A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Dose-Ranging Study to Evaluate the Safety and Efficacy of Eluxadoline in Pediatric Participants (Age 6 to 17 Years) with Irritable Bowel Syndrome with Diarrhea (IBS-D)

To be eligible to participate in the study, participants must meet the
following criteria:, 1. Participant must provide written or verbal informed
assent and the parent/guardian/LAR must provide written informed consent before
the initiation of any study-specific procedures., 2. Participant is a male or
female outpatient, 6 to 17 years of age inclusive, at the time the participant
provides assent for the study and parent/guardian/LAR has provided signed
consent., 3. Participant is able to read and understand the assessments in the
eDiary., 4. Female participants of childbearing potential must have a negative
serum pregnancy test at Visit 1 (screening) and a negative urine pregnancy test
at Visit 3 (randomization) prior to dosing., 5. Female participants who have
had their first menstrual period and are sexually active must agree to use a
reliable form of contraception. Reliable contraception is defined as:, a)
Hormonal contraception (eg, oral contraceptive, contraceptive implant, or
injectable hormonal contraceptive)., b) Double-barrier method (eg, condom plus
intrauterine device, diaphragm plus spermicide)., 6. Participant has a
diagnosis of IBS-D as defined by the modified Rome IV child/adolescent
criteria*: Must include all of the following:, 1. Abdominal pain at least 4
days per month over at least 2 months associated, with one or more of the
following:, a. Related to defecation, b. A change in frequency of stool, c. A
change in form (appearance) of stool, 2. After appropriate evaluation, the
symptoms cannot be fully explained by another medical condition, 3. Participant
has predominantly diarrheal stool symptoms defined as Bristol stool types 6 or
7 for >25% of bowel movements and Bristol stool types 1 or 2 for <25% of bowel
movements that occur in the absence of laxatives, *All criteria fulfilled for
at least 2 months prior to Visit 1 (screening)., 7. Participant has been
compliant with the eDiary by completing both the morning and evening
assessments for at least 8 out of the 14 days immediately preceding Visit 3
(randomization)., 8. Participant has an average daytime abdominal pain score
*2.0 over the 2 weeks prior to randomization., 9. Participant has at least 1
daytime bowel movement with a consistency of Type 6 or Type 7 on the pediatric
Bristol Stool Form Scale (p-BSFS) on at least 2 days per week during the 2
weeks prior to randomization that occurs in the absence of laxatives., 10.
Participant has no clinically significant findings on a physical examination,
vital sign assessment, electrocardiogram (ECG), and clinical laboratory tests
(clinical chemistry panel, liver biochemical tests, complete blood count, urine
drug screen, urinalysis) after providing informed assent and after written
consent is obtained, but before receiving the first dose of study treatment. (A
central laboratory will be used to evaluate all urine [except urine pregnancy
tests] and blood samples and will, utilize reference ranges specific to a
patient*s age and gender. ECGs will be performed and electronically transmitted
to a central ECG laboratory for analysis by a pediatric cardiologist in
accordance with the instructions provided by the central ECG laboratory. The
Investigator will determine if a particular finding is clinically significant.
[In making this determination, the Investigator will consider whether the
particular finding could represent a condition that would exclude the
participant from the study, could represent a safety concern if the participant
participates in the study, or could confound the study-specific assessments of
safety or efficacy.])

