Eluxadoline Bile Acid Malabsorption (BAM) Study

• Sponsor: Allergan (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03441581
• Collaborator: (none)
• Enrollment: 24
• Location: 1
• Arms: 2
• Actual Duration (Months): 26.1
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

This study will evaluate the possibility of a differential effect of eluxadoline on altered bowel function in Irritable Bowel Syndrome with Diarrhea (IBS-D) participants with and without evidence of Bile Acid Malabsorption (BAM).

Condition or Disease	Intervention/Treatment	Phase
Irritable Bowel Syndrome With Diarrhea	Drug: Eluxadoline	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 3030-401-002: An Open-Label Pilot Study of Eluxadoline in Participants With Irritable Bowel Syndrome With Diarrhea (IBS-D) Who Have Evidence of Bile Acid Malabsorption (BAM)
• Actual Study Start Date: Feb 23, 2018
• Actual Primary Completion Date: Apr 28, 2020
• Actual Study Completion Date: Apr 28, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Eluxadoline 100 mg with BAM IBS-D participants with evidence of Bile Acid Malabsorption (BAM) treated with eluxadoline 100 mg oral tablets twice daily (BID) with food for 4 weeks.	Drug: Eluxadoline; Eluxadoline 100 mg oral tablets BID with food.
Experimental: Eluxadoline 100 mg without BAM IBS-D participants without evidence of BAM treated with eluxadoline 100 mg oral tablets BID with food for 4 weeks.	Drug: Eluxadoline; Eluxadoline 100 mg oral tablets BID with food.

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Average Bristol Stool Form Scale (BSFS) Score Over 4 Weeks of Treatment Period [Baseline (Day 1) to Week 4]

   Stool consistency was assessed using the BSFS where: 1=Separate hard lumps like nuts to 7=Watery. The score was recorded by the participant in an electronic diary (e-diary). The score for each day was averaged over the 4-week period. A negative change from Baseline indicates improvement.

2. Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) [Baseline (Day 1) to Week 4]

   An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A TEAE is an AE that occurs or worsens after receiving investigational study drug.

3. Number of Participants Who Experienced Potentially Clinically Significant Change in Laboratory Tests [Baseline (Day 1) to Week 4]

   Laboratory tests included tests of Clinical Chemistry, Hematology, and Urinalysis. The investigator determined if the result was potentially clinically significant.

4. Number of Participants Who Experienced Potentially Clinically Significant Change in Vital Signs [Baseline (Day 1) to Week 4]

   Vital signs assessments included: pulse, respiratory rate, and blood pressure (systolic and diastolic). The investigator determined if the result was potentially clinically significant.

5. Number of Participants Who Experienced Clinically Significant Change From Baseline in General Physical Condition as Measured Through General Physical Exam [Baseline (Day 1) to Week 4]

   General Physical Examination consisted of a full review of body systems excluding pelvic and rectal exams. The investigator determined if the result was clinically significant.

Secondary Outcome Measures

1. Change From Baseline in the 4-week Average of Daily Bowel Movement Frequency During the Treatment Period [Baseline (Day 1) to Week 4]

   Bowel movements were recorded by the participant in an electronic diary (e-diary). The number of bowel movements per day was averaged over the 4-week period. A negative change from Baseline indicates improvement.

2. Change From Baseline in the 4-week Average of Daily Worst Abdominal Pain Scores During the Treatment Period [Baseline (Day 1) to Week 4]

   The participant recorded their worst abdominal pain score in the past 24 hours each day in an e-diary where: 0=no pain to 10=worst imaginable pain. The score each day was averaged over the 4-week period. A negative change from Baseline indicates improvement.

3. Change From Baseline in the 4-week Average of Daily Bloating Scores During the Treatment Period [Baseline (Day 1) to Week 4]

   The participant recorded their bloating score in the past 24 hours each day in an e-diary where: 0=no bloating to 10=worst imaginable bloating. The score each day was averaged over the 4-week period. A negative change from Baseline indicates improvement.

