Clinical trial NCT03441581: Eluxadoline Bile Acid Malabsorption (BAM) Study
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Irritable Bowel Syndrome With Diarrhea
Keywords: IBS-D
BAM
Lead sponsor: Allergan
Sponsor class: INDUSTRY
First posted: 2018-02-22
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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.

Primary outcomes:
measure: Change From Baseline in Average Bristol Stool Form Scale (BSFS) Score Over 4 Weeks of Treatment Period
timeFrame: Baseline (Day 1) to Week 4
measure: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Baseline (Day 1) to Week 4
measure: Number of Participants Who Experienced Potentially Clinically Significant Change in Laboratory Tests
timeFrame: Baseline (Day 1) to Week 4
measure: Number of Participants Who Experienced Potentially Clinically Significant Change in Vital Signs
timeFrame: Baseline (Day 1) to Week 4
measure: Number of Participants Who Experienced Clinically Significant Change From Baseline in General Physical Condition as Measured Through General Physical Exam
timeFrame: Baseline (Day 1) to Week 4
Secondary outcomes:
measure: Change From Baseline in the 4-week Average of Daily Bowel Movement Frequency During the Treatment Period
timeFrame: Baseline (Day 1) to Week 4
measure: Change From Baseline in the 4-week Average of Daily Worst Abdominal Pain Scores During the Treatment Period
timeFrame: Baseline (Day 1) to Week 4
measure: Change From Baseline in the 4-week Average of Daily Bloating Scores During the Treatment Period
timeFrame: Baseline (Day 1) to Week 4
measure: Change From Baseline in the 4-week Average Number of Daily Urgent Bowel Movements During the Treatment Period
timeFrame: Baseline (Day 1) to Week 4
measure: Percentage of Participants With Any Fecal Incontinence During the Treatment Period
timeFrame: Baseline (Day 1) to Week 4
measure: Change From Baseline in Irritable Bowel Syndrome Quality of Life (IBS-QOL) Total Score at the End of the Treatment Period
timeFrame: Baseline (Day1) to End of Treatment (Up to Week 4)
measure: Change From Baseline in Fasting Serum 7α-hydroxy-4-cholesten-3-one (7αC4) Levels at the End of the Treatment Period
timeFrame: Baseline (Day 1) to End of Treatment (Up to Week 4)
measure: Cmax: Maximum Concentration for Eluxadoline
timeFrame: Predose and at the intervals 1-2, 3-4 and 5-8 hours postdose at Week 2
measure: Cmin: Minimum Concentration for Eluxadoline
timeFrame: Predose and at the intervals 1-2, 3-4 and 5-8 hours postdose at Week 2
measure: AUC: Area Under the Concentration-time Curve During the Dosing Interval for Eluxadoline
timeFrame: Predose and at the intervals 1-2, 3-4 and 5-8 hours postdose at Week 2
measure: Tmax: Time to Cmax for Eluxadoline
timeFrame: Predose and at the intervals 1-2, 3-4 and 5-8 hours postdose at Week 2
measure: t1/2: Half-Life for Eluxadoline
timeFrame: Predose and at the intervals 1-2, 3-4 and 5-8 hours postdose at Week 2
measure: CL/F: Apparent Total Clearance of the Drug From Plasma After Oral Administration for Eluxadoline
timeFrame: Predose and at the intervals 1-2, 3-4 and 5-8 hours postdose at Week 2
measure: Vc/F: Apparent Volume of Distribution for Eluxadoline
timeFrame: Predose and at the intervals 1-2, 3-4 and 5-8 hours postdose at Week 2
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Allergan
name: Anna Muslin
role: STUDY_DIRECTOR
References: