Irritable Bowel Syndrome
Conditions
Brief summary
The purpose of this study is to determine the efficacy, safety, and tolerability of different doses of eluxadoline (JNJ-27018966) compared with placebo in the treatment of participants with diarrhea-predominant irritable bowel syndrome.
Interventions
DRUGEluxadoline
Oral tablets twice daily
DRUGPlacebo
Oral tablets twice daily
Sponsors
Furiex Pharmaceuticals, Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Participant has a diagnosis of irritable bowel syndrome (IBS) with a subtype of diarrhea defined by the Rome III criteria. 2. Participant has had a colonoscopy performed: * Within 10 years prior to Prescreening if participant is at least 50 years of age (sigmoidoscopy, double contrast barium enema, or computed tomography (CT) colonography within the past 5 years is acceptable) * Since the onset (if applicable) of any of the following alarm features for participants of any age: * Participant has documented weight loss within the past 6 months * Participant has nocturnal symptoms * Participant has a familial history of first-degree relatives with colon cancer or * Participant has blood mixed with their stool (excluding blood from hemorrhoids). 3. Female participants must be: * Postmenopausal, defined as 52 years or older and amenorrheic for at least 2 years at Prescreening, * Surgically sterile (have had a hysterectomy or bilateral oophorectomy, tubal ligation, or otherwise be incapable of pregnancy), * Abstinent, or * If sexually active, be practicing an effective method of birth control.
Exclusion criteria
1. Participant has a diagnosis of IBS with a subtype of constipation, mixed IBS, or unsubtyped IBS by the Rome III criteria. 2. Participant has a history of inflammatory or immune-mediated gastrointestinal (GI) disorders including inflammatory bowel disease (ie, Crohn's disease, ulcerative colitis) and celiac disease. 3. Participant has a history of diverticulitis within 3 months prior to Prescreening. 4. Participant has a history of intestinal obstruction, stricture, toxic megacolon, GI perforation, fecal impaction, gastric banding, bariatric surgery, adhesions, ischemic colitis, or impaired intestinal circulation (eg, aortoiliac disease). 5. Participant has any of the following surgical history: * Cholecystectomy with any history of post cholecystectomy biliary tract pain * Any abdominal surgery within the 3 months prior to Prescreening * Participant has a history of major gastric, hepatic, pancreatic, or intestinal surgery (appendectomy, hemorrhoidectomy, or polypectomy greater than 3 months post surgery are allowed) Other protocol-specific eligibility criteria may apply.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Were Composite Responders Based on Improvements From Baseline in Daily Worst Abdominal Pain And Daily Stool Consistency Scores | Up to 12 Weeks | Composite responders were defined as a participant who met the daily response criteria for at least 50% of the days with diary entries during the interval of interest. A participant must had met both of the following criteria on a given day to be a daily responder: 1) Daily pain response: worst abdominal pain scores in the past 24 hours improved by ≥30% compared to baseline (average of daily worst abdominal pain the week prior to randomization). 2) Daily stool consistency response: Bristol Stool Scale (BSS) score \<5 (ie, score of 1, 2, 3, or 4) or the absence of a bowel movement if accompanied by ≥30% improvement in worst abdominal pain compared to baseline pain. Bristol stool scale was defined as 7-point Scale in which a score of 1 = separate hard lumps, 2 = sausage shaped but lumpy, 3 = sausage-like with cracks on the surface, 4 = sausage-like but smooth and soft, 5 = soft blobs with clear cut edges, 6 = fluffy pieces with ragged edges, and 7 = watery with no solid pieces. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Were Pain Responders In Daily Worst Abdominal Pain Scores by Intervals | 12-week interval (Weeks 1-12), 26-week interval (Weeks 1-26), and 4-week interval (Weeks 1-4, 5-8, 9-12, 13-16, 17-20, and 21-24) | Pain responders were defined as participants who met the daily pain response criteria (ie, the worst abdominal pain score in the past 24 hours improved by ≥30% compared to baseline) for at least 50% of days with diary entries during each interval. A participant must have had a minimum of 20 days of diary entries over any 4-week interval, a minimum of 60 days of diary entries over the 12-week interval, and a minimum of 110 days of diary entries over the 26-week interval to be a responder. |
| Percentage of Participants Who Were Responders In Daily Stool Consistency Scores by Intervals | 12-week interval (Weeks 1-12), 26-week interval (Weeks 1-26), and 4-week interval (Weeks 1-4, 5-8, 9-12, 13-16, 17-20, and 21-24) | Stool consistency responders: participants who met daily stool consistency response criterion (ie,score of 1, 2, 3, or 4 or absence of bowel movement if accompanied by ≥30% improvement in worst abdominal pain compared to baseline pain) for at least 50% of days with diary entries during each interval. BSS was defined as 7-point Scale in which score of 1= separate hard lumps, 2= sausage shaped but lumpy, 3= sausage-like with cracks on the surface, 4= sausage-like but smooth and soft, 5= soft blobs with clear cut edges, 6= fluffy pieces with ragged edges, and 7= watery with no solid pieces. A participant must have had a minimum of 20 days of diary entries over any 4-week interval, a minimum of 60 days of diary entries over 12-week interval, and a minimum of 110 days of diary entries over 26-week interval to be a responder. |
| Percentage of Participants Who Were Responders In Irritable Bowel Syndrome, Diarrhea Predominant (IBS-d) Global Symptom Scale by Intervals | 12-week interval (Weeks 1-12), 26-week interval (Weeks 1-26), and 4-week interval (Weeks 1-4, 5-8, 9-12, 13-16, 17-20, and 21-24) | IBS-d global symptom responders were defined as those participants who met the daily IBS-d global symptom response criteria (ie, IBS-d global symptom score of 0 \[none\] or 1 \[mild\]; or a daily IBS-d global symptom score improved by ≥2.0 compared to the baseline average) for at least 50% of days with diary entries during each interval. IBS-d Global Symptom Scale was a 5 point scale, score ranging from 0 to 4. 0= no symptoms, 1= mild symptoms, 2= moderate symptoms, 3= severe symptoms and 4 = very severe symptoms. A participant must have had a minimum of 20 days of diary entries over any 4-week interval, a minimum of 60 days of diary entries over the 12-week interval, and a minimum of 110 days of diary entries over the 26-week interval to be a responder. |
| Percentage of Participants Who Were Responders to the Irritable Bowel Syndrome Quality of Life Measure (IBS-QoL) Scale | Weeks 4, 8, 12, 18, 26, 36, 44, and 52 (End of Treatment [EOT]) | IBS-QoL responders were defined as participants who achieved at least a 14-point improvement in IBS-QoL total score from baseline to the applicable visit. The IBS-QoL consists of 34 items each with a 5-point response scale, where 1 generally represents better responses on items and 5 represents worse responses. The individual responses to the answered items were summed and standardized for a total score and then transformed to a 0- to 100-point (0= worst; 100=better) scale for ease of interpretation. |
| Percentage of Participants With Irritable Bowel Syndrome - Adequate Relief (IBS-AR) Scale | 12-week interval (Weeks 1-12) and 26-week interval (Weeks 1-26) | Adequate relief of IBS symptoms was assessed once weekly by participants answering the IBS-AR item in the electronic diary. IBS-AR responders were defined as participants with a weekly response of Yes to adequate relief of their IBS symptoms for at least 50% of the total weeks during the interval. A participant must have had a positive response on ≥6 weeks for the 12-week interval and ≥13 weeks for the 26-week interval, regardless of diary compliance, to be a responder. |
| Change From Baseline in Daily Abdominal Discomfort Scores | Baseline, Weeks 4, 12 and 26 | Symptoms of abdominal discomfort were recorded on a 0 to 10 scale, where 0 corresponded to no discomfort and 10 corresponded to worst imaginable discomfort. A negative change from Baseline indicates the discomfort decreased. |
| Percentage of Participants Who Were Composite Responders Based on Improvements From Baseline in Daily Worst Abdominal Pain And Daily Stool Consistency Scores | Up to 26 Weeks | Composite responders were defined as a participant who met the daily response criteria for at least 50% of the days with diary entries during the interval of interest. A participant must had met both of the following criteria on a given day to be a daily responder: 1) Daily pain response: worst abdominal pain scores in the past 24 hours improved by ≥30% compared to baseline (average of daily worst abdominal pain the week prior to randomization). 2) Daily stool consistency response: Bristol Stool Scale (BSS) score \<5 (ie, score of 1, 2, 3, or 4) or the absence of a bowel movement if accompanied by ≥30% improvement in worst abdominal pain compared to baseline pain. Bristol stool scale was defined as 7-point Scale in which a score of 1 = separate hard lumps, 2 = sausage shaped but lumpy, 3 = sausage-like with cracks on the surface, 4 = sausage-like but smooth and soft, 5 = soft blobs with clear cut edges, 6 = fluffy pieces with ragged edges, and 7 = watery with no solid pieces. |
| Number of Bowel Movements Per Day | Weeks 4, 12 and 26 | Participants recorded the number of bowel movements over 24 hours daily throughout the treatment. |
| Number of Bowel Incontinence Episodes | Weeks 4, 12 and 26 | Participants recorded the number of incontinence episodes over 24 hours daily throughout the treatment. |
| Number of Bowel Incontinence Free Days | Weeks 4, 12 and 26 | An incontinence free day was one where the participant reports zero incontinence episodes. The number of incontinence free days for a participant was assessed each week based on the number of reported days. |
| Number of Urgency Episodes Per Day | Weeks 4, 12 and 26 | Participants recorded the number of urgency episodes over 24 hours daily throughout the treatment. |
| IBS-QoL Total Scores | Weeks 4, 8, 12, 18, 26, 36, 44, and 52 (EOT) | The IBS-QoL consists of 34 items each with a 5-point response scale, where 1 generally represents better responses on items and 5 represents worse responses. 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. |
| Change From Baseline in IBS-QoL Total Scores | Baseline, Weeks 4, 8, 12, 18, 26, 36, 44, and 52/EOT | The IBS-QoL consists of 34 items each with a 5-point response scale, where 1 generally represents better responses on items and 5 represents worse responses. 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 that quality of life improved. |
| Change From Baseline in Daily Abdominal Bloating Scores | Baseline, Weeks 4, 12 and 26 | Symptoms of abdominal bloating were recorded on a 0 to 10 scale, where 0 corresponded to no bloating and 10 corresponded to worst imaginable bloating. A negative change from Baseline indicates the bloating decreased. |
Countries
Canada, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Eluxadoline 75 mg Eluxadoline 75 mg tablets, orally, twice daily for up to 52 weeks period. | 429 |
| Eluxadoline 100 mg Eluxadoline 100 mg tablets, orally, twice daily for up to 52 weeks period. | 426 |
| Placebo Eluxadoline placebo matching tablets, orally, twice daily for up to 52 weeks period. | 427 |
| Total | 1,282 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 36 | 45 | 16 |
| Overall Study | Lost to Follow-up | 25 | 23 | 16 |
| Overall Study | Physician decision: lack of efficacy | 2 | 3 | 7 |
| Overall Study | Physician decision: other | 11 | 14 | 16 |
| Overall Study | Protocol Violation | 3 | 4 | 4 |
| Overall Study | Randomized and never dispensed drug | 0 | 1 | 0 |
| Overall Study | Sponsor decision | 1 | 0 | 3 |
| Overall Study | Voluntarily withdrew | 94 | 79 | 96 |
Baseline characteristics
| Characteristic | Eluxadoline 100 mg | Placebo | Eluxadoline 75 mg | Total |
|---|---|---|---|---|
| Age, Continuous | 44.4 years STANDARD_DEVIATION 13.91 | 45.8 years STANDARD_DEVIATION 14.1 | 44.5 years STANDARD_DEVIATION 13.18 | 44.9 years STANDARD_DEVIATION 13.74 |
| Age, Customized 18-40 years | 166 Participants | 159 Participants | 173 Participants | 498 Participants |
| Age, Customized 41-64 years | 225 Participants | 217 Participants | 227 Participants | 669 Participants |
| Age, Customized ≥65 years | 35 Participants | 51 Participants | 29 Participants | 115 Participants |
| Body Mass Index (BMI) | 31.22 kg/m^2 STANDARD_DEVIATION 7.858 | 30.63 kg/m^2 STANDARD_DEVIATION 7.253 | 30.70 kg/m^2 STANDARD_DEVIATION 7.421 | 30.85 kg/m^2 STANDARD_DEVIATION 7.513 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 2 Participants | 1 Participants | 1 Participants | 4 Participants |
| Race/Ethnicity, Customized Asian | 3 Participants | 4 Participants | 3 Participants | 10 Participants |
| Race/Ethnicity, Customized Black | 48 Participants | 46 Participants | 46 Participants | 140 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 117 Participants | 125 Participants | 119 Participants | 361 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 309 Participants | 302 Participants | 310 Participants | 921 Participants |
| Race/Ethnicity, Customized Other | 4 Participants | 6 Participants | 5 Participants | 15 Participants |
| Race/Ethnicity, Customized White | 368 Participants | 370 Participants | 374 Participants | 1112 Participants |
| Sex: Female, Male Female | 283 Participants | 277 Participants | 278 Participants | 838 Participants |
| Sex: Female, Male Male | 143 Participants | 150 Participants | 151 Participants | 444 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 428 | 0 / 479 | 0 / 427 |
| other Total, other adverse events | 84 / 428 | 89 / 479 | 47 / 427 |
| serious Total, serious adverse events | 25 / 428 | 27 / 479 | 16 / 427 |
Outcome results
Primary
Percentage of Participants Who Were Composite Responders Based on Improvements From Baseline in Daily Worst Abdominal Pain And Daily Stool Consistency Scores
Composite responders were defined as a participant who met the daily response criteria for at least 50% of the days with diary entries during the interval of interest. A participant must had met both of the following criteria on a given day to be a daily responder: 1) Daily pain response: worst abdominal pain scores in the past 24 hours improved by ≥30% compared to baseline (average of daily worst abdominal pain the week prior to randomization). 2) Daily stool consistency response: Bristol Stool Scale (BSS) score \<5 (ie, score of 1, 2, 3, or 4) or the absence of a bowel movement if accompanied by ≥30% improvement in worst abdominal pain compared to baseline pain. Bristol stool scale was defined as 7-point Scale in which a score of 1 = separate hard lumps, 2 = sausage shaped but lumpy, 3 = sausage-like with cracks on the surface, 4 = sausage-like but smooth and soft, 5 = soft blobs with clear cut edges, 6 = fluffy pieces with ragged edges, and 7 = watery with no solid pieces.
Time frame: Up to 12 Weeks
Population: Intent to Treat (ITT) analysis set included all participants who were randomized into a treatment group and presents data for participants according to their randomization assignment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Eluxadoline 75 mg | Percentage of Participants Who Were Composite Responders Based on Improvements From Baseline in Daily Worst Abdominal Pain And Daily Stool Consistency Scores | 23.9 percentage of participants |
| Eluxadoline 100 mg | Percentage of Participants Who Were Composite Responders Based on Improvements From Baseline in Daily Worst Abdominal Pain And Daily Stool Consistency Scores | 25.1 percentage of participants |
| Placebo | Percentage of Participants Who Were Composite Responders Based on Improvements From Baseline in Daily Worst Abdominal Pain And Daily Stool Consistency Scores | 17.1 percentage of participants |
Comparison: The family-wise error rate was controlled by Bonferroni adjustment for each active dose versus placebo.p-value: 0.014Chi-square test statistic
Comparison: The family-wise error rate was controlled by Bonferroni adjustment for each active dose versus placebo.p-value: 0.004Chi-square test statistic
Secondary
Change From Baseline in Daily Abdominal Bloating Scores
Symptoms of abdominal bloating were recorded on a 0 to 10 scale, where 0 corresponded to no bloating and 10 corresponded to worst imaginable bloating. A negative change from Baseline indicates the bloating decreased.
Time frame: Baseline, Weeks 4, 12 and 26
Population: Intent to Treat (ITT) analysis set included all participants who were randomized into a treatment group and presents data for participants according to their randomization assignment. Here, number analyzed is the participants who were evaluable at specific time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eluxadoline 75 mg | Change From Baseline in Daily Abdominal Bloating Scores | Change at Week 12 | -2.42 score on a scale | Standard Deviation 2.616 |
| Eluxadoline 75 mg | Change From Baseline in Daily Abdominal Bloating Scores | Change at Week 4 | -1.84 score on a scale | Standard Deviation 2.303 |
| Eluxadoline 75 mg | Change From Baseline in Daily Abdominal Bloating Scores | Change at Week 26 | -2.76 score on a scale | Standard Deviation 2.823 |
| Eluxadoline 100 mg | Change From Baseline in Daily Abdominal Bloating Scores | Change at Week 12 | -2.49 score on a scale | Standard Deviation 2.533 |
| Eluxadoline 100 mg | Change From Baseline in Daily Abdominal Bloating Scores | Change at Week 4 | -2.03 score on a scale | Standard Deviation 2.333 |
| Eluxadoline 100 mg | Change From Baseline in Daily Abdominal Bloating Scores | Change at Week 26 | -2.94 score on a scale | Standard Deviation 2.576 |
| Placebo | Change From Baseline in Daily Abdominal Bloating Scores | Change at Week 4 | -1.72 score on a scale | Standard Deviation 2.303 |
| Placebo | Change From Baseline in Daily Abdominal Bloating Scores | Change at Week 26 | -2.47 score on a scale | Standard Deviation 2.562 |
| Placebo | Change From Baseline in Daily Abdominal Bloating Scores | Change at Week 12 | -2.16 score on a scale | Standard Deviation 2.544 |
Secondary
Change From Baseline in Daily Abdominal Discomfort Scores
Symptoms of abdominal discomfort were recorded on a 0 to 10 scale, where 0 corresponded to no discomfort and 10 corresponded to worst imaginable discomfort. A negative change from Baseline indicates the discomfort decreased.
Time frame: Baseline, Weeks 4, 12 and 26
Population: Intent to Treat (ITT) analysis set included all participants who were randomized into a treatment group and presents data for participants according to their randomization assignment. Here, number analyzed is the participants who were evaluable at specific time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eluxadoline 75 mg | Change From Baseline in Daily Abdominal Discomfort Scores | Change at Week 12 | -2.75 score on a scale | Standard Deviation 2.534 |
| Eluxadoline 75 mg | Change From Baseline in Daily Abdominal Discomfort Scores | Change at Week 4 | -2.24 score on a scale | Standard Deviation 2.204 |
| Eluxadoline 75 mg | Change From Baseline in Daily Abdominal Discomfort Scores | Change at Week 26 | -3.27 score on a scale | Standard Deviation 2.578 |
| Eluxadoline 100 mg | Change From Baseline in Daily Abdominal Discomfort Scores | Change at Week 12 | -2.97 score on a scale | Standard Deviation 2.526 |
| Eluxadoline 100 mg | Change From Baseline in Daily Abdominal Discomfort Scores | Change at Week 4 | -2.41 score on a scale | Standard Deviation 2.326 |
| Eluxadoline 100 mg | Change From Baseline in Daily Abdominal Discomfort Scores | Change at Week 26 | -3.52 score on a scale | Standard Deviation 2.543 |
| Placebo | Change From Baseline in Daily Abdominal Discomfort Scores | Change at Week 4 | -2.01 score on a scale | Standard Deviation 2.156 |
| Placebo | Change From Baseline in Daily Abdominal Discomfort Scores | Change at Week 26 | -3.00 score on a scale | Standard Deviation 2.579 |
| Placebo | Change From Baseline in Daily Abdominal Discomfort Scores | Change at Week 12 | -2.61 score on a scale | Standard Deviation 2.444 |
Secondary
Change From Baseline in IBS-QoL Total Scores
The IBS-QoL consists of 34 items each with a 5-point response scale, where 1 generally represents better responses on items and 5 represents worse responses. 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 that quality of life improved.
Time frame: Baseline, Weeks 4, 8, 12, 18, 26, 36, 44, and 52/EOT
Population: Intent to Treat (ITT) analysis set included all participants who were randomized into a treatment group and presents data for participants according to their randomization assignment. Here, number analyzed is the participants who were evaluable at specific time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eluxadoline 75 mg | Change From Baseline in IBS-QoL Total Scores | Change at Week 4 | 16.49 score on a scale | Standard Deviation 20.693 |
| Eluxadoline 75 mg | Change From Baseline in IBS-QoL Total Scores | Change at Week 8 | 19.88 score on a scale | Standard Deviation 21.855 |
| Eluxadoline 75 mg | Change From Baseline in IBS-QoL Total Scores | Change at Week 12 | 20.26 score on a scale | Standard Deviation 23.412 |
| Eluxadoline 75 mg | Change From Baseline in IBS-QoL Total Scores | Change at Week 18 | 23.09 score on a scale | Standard Deviation 23.846 |
| Eluxadoline 75 mg | Change From Baseline in IBS-QoL Total Scores | Change at Week 26 | 25.28 score on a scale | Standard Deviation 23.679 |
| Eluxadoline 75 mg | Change From Baseline in IBS-QoL Total Scores | Change at Week 36 | 25.37 score on a scale | Standard Deviation 24.603 |
| Eluxadoline 75 mg | Change From Baseline in IBS-QoL Total Scores | Change at Week 44 | 25.13 score on a scale | Standard Deviation 24.948 |
| Eluxadoline 75 mg | Change From Baseline in IBS-QoL Total Scores | Change at Week 52/EOT | 23.30 score on a scale | Standard Deviation 23.959 |
| Eluxadoline 100 mg | Change From Baseline in IBS-QoL Total Scores | Change at Week 12 | 22.76 score on a scale | Standard Deviation 22.592 |
| Eluxadoline 100 mg | Change From Baseline in IBS-QoL Total Scores | Change at Week 44 | 26.64 score on a scale | Standard Deviation 25.017 |
| Eluxadoline 100 mg | Change From Baseline in IBS-QoL Total Scores | Change at Week 18 | 24.18 score on a scale | Standard Deviation 23.025 |
| Eluxadoline 100 mg | Change From Baseline in IBS-QoL Total Scores | Change at Week 26 | 25.80 score on a scale | Standard Deviation 23.998 |
| Eluxadoline 100 mg | Change From Baseline in IBS-QoL Total Scores | Change at Week 36 | 27.18 score on a scale | Standard Deviation 24.201 |
| Eluxadoline 100 mg | Change From Baseline in IBS-QoL Total Scores | Change at Week 4 | 17.86 score on a scale | Standard Deviation 20.191 |
| Eluxadoline 100 mg | Change From Baseline in IBS-QoL Total Scores | Change at Week 8 | 21.08 score on a scale | Standard Deviation 21.347 |
| Eluxadoline 100 mg | Change From Baseline in IBS-QoL Total Scores | Change at Week 52/EOT | 25.86 score on a scale | Standard Deviation 23.854 |
| Placebo | Change From Baseline in IBS-QoL Total Scores | Change at Week 12 | 17.76 score on a scale | Standard Deviation 21.523 |
| Placebo | Change From Baseline in IBS-QoL Total Scores | Change at Week 8 | 15.76 score on a scale | Standard Deviation 19.398 |
| Placebo | Change From Baseline in IBS-QoL Total Scores | Change at Week 4 | 13.25 score on a scale | Standard Deviation 18.475 |
| Placebo | Change From Baseline in IBS-QoL Total Scores | Change at Week 18 | 19.80 score on a scale | Standard Deviation 22.368 |
| Placebo | Change From Baseline in IBS-QoL Total Scores | Change at Week 44 | 21.77 score on a scale | Standard Deviation 23.977 |
| Placebo | Change From Baseline in IBS-QoL Total Scores | Change at Week 36 | 22.64 score on a scale | Standard Deviation 23.414 |
| Placebo | Change From Baseline in IBS-QoL Total Scores | Change at Week 26 | 20.62 score on a scale | Standard Deviation 22.306 |
| Placebo | Change From Baseline in IBS-QoL Total Scores | Change at Week 52/EOT | 20.66 score on a scale | Standard Deviation 23.956 |
Secondary
IBS-QoL Total Scores
The IBS-QoL consists of 34 items each with a 5-point response scale, where 1 generally represents better responses on items and 5 represents worse responses. 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.
Time frame: Weeks 4, 8, 12, 18, 26, 36, 44, and 52 (EOT)
Population: Intent to Treat (ITT) analysis set included all participants who were randomized into a treatment group and presents data for participants according to their randomization assignment. Here, number analyzed is the participants who were evaluable at specific time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eluxadoline 75 mg | IBS-QoL Total Scores | Responders at Week 8 | 66.22 score on a scale | Standard Deviation 23.919 |
| Eluxadoline 75 mg | IBS-QoL Total Scores | Responders at Week 12 | 66.80 score on a scale | Standard Deviation 24.131 |
| Eluxadoline 75 mg | IBS-QoL Total Scores | Responders at Week 4 | 62.37 score on a scale | Standard Deviation 23.747 |
| Eluxadoline 75 mg | IBS-QoL Total Scores | Responders at Week 18 | 68.75 score on a scale | Standard Deviation 23.902 |
| Eluxadoline 75 mg | IBS-QoL Total Scores | Responders at Week 26 | 70.74 score on a scale | Standard Deviation 23.312 |
| Eluxadoline 75 mg | IBS-QoL Total Scores | Responders at Week 36 | 70.53 score on a scale | Standard Deviation 23.043 |
| Eluxadoline 75 mg | IBS-QoL Total Scores | Responders at Week 44 | 70.30 score on a scale | Standard Deviation 24.408 |
| Eluxadoline 75 mg | IBS-QoL Total Scores | Responders at Week 52/EOT | 68.85 score on a scale | Standard Deviation 24.754 |
| Eluxadoline 100 mg | IBS-QoL Total Scores | Responders at Week 52/EOT | 71.02 score on a scale | Standard Deviation 24.294 |
| Eluxadoline 100 mg | IBS-QoL Total Scores | Responders at Week 44 | 72.15 score on a scale | Standard Deviation 24.398 |
| Eluxadoline 100 mg | IBS-QoL Total Scores | Responders at Week 18 | 70.05 score on a scale | Standard Deviation 23.662 |
| Eluxadoline 100 mg | IBS-QoL Total Scores | Responders at Week 26 | 71.34 score on a scale | Standard Deviation 23.106 |
| Eluxadoline 100 mg | IBS-QoL Total Scores | Responders at Week 36 | 72.37 score on a scale | Standard Deviation 23.246 |
| Eluxadoline 100 mg | IBS-QoL Total Scores | Responders at Week 8 | 67.73 score on a scale | Standard Deviation 23.421 |
| Eluxadoline 100 mg | IBS-QoL Total Scores | Responders at Week 12 | 68.93 score on a scale | Standard Deviation 23.938 |
| Eluxadoline 100 mg | IBS-QoL Total Scores | Responders at Week 4 | 64.34 score on a scale | Standard Deviation 24.049 |
| Placebo | IBS-QoL Total Scores | Responders at Week 4 | 57.13 score on a scale | Standard Deviation 24.318 |
| Placebo | IBS-QoL Total Scores | Responders at Week 12 | 61.72 score on a scale | Standard Deviation 25.545 |
| Placebo | IBS-QoL Total Scores | Responders at Week 8 | 59.46 score on a scale | Standard Deviation 24.323 |
| Placebo | IBS-QoL Total Scores | Responders at Week 18 | 63.60 score on a scale | Standard Deviation 24.618 |
| Placebo | IBS-QoL Total Scores | Responders at Week 44 | 65.59 score on a scale | Standard Deviation 25.045 |
| Placebo | IBS-QoL Total Scores | Responders at Week 36 | 66.47 score on a scale | Standard Deviation 24.034 |
| Placebo | IBS-QoL Total Scores | Responders at Week 26 | 64.83 score on a scale | Standard Deviation 24.38 |
| Placebo | IBS-QoL Total Scores | Responders at Week 52/EOT | 63.93 score on a scale | Standard Deviation 26.359 |
Secondary
Number of Bowel Incontinence Episodes
Participants recorded the number of incontinence episodes over 24 hours daily throughout the treatment.
Time frame: Weeks 4, 12 and 26
Population: Intent to Treat (ITT) analysis set included all participants who were randomized into a treatment group and presents data for participants according to their randomization assignment. Here, number analyzed is the participants who were evaluable at specific time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eluxadoline 75 mg | Number of Bowel Incontinence Episodes | Week 12 | 0.63 incontinence episodes | Standard Deviation 1.542 |
| Eluxadoline 75 mg | Number of Bowel Incontinence Episodes | Week 4 | 0.74 incontinence episodes | Standard Deviation 1.603 |
| Eluxadoline 75 mg | Number of Bowel Incontinence Episodes | Week 26 | 0.46 incontinence episodes | Standard Deviation 1.298 |
| Eluxadoline 100 mg | Number of Bowel Incontinence Episodes | Week 12 | 0.71 incontinence episodes | Standard Deviation 1.663 |
| Eluxadoline 100 mg | Number of Bowel Incontinence Episodes | Week 4 | 0.72 incontinence episodes | Standard Deviation 1.534 |
| Eluxadoline 100 mg | Number of Bowel Incontinence Episodes | Week 26 | 0.58 incontinence episodes | Standard Deviation 1.358 |
| Placebo | Number of Bowel Incontinence Episodes | Week 4 | 0.93 incontinence episodes | Standard Deviation 2.14 |
| Placebo | Number of Bowel Incontinence Episodes | Week 26 | 0.69 incontinence episodes | Standard Deviation 1.5 |
| Placebo | Number of Bowel Incontinence Episodes | Week 12 | 0.94 incontinence episodes | Standard Deviation 3.612 |
Secondary
Number of Bowel Incontinence Free Days
An incontinence free day was one where the participant reports zero incontinence episodes. The number of incontinence free days for a participant was assessed each week based on the number of reported days.
Time frame: Weeks 4, 12 and 26
Population: Intent to Treat (ITT) analysis set included all participants who were randomized into a treatment group and presents data for participants according to their randomization assignment. Here, number analyzed is the participants who were evaluable at specific time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eluxadoline 75 mg | Number of Bowel Incontinence Free Days | Week 12 | 4.96 days | Standard Deviation 2.672 |
| Eluxadoline 75 mg | Number of Bowel Incontinence Free Days | Week 4 | 4.83 days | Standard Deviation 2.745 |
| Eluxadoline 75 mg | Number of Bowel Incontinence Free Days | Week 26 | 4.39 days | Standard Deviation 2.465 |
| Eluxadoline 100 mg | Number of Bowel Incontinence Free Days | Week 12 | 4.79 days | Standard Deviation 2.671 |
| Eluxadoline 100 mg | Number of Bowel Incontinence Free Days | Week 4 | 4.95 days | Standard Deviation 2.618 |
| Eluxadoline 100 mg | Number of Bowel Incontinence Free Days | Week 26 | 4.35 days | Standard Deviation 2.449 |
| Placebo | Number of Bowel Incontinence Free Days | Week 4 | 4.63 days | Standard Deviation 2.741 |
| Placebo | Number of Bowel Incontinence Free Days | Week 26 | 4.00 days | Standard Deviation 2.539 |
| Placebo | Number of Bowel Incontinence Free Days | Week 12 | 4.64 days | Standard Deviation 2.704 |
Secondary
Number of Bowel Movements Per Day
Participants recorded the number of bowel movements over 24 hours daily throughout the treatment.
Time frame: Weeks 4, 12 and 26
Population: Intent to Treat (ITT) analysis set included all participants who were randomized into a treatment group and presents data for participants according to their randomization assignment. Here, number analyzed is the participants who were evaluable at specific time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eluxadoline 75 mg | Number of Bowel Movements Per Day | Week 12 | 3.12 bowel movements per day | Standard Deviation 2.143 |
| Eluxadoline 75 mg | Number of Bowel Movements Per Day | Week 4 | 3.20 bowel movements per day | Standard Deviation 2.09 |
| Eluxadoline 75 mg | Number of Bowel Movements Per Day | Week 26 | 2.83 bowel movements per day | Standard Deviation 2.158 |
| Eluxadoline 100 mg | Number of Bowel Movements Per Day | Week 12 | 3.09 bowel movements per day | Standard Deviation 2.318 |
| Eluxadoline 100 mg | Number of Bowel Movements Per Day | Week 4 | 3.20 bowel movements per day | Standard Deviation 2.236 |
| Eluxadoline 100 mg | Number of Bowel Movements Per Day | Week 26 | 2.79 bowel movements per day | Standard Deviation 2.27 |
| Placebo | Number of Bowel Movements Per Day | Week 4 | 3.72 bowel movements per day | Standard Deviation 2.1 |
| Placebo | Number of Bowel Movements Per Day | Week 26 | 3.12 bowel movements per day | Standard Deviation 1.831 |
| Placebo | Number of Bowel Movements Per Day | Week 12 | 3.44 bowel movements per day | Standard Deviation 1.987 |
Secondary
Number of Urgency Episodes Per Day
Participants recorded the number of urgency episodes over 24 hours daily throughout the treatment.
Time frame: Weeks 4, 12 and 26
Population: Intent to Treat (ITT) analysis set included all participants who were randomized into a treatment group and presents data for participants according to their randomization assignment. Here, number analyzed is the participants who were evaluable at specific time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eluxadoline 75 mg | Number of Urgency Episodes Per Day | Week 12 | 1.55 episodes per day | Standard Deviation 1.777 |
| Eluxadoline 75 mg | Number of Urgency Episodes Per Day | Week 4 | 1.75 episodes per day | Standard Deviation 1.84 |
| Eluxadoline 75 mg | Number of Urgency Episodes Per Day | Week 26 | 1.25 episodes per day | Standard Deviation 1.773 |
| Eluxadoline 100 mg | Number of Urgency Episodes Per Day | Week 12 | 1.60 episodes per day | Standard Deviation 1.995 |
| Eluxadoline 100 mg | Number of Urgency Episodes Per Day | Week 4 | 1.74 episodes per day | Standard Deviation 1.879 |
| Eluxadoline 100 mg | Number of Urgency Episodes Per Day | Week 26 | 1.45 episodes per day | Standard Deviation 2.113 |
| Placebo | Number of Urgency Episodes Per Day | Week 4 | 2.19 episodes per day | Standard Deviation 2.082 |
| Placebo | Number of Urgency Episodes Per Day | Week 26 | 1.55 episodes per day | Standard Deviation 1.853 |
| Placebo | Number of Urgency Episodes Per Day | Week 12 | 1.81 episodes per day | Standard Deviation 1.883 |
Secondary
Percentage of Participants Who Were Composite Responders Based on Improvements From Baseline in Daily Worst Abdominal Pain And Daily Stool Consistency Scores
Composite responders were defined as a participant who met the daily response criteria for at least 50% of the days with diary entries during the interval of interest. A participant must had met both of the following criteria on a given day to be a daily responder: 1) Daily pain response: worst abdominal pain scores in the past 24 hours improved by ≥30% compared to baseline (average of daily worst abdominal pain the week prior to randomization). 2) Daily stool consistency response: Bristol Stool Scale (BSS) score \<5 (ie, score of 1, 2, 3, or 4) or the absence of a bowel movement if accompanied by ≥30% improvement in worst abdominal pain compared to baseline pain. Bristol stool scale was defined as 7-point Scale in which a score of 1 = separate hard lumps, 2 = sausage shaped but lumpy, 3 = sausage-like with cracks on the surface, 4 = sausage-like but smooth and soft, 5 = soft blobs with clear cut edges, 6 = fluffy pieces with ragged edges, and 7 = watery with no solid pieces.
Time frame: Up to 26 Weeks
Population: ITT analysis set included all participants who were randomized into a treatment group and presents data for participants according to their randomization assignment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Eluxadoline 75 mg | Percentage of Participants Who Were Composite Responders Based on Improvements From Baseline in Daily Worst Abdominal Pain And Daily Stool Consistency Scores | 23.4 percentage of participants |
| Eluxadoline 100 mg | Percentage of Participants Who Were Composite Responders Based on Improvements From Baseline in Daily Worst Abdominal Pain And Daily Stool Consistency Scores | 29.3 percentage of participants |
| Placebo | Percentage of Participants Who Were Composite Responders Based on Improvements From Baseline in Daily Worst Abdominal Pain And Daily Stool Consistency Scores | 19.0 percentage of participants |
Comparison: The family-wise error rate was controlled by Bonferroni adjustment for each active dose versus placebo.p-value: 0.112Chi-square test statistic
Comparison: The family-wise error rate was controlled by Bonferroni adjustment for each active dose versus placebo.p-value: <0.001Chi-square test statistic
Secondary
Percentage of Participants Who Were Pain Responders In Daily Worst Abdominal Pain Scores by Intervals
Pain responders were defined as participants who met the daily pain response criteria (ie, the worst abdominal pain score in the past 24 hours improved by ≥30% compared to baseline) for at least 50% of days with diary entries during each interval. A participant must have had a minimum of 20 days of diary entries over any 4-week interval, a minimum of 60 days of diary entries over the 12-week interval, and a minimum of 110 days of diary entries over the 26-week interval to be a responder.
