Eluxadoline Bile Acid Malabsorption (BAM) Study

• ClinicalTrials.gov Identifier: NCT03441581
• Recruitment Status: Completed
• First Posted: February 22, 2018
• Results First Posted: May 19, 2021
• Last Update Posted: May 19, 2021
• Sponsor: Allergan
• Information provided by (Responsible Party): Allergan

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 (Clinical Trial)
• 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: February 23, 2018
• Actual Primary Completion Date: April 28, 2020
• Actual Study Completion Date: April 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 [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Predose and at the intervals 1-2, 3-4 and 5-8 hours postdose at Week 2 ]
9. Cmin: Minimum Concentration for Eluxadoline [ Time Frame: 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 [ Time Frame: Predose and at the intervals 1-2, 3-4 and 5-8 hours postdose at Week 2 ]
11. 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 ]
12. 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 ]
13. 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 ]
14. 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 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, Minnesota

Mayo Clinic

Rochester, Minnesota, United States, 55905

Sponsors and Collaborators

Allergan

Investigators

• Study Director: Anna Muslin; Allergan

  Study Documents (Full-Text)

Documents provided by Allergan:

Study Protocol  [PDF] April 17, 2019

Statistical Analysis Plan  [PDF] March 20, 2020

More Information

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

Individual Participant Data (IPD) Sharing Statement:

• 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; Disease; Pathologic Processes; Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Signs and Symptoms, Digestive; Metabolic Diseases; Eluxadoline; Gastrointestinal Agents