Eluxadoline Bile Acid Malabsorption (BAM) Study

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Primary Purpose

Status

Completed

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Eluxadoline

About this trial

This is an interventional treatment trial for Irritable Bowel Syndrome With Diarrhea focused on measuring IBS-D, BAM

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Mayo Clinic

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Eluxadoline 100 mg with BAM

Eluxadoline 100 mg without BAM

Arm 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.

Outcomes

Primary Outcome Measures

Change From Baseline in Average Bristol Stool Form Scale (BSFS) Score Over 4 Weeks of Treatment Period

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.

Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)

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.

Number of Participants Who Experienced Potentially Clinically Significant Change in Laboratory Tests

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

Number of Participants Who Experienced Potentially Clinically Significant Change in Vital Signs

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

Number of Participants Who Experienced Clinically Significant Change From Baseline in General Physical Condition as Measured Through General Physical Exam

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

Change From Baseline in the 4-week Average of Daily Bowel Movement Frequency During the Treatment Period

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.

Change From Baseline in the 4-week Average of Daily Worst Abdominal Pain Scores During the Treatment Period

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.

Change From Baseline in the 4-week Average of Daily Bloating Scores During the Treatment Period

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.

Change From Baseline in the 4-week Average Number of Daily Urgent Bowel Movements During the Treatment Period

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.

Percentage of Participants With Any Fecal Incontinence During the Treatment Period

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.

Change From Baseline in Irritable Bowel Syndrome Quality of Life (IBS-QOL) Total Score at the End of the Treatment Period

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.

Change From Baseline in Fasting Serum 7α-hydroxy-4-cholesten-3-one (7αC4) Levels at the End of the Treatment Period

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.

Cmax: Maximum Concentration for Eluxadoline

Cmin: Minimum Concentration for Eluxadoline

AUC: Area Under the Concentration-time Curve During the Dosing Interval for Eluxadoline

Tmax: Time to Cmax for Eluxadoline

t1/2: Half-Life for Eluxadoline

CL/F: Apparent Total Clearance of the Drug From Plasma After Oral Administration for Eluxadoline

Vc/F: Apparent Volume of Distribution for Eluxadoline

Full Information

NCT ID

NCT03441581

First Posted

January 19, 2018

Last Updated

April 28, 2021

Sponsor

Allergan

1. Study Identification

Unique Protocol Identification Number

NCT03441581

Brief Title

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

2. Study Status

Record Verification Date

April 2021

Overall Recruitment Status

Completed

Study Start Date

February 23, 2018 (Actual)

Primary Completion Date

April 28, 2020 (Actual)

Study Completion Date

April 28, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Allergan

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

No

5. 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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Irritable Bowel Syndrome With Diarrhea

Keywords

IBS-D, BAM

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

24 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Eluxadoline 100 mg with BAM

Arm Type

Experimental

Arm 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.

Arm Title

Eluxadoline 100 mg without BAM

Arm Type

Experimental

Arm Description

IBS-D participants without evidence of BAM treated with eluxadoline 100 mg oral tablets BID with food for 4 weeks.

Intervention Type

Drug

Intervention Name(s)

Eluxadoline

Intervention Description

Eluxadoline 100 mg oral tablets BID with food.

Primary Outcome Measure Information:

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

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

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

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

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

Secondary Outcome Measure Information:

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

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

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

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

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

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)

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)

Title

Cmax: Maximum Concentration for Eluxadoline

Time Frame