility: Gastroenterology Associates of Western Michigan, PLC
state: Michigan
city: Biloxi
country: United States
facility: The Center for Clinical Trials
state: Mississippi
city: Lincoln
country: United States
facility: Women's Clinic of Lincoln, P.C.
state: Nebraska
city: Omaha
country: United States
facility: Quality Clinical Research Inc.
state: Nebraska
city: Las Vegas
country: United States
facility: Advanced Biomedical Research of America
state: Nevada
city: Reno
country: United States
facility: Advanced Research Institute
state: Nevada
city: Brooklyn
country: United States
facility: Drug Trials Brooklyn
state: New York
city: Brooklyn
country: United States
facility: NY Scientific
state: New York
city: Great Neck
country: United States
facility: Long Island Gastrointestinal Group LLP
state: New York
city: Kew Gardens
country: United States
facility: IMA Medical Research, PC
state: New York
city: Charlotte
country: United States
facility: Charlotte Gastroenterology & Hepatology, PLLC
state: North Carolina
city: High Point
country: United States
facility: Peters Medical Research LLC
state: North Carolina
city: Lenoir
country: United States
facility: North State Clincial Research PLLC
state: North Carolina
city: Raleigh
country: United States
facility: Wake Research Associates LLC
state: North Carolina
city: Wilmington
country: United States
facility: Trial Management Associates, LLC
state: North Carolina
city: Beavercreek
country: United States
facility: Clinical Inquest Center Ltd
state: Ohio
city: Cincinnati
country: United States
facility: Hometown Urgent Care and Research
state: Ohio
city: Columbus
country: United States
facility: Buckeye Health and Research
state: Ohio
city: Columbus
country: United States
facility: Hometown Urgent Care and Research
state: Ohio
city: Huber Heights
country: United States
facility: Hometown Urgent Care and Research
state: Ohio
city: Norman
country: United States
facility: Central Sooner Research
state: Oklahoma
city: Salem
country: United States
facility: The Oregon Center for Clinical Investigations, INC.
state: Oregon
city: Cumberland
country: United States
facility: Partners in Clinical Research
state: Rhode Island
city: Chattanooga
country: United States
facility: WR-ClinSearch, LLC
state: Tennessee
city: Knoxville
country: United States
facility: New Phase Research & Development
state: Tennessee
city: Memphis
country: United States
facility: CNS Healthcare
state: Tennessee
city: Austin
country: United States
facility: Premier Family Physicians
state: Texas
city: Carrollton
country: United States
facility: Family Medicine Associate of Texas
state: Texas
city: San Antonio
country: United States
facility: Multi-Phase Trials LLC
state: Texas
city: San Antonio
country: United States
facility: Health Texas Research Institute
state: Texas
city: San Antonio
country: United States
facility: Discovery Clinical Trials - Stone Oak
state: Texas
city: Sugar Land
country: United States
facility: Carl Meisner Medical Clinic
state: Texas
city: Ogden
country: United States
facility: Advanced Research Institute - Ogden
state: Utah
city: Salt Lake City
country: United States
facility: Wasatch Clinical Research, LLC
state: Utah
city: Fairfax
country: United States
facility: Gastroenterology Associates of Northern Virginia
state: Virginia
city: Lynchburg
country: United States
facility: Blue Ridge Medical Research
state: Virginia
city: Corunna
country: Canada
facility: Corunna Medical Research Centre
state: Ontario
city: Etobicoke
country: Canada
facility: Manna Research
state: Ontario
city: Newmarket
country: Canada
facility: SKDS Research Inc
state: Ontario
city: Calgary
country: Canada
facility: University of Calgary
city: Nova Scotia
country: Canada
facility: Viable Clinical Research Corp.
city: Quebec
country: Canada
facility: Centre de reserche St Louis
city: Quebec
country: Canada
facility: Dynamik Research Inc
Study officials:
affiliation: Allergan
name: Esther Jo
role: STUDY_DIRECTOR
References: