Irritable Bowel Syndrome With Diarrhea
Conditions
Keywords
IBS-D, BAM
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).
Interventions
DRUGEluxadoline
Eluxadoline 100 mg oral tablets BID with food.
Sponsors
Allergan
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| Cmax: Maximum Concentration for Eluxadoline | Predose and at the intervals 1-2, 3-4 and 5-8 hours postdose at Week 2 | — |
| Cmin: Minimum Concentration for Eluxadoline | Predose and at the intervals 1-2, 3-4 and 5-8 hours postdose at Week 2 | — |
| 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. |
| Tmax: Time to Cmax for Eluxadoline | Predose and at the intervals 1-2, 3-4 and 5-8 hours postdose at Week 2 | — |
| t1/2: Half-Life for Eluxadoline | Predose and at the intervals 1-2, 3-4 and 5-8 hours postdose at Week 2 | — |
| 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 | — |
| 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 | — |
| 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 | — |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 12 |
| 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. | 12 |
| Total | 24 |
Baseline characteristics
| Characteristic | Eluxadoline 100 mg Without BAM | Total | Eluxadoline 100 mg With BAM |
|---|---|---|---|
| Age, Continuous | 40.2 years STANDARD_DEVIATION 13.72 | 40.9 years STANDARD_DEVIATION 10.4 | 41.6 years STANDARD_DEVIATION 6.07 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants | 23 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 11 Participants | 23 Participants | 12 Participants |
| Sex: Female, Male Female | 9 Participants | 16 Participants | 7 Participants |
| Sex: Female, Male Male | 3 Participants | 8 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 11 / 12 | 7 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 |
Outcome results
Primary
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.
Time frame: Baseline (Day 1) to Week 4
Population: Modified Intent-to-Treat (mITT) Population included of all participants in Enrolled Population with ≥ 1 postbaseline assessment for BSFS.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eluxadoline 100 mg With BAM | Change From Baseline in Average Bristol Stool Form Scale (BSFS) Score Over 4 Weeks of Treatment Period | Baseline | 5.89 score on a scale | Standard Deviation 0.639 |
| Eluxadoline 100 mg With BAM | Change From Baseline in Average Bristol Stool Form Scale (BSFS) Score Over 4 Weeks of Treatment Period | Change From Baseline at Week 4 | -1.25 score on a scale | Standard Deviation 0.914 |
| Eluxadoline 100 mg Without BAM | Change From Baseline in Average Bristol Stool Form Scale (BSFS) Score Over 4 Weeks of Treatment Period | Baseline | 5.34 score on a scale | Standard Deviation 0.777 |
| Eluxadoline 100 mg Without BAM | Change From Baseline in Average Bristol Stool Form Scale (BSFS) Score Over 4 Weeks of Treatment Period | Change From Baseline at Week 4 | -1.09 score on a scale | Standard Deviation 0.902 |
Primary
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.
Time frame: Baseline (Day 1) to Week 4
Population: Safety Population included of all participants who received ≥ 1 dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Eluxadoline 100 mg With BAM | Number of Participants Who Experienced Clinically Significant Change From Baseline in General Physical Condition as Measured Through General Physical Exam | 0 Participants |
| Eluxadoline 100 mg Without BAM | Number of Participants Who Experienced Clinically Significant Change From Baseline in General Physical Condition as Measured Through General Physical Exam | 0 Participants |
Primary
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.
Time frame: Baseline (Day 1) to Week 4
Population: Safety Population included of all participants who received ≥ 1 dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Eluxadoline 100 mg With BAM | Number of Participants Who Experienced Potentially Clinically Significant Change in Laboratory Tests | 0 Participants |
| Eluxadoline 100 mg Without BAM | Number of Participants Who Experienced Potentially Clinically Significant Change in Laboratory Tests | 2 Participants |
Primary
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.
Time frame: Baseline (Day 1) to Week 4
Population: Safety Population included of all participants who received ≥ 1 dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Eluxadoline 100 mg With BAM | Number of Participants Who Experienced Potentially Clinically Significant Change in Vital Signs | 0 Participants |
| Eluxadoline 100 mg Without BAM | Number of Participants Who Experienced Potentially Clinically Significant Change in Vital Signs | 1 Participants |
Primary
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.
Time frame: Baseline (Day 1) to Week 4
Population: Safety Population included of all participants who received ≥ 1 dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Eluxadoline 100 mg With BAM | Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) | 91.7 percentage of participants |
| Eluxadoline 100 mg Without BAM | Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) | 58.3 percentage of participants |
Secondary
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
Population: PK population included all participants in the enrolled population and whose DBS was collected.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Eluxadoline 100 mg With BAM | AUC: Area Under the Concentration-time Curve During the Dosing Interval for Eluxadoline | 9.22 nanogram* hour/milliliter (ng*h/mL) | Standard Deviation 8.46 |
| Eluxadoline 100 mg Without BAM | AUC: Area Under the Concentration-time Curve During the Dosing Interval for Eluxadoline | 7.75 nanogram* hour/milliliter (ng*h/mL) | Standard Deviation 8.48 |
Secondary
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.
Time frame: Baseline (Day 1) to End of Treatment (Up to Week 4)
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eluxadoline 100 mg With BAM | Change From Baseline in Fasting Serum 7α-hydroxy-4-cholesten-3-one (7αC4) Levels at the End of the Treatment Period | Baseline | 42.95 nanogram/milliliter (ng/mL) | Standard Deviation 27.259 |
| Eluxadoline 100 mg With BAM | Change From Baseline in Fasting Serum 7α-hydroxy-4-cholesten-3-one (7αC4) Levels at the End of the Treatment Period | Change from Baseline at End of Treatment | -5.59 nanogram/milliliter (ng/mL) | Standard Deviation 32.841 |
| Eluxadoline 100 mg Without BAM | Change From Baseline in Fasting Serum 7α-hydroxy-4-cholesten-3-one (7αC4) Levels at the End of the Treatment Period | Baseline | 30.58 nanogram/milliliter (ng/mL) | Standard Deviation 17.248 |
| Eluxadoline 100 mg Without BAM | Change From Baseline in Fasting Serum 7α-hydroxy-4-cholesten-3-one (7αC4) Levels at the End of the Treatment Period | Change from Baseline at End of Treatment | -8.78 nanogram/milliliter (ng/mL) | Standard Deviation 12.05 |
Secondary
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.
Time frame: Baseline (Day1) to End of Treatment (Up to Week 4)
Population: mITT Population included of all participants in enrolled population with ≥ 1 postbaseline assessment for BSFS.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eluxadoline 100 mg With BAM | Change From Baseline in Irritable Bowel Syndrome Quality of Life (IBS-QOL) Total Score at the End of the Treatment Period | Baseline | 75.1 score on a scale | Standard Deviation 14.43 |
| Eluxadoline 100 mg With BAM | Change From Baseline in Irritable Bowel Syndrome Quality of Life (IBS-QOL) Total Score at the End of the Treatment Period | Change from Baseline at Week 4 | 8.8 score on a scale | Standard Deviation 11.7 |
| Eluxadoline 100 mg Without BAM | Change From Baseline in Irritable Bowel Syndrome Quality of Life (IBS-QOL) Total Score at the End of the Treatment Period | Baseline | 71.4 score on a scale | Standard Deviation 13.42 |
| Eluxadoline 100 mg Without BAM | Change From Baseline in Irritable Bowel Syndrome Quality of Life (IBS-QOL) Total Score at the End of the Treatment Period | Change from Baseline at Week 4 | 13.2 score on a scale | Standard Deviation 10.63 |
Secondary
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.
Time frame: Baseline (Day 1) to Week 4
Population: mITT Population included of all participants in enrolled population with ≥ 1 postbaseline assessment for BSFS.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eluxadoline 100 mg With BAM | Change From Baseline in the 4-week Average Number of Daily Urgent Bowel Movements During the Treatment Period | Baseline | 1.67 urgent bowel movements per day | Standard Deviation 1.179 |
| Eluxadoline 100 mg With BAM | Change From Baseline in the 4-week Average Number of Daily Urgent Bowel Movements During the Treatment Period | Change from Baseline at Week 4 | -0.52 urgent bowel movements per day | Standard Deviation 0.736 |
| Eluxadoline 100 mg Without BAM | Change From Baseline in the 4-week Average Number of Daily Urgent Bowel Movements During the Treatment Period | Baseline | 1.22 urgent bowel movements per day | Standard Deviation 0.652 |
| Eluxadoline 100 mg Without BAM | Change From Baseline in the 4-week Average Number of Daily Urgent Bowel Movements During the Treatment Period | Change from Baseline at Week 4 | -0.80 urgent bowel movements per day | Standard Deviation 0.651 |
Secondary
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.
Time frame: Baseline (Day 1) to Week 4
Population: mITT Population included of all participants in enrolled population with ≥ 1 postbaseline assessment for BSFS.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eluxadoline 100 mg With BAM | Change From Baseline in the 4-week Average of Daily Bloating Scores During the Treatment Period | Baseline | 2.31 score on a scale | Standard Deviation 2.291 |
| Eluxadoline 100 mg With BAM | Change From Baseline in the 4-week Average of Daily Bloating Scores During the Treatment Period | Change from Baseline at Week 4 | -0.47 score on a scale | Standard Deviation 1.572 |
| Eluxadoline 100 mg Without BAM | Change From Baseline in the 4-week Average of Daily Bloating Scores During the Treatment Period | Baseline | 4.07 score on a scale | Standard Deviation 2.496 |
| Eluxadoline 100 mg Without BAM | Change From Baseline in the 4-week Average of Daily Bloating Scores During the Treatment Period | Change from Baseline at Week 4 | -1.46 score on a scale | Standard Deviation 1.297 |
Secondary
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.
Time frame: Baseline (Day 1) to Week 4
Population: mITT Population included of all participants in enrolled population with ≥ 1 postbaseline assessment for BSFS.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eluxadoline 100 mg With BAM | Change From Baseline in the 4-week Average of Daily Bowel Movement Frequency During the Treatment Period | Baseline | 4.18 bowel movements per day | Standard Deviation 2.792 |
| Eluxadoline 100 mg With BAM | Change From Baseline in the 4-week Average of Daily Bowel Movement Frequency During the Treatment Period | Change from Baseline at Week 4 | -1.48 bowel movements per day | Standard Deviation 1.509 |
| Eluxadoline 100 mg Without BAM | Change From Baseline in the 4-week Average of Daily Bowel Movement Frequency During the Treatment Period | Baseline | 2.86 bowel movements per day | Standard Deviation 1.071 |
| Eluxadoline 100 mg Without BAM | Change From Baseline in the 4-week Average of Daily Bowel Movement Frequency During the Treatment Period | Change from Baseline at Week 4 | -0.79 bowel movements per day | Standard Deviation 0.42 |
Secondary
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.
Time frame: Baseline (Day 1) to Week 4
Population: mITT Population included of all participants in enrolled population with ≥ 1 postbaseline assessment for BSFS.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eluxadoline 100 mg With BAM | Change From Baseline in the 4-week Average of Daily Worst Abdominal Pain Scores During the Treatment Period | Baseline | 1.77 score on a scale | Standard Deviation 1.51 |
| Eluxadoline 100 mg With BAM | Change From Baseline in the 4-week Average of Daily Worst Abdominal Pain Scores During the Treatment Period | Change from Baseline at Week 4 | -0.12 score on a scale | Standard Deviation 0.769 |
| Eluxadoline 100 mg Without BAM | Change From Baseline in the 4-week Average of Daily Worst Abdominal Pain Scores During the Treatment Period | Baseline | 3.13 score on a scale | Standard Deviation 1.755 |
| Eluxadoline 100 mg Without BAM | Change From Baseline in the 4-week Average of Daily Worst Abdominal Pain Scores During the Treatment Period | Change from Baseline at Week 4 | -1.28 score on a scale | Standard Deviation 1.004 |
Secondary
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
Population: PK population included all participants in the enrolled population and whose DBS was collected.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Eluxadoline 100 mg With BAM | CL/F: Apparent Total Clearance of the Drug From Plasma After Oral Administration for Eluxadoline | 20236 liter/hour (L/h) | Standard Deviation 13280 |
| Eluxadoline 100 mg Without BAM | CL/F: Apparent Total Clearance of the Drug From Plasma After Oral Administration for Eluxadoline | 21901 liter/hour (L/h) | Standard Deviation 11921 |
Secondary
Cmax: Maximum Concentration for Eluxadoline
Time frame: Predose and at the intervals 1-2, 3-4 and 5-8 hours postdose at Week 2
Population: Pharmacokinetic (PK) population included all participants in the enrolled population and whose dry blood sample (DBS) was collected.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Eluxadoline 100 mg With BAM | Cmax: Maximum Concentration for Eluxadoline | 1.40 ng/mL | Standard Deviation 1.34 |
| Eluxadoline 100 mg Without BAM | Cmax: Maximum Concentration for Eluxadoline | 0.91 ng/mL | Standard Deviation 0.8 |
Secondary
Cmin: Minimum Concentration for Eluxadoline
Time frame: Predose and at the intervals 1-2, 3-4 and 5-8 hours postdose at Week 2
Population: PK population included all participants in the enrolled population and whose DBS was collected.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Eluxadoline 100 mg With BAM | Cmin: Minimum Concentration for Eluxadoline | 0.39 ng/mL | Standard Deviation 0.44 |
| Eluxadoline 100 mg Without BAM | Cmin: Minimum Concentration for Eluxadoline | 0.42 ng/mL | Standard Deviation 0.59 |
Secondary
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.
Time frame: Baseline (Day 1) to Week 4
Population: mITT Population included of all participants in enrolled population with ≥ 1 postbaseline assessment for BSFS.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Eluxadoline 100 mg With BAM | Percentage of Participants With Any Fecal Incontinence During the Treatment Period | 33.3 percentage of participants |
| Eluxadoline 100 mg Without BAM | Percentage of Participants With Any Fecal Incontinence During the Treatment Period | 33.3 percentage of participants |
Secondary
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
Population: PK population included all participants in the enrolled population and whose DBS was collected.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Eluxadoline 100 mg With BAM | t1/2: Half-Life for Eluxadoline | 30.5 h |
| Eluxadoline 100 mg Without BAM | t1/2: Half-Life for Eluxadoline | 35.2 h |
Secondary
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
Population: PK population included all participants in the enrolled population and whose DBS was collected.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Eluxadoline 100 mg With BAM | Tmax: Time to Cmax for Eluxadoline | 1.5 hours (h) |
| Eluxadoline 100 mg Without BAM | Tmax: Time to Cmax for Eluxadoline | 2.0 hours (h) |
Secondary
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
Population: PK population included all participants in the enrolled population and whose DBS was collected.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Eluxadoline 100 mg With BAM | Vc/F: Apparent Volume of Distribution for Eluxadoline | 29432 L | Standard Deviation 11000 |
| Eluxadoline 100 mg Without BAM | Vc/F: Apparent Volume of Distribution for Eluxadoline | 39799 L | Standard Deviation 10637 |