Time frame: 12-week interval (Weeks 1-12), 26-week interval (Weeks 1-26), and 4-week interval (Weeks 1-4, 5-8, 9-12, 13-16, 17-20, and 21-24)
Population: ITT analysis set included all participants who were randomized into a treatment group and presents data for participants according to their randomization assignment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Eluxadoline 75 mg | Percentage of Participants Who Were Pain Responders In Daily Worst Abdominal Pain Scores by Intervals | Responders during Weeks 1-12 | 42.4 percentage of participants |
| Eluxadoline 75 mg | Percentage of Participants Who Were Pain Responders In Daily Worst Abdominal Pain Scores by Intervals | Responders during Weeks 1-26 | 45.2 percentage of participants |
| Eluxadoline 75 mg | Percentage of Participants Who Were Pain Responders In Daily Worst Abdominal Pain Scores by Intervals | Responders during Weeks 1-4 | 40.5 percentage of participants |
| Eluxadoline 75 mg | Percentage of Participants Who Were Pain Responders In Daily Worst Abdominal Pain Scores by Intervals | Responders during Weeks 5-8 | 44.5 percentage of participants |
| Eluxadoline 75 mg | Percentage of Participants Who Were Pain Responders In Daily Worst Abdominal Pain Scores by Intervals | Responders during Weeks 9-12 | 44.5 percentage of participants |
| Eluxadoline 75 mg | Percentage of Participants Who Were Pain Responders In Daily Worst Abdominal Pain Scores by Intervals | Responders during Weeks 13-16 | 44.3 percentage of participants |
| Eluxadoline 75 mg | Percentage of Participants Who Were Pain Responders In Daily Worst Abdominal Pain Scores by Intervals | Responders during Weeks 17-20 | 44.7 percentage of participants |
| Eluxadoline 75 mg | Percentage of Participants Who Were Pain Responders In Daily Worst Abdominal Pain Scores by Intervals | Responders during Weeks 21-24 | 44.7 percentage of participants |
| Eluxadoline 100 mg | Percentage of Participants Who Were Pain Responders In Daily Worst Abdominal Pain Scores by Intervals | Responders during Weeks 1-4 | 44.4 percentage of participants |
| Eluxadoline 100 mg | Percentage of Participants Who Were Pain Responders In Daily Worst Abdominal Pain Scores by Intervals | Responders during Weeks 17-20 | 43.2 percentage of participants |
| Eluxadoline 100 mg | Percentage of Participants Who Were Pain Responders In Daily Worst Abdominal Pain Scores by Intervals | Responders during Weeks 5-8 | 47.2 percentage of participants |
| Eluxadoline 100 mg | Percentage of Participants Who Were Pain Responders In Daily Worst Abdominal Pain Scores by Intervals | Responders during Weeks 9-12 | 45.8 percentage of participants |
| Eluxadoline 100 mg | Percentage of Participants Who Were Pain Responders In Daily Worst Abdominal Pain Scores by Intervals | Responders during Weeks 13-16 | 44.1 percentage of participants |
| Eluxadoline 100 mg | Percentage of Participants Who Were Pain Responders In Daily Worst Abdominal Pain Scores by Intervals | Responders during Weeks 1-12 | 43.2 percentage of participants |
| Eluxadoline 100 mg | Percentage of Participants Who Were Pain Responders In Daily Worst Abdominal Pain Scores by Intervals | Responders during Weeks 1-26 | 46.5 percentage of participants |
| Eluxadoline 100 mg | Percentage of Participants Who Were Pain Responders In Daily Worst Abdominal Pain Scores by Intervals | Responders during Weeks 21-24 | 42.0 percentage of participants |
| Placebo | Percentage of Participants Who Were Pain Responders In Daily Worst Abdominal Pain Scores by Intervals | Responders during Weeks 1-4 | 37.5 percentage of participants |
| Placebo | Percentage of Participants Who Were Pain Responders In Daily Worst Abdominal Pain Scores by Intervals | Responders during Weeks 1-26 | 43.3 percentage of participants |
| Placebo | Percentage of Participants Who Were Pain Responders In Daily Worst Abdominal Pain Scores by Intervals | Responders during Weeks 1-12 | 39.6 percentage of participants |
| Placebo | Percentage of Participants Who Were Pain Responders In Daily Worst Abdominal Pain Scores by Intervals | Responders during Weeks 5-8 | 45.4 percentage of participants |
| Placebo | Percentage of Participants Who Were Pain Responders In Daily Worst Abdominal Pain Scores by Intervals | Responders during Weeks 17-20 | 41.5 percentage of participants |
| Placebo | Percentage of Participants Who Were Pain Responders In Daily Worst Abdominal Pain Scores by Intervals | Responders during Weeks 13-16 | 45.4 percentage of participants |
| Placebo | Percentage of Participants Who Were Pain Responders In Daily Worst Abdominal Pain Scores by Intervals | Responders during Weeks 9-12 | 43.8 percentage of participants |
| Placebo | Percentage of Participants Who Were Pain Responders In Daily Worst Abdominal Pain Scores by Intervals | Responders during Weeks 21-24 | 38.4 percentage of participants |
Secondary
Percentage of Participants Who Were Responders In Daily Stool Consistency Scores by Intervals
Stool consistency responders: participants who met daily stool consistency response criterion (ie,score of 1, 2, 3, or 4 or absence of bowel movement if accompanied by ≥30% improvement in worst abdominal pain compared to baseline pain) for at least 50% of days with diary entries during each interval. BSS was defined as 7-point Scale in which score of 1= separate hard lumps, 2= sausage shaped but lumpy, 3= sausage-like with cracks on the surface, 4= sausage-like but smooth and soft, 5= soft blobs with clear cut edges, 6= fluffy pieces with ragged edges, and 7= watery with no solid pieces. A participant must have had a minimum of 20 days of diary entries over any 4-week interval, a minimum of 60 days of diary entries over 12-week interval, and a minimum of 110 days of diary entries over 26-week interval to be a responder.
Time frame: 12-week interval (Weeks 1-12), 26-week interval (Weeks 1-26), and 4-week interval (Weeks 1-4, 5-8, 9-12, 13-16, 17-20, and 21-24)
Population: ITT analysis set included all participants who were randomized into a treatment group and presents data for participants according to their randomization assignment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Eluxadoline 75 mg | Percentage of Participants Who Were Responders In Daily Stool Consistency Scores by Intervals | Responders during Weeks 1-12 | 30.0 percentage of participants |
| Eluxadoline 75 mg | Percentage of Participants Who Were Responders In Daily Stool Consistency Scores by Intervals | Responders during Weeks 1-26 | 28.1 percentage of participants |
| Eluxadoline 75 mg | Percentage of Participants Who Were Responders In Daily Stool Consistency Scores by Intervals | Responders during Weeks 1-4 | 28.8 percentage of participants |
| Eluxadoline 75 mg | Percentage of Participants Who Were Responders In Daily Stool Consistency Scores by Intervals | Responders during Weeks 5-8 | 31.1 percentage of participants |
| Eluxadoline 75 mg | Percentage of Participants Who Were Responders In Daily Stool Consistency Scores by Intervals | Responders during Weeks 9-12 | 29.0 percentage of participants |
| Eluxadoline 75 mg | Percentage of Participants Who Were Responders In Daily Stool Consistency Scores by Intervals | Responders during Weeks 13-16 | 27.6 percentage of participants |
| Eluxadoline 75 mg | Percentage of Participants Who Were Responders In Daily Stool Consistency Scores by Intervals | Responders during Weeks 17-20 | 31.9 percentage of participants |
| Eluxadoline 75 mg | Percentage of Participants Who Were Responders In Daily Stool Consistency Scores by Intervals | Responders during Weeks 21-24 | 30.2 percentage of participants |
| Eluxadoline 100 mg | Percentage of Participants Who Were Responders In Daily Stool Consistency Scores by Intervals | Responders during Weeks 1-4 | 31.5 percentage of participants |
| Eluxadoline 100 mg | Percentage of Participants Who Were Responders In Daily Stool Consistency Scores by Intervals | Responders during Weeks 17-20 | 31.5 percentage of participants |
| Eluxadoline 100 mg | Percentage of Participants Who Were Responders In Daily Stool Consistency Scores by Intervals | Responders during Weeks 5-8 | 35.2 percentage of participants |
| Eluxadoline 100 mg | Percentage of Participants Who Were Responders In Daily Stool Consistency Scores by Intervals | Responders during Weeks 9-12 | 35.2 percentage of participants |
| Eluxadoline 100 mg | Percentage of Participants Who Were Responders In Daily Stool Consistency Scores by Intervals | Responders during Weeks 13-16 | 32.9 percentage of participants |
| Eluxadoline 100 mg | Percentage of Participants Who Were Responders In Daily Stool Consistency Scores by Intervals | Responders during Weeks 1-12 | 34.3 percentage of participants |
| Eluxadoline 100 mg | Percentage of Participants Who Were Responders In Daily Stool Consistency Scores by Intervals | Responders during Weeks 1-26 | 34.0 percentage of participants |
| Eluxadoline 100 mg | Percentage of Participants Who Were Responders In Daily Stool Consistency Scores by Intervals | Responders during Weeks 21-24 | 30.3 percentage of participants |
| Placebo | Percentage of Participants Who Were Responders In Daily Stool Consistency Scores by Intervals | Responders during Weeks 1-4 | 19.0 percentage of participants |
| Placebo | Percentage of Participants Who Were Responders In Daily Stool Consistency Scores by Intervals | Responders during Weeks 1-26 | 24.1 percentage of participants |
| Placebo | Percentage of Participants Who Were Responders In Daily Stool Consistency Scores by Intervals | Responders during Weeks 1-12 | 22.0 percentage of participants |
| Placebo | Percentage of Participants Who Were Responders In Daily Stool Consistency Scores by Intervals | Responders during Weeks 5-8 | 24.1 percentage of participants |
| Placebo | Percentage of Participants Who Were Responders In Daily Stool Consistency Scores by Intervals | Responders during Weeks 17-20 | 23.7 percentage of participants |
| Placebo | Percentage of Participants Who Were Responders In Daily Stool Consistency Scores by Intervals | Responders during Weeks 13-16 | 24.4 percentage of participants |
| Placebo | Percentage of Participants Who Were Responders In Daily Stool Consistency Scores by Intervals | Responders during Weeks 9-12 | 24.6 percentage of participants |
| Placebo | Percentage of Participants Who Were Responders In Daily Stool Consistency Scores by Intervals | Responders during Weeks 21-24 | 24.4 percentage of participants |
Secondary
Percentage of Participants Who Were Responders In Irritable Bowel Syndrome, Diarrhea Predominant (IBS-d) Global Symptom Scale by Intervals
IBS-d global symptom responders were defined as those participants who met the daily IBS-d global symptom response criteria (ie, IBS-d global symptom score of 0 \[none\] or 1 \[mild\]; or a daily IBS-d global symptom score improved by ≥2.0 compared to the baseline average) for at least 50% of days with diary entries during each interval. IBS-d Global Symptom Scale was a 5 point scale, score ranging from 0 to 4. 0= no symptoms, 1= mild symptoms, 2= moderate symptoms, 3= severe symptoms and 4 = very severe symptoms. A participant must have had a minimum of 20 days of diary entries over any 4-week interval, a minimum of 60 days of diary entries over the 12-week interval, and a minimum of 110 days of diary entries over the 26-week interval to be a responder.