Participants who meet any of the following criteria will not be eligible to
participate in the study:, 1.has no gallbladder, 2.has had any of the following
surgeries:, a)Any abdominal surgery within the 3 months prior to trial;, b)A
history of major gastric, hepatic, pancreatic, or intestinal surgery, 3.has
known or suspected biliary duct obstruction, or sphincter of Oddi disease or
dysfunction, 4.has a history of pancreatitis; structural diseases of the
pancreas, known or, suspected pancreatic duct obstruction, 5.has a history of
cholecystitis within 6months before trial., 6.has known or suspected bile acid
malabsorption., 7.is a current regular alcohol drinker and/or binge drinker,
and/or has a history, of alcoholism, alcohol abuse, or alcohol addiction,
and/or intends to consume alcohol during the trial. , 8.has had chronic or
severe constipation or sequelae from constipation,, or known or suspected
mechanical GI obstruction or pseudo obstruction., 9.has had or current
diagnosis of constipation with encopresis., 10.meets the child/adolescent Rome
IV criteria of IBS with constipation, IBS, with constipation and diarrhea
(mixed), unspecified IBS, or functional constipation., 11.has had intestinal
obstruction, stricture, toxic megacolon, GI perforation, fecal impaction,
gastric banding, bariatric surgery, adhesions, ischemic colitis, or impaired
intestinal circulation., 12.has a history of hepatic impairment as defined by
Child-Pugh Classification Grade A,B or C, 13.has a history or current diagnosis
of inflammatory or immune-mediated lower, GI disorders including inflammatory
bowel disease, 14.has celiac disease,or a positive serological test for celiac
disease and the, condition has not been ruled out by endoscopic biopsy, 15.has
any congenital and/or acquired malabsorption syndrome, 16.has a history of a
microbiologically documented GI infection within 3months prior to trial, 17.has
a known lactose or fructose intolerance, 18.has a history of diverticulitis
within 3 months prior to trial, 19.has had within 5 years prior to trial or
current evidence of laxative abuse, 20.has a history of either hypo-or
hyperthyroidism that is untreated or treated, with medication at a dose that
has not been stable for at least 3months prior to, trial., 21.Participant*s
diarrhea is deemed by the Investigator to be caused by infectious, 22.has had
or current evidence of blood in the stool , 23.currently has both unexplained
and clinically significant alarm symptoms and systemic signs of infection or
colitis, or any neoplastic process, 24.has a history or current diagnosis of
eosinophilic gastroenteritis, 25.has Cystic Fibrosis, and or any other causes
of pancreatic exocrine insufficiency, 26.is receiving enteral tube feeding,
27.has a history of a cardiovascular event, including stroke, myocardial
infarction, congestive heart failure, or transient ischemic attack within
6months prior to trial, 28.has an unstable renal, hepatic, metabolic, or
hematologic condition, 29.has a history of malignancy within 5 years before
Screening, which includes any new diagnosis of malignancy or any treatment for
or recurrence of a malignancy that was diagnosed 5 or more years prior. In
order to be eligible for the study, patient must be malignancy free for the
past 5years, 30.has a history of immunodeficiency, 31.has a history of drug
abuse, 32.has a positive urine drug result, 33.has a weight and BMI less than
the 3rd percentile., 34.has had an unintentional weight loss greater than or
equal to 5% of his/her, body weight within the last 3months, 35.Female
participants who are pregnant or nursing, or plan to become pregnant or nurse
during the trial, 36.has known allergies or hypersensitivity to opioids,
37.used a prohibited medication or failed to meet the stable dose, 38.is unable
to tolerate the placebo oral tablets prior to randomization., 39.has any
condition that, in the opinion of the Investigator, would contribute to, the
patient*s IBS-D symptoms or confound the evaluation of safety or efficacy of
the IMP, 40.has neurodevelopmental disabilities producing a cognitive delay
that precludes comprehension and completion of the daily eDiary or other
study-related questionnaires, 41.has a poorly treated or poorly controlled
psychiatric disorder that might, influence the patient*s ability to participate
in the study, 42.has an acute or chronic condition that, in the Investigator's
opinion, would, limit the participants' ability to complete or participate in
this clinical study, 43.has any condition that, in the opinion of the
Investigator, would compromise, the well-being of the patient, 44.received an
investigational product during the 30 days before Visit1 or is planning to
receive an IMP or use an investigational device at any time during the, study,
45. Participant*s parent/guardian/LAR has been directly or indirectly involved
in the conduct and administration of this study as an Investigator,
Sub-Investigator, Study Coordinator, or other study member