Efficacy of Eluxadoline in the Treatment of Irritable Bowel Syndrome With Diarrhea in Patients With Inadequate Control of Symptoms With Prior Loperamide Use
Condition: Irritable Bowel Syndrome With Diarrhea
MeSH terms: Irritable Bowel Syndrome; Syndrome; Diarrhea
Intervention: Eluxadoline; Placebo
Intervention description: Eluxadoline 100 mg oral tablets BID with food.; Placebo matching eluxadoline oral tablets BID with food.
Intervention MeSH terms: Eluxadoline
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 346.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No

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.