4. Change From Baseline in the 4-week Average Number of Daily Urgent Bowel Movements During the Treatment Period [Baseline (Day 1) to Week 4]

   The participant recorded the number of urgent bowel movements in the past 24 hours each day in an e-diary. The number of urgent bowel movements per day was averaged over the 4-week period. A negative change from Baseline indicates improvement.

5. Percentage of Participants With Any Fecal Incontinence During the Treatment Period [Baseline (Day 1) to Week 4]

   The participant recorded the number of fecal incontinences in the past 24 hours each day in an e-diary. Fecal incontinence is the inability to control the passage of gas or stools. The number of fecal incontinences per day was averaged over the 4-week period. A negative change from Baseline indicates improvement.

6. Change From Baseline in Irritable Bowel Syndrome Quality of Life (IBS-QOL) Total Score at the End of the Treatment Period [Baseline (Day1) to End of Treatment (Up to Week 4)]

   IBS-QOL is composed of 34 items about how the symptoms of IBS are impacting the participant's life scored on a 1 to 5 scale, where lower item scores indicate greater quality of life. The individual responses to the answered items were summed and standardized for a total score and then transformed to a 0 to 100-point scale (0=worst; 100=better) for ease of interpretation. A positive change from Baseline indicates improved quality of life.

7. Change From Baseline in Fasting Serum 7α-hydroxy-4-cholesten-3-one (7αC4) Levels at the End of the Treatment Period [Baseline (Day 1) to End of Treatment (Up to Week 4)]

   Participants fasted for at least 8 hours prior to the test. Fasting serum 7αC4 level was measured at Baseline and End of Treatment to determine whether any changes occurred following treatment with eluxadoline. The negative change from Baseline indicates improvement.

8. Cmax: Maximum Concentration for Eluxadoline [Predose and at the intervals 1-2, 3-4 and 5-8 hours postdose at Week 2]

9. Cmin: Minimum Concentration for Eluxadoline [Predose and at the intervals 1-2, 3-4 and 5-8 hours postdose at Week 2]

10. AUC: Area Under the Concentration-time Curve During the Dosing Interval for Eluxadoline [Predose and at the intervals 1-2, 3-4 and 5-8 hours postdose at Week 2]

11. Tmax: Time to Cmax for Eluxadoline [Predose and at the intervals 1-2, 3-4 and 5-8 hours postdose at Week 2]

12. t1/2: Half-Life for Eluxadoline [Predose and at the intervals 1-2, 3-4 and 5-8 hours postdose at Week 2]

13. CL/F: Apparent Total Clearance of the Drug From Plasma After Oral Administration for Eluxadoline [Predose and at the intervals 1-2, 3-4 and 5-8 hours postdose at Week 2]

14. Vc/F: Apparent Volume of Distribution for Eluxadoline [Predose and at the intervals 1-2, 3-4 and 5-8 hours postdose at Week 2]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Adult men or women aged 18 to 75 years inclusive with a diagnosis of IBS-D per Rome IV criteria.

• Participants with evidence of BAM must have a fasting serum 7a-hydroxy-4-cholesten-3-one (7αC4) level ≥ 52.5 ng/mL or total fecal bile acid (BA) > 2337 micromoles/48 hours (positive result) at screening or within 1 calendar year prior to screening.

• Participants without BAM must have a fasting serum 7αC4 level ≤ 47.1 ng/mL or total fecal BA < 2200 micromoles/48 hours (negative result) at screening or within 1 calendar year prior to screening.

• Has an average daily Bristol Stool Form Scale (BSFS) score ≥ 5.0 or ≥ 25% of diary entry days with a BSFS score of 6 or 7 during the 14 days prior to Day 1.

• Women of childbearing potential must use hormonal or double barrier contraception or maintain a monogamous relationship with a vasectomized male partner from the date of informed consent until 24 hours after final dose of study drug.

• Completed the electronic diary (eDiary) on ≥ 10 of the 14 days prior to Day 1.

• Has not used loperamide rescue medication on > 3 of the 14 days prior to Day 1.

Exclusion Criteria:

• Has a diagnosis of IBS with a subtype of irritable bowel syndrome with constipation (IBS-C), mixed IBS, or unsubtyped IBS per Rome IV criteria.

• Does not have a gallbladder.

• Has known or suspected biliary duct obstruction, or sphincter of Oddi disease or dysfunction. (Participants with a history of gallstones may be enrolled).

• Has a history of alcoholism, alcohol abuse or alcohol addiction, or drinks more than 3 alcoholic beverages per day.

• Has a history of pancreatitis; structural diseases of the pancreas, including known or suspected pancreatic duct obstruction.

• Has a history of mild, moderate, or severe hepatic impairment according to Child-Pugh classification. History or current diagnosis of inflammatory or immune-mediated gastrointestinal (GI) disorders.

• Has Celiac disease or a positive serological test for celiac disease.

• Has known lactose or fructose intolerance associated with diarrhea, abdominal pain or discomfort, that could confound assessments in the study.

• Women who are currently pregnant or nursing, or plan to become pregnant or nurse during the study.

• Has known allergies or hypersensitivity to opioids.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic	Rochester	Minnesota	United States	55905

Sponsors and Collaborators

• Allergan

Investigators

• Study Director: Anna Muslin, Allergan

Study Documents (Full-Text)

• Study Protocol - Apr 17, 2019
• Statistical Analysis Plan - Mar 20, 2020

More Information

Publications

None provided.

• Responsible Party: Allergan
• ClinicalTrials.gov Identifier: NCT03441581
• Other Study ID Numbers: 3030-401-002
• First Posted: Feb 22, 2018
• Last Update Posted: May 19, 2021
• Last Verified: Apr 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Allergan: IBS-D; BAM
• Additional relevant MeSH terms: Irritable Bowel Syndrome; Malabsorption Syndromes; Syndrome; Diarrhea; Eluxadoline

Study Results

Participant Flow

Arm/Group Title	Eluxadoline 100 mg With BAM	Eluxadoline 100 mg Without BAM
Arm/Group Description	IBS-D participants with evidence of Bile Acid Malabsorption (BAM) treated with eluxadoline 100 mg oral tablets twice daily (BID) with food for 4 weeks.	IBS-D participants without evidence of BAM treated with eluxadoline 100 mg oral tablets BID with food for 4 weeks.
Period Title: Overall Study
STARTED	12	12
COMPLETED	12	12
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Eluxadoline 100 mg With BAM	Eluxadoline 100 mg Without BAM	Total
Arm/Group Description	IBS-D participants with evidence of Bile Acid Malabsorption (BAM) treated with eluxadoline 100 mg oral tablets twice daily (BID) with food for 4 weeks.	IBS-D participants without evidence of BAM treated with eluxadoline 100 mg oral tablets BID with food for 4 weeks.	Total of all reporting groups
Overall Participants	12	12	24
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	41.6 (6.07)	40.2 (13.72)	40.9 (10.40)
Sex: Female, Male (Count of Participants)
Female	7 58.3%	9 75%	16 66.7%
Male	5 41.7%	3 25%	8 33.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	1 8.3%	1 4.2%
Not Hispanic or Latino	12 100%	11 91.7%	23 95.8%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	1 8.3%	1 4.2%
White	12 100%	11 91.7%	23 95.8%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Average Bristol Stool Form Scale (BSFS) Score Over 4 Weeks of Treatment Period
Description	Stool consistency was assessed using the BSFS where: 1=Separate hard lumps like nuts to 7=Watery. The score was recorded by the participant in an electronic diary (e-diary). The score for each day was averaged over the 4-week period. A negative change from Baseline indicates improvement.
Time Frame	Baseline (Day 1) to Week 4

Outcome Measure Data

Analysis Population Description

Modified Intent-to-Treat (mITT) Population included of all participants in Enrolled Population with ≥ 1 postbaseline assessment for BSFS.

Arm/Group Title	Eluxadoline 100 mg With BAM	Eluxadoline 100 mg Without BAM
Arm/Group Description	IBS-D participants with evidence of Bile Acid Malabsorption (BAM) treated with eluxadoline 100 mg oral tablets twice daily (BID) with food for 4 weeks.	IBS-D participants without evidence of BAM treated with eluxadoline 100 mg oral tablets BID with food for 4 weeks.
Measure Participants	12	12
Baseline	5.89 (0.639)	5.34 (0.777)
Change From Baseline at Week 4	-1.25 (0.914)	-1.09 (0.902)

2. Primary Outcome

Title	Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)
Description	An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A TEAE is an AE that occurs or worsens after receiving investigational study drug.
Time Frame	Baseline (Day 1) to Week 4

Outcome Measure Data

Analysis Population Description

Safety Population included of all participants who received ≥ 1 dose of study treatment.

Arm/Group Title	Eluxadoline 100 mg With BAM	Eluxadoline 100 mg Without BAM
Arm/Group Description	IBS-D participants with evidence of Bile Acid Malabsorption (BAM) treated with eluxadoline 100 mg oral tablets twice daily (BID) with food for 4 weeks.	IBS-D participants without evidence of BAM treated with eluxadoline 100 mg oral tablets BID with food for 4 weeks.
Measure Participants	12	12
Number [percentage of participants]	91.7 764.2%	58.3 485.8%

3. Primary Outcome

Title	Number of Participants Who Experienced Potentially Clinically Significant Change in Laboratory Tests
Description	Laboratory tests included tests of Clinical Chemistry, Hematology, and Urinalysis. The investigator determined if the result was potentially clinically significant.
Time Frame	Baseline (Day 1) to Week 4

Outcome Measure Data

Analysis Population Description

Safety Population included of all participants who received ≥ 1 dose of study treatment.

Arm/Group Title	Eluxadoline 100 mg With BAM	Eluxadoline 100 mg Without BAM
Arm/Group Description	IBS-D participants with evidence of Bile Acid Malabsorption (BAM) treated with eluxadoline 100 mg oral tablets twice daily (BID) with food for 4 weeks.	IBS-D participants without evidence of BAM treated with eluxadoline 100 mg oral tablets BID with food for 4 weeks.
Measure Participants	12	12
Count of Participants [Participants]	0 0%	2 16.7%

4. Primary Outcome

Title	Number of Participants Who Experienced Potentially Clinically Significant Change in Vital Signs
Description	Vital signs assessments included: pulse, respiratory rate, and blood pressure (systolic and diastolic). The investigator determined if the result was potentially clinically significant.
Time Frame	Baseline (Day 1) to Week 4

Outcome Measure Data

Analysis Population Description

Safety Population included of all participants who received ≥ 1 dose of study treatment.

Arm/Group Title	Eluxadoline 100 mg With BAM	Eluxadoline 100 mg Without BAM
Arm/Group Description	IBS-D participants with evidence of Bile Acid Malabsorption (BAM) treated with eluxadoline 100 mg oral tablets twice daily (BID) with food for 4 weeks.	IBS-D participants without evidence of BAM treated with eluxadoline 100 mg oral tablets BID with food for 4 weeks.
Measure Participants	12	12
Count of Participants [Participants]	0 0%	1 8.3%

5. Primary Outcome

Title	Number of Participants Who Experienced Clinically Significant Change From Baseline in General Physical Condition as Measured Through General Physical Exam
Description	General Physical Examination consisted of a full review of body systems excluding pelvic and rectal exams. The investigator determined if the result was clinically significant.
Time Frame	Baseline (Day 1) to Week 4

Outcome Measure Data

Analysis Population Description

Safety Population included of all participants who received ≥ 1 dose of study treatment.

Arm/Group Title	Eluxadoline 100 mg With BAM	Eluxadoline 100 mg Without BAM
Arm/Group Description	IBS-D participants with evidence of Bile Acid Malabsorption (BAM) treated with eluxadoline 100 mg oral tablets twice daily (BID) with food for 4 weeks.	IBS-D participants without evidence of BAM treated with eluxadoline 100 mg oral tablets BID with food for 4 weeks.
Measure Participants	12	12
Count of Participants [Participants]	0 0%	0 0%

6. Secondary Outcome

Title	Change From Baseline in the 4-week Average of Daily Bowel Movement Frequency During the Treatment Period
Description	Bowel movements were recorded by the participant in an electronic diary (e-diary). The number of bowel movements per day was averaged over the 4-week period. A negative change from Baseline indicates improvement.
Time Frame	Baseline (Day 1) to Week 4

Outcome Measure Data

Analysis Population Description

mITT Population included of all participants in enrolled population with ≥ 1 postbaseline assessment for BSFS.

Arm/Group Title	Eluxadoline 100 mg With BAM	Eluxadoline 100 mg Without BAM
Arm/Group Description	IBS-D participants with evidence of Bile Acid Malabsorption (BAM) treated with eluxadoline 100 mg oral tablets twice daily (BID) with food for 4 weeks.	IBS-D participants without evidence of BAM treated with eluxadoline 100 mg oral tablets BID with food for 4 weeks.
Measure Participants	12	12
Baseline	4.18 (2.792)	2.86 (1.071)
Change from Baseline at Week 4	-1.48 (1.509)	-0.79 (0.420)

7. Secondary Outcome

Title	Change From Baseline in the 4-week Average of Daily Worst Abdominal Pain Scores During the Treatment Period
Description	The participant recorded their worst abdominal pain score in the past 24 hours each day in an e-diary where: 0=no pain to 10=worst imaginable pain. The score each day was averaged over the 4-week period. A negative change from Baseline indicates improvement.
Time Frame	Baseline (Day 1) to Week 4

Outcome Measure Data

Analysis Population Description

mITT Population included of all participants in enrolled population with ≥ 1 postbaseline assessment for BSFS.

Arm/Group Title	Eluxadoline 100 mg With BAM	Eluxadoline 100 mg Without BAM
Arm/Group Description	IBS-D participants with evidence of Bile Acid Malabsorption (BAM) treated with eluxadoline 100 mg oral tablets twice daily (BID) with food for 4 weeks.	IBS-D participants without evidence of BAM treated with eluxadoline 100 mg oral tablets BID with food for 4 weeks.
Measure Participants	12	12
Baseline	1.77 (1.510)	3.13 (1.755)
Change from Baseline at Week 4	-0.12 (0.769)	-1.28 (1.004)

8. Secondary Outcome

Title	Change From Baseline in the 4-week Average of Daily Bloating Scores During the Treatment Period
Description	The participant recorded their bloating score in the past 24 hours each day in an e-diary where: 0=no bloating to 10=worst imaginable bloating. The score each day was averaged over the 4-week period. A negative change from Baseline indicates improvement.
Time Frame	Baseline (Day 1) to Week 4

Outcome Measure Data

Analysis Population Description

mITT Population included of all participants in enrolled population with ≥ 1 postbaseline assessment for BSFS.

Arm/Group Title	Eluxadoline 100 mg With BAM	Eluxadoline 100 mg Without BAM
Arm/Group Description	IBS-D participants with evidence of Bile Acid Malabsorption (BAM) treated with eluxadoline 100 mg oral tablets twice daily (BID) with food for 4 weeks.	IBS-D participants without evidence of BAM treated with eluxadoline 100 mg oral tablets BID with food for 4 weeks.
Measure Participants	12	12
Baseline	2.31 (2.291)	4.07 (2.496)
Change from Baseline at Week 4	-0.47 (1.572)	-1.46 (1.297)

9. Secondary Outcome

Title	Change From Baseline in the 4-week Average Number of Daily Urgent Bowel Movements During the Treatment Period
Description	The participant recorded the number of urgent bowel movements in the past 24 hours each day in an e-diary. The number of urgent bowel movements per day was averaged over the 4-week period. A negative change from Baseline indicates improvement.
Time Frame	Baseline (Day 1) to Week 4

Outcome Measure Data

Analysis Population Description

mITT Population included of all participants in enrolled population with ≥ 1 postbaseline assessment for BSFS.

Arm/Group Title	Eluxadoline 100 mg With BAM	Eluxadoline 100 mg Without BAM
Arm/Group Description	IBS-D participants with evidence of Bile Acid Malabsorption (BAM) treated with eluxadoline 100 mg oral tablets twice daily (BID) with food for 4 weeks.	IBS-D participants without evidence of BAM treated with eluxadoline 100 mg oral tablets BID with food for 4 weeks.
Measure Participants	12	12
Baseline	1.67 (1.179)	1.22 (0.652)
Change from Baseline at Week 4	-0.52 (0.736)	-0.80 (0.651)

10. Secondary Outcome

Title	Percentage of Participants With Any Fecal Incontinence During the Treatment Period
Description	The participant recorded the number of fecal incontinences in the past 24 hours each day in an e-diary. Fecal incontinence is the inability to control the passage of gas or stools. The number of fecal incontinences per day was averaged over the 4-week period. A negative change from Baseline indicates improvement.
Time Frame	Baseline (Day 1) to Week 4

Outcome Measure Data

Analysis Population Description

mITT Population included of all participants in enrolled population with ≥ 1 postbaseline assessment for BSFS.

Arm/Group Title	Eluxadoline 100 mg With BAM	Eluxadoline 100 mg Without BAM
Arm/Group Description	IBS-D participants with evidence of Bile Acid Malabsorption (BAM) treated with eluxadoline 100 mg oral tablets twice daily (BID) with food for 4 weeks.	IBS-D participants without evidence of BAM treated with eluxadoline 100 mg oral tablets BID with food for 4 weeks.
Measure Participants	12	12
Number [percentage of participants]	33.3 277.5%	33.3 277.5%

11. Secondary Outcome

Title	Change From Baseline in Irritable Bowel Syndrome Quality of Life (IBS-QOL) Total Score at the End of the Treatment Period
Description	IBS-QOL is composed of 34 items about how the symptoms of IBS are impacting the participant's life scored on a 1 to 5 scale, where lower item scores indicate greater quality of life. The individual responses to the answered items were summed and standardized for a total score and then transformed to a 0 to 100-point scale (0=worst; 100=better) for ease of interpretation. A positive change from Baseline indicates improved quality of life.
Time Frame	Baseline (Day1) to End of Treatment (Up to Week 4)

Outcome Measure Data

Analysis Population Description

mITT Population included of all participants in enrolled population with ≥ 1 postbaseline assessment for BSFS.

Arm/Group Title	Eluxadoline 100 mg With BAM	Eluxadoline 100 mg Without BAM
Arm/Group Description	IBS-D participants with evidence of Bile Acid Malabsorption (BAM) treated with eluxadoline 100 mg oral tablets twice daily (BID) with food for 4 weeks.	IBS-D participants without evidence of BAM treated with eluxadoline 100 mg oral tablets BID with food for 4 weeks.
Measure Participants	12	12
Baseline	75.1 (14.43)	71.4 (13.42)
Change from Baseline at Week 4	8.8 (11.70)	13.2 (10.63)

12. Secondary Outcome

Title	Change From Baseline in Fasting Serum 7α-hydroxy-4-cholesten-3-one (7αC4) Levels at the End of the Treatment Period
Description	Participants fasted for at least 8 hours prior to the test. Fasting serum 7αC4 level was measured at Baseline and End of Treatment to determine whether any changes occurred following treatment with eluxadoline. The negative change from Baseline indicates improvement.
Time Frame	Baseline (Day 1) to End of Treatment (Up to Week 4)

Outcome Measure Data

Analysis Population Description

mITT Population included of all participants in enrolled population with ≥ 1 postbaseline assessment for BSFS. Number analyzed is the number of participants with data available for analyses.

Arm/Group Title	Eluxadoline 100 mg With BAM	Eluxadoline 100 mg Without BAM
Arm/Group Description	IBS-D participants with evidence of Bile Acid Malabsorption (BAM) treated with eluxadoline 100 mg oral tablets twice daily (BID) with food for 4 weeks.	IBS-D participants without evidence of BAM treated with eluxadoline 100 mg oral tablets BID with food for 4 weeks.
Measure Participants	12	12
Baseline	42.95 (27.259)	30.58 (17.248)
Change from Baseline at End of Treatment	-5.59 (32.841)	-8.78 (12.050)

13. Secondary Outcome

Title	Cmax: Maximum Concentration for Eluxadoline
Time Frame	Predose and at the intervals 1-2, 3-4 and 5-8 hours postdose at Week 2

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) population included all participants in the enrolled population and whose dry blood sample (DBS) was collected.

Arm/Group Title	Eluxadoline 100 mg With BAM	Eluxadoline 100 mg Without BAM
Arm/Group Description	IBS-D participants with evidence of Bile Acid Malabsorption (BAM) treated with eluxadoline 100 mg oral tablets twice daily (BID) with food for 4 weeks.	IBS-D participants without evidence of BAM treated with eluxadoline 100 mg oral tablets BID with food for 4 weeks.
Measure Participants	12	12
Mean (Standard Deviation) [ng/mL]	1.40 (1.34)	0.91 (0.80)

14. Secondary Outcome

Title	Cmin: Minimum Concentration for Eluxadoline
Time Frame	Predose and at the intervals 1-2, 3-4 and 5-8 hours postdose at Week 2

Outcome Measure Data

Analysis Population Description

PK population included all participants in the enrolled population and whose DBS was collected.

Arm/Group Title	Eluxadoline 100 mg With BAM	Eluxadoline 100 mg Without BAM
Arm/Group Description	IBS-D participants with evidence of Bile Acid Malabsorption (BAM) treated with eluxadoline 100 mg oral tablets twice daily (BID) with food for 4 weeks.	IBS-D participants without evidence of BAM treated with eluxadoline 100 mg oral tablets BID with food for 4 weeks.
Measure Participants	12	12
Mean (Standard Deviation) [ng/mL]	0.39 (0.44)	0.42 (0.59)

15. Secondary Outcome

Title	AUC: Area Under the Concentration-time Curve During the Dosing Interval for Eluxadoline
Time Frame	Predose and at the intervals 1-2, 3-4 and 5-8 hours postdose at Week 2

Outcome Measure Data

Analysis Population Description

PK population included all participants in the enrolled population and whose DBS was collected.

Arm/Group Title	Eluxadoline 100 mg With BAM	Eluxadoline 100 mg Without BAM
Arm/Group Description	IBS-D participants with evidence of Bile Acid Malabsorption (BAM) treated with eluxadoline 100 mg oral tablets twice daily (BID) with food for 4 weeks.	IBS-D participants without evidence of BAM treated with eluxadoline 100 mg oral tablets BID with food for 4 weeks.
Measure Participants	12	12
Mean (Standard Deviation) [nanogram* hour/milliliter (ng*h/mL)]	9.22 (8.46)	7.75 (8.48)

16. Secondary Outcome

Title	Tmax: Time to Cmax for Eluxadoline
Time Frame	Predose and at the intervals 1-2, 3-4 and 5-8 hours postdose at Week 2

Outcome Measure Data

Analysis Population Description

PK population included all participants in the enrolled population and whose DBS was collected.

Arm/Group Title	Eluxadoline 100 mg With BAM	Eluxadoline 100 mg Without BAM
Arm/Group Description	IBS-D participants with evidence of Bile Acid Malabsorption (BAM) treated with eluxadoline 100 mg oral tablets twice daily (BID) with food for 4 weeks.	IBS-D participants without evidence of BAM treated with eluxadoline 100 mg oral tablets BID with food for 4 weeks.
Measure Participants	12	12
Median (Full Range) [hours (h)]	1.5	2.0

17. Secondary Outcome

Title	t1/2: Half-Life for Eluxadoline
Time Frame	Predose and at the intervals 1-2, 3-4 and 5-8 hours postdose at Week 2

Outcome Measure Data

Analysis Population Description

PK population included all participants in the enrolled population and whose DBS was collected.

Arm/Group Title	Eluxadoline 100 mg With BAM	Eluxadoline 100 mg Without BAM
Arm/Group Description	IBS-D participants with evidence of Bile Acid Malabsorption (BAM) treated with eluxadoline 100 mg oral tablets twice daily (BID) with food for 4 weeks.	IBS-D participants without evidence of BAM treated with eluxadoline 100 mg oral tablets BID with food for 4 weeks.
Measure Participants	12	12
Median (Full Range) [h]	30.5	35.2

18. Secondary Outcome

Title	CL/F: Apparent Total Clearance of the Drug From Plasma After Oral Administration for Eluxadoline
Time Frame	Predose and at the intervals 1-2, 3-4 and 5-8 hours postdose at Week 2

Outcome Measure Data

Analysis Population Description

PK population included all participants in the enrolled population and whose DBS was collected.