Time frame: 12-week interval (Weeks 1-12), 26-week interval (Weeks 1-26), and 4-week interval (Weeks 1-4, 5-8, 9-12, 13-16, 17-20, and 21-24)
Population: ITT analysis set included all participants who were randomized into a treatment group and presents data for participants according to their randomization assignment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Eluxadoline 75 mg | Percentage of Participants Who Were Responders In Irritable Bowel Syndrome, Diarrhea Predominant (IBS-d) Global Symptom Scale by Intervals | Responders during Weeks 1-12 | 35.1 percentage of participants |
| Eluxadoline 75 mg | Percentage of Participants Who Were Responders In Irritable Bowel Syndrome, Diarrhea Predominant (IBS-d) Global Symptom Scale by Intervals | Responders during Weeks 1-26 | 36.3 percentage of participants |
| Eluxadoline 75 mg | Percentage of Participants Who Were Responders In Irritable Bowel Syndrome, Diarrhea Predominant (IBS-d) Global Symptom Scale by Intervals | Responders during Weeks 1-4 | 32.6 percentage of participants |
| Eluxadoline 75 mg | Percentage of Participants Who Were Responders In Irritable Bowel Syndrome, Diarrhea Predominant (IBS-d) Global Symptom Scale by Intervals | Responders during Weeks 5-8 | 37.0 percentage of participants |
| Eluxadoline 75 mg | Percentage of Participants Who Were Responders In Irritable Bowel Syndrome, Diarrhea Predominant (IBS-d) Global Symptom Scale by Intervals | Responders during Weeks 9-12 | 35.6 percentage of participants |
| Eluxadoline 75 mg | Percentage of Participants Who Were Responders In Irritable Bowel Syndrome, Diarrhea Predominant (IBS-d) Global Symptom Scale by Intervals | Responders during Weeks 13-16 | 35.8 percentage of participants |
| Eluxadoline 75 mg | Percentage of Participants Who Were Responders In Irritable Bowel Syndrome, Diarrhea Predominant (IBS-d) Global Symptom Scale by Intervals | Responders during Weeks 17-20 | 37.5 percentage of participants |
| Eluxadoline 75 mg | Percentage of Participants Who Were Responders In Irritable Bowel Syndrome, Diarrhea Predominant (IBS-d) Global Symptom Scale by Intervals | Responders during Weeks 21-24 | 36.8 percentage of participants |
| Eluxadoline 100 mg | Percentage of Participants Who Were Responders In Irritable Bowel Syndrome, Diarrhea Predominant (IBS-d) Global Symptom Scale by Intervals | Responders during Weeks 1-4 | 31.9 percentage of participants |
| Eluxadoline 100 mg | Percentage of Participants Who Were Responders In Irritable Bowel Syndrome, Diarrhea Predominant (IBS-d) Global Symptom Scale by Intervals | Responders during Weeks 17-20 | 36.4 percentage of participants |
| Eluxadoline 100 mg | Percentage of Participants Who Were Responders In Irritable Bowel Syndrome, Diarrhea Predominant (IBS-d) Global Symptom Scale by Intervals | Responders during Weeks 5-8 | 38.7 percentage of participants |
| Eluxadoline 100 mg | Percentage of Participants Who Were Responders In Irritable Bowel Syndrome, Diarrhea Predominant (IBS-d) Global Symptom Scale by Intervals | Responders during Weeks 9-12 | 36.6 percentage of participants |
| Eluxadoline 100 mg | Percentage of Participants Who Were Responders In Irritable Bowel Syndrome, Diarrhea Predominant (IBS-d) Global Symptom Scale by Intervals | Responders during Weeks 13-16 | 35.9 percentage of participants |
| Eluxadoline 100 mg | Percentage of Participants Who Were Responders In Irritable Bowel Syndrome, Diarrhea Predominant (IBS-d) Global Symptom Scale by Intervals | Responders during Weeks 1-12 | 34.7 percentage of participants |
| Eluxadoline 100 mg | Percentage of Participants Who Were Responders In Irritable Bowel Syndrome, Diarrhea Predominant (IBS-d) Global Symptom Scale by Intervals | Responders during Weeks 1-26 | 37.1 percentage of participants |
| Eluxadoline 100 mg | Percentage of Participants Who Were Responders In Irritable Bowel Syndrome, Diarrhea Predominant (IBS-d) Global Symptom Scale by Intervals | Responders during Weeks 21-24 | 35.2 percentage of participants |
| Placebo | Percentage of Participants Who Were Responders In Irritable Bowel Syndrome, Diarrhea Predominant (IBS-d) Global Symptom Scale by Intervals | Responders during Weeks 1-4 | 26.9 percentage of participants |
| Placebo | Percentage of Participants Who Were Responders In Irritable Bowel Syndrome, Diarrhea Predominant (IBS-d) Global Symptom Scale by Intervals | Responders during Weeks 1-26 | 32.3 percentage of participants |
| Placebo | Percentage of Participants Who Were Responders In Irritable Bowel Syndrome, Diarrhea Predominant (IBS-d) Global Symptom Scale by Intervals | Responders during Weeks 1-12 | 28.8 percentage of participants |
| Placebo | Percentage of Participants Who Were Responders In Irritable Bowel Syndrome, Diarrhea Predominant (IBS-d) Global Symptom Scale by Intervals | Responders during Weeks 5-8 | 32.8 percentage of participants |
| Placebo | Percentage of Participants Who Were Responders In Irritable Bowel Syndrome, Diarrhea Predominant (IBS-d) Global Symptom Scale by Intervals | Responders during Weeks 17-20 | 33.3 percentage of participants |
| Placebo | Percentage of Participants Who Were Responders In Irritable Bowel Syndrome, Diarrhea Predominant (IBS-d) Global Symptom Scale by Intervals | Responders during Weeks 13-16 | 35.4 percentage of participants |
| Placebo | Percentage of Participants Who Were Responders In Irritable Bowel Syndrome, Diarrhea Predominant (IBS-d) Global Symptom Scale by Intervals | Responders during Weeks 9-12 | 34.0 percentage of participants |
| Placebo | Percentage of Participants Who Were Responders In Irritable Bowel Syndrome, Diarrhea Predominant (IBS-d) Global Symptom Scale by Intervals | Responders during Weeks 21-24 | 29.5 percentage of participants |
Secondary
Percentage of Participants Who Were Responders to the Irritable Bowel Syndrome Quality of Life Measure (IBS-QoL) Scale
IBS-QoL responders were defined as participants who achieved at least a 14-point improvement in IBS-QoL total score from baseline to the applicable visit. The IBS-QoL consists of 34 items each with a 5-point response scale, where 1 generally represents better responses on items and 5 represents worse responses. The individual responses to the answered items were summed and standardized for a total score and then transformed to a 0- to 100-point (0= worst; 100=better) scale for ease of interpretation.
