Irritable Bowel Syndrome
Conditions
Keywords
Irritable bowel syndrome with diarrhea, Irritable bowel syndrome, Diarrhea predominant irritable bowel syndrome, Colonic diseases, Colonic diseases, functional, Digestive system disease, Gastrointestinal disease, Intestinal disease, Colonic pseudo-obstruction, Diarrhea, Signs and Symptoms, Digestive
Brief summary
The purpose of this study is to determine the efficacy, safety, and tolerability of different doses of JNJ-27018966 (eluxadoline) compared with placebo in the treatment of patients with irritable bowel syndrome with diarrhea (IBS-d).
Interventions
DRUGEluxadoline
Tablets, orally, twice daily.
DRUGPlacebo
Matching placebo oral tablets twice daily.
Sponsors
Furiex Pharmaceuticals, Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Patient has a diagnosis of IBS by Rome III criteria with a subtype of diarrhea * Female patients must be: * postmenopausal, defined as amenorrhea 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. Key
Exclusion criteria
* Patient has a diagnosis of IBS by Rome III criteria with a subtype of constipation, mixed IBS, or unsubtyped IBS * Patient has a history of inflammatory or immune-mediated gastrointestinal (GI) disorders including inflammatory bowel disease (ie, Crohn's disease, ulcerative colitis) and celiac disease * Patient has a history of diverticulitis within 6 months prior to Prescreening * Patient has a history of intestinal obstruction, stricture, toxic megacolon, GI perforation, fecal impaction, gastric banding, bariatric surgery, adhesions, ischemic colitis, impaired intestinal circulation (eg, aortoiliac disease), thrombophlebitis of a major vein, or hypercoagulable states. 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 at Week 4 | Baseline (Week prior to Randomization) to Week 4 | Composite responders were defined as participants who completed at least 5 out of 7 days with diary entries during the interval of interest and met both of the following criteria: 1) Average daily pain response scores over the past week improved by ≥30% and at least 2 points as compared with the baseline average pain score (average of daily worst abdominal pain the week prior to randomization), 2) Bristol Stool Scale (BSS) score of 3 or 4 on 66% of reported days in the past week. Abdominal pain was assessed on an 11-point scale where: 0=no pain to 10=worst pain imaginable. Stool consistency was assessed using the BSS 7-point scale where: 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. |
| Percentage of Participants Who Were Composite Responders Based on Improvements From Baseline in Daily Worst Abdominal Pain and Daily Stool Consistency Scores at Week 12 | Baseline (Week prior to Randomization) to Week 12 | Composite responders were defined as participants who completed at least 5 out of 7 days with diary entries during the interval of interest and met both of the following criteria: 1) Average daily pain response scores over the past week improved by ≥30% and at least 2 points as compared with the baseline average pain score (average of daily worst abdominal pain the week prior to randomization), 2) Bristol Stool Scale (BSS) score of 3 or 4 on 66% of reported days in the past week. The participant recorded their abdominal pain in a daily diary using an 11-point scale where: 0=no pain to 10=worst pain imaginable. The participant recorded stool consistency in a daily diary using the BSS 7-point scale where: 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 |
|---|---|---|
| Change From Baseline in Weekly BSS Scores | Baseline (Week prior to Randomization) to Weeks 4, 8, and 12 | The patient recorded stool consistency in a daily diary using the BSS 7-point scale where: 1=hard stool to 7=watery diarrhea. The daily scores over the previous week were averaged. A negative change from Baseline indicates improvement. |
| Change From Baseline in the Weekly Pain Scores | Baseline (Week Prior to Randomization) to Weeks 4, 8, and 12 | The participant recorded their worst daily pain score in a diary using an 11-point scale where: 0=no pain to 10=worst pain imaginable. The daily scores over the previous week were averaged. A negative change from Baseline indicates improvement. |
| Change From Baseline in the Number of Daily Bowel Movements | Baseline (Week prior to Randomization) to Weeks 4, 8, and 12 | Participants recorded the number of bowel movements in a daily diary at the same time each day. The number of daily bowel movements over the previous week were averaged. A negative change from Baseline indicates improvement. |
| Percentage of Participants With Response Based on Participants Achieving Prespecified Improvement in Symptoms for at Least 50% of the Time | Baseline (Week Prior to Randomization) to Weeks 1-12 | Responders were participants that met both of the following criteria on the same week for at least 50% of time on study: 1) average of daily pain scores over the past week improved by ≥30% compared with baseline average in pain score, 2) ≥50% reduction in the number of days over the past week with a BSS score ≥5 compared with Baseline. Participants must also have had at least 5/7 days diary entry to be considered a responder for that week. Abdominal pain was assessed on an 11-point scale where a score of 0=no pain to 10=worst pain imaginable. Stool consistency was assessed using the BSS 7-point scale where: 1=separate hard lumps to 7=watery with no solid pieces. Response rates (percentage of participants) are based on model estimates from the logistic regression. |
Countries
United States
Participant flow
Recruitment details
9 patients were randomized more than once, enrolling at a second (or third) site after discontinuation from the first site. Safety data was analyzed according to the highest dose received. Safety Analysis Set: Highest Dose Level in the Participant Flow reflects the reassignment of patients randomized more than once to the highest dose level arm.
Pre-assignment details
807 patients were randomized in the trial. 18 of these patients were enrolled at a site terminated by Furiex, reported to the FDA for potential scientific misconduct, and were excluded from all datasets. All Randomized Patients=789 patients.
Participants by arm
| Arm | Count |
|---|---|
| Eluxadoline 5 mg Eluxadoline 5 mg tablets, orally, twice daily for up to 12 weeks. | 107 |
| Eluxadoline 25 mg Eluxadoline 25 mg tablets, orally, twice daily for up to 12 weeks. | 173 |
| Eluxadoline 100 mg Eluxadoline 100 mg tablets, orally, twice daily for up to 12 weeks. | 169 |
| Eluxadoline 200 mg Eluxadoline 200 mg tablets, orally, twice daily for up to 12 weeks. | 171 |
| Placebo Eluxadoline placebo matching tablets, orally, twice daily for up to 12 weeks. | 169 |
| Total | 789 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 5 | 6 | 22 | 7 |
| Overall Study | IVRS-confirmed constipation | 0 | 1 | 1 | 2 | 0 |
| Overall Study | Lack of efficacy- uncontrolled diarrhea | 1 | 1 | 0 | 0 | 2 |
| Overall Study | Lack of efficacy-uncontrolled IBS-d pain | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Lost to Follow-up | 4 | 3 | 4 | 7 | 6 |
| Overall Study | Physician Decision | 1 | 1 | 0 | 1 | 2 |
| Overall Study | Protocol Violation | 0 | 0 | 3 | 5 | 5 |
| Overall Study | Rescue medications due to diarrhea | 3 | 5 | 8 | 8 | 6 |
| Overall Study | Sponsor decision | 6 | 15 | 16 | 13 | 16 |
| Overall Study | Study arm discontinued | 38 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 4 | 11 | 10 | 9 | 8 |
Baseline characteristics
| Characteristic | Eluxadoline 5 mg | Eluxadoline 25 mg | Eluxadoline 100 mg | Eluxadoline 200 mg | Placebo | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 45.4 years STANDARD_DEVIATION 13 | 45.5 years STANDARD_DEVIATION 11.91 | 43.6 years STANDARD_DEVIATION 10.89 | 45.0 years STANDARD_DEVIATION 11.65 | 44.5 years STANDARD_DEVIATION 12.31 | 44.8 years STANDARD_DEVIATION 11.88 |
| Age, Customized 18 to 25 years | 13 Participants | 11 Participants | 11 Participants | 10 Participants | 11 Participants | 56 Participants |
| Age, Customized 26 to 35 years | 14 Participants | 33 Participants | 31 Participants | 32 Participants | 35 Participants | 145 Participants |
| Age, Customized 36 to 45 years | 21 Participants | 33 Participants | 45 Participants | 37 Participants | 33 Participants | 169 Participants |
| Age, Customized 46 to 55 years | 29 Participants | 54 Participants | 58 Participants | 60 Participants | 52 Participants | 253 Participants |
| Age, Customized 56 to 65 years | 30 Participants | 42 Participants | 24 Participants | 32 Participants | 38 Participants | 166 Participants |
| Body Mass Index (BMI) | 31.88 kg/m^2 STANDARD_DEVIATION 7.739 | 30.41 kg/m^2 STANDARD_DEVIATION 8.398 | 30.16 kg/m^2 STANDARD_DEVIATION 7.059 | 30.71 kg/m^2 STANDARD_DEVIATION 7.29 | 30.81 kg/m^2 STANDARD_DEVIATION 7.443 | 30.71 kg/m^2 STANDARD_DEVIATION 7.595 |
| Height | 167.05 cm STANDARD_DEVIATION 9.807 | 166.26 cm STANDARD_DEVIATION 9.523 | 168.38 cm STANDARD_DEVIATION 9.941 | 167.82 cm STANDARD_DEVIATION 9.201 | 167.40 cm STANDARD_DEVIATION 9.725 | 167.40 cm STANDARD_DEVIATION 9.632 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Asian | 3 Participants | 4 Participants | 3 Participants | 4 Participants | 2 Participants | 16 Participants |
| Race/Ethnicity, Customized Black or African American | 12 Participants | 21 Participants | 18 Participants | 18 Participants | 17 Participants | 86 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 13 Participants | 31 Participants | 32 Participants | 22 Participants | 24 Participants | 122 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 94 Participants | 142 Participants | 137 Participants | 149 Participants | 145 Participants | 667 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 2 Participants | 3 Participants | 2 Participants | 0 Participants | 8 Participants |
| Race/Ethnicity, Customized White | 90 Participants | 144 Participants | 145 Participants | 147 Participants | 150 Participants | 676 Participants |
