Study to Explore the Therapeutic Effect of Eluxadoline in Treating Irritable Bowel Syndrome With Diarrhea in Children

Study Overview
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Brief Summary
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The primary objectives of this study are to explore the therapeutic effect of eluxadoline in treating irritable bowel syndrome with diarrhea (IBS-D) in pediatric participants 6-17 years of age, to evaluate the pharmacokinetics of eluxadoline in pediatric participants with IBS-D, and to evaluate the safety and tolerability of eluxadoline in pediatric participants with IBS-D. Enrollment of 12-17 years old age group is closed, enrollment of the 6-11 years old age group will continue.

Official Title
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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)

Conditions
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Irritable Bowel Syndrome

Intervention / Treatment
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* Drug: Eluxadoline
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. 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. Participant is able to read and understand the assessments in the eDiary. If the participant is 6 to 11 years of age and does not meet this criterion, the interviewer-administered version of the eDiary must be used and the parent/guardian/LAR or caregiver who will be administering the interviewer-administered version of the eDiary must be able to read and understand the assessments in the eDiary and must undergo training. Female participants must not be pregnant, breastfeeding, or considering becoming pregnant during the study or for approximately 30 days after the last dose of study drug. 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. Female participants of childbearing potential must practice at least 1 protocol-specified method of birth control, that is effective from Study Day 1 through at least 30 days after the last dose of study drug. Local practices may require 2 methods of birth control. Female participants of non-childbearing potential do not need to use birth control. Participant has a diagnosis of IBS-D as defined by the modified Rome IV child/adolescent criteria: Must include all of the following: -- Abdominal pain at least 4 days per month over at least 2 months associated with one or more of the following: Related to defecation A change in frequency of stool A change in form (appearance) of stool After appropriate evaluation, the symptoms cannot be fully explained by another medical condition. Participant has predominantly diarrheal stool symptoms defined as Bristol stool types 6 or 7 for more than 25% of bowel movements and Bristol stool types 1 or 2 for less than 25% of bowel movements that occur in the absence of laxative. Participant may be newly diagnosed with IBS-D by the investigator at Visit 1. All criteria for diagnosis must be fulfilled for at least 2 months prior to Visit 1 (screening). 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). Participant has an average daytime abdominal pain score greater than or equal to 1.0 over the 2 weeks prior to randomization. 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 immediately prior to randomization and that occurs in the absence of laxatives. Exclusion Criteria: Participant has no gallbladder, (ie, agenesis of the gallbladder or cholecystectomy). Participant has had any of the following surgeries: Any abdominal surgery within the 3 months prior to Screening; or A history of major gastric, hepatic, pancreatic, or intestinal surgery. (Note: appendectomy, hemorrhoidectomy, or polypectomy greater than 3 months post-surgery are allowed. For the purposes of this study, laparoscopic surgeries without complication are considered minor and non-exclusionary, provided the condition for which the surgery was performed was not exclusionary.) Participant has a history of chronic or severe constipation or sequelae from constipation, or known or suspected mechanical GI obstruction or pseudo obstruction. Participant has a history or current diagnosis of constipation with encopresis. Participant meets the child/adolescent Rome IV criteria of IBS with constipation, IBS with constipation and diarrhea (mixed), unspecified IBS, or functional constipation. Participant has a history of intestinal obstruction, stricture, toxic megacolon, GI perforation, fecal impaction, gastric banding, bariatric surgery, adhesions, ischemic colitis, or impaired intestinal circulation. Participant has a documented history of hepatic impairment as defined by Child-Pugh Classification Grade A, B or C. Participant has a history or current diagnosis of inflammatory or immune-mediated lower GI disorders including inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis, microscopic colitis). Crohn's disease affecting the upper GI tract would also be exclusionary. Participant has celiac disease, or a positive serological test for celiac disease and the condition has not been ruled out by endoscopic biopsy. Participant has any congenital and/or acquired malabsorption syndrome (eg, Shwachman-Diamond syndrome). Participant has a history of a microbiologically documented (ie, stool culture or medical history) GI infection within 3 months prior to Screening. Participant has a known lactose or fructose intolerance that is associated with diarrhea, abdominal pain or discomfort, and that could confound assessments in the study. Participant has a history of diverticulitis within 3 months prior to Screening.

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Eluxadoline 25mg<br>Eluxadoline 25mg, oral administration, twice daily | Drug: Eluxadoline<br>* Oral tablets<br>* Other names: Viberzi;|
| Experimental: Eluxadoline 50mg<br>Eluxadoline 50mg, oral administration, twice daily | Drug: Eluxadoline<br>* Oral tablets<br>* Other names: Viberzi;|
| Experimental: Eluxadoline 100mg<br>Eluxadoline 100mg, oral administration, twice daily | Drug: Eluxadoline<br>* Oral tablets<br>* Other names: Viberzi;|
| Experimental: Placebo<br>Dose-matched placebo, oral administration, twice daily | Drug: Placebo<br>* Oral tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in stool consistency averaged over the 4-week Treatment Period | Stool consistency will be assessed using the Pediatric Bristol Stool Form Scale (p-BSFS) on a range from 1 (Hard Lumps) to 7 (Watery). | Baseline (2 Weeks prior to randomization) to Week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in stool consistency for daily daytime and nighttime stool consistency scores | Stool consistency will be assessed using the Pediatric Bristol Stool Form Scale (p-BSFS) on a range from 1 (Hard Lumps) to 7 (Watery). | Baseline (2 Weeks prior to randomization) to Week 4 | 
| Change from baseline for daytime, nighttime, and 24-hour abdominal pain scores | Abdominal Pain is scored on a five-point ordinal scale, with 0 meaning no pain, and 4 meaning a lot of pain. | Baseline (2 Weeks prior to randomization) to Week 4 | 
| Change from baseline for daytime, nighttime, and 24-hour bowel movement frequency | Change from baseline in the number of bowel movements. | Baseline (2 Weeks prior to randomization) to Week 4 | 
| Change from baseline for daytime, nighttime, and 24 hour urgency-free days | Change from baseline in the number of urgency free days in a week. | Baseline (2 Weeks prior to randomization) to Week 4 | 
| Change from baseline for daytime, nighttime, and 24 hour number of fecal incontinence-free days | Change from baseline in the number of fecal incontinence-free days in a week. | Baseline (2 Weeks prior to randomization) to Week 4 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Irritable Bowel Syndrome with Diarrhea, IBS, IBSD, IBS-D, Irritable Bowel Syndrome, Pediatric