Arm/Group Title	Eluxadoline 100 mg With BAM	Eluxadoline 100 mg Without BAM
Arm/Group Description	IBS-D participants with evidence of Bile Acid Malabsorption (BAM) treated with eluxadoline 100 mg oral tablets twice daily (BID) with food for 4 weeks.	IBS-D participants without evidence of BAM treated with eluxadoline 100 mg oral tablets BID with food for 4 weeks.
Measure Participants	12	12
Mean (Standard Deviation) [liter/hour (L/h)]	20236 (13280)	21901 (11921)

19. Secondary Outcome

Title	Vc/F: Apparent Volume of Distribution for Eluxadoline
Time Frame	Predose and at the intervals 1-2, 3-4 and 5-8 hours postdose at Week 2

Outcome Measure Data

Analysis Population Description

PK population included all participants in the enrolled population and whose DBS was collected.

Arm/Group Title	Eluxadoline 100 mg With BAM	Eluxadoline 100 mg Without BAM
Arm/Group Description	IBS-D participants with evidence of Bile Acid Malabsorption (BAM) treated with eluxadoline 100 mg oral tablets twice daily (BID) with food for 4 weeks.	IBS-D participants without evidence of BAM treated with eluxadoline 100 mg oral tablets BID with food for 4 weeks.
Measure Participants	12	12
Mean (Standard Deviation) [L]	29432 (11000)	39799 (10637)

Adverse Events

Time Frame	Up to 6 weeks
Arm/Group Title	Eluxadoline 100 mg With BAM		Eluxadoline 100 mg Without BAM
Arm/Group Description	IBS-D participants with evidence of Bile Acid Malabsorption (BAM) treated with eluxadoline 100 mg oral tablets twice daily (BID) with food for 4 weeks.		IBS-D participants without evidence of BAM treated with eluxadoline 100 mg oral tablets BID with food for 4 weeks.
All Cause Mortality
	Eluxadoline 100 mg With BAM		Eluxadoline 100 mg Without BAM
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/12 (0%)
Serious Adverse Events
	Eluxadoline 100 mg With BAM		Eluxadoline 100 mg Without BAM
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/12 (0%)
Other (Not Including Serious) Adverse Events
	Eluxadoline 100 mg With BAM		Eluxadoline 100 mg Without BAM
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/12 (91.7%)		7/12 (58.3%)
Endocrine disorders
Hypothyroidism	1/12 (8.3%)		0/12 (0%)
Gastrointestinal disorders
Abdominal pain	6/12 (50%)		1/12 (8.3%)
Flatulence	2/12 (16.7%)		4/12 (33.3%)
Abdominal distension	2/12 (16.7%)		3/12 (25%)
Nausea	4/12 (33.3%)		1/12 (8.3%)
Constipation	1/12 (8.3%)		2/12 (16.7%)
Abdominal discomfort	2/12 (16.7%)		0/12 (0%)
Diarrhoea	2/12 (16.7%)		0/12 (0%)
Dry mouth	2/12 (16.7%)		0/12 (0%)
Dyspepsia	2/12 (16.7%)		0/12 (0%)
Bowel movement irregularity	1/12 (8.3%)		0/12 (0%)
Dyschezia	1/12 (8.3%)		0/12 (0%)
Rectal haemorrhage	0/12 (0%)		1/12 (8.3%)
Vomiting	1/12 (8.3%)		0/12 (0%)
Metabolism and nutrition disorders
Impaired fasting glucose	1/12 (8.3%)		0/12 (0%)
Musculoskeletal and connective tissue disorders
Muscular weakness	1/12 (8.3%)		0/12 (0%)
Nervous system disorders
Dizziness	2/12 (16.7%)		0/12 (0%)
Headache	2/12 (16.7%)		0/12 (0%)
Dysgeusia	1/12 (8.3%)		0/12 (0%)
Hypotonia	0/12 (0%)		1/12 (8.3%)
Psychiatric disorders
Anxiety	1/12 (8.3%)		0/12 (0%)
Vascular disorders
Hot flush	1/12 (8.3%)		0/12 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

A disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 90 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.