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

Sponsor

Allergan (Industry)

Overall Status

Recruiting

CT.gov ID

NCT03339128

Collaborator

(none)

120

Enrollment

Locations

Arms

Anticipated Duration (Months)

2.4

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Irritable Bowel Syndrome	Drug: Eluxadoline Drug: Placebo	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

120 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

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)

Actual Study Start Date :

Nov 15, 2017

Anticipated Primary Completion Date :

Jul 25, 2023

Anticipated Study Completion Date :

Aug 17, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Eluxadoline 25mg Eluxadoline 25mg, oral administration, twice daily	Drug: Eluxadoline Oral tablets Other Names: Viberzi, Truberzi
Experimental: Eluxadoline 50mg Eluxadoline 50mg, oral administration, twice daily	Drug: Eluxadoline Oral tablets Other Names: Viberzi, Truberzi
Experimental: Eluxadoline 100mg Eluxadoline 100mg, oral administration, twice daily	Drug: Eluxadoline Oral tablets Other Names: Viberzi, Truberzi
Experimental: Placebo Dose-matched placebo, oral administration, twice daily	Drug: Placebo Oral tablets

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

6 Years to 17 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 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 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:
Hormonal contraception (eg, oral contraceptive, contraceptive implant, or injectable hormonal contraceptive).
Double-barrier method (eg, condom plus intrauterine device, diaphragm plus spermicide).
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.
All criteria 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 scoreless than or equal to 2.0 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 prior to randomization that occurs in the absence of laxatives.
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.])

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	HealthStar Research of Hot Springs PLLC /ID# 234609	Hot Springs	Arkansas	United States	71913
2	Applied Research Center of Arkansas /ID# 238070	Little Rock	Arkansas	United States	72212-4187
3	Kindred Medical Institute, LLC /ID# 237368	Corona	California	United States	92879
4	VVCRD Research /ID# 234606	Garden Grove	California	United States	92845
5	Center for Clinical Trials LLC /ID# 234630	Paramount	California	United States	90723
6	Children's National Medical Center /ID# 237802	Washington	District of Columbia	United States	20010-2916
7	The Ctr for Gastro Disorders /ID# 236961	Hollywood	Florida	United States	33021
8	Wellness Clinical Research /ID# 237401	Miami Lakes	Florida	United States	33016
9	Sunrise Research Institute /ID# 237382	Miami	Florida	United States	33130
10	South Miami Medical & Research Group Inc. /ID# 234655	Miami	Florida	United States	33155
11	Valencia Medical & Research Center /ID# 234672	Miami	Florida	United States	33165
12	Florida Research Center, Inc. /ID# 236514	Miami	Florida	United States	33174
13	Treken Primary Care /ID# 234646	Atlanta	Georgia	United States	30315
14	Children's Ctr Digestive, US /ID# 237575	Atlanta	Georgia	United States	30342
15	Sleep Care Research Institute d/b/a Clinical Research Institute /ID# 236343	Stockbridge	Georgia	United States	30281
16	Center for Children's Digestive Health /ID# 235388	Park Ridge	Illinois	United States	60068
17	Riley Hospital for Children at Indiana University Health /ID# 235400	Indianapolis	Indiana	United States	46202
18	Michael W. Simon, MD, PSC /ID# 236517	Lexington	Kentucky	United States	40517
19	Virgo Carter Pediatrics /ID# 234519	Silver Spring	Maryland	United States	20910
20	Minnesota Gastroenterology /ID# 238057	Minneapolis	Minnesota	United States	55413
21	Celen Medical Group Corp /ID# 234922	Marlton	New Jersey	United States	08053
22	UH Cleveland Medical Center /ID# 237918	Cleveland	Ohio	United States	44106
23	IPS Research Company /ID# 237672	Oklahoma City	Oklahoma	United States	73106
24	Children's Hospital of Philadelphia - Main /ID# 234313	Philadelphia	Pennsylvania	United States	19104-4319
25	Preferred Primary Care Physicians, Inc. /ID# 236436	Pittsburgh	Pennsylvania	United States	15236
26	Cook Children's Med. Center /ID# 237537	Fort Worth	Texas	United States	76104
27	Texas Children's Hospital /ID# 238304	Houston	Texas	United States	77030-2608
28	Sun Research Institute /ID# 236933	San Antonio	Texas	United States	78215
29	Primary Children's /ID# 237984	Salt Lake City	Utah	United States	84113
30	MHATSv.Ivan Rilski /ID# 235399	Kozloduy		Bulgaria	3320
31	University Hospital Plovdiv /ID# 235450	Plovdiv		Bulgaria	4001
32	UMHAT Kanev /ID# 237808	Ruse		Bulgaria	7002
33	Medical center 1 Sevlievo /ID# 237473	Sevlievo		Bulgaria	5400
34	UMHAT Sveta Marina /ID# 237833	Varna		Bulgaria	9010
35	Edmonton Clinic Health Academy (ECHA) /ID# 234917	Edmonton		Canada	T6G 1C9
36	Eszak-Kozep-budai Centrum, Uj Szent Janos Korhaz /ID# 236993	Budapest		Hungary	1125
37	Soproni Erzsebet Oktato Korhaz es Rehabilitacios Intezet /ID# 237341	Sopron		Hungary	9400
38	Vita Verum Medical Bt. /ID# 234321	Szekesfehervar		Hungary	8000
39	IRCCS Ospedale Pediatrico Bambino Gesu /ID# 238184	Rome	Lazio	Italy	00165
40	AORN Santobono-Pausilipon /ID# 235653	Naples		Italy	80129
41	Academisch Medisch Centrum /ID# 237117	Amsterdam		Netherlands	1105 AZ
42	Instytut Centrum Zdrowia Matki Polki /ID# 237438	Lodz	Lodzkie	Poland	93-338
43	Specjalistyczne Gabinety Sp. z o.o. /ID# 236347	Krakow	Malopolskie	Poland	30-539
44	Centrum Zdrowia MDM /ID# 237269	Warszawa	Mazowieckie	Poland	00-635
45	Instytut Pomnik - Centrum Zdrowia Dziecka /ID# 234311	Warszawa	Mazowieckie	Poland	04-730
46	Copertnicus Podmiot Leczniczy Sp. z o.o. /ID# 235656	Gdansk		Poland	80-803
47	Korczowski Bartosz Gabinet Lekarski /ID# 234683	Rzeszow		Poland	35-302
48	Hospital Universitario Dr. Peset /ID# 236755	Valencia		Spain	46017
49	Manchester University NHS Foundation Trust /ID# 234663	Manchester	Lancashire	United Kingdom	M13 9WL
50	Blackpool Teaching Hospitals NHS Foundation Trust /ID# 237273	Blackpool		United Kingdom	FY3 8NR
51	King's College Hospital NHS Foundation Trust /ID# 236305	London		United Kingdom	SE5 9RS