Time frame: Weeks 4, 8, 12, 18, 26, 36, 44, and 52 (End of Treatment [EOT])
Population: ITT analysis set included all participants who were randomized into a treatment group and presents data for participants according to their randomization assignment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Eluxadoline 75 mg | Percentage of Participants Who Were Responders to the Irritable Bowel Syndrome Quality of Life Measure (IBS-QoL) Scale | Responders at Week 4 | 42.6 percentage of participants |
| Eluxadoline 75 mg | Percentage of Participants Who Were Responders to the Irritable Bowel Syndrome Quality of Life Measure (IBS-QoL) Scale | Responders at Week 8 | 43.8 percentage of participants |
| Eluxadoline 75 mg | Percentage of Participants Who Were Responders to the Irritable Bowel Syndrome Quality of Life Measure (IBS-QoL) Scale | Responders at Week 12 | 44.3 percentage of participants |
| Eluxadoline 75 mg | Percentage of Participants Who Were Responders to the Irritable Bowel Syndrome Quality of Life Measure (IBS-QoL) Scale | Responders at Week 18 | 44.5 percentage of participants |
| Eluxadoline 75 mg | Percentage of Participants Who Were Responders to the Irritable Bowel Syndrome Quality of Life Measure (IBS-QoL) Scale | Responders at Week 26 | 45.4 percentage of participants |
| Eluxadoline 75 mg | Percentage of Participants Who Were Responders to the Irritable Bowel Syndrome Quality of Life Measure (IBS-QoL) Scale | Responders at Week 36 | 41.0 percentage of participants |
| Eluxadoline 75 mg | Percentage of Participants Who Were Responders to the Irritable Bowel Syndrome Quality of Life Measure (IBS-QoL) Scale | Responders at Week 44 | 39.6 percentage of participants |
| Eluxadoline 75 mg | Percentage of Participants Who Were Responders to the Irritable Bowel Syndrome Quality of Life Measure (IBS-QoL) Scale | Responders at Week 52/EOT | 49.4 percentage of participants |
| Eluxadoline 100 mg | Percentage of Participants Who Were Responders to the Irritable Bowel Syndrome Quality of Life Measure (IBS-QoL) Scale | Responders at Week 12 | 48.1 percentage of participants |
| Eluxadoline 100 mg | Percentage of Participants Who Were Responders to the Irritable Bowel Syndrome Quality of Life Measure (IBS-QoL) Scale | Responders at Week 44 | 40.1 percentage of participants |
| Eluxadoline 100 mg | Percentage of Participants Who Were Responders to the Irritable Bowel Syndrome Quality of Life Measure (IBS-QoL) Scale | Responders at Week 18 | 45.1 percentage of participants |
| Eluxadoline 100 mg | Percentage of Participants Who Were Responders to the Irritable Bowel Syndrome Quality of Life Measure (IBS-QoL) Scale | Responders at Week 26 | 45.1 percentage of participants |
| Eluxadoline 100 mg | Percentage of Participants Who Were Responders to the Irritable Bowel Syndrome Quality of Life Measure (IBS-QoL) Scale | Responders at Week 36 | 43.2 percentage of participants |
| Eluxadoline 100 mg | Percentage of Participants Who Were Responders to the Irritable Bowel Syndrome Quality of Life Measure (IBS-QoL) Scale | Responders at Week 4 | 44.1 percentage of participants |
| Eluxadoline 100 mg | Percentage of Participants Who Were Responders to the Irritable Bowel Syndrome Quality of Life Measure (IBS-QoL) Scale | Responders at Week 8 | 49.8 percentage of participants |
| Eluxadoline 100 mg | Percentage of Participants Who Were Responders to the Irritable Bowel Syndrome Quality of Life Measure (IBS-QoL) Scale | Responders at Week 52/EOT | 54.9 percentage of participants |
| Placebo | Percentage of Participants Who Were Responders to the Irritable Bowel Syndrome Quality of Life Measure (IBS-QoL) Scale | Responders at Week 12 | 44.0 percentage of participants |
| Placebo | Percentage of Participants Who Were Responders to the Irritable Bowel Syndrome Quality of Life Measure (IBS-QoL) Scale | Responders at Week 8 | 41.7 percentage of participants |
| Placebo | Percentage of Participants Who Were Responders to the Irritable Bowel Syndrome Quality of Life Measure (IBS-QoL) Scale | Responders at Week 4 | 37.0 percentage of participants |
| Placebo | Percentage of Participants Who Were Responders to the Irritable Bowel Syndrome Quality of Life Measure (IBS-QoL) Scale | Responders at Week 18 | 43.3 percentage of participants |
| Placebo | Percentage of Participants Who Were Responders to the Irritable Bowel Syndrome Quality of Life Measure (IBS-QoL) Scale | Responders at Week 44 | 37.5 percentage of participants |
| Placebo | Percentage of Participants Who Were Responders to the Irritable Bowel Syndrome Quality of Life Measure (IBS-QoL) Scale | Responders at Week 36 | 39.6 percentage of participants |
| Placebo | Percentage of Participants Who Were Responders to the Irritable Bowel Syndrome Quality of Life Measure (IBS-QoL) Scale | Responders at Week 26 | 40.0 percentage of participants |
| Placebo | Percentage of Participants Who Were Responders to the Irritable Bowel Syndrome Quality of Life Measure (IBS-QoL) Scale | Responders at Week 52/EOT | 47.8 percentage of participants |
Secondary
Percentage of Participants With Irritable Bowel Syndrome - Adequate Relief (IBS-AR) Scale
Adequate relief of IBS symptoms was assessed once weekly by participants answering the IBS-AR item in the electronic diary. IBS-AR responders were defined as participants with a weekly response of Yes to adequate relief of their IBS symptoms for at least 50% of the total weeks during the interval. A participant must have had a positive response on ≥6 weeks for the 12-week interval and ≥13 weeks for the 26-week interval, regardless of diary compliance, to be a responder.
Time frame: 12-week interval (Weeks 1-12) and 26-week interval (Weeks 1-26)
Population: ITT analysis set included all participants who were randomized into a treatment group and presents data for participants according to their randomization assignment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Eluxadoline 75 mg | Percentage of Participants With Irritable Bowel Syndrome - Adequate Relief (IBS-AR) Scale | Responders during Weeks 1-12 | 52.9 percentage of participants |
| Eluxadoline 75 mg | Percentage of Participants With Irritable Bowel Syndrome - Adequate Relief (IBS-AR) Scale | Responders during Weeks 1-26 | 45.7 percentage of participants |
| Eluxadoline 100 mg | Percentage of Participants With Irritable Bowel Syndrome - Adequate Relief (IBS-AR) Scale | Responders during Weeks 1-12 | 54.2 percentage of participants |
| Eluxadoline 100 mg | Percentage of Participants With Irritable Bowel Syndrome - Adequate Relief (IBS-AR) Scale | Responders during Weeks 1-26 | 49.5 percentage of participants |
| Placebo | Percentage of Participants With Irritable Bowel Syndrome - Adequate Relief (IBS-AR) Scale | Responders during Weeks 1-12 | 43.8 percentage of participants |
| Placebo | Percentage of Participants With Irritable Bowel Syndrome - Adequate Relief (IBS-AR) Scale | Responders during Weeks 1-26 | 40.0 percentage of participants |