| Sex: Female, Male Female | 76 Participants | 120 Participants | 117 Participants | 119 Participants | 118 Participants | 550 Participants |
| Sex: Female, Male Male | 31 Participants | 53 Participants | 52 Participants | 52 Participants | 51 Participants | 239 Participants |
| Weight | 89.10 kg STANDARD_DEVIATION 23.027 | 83.95 kg STANDARD_DEVIATION 23.657 | 86.04 kg STANDARD_DEVIATION 23.796 | 86.53 kg STANDARD_DEVIATION 21.584 | 86.28 kg STANDARD_DEVIATION 21.246 | 86.15 kg STANDARD_DEVIATION 22.671 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 25 / 159 | 20 / 105 | 34 / 170 | 27 / 165 | 43 / 172 |
| serious Total, serious adverse events | 1 / 159 | 1 / 105 | 3 / 170 | 1 / 165 | 3 / 172 |
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 at Week 12
Composite responders were defined as participants who completed at least 5 out of 7 days with diary entries during the interval of interest and met both of the following criteria: 1) Average daily pain response scores over the past week improved by ≥30% and at least 2 points as compared with the baseline average pain score (average of daily worst abdominal pain the week prior to randomization), 2) Bristol Stool Scale (BSS) score of 3 or 4 on 66% of reported days in the past week. The participant recorded their abdominal pain in a daily diary using an 11-point scale where: 0=no pain to 10=worst pain imaginable. The participant recorded stool consistency in a daily diary using the BSS 7-point scale where: 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: Baseline (Week prior to Randomization) to Week 12
Population: ITT analysis set was defined as the 754 participants that received at least 1 dose of study drug and had baseline and at least 1 postrandomization daily pain rating and 1 postrandomization Bristol Stool Scale (BSS) rating.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Eluxadoline 5 mg | Percentage of Participants Who Were Composite Responders Based on Improvements From Baseline in Daily Worst Abdominal Pain and Daily Stool Consistency Scores at Week 12 | 8.6 percentage of participants |
| Eluxadoline 25 mg | Percentage of Participants Who Were Composite Responders Based on Improvements From Baseline in Daily Worst Abdominal Pain and Daily Stool Consistency Scores at Week 12 | 13.2 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 at Week 12 | 20.2 percentage of participants |
| Eluxadoline 200 mg | Percentage of Participants Who Were Composite Responders Based on Improvements From Baseline in Daily Worst Abdominal Pain and Daily Stool Consistency Scores at Week 12 | 15.0 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 at Week 12 | 11.3 percentage of participants |
p-value: 0.44995% CI: [0.306, 1.689]ANCOVA
p-value: 0.58395% CI: [0.615, 2.373]ANCOVA
p-value: 0.0395% CI: [1.069, 3.795]ANCOVA
p-value: 0.32695% CI: [0.717, 2.716]ANCOVA
Primary
Percentage of Participants Who Were Composite Responders Based on Improvements From Baseline in Daily Worst Abdominal Pain and Daily Stool Consistency Scores at Week 4
Composite responders were defined as participants who completed at least 5 out of 7 days with diary entries during the interval of interest and met both of the following criteria: 1) Average daily pain response scores over the past week improved by ≥30% and at least 2 points as compared with the baseline average pain score (average of daily worst abdominal pain the week prior to randomization), 2) Bristol Stool Scale (BSS) score of 3 or 4 on 66% of reported days in the past week. Abdominal pain was assessed on an 11-point scale where: 0=no pain to 10=worst pain imaginable. Stool consistency was assessed using the BSS 7-point scale where: 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: Baseline (Week prior to Randomization) to Week 4
Population: Intent to treat (ITT) set was defined as the 754 participants that received at least 1 dose of study drug and had baseline and at least 1 postrandomization daily pain rating and 1 postrandomization Bristol Stool Scale (BSS) rating.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Eluxadoline 5 mg | Percentage of Participants Who Were Composite Responders Based on Improvements From Baseline in Daily Worst Abdominal Pain and Daily Stool Consistency Scores at Week 4 | 12.4 percentage of participants |
| Eluxadoline 25 mg | Percentage of Participants Who Were Composite Responders Based on Improvements From Baseline in Daily Worst Abdominal Pain and Daily Stool Consistency Scores at Week 4 | 12.0 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 at Week 4 | 11.0 percentage of participants |
| Eluxadoline 200 mg | Percentage of Participants Who Were Composite Responders Based on Improvements From Baseline in Daily Worst Abdominal Pain and Daily Stool Consistency Scores at Week 4 | 13.8 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 at Week 4 | 5.7 percentage of participants |
p-value: 0.05295% CI: [0.994, 6.077]ANCOVA
p-value: 0.04195% CI: [1.036, 5.478]ANCOVA
p-value: 0.0995% CI: [0.893, 4.842]ANCOVA
p-value: 0.01595% CI: [1.227, 6.376]ANCOVA
Secondary
Change From Baseline in the Number of Daily Bowel Movements
Participants recorded the number of bowel movements in a daily diary at the same time each day. The number of daily bowel movements over the previous week were averaged. A negative change from Baseline indicates improvement.
Time frame: Baseline (Week prior to Randomization) to Weeks 4, 8, and 12
Population: ITT analysis set was defined as the 754 participants that received at least 1 dose of study drug and had baseline and at least 1 postrandomization daily pain rating and 1 postrandomization Bristol Stool Scale (BSS) rating. Number analyzed is the number of participants with data available at the given time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eluxadoline 5 mg | Change From Baseline in the Number of Daily Bowel Movements | Baseline | 4.55 bowel movements per day | Standard Deviation 2.474 |
| Eluxadoline 5 mg | Change From Baseline in the Number of Daily Bowel Movements | Change from Baseline to Week 12 | -1.59 bowel movements per day | Standard Deviation 2.413 |
| Eluxadoline 5 mg | Change From Baseline in the Number of Daily Bowel Movements | Change from Baseline to Week 8 | -1.40 bowel movements per day | Standard Deviation 2.093 |
| Eluxadoline 5 mg | Change From Baseline in the Number of Daily Bowel Movements | Change from Baseline to Week 4 | -1.14 bowel movements per day | Standard Deviation 1.702 |
| Eluxadoline 25 mg | Change From Baseline in the Number of Daily Bowel Movements | Change from Baseline to Week 12 | -1.38 bowel movements per day | Standard Deviation 1.727 |
| Eluxadoline 25 mg | Change From Baseline in the Number of Daily Bowel Movements | Change from Baseline to Week 4 | -1.19 bowel movements per day | Standard Deviation 1.673 |
| Eluxadoline 25 mg | Change From Baseline in the Number of Daily Bowel Movements | Baseline | 4.43 bowel movements per day | Standard Deviation 3.155 |
| Eluxadoline 25 mg | Change From Baseline in the Number of Daily Bowel Movements | Change from Baseline to Week 8 | -1.31 bowel movements per day | Standard Deviation 1.607 |
| Eluxadoline 100 mg | Change From Baseline in the Number of Daily Bowel Movements | Change from Baseline to Week 8 | -1.85 bowel movements per day | Standard Deviation 1.944 |
| Eluxadoline 100 mg | Change From Baseline in the Number of Daily Bowel Movements | Baseline | 5.13 bowel movements per day | Standard Deviation 3.59 |
| Eluxadoline 100 mg | Change From Baseline in the Number of Daily Bowel Movements | Change from Baseline to Week 12 | -2.13 bowel movements per day | Standard Deviation 2.139 |
| Eluxadoline 100 mg | Change From Baseline in the Number of Daily Bowel Movements | Change from Baseline to Week 4 | -1.71 bowel movements per day | Standard Deviation 1.989 |
| Eluxadoline 200 mg | Change From Baseline in the Number of Daily Bowel Movements | Change from Baseline to Week 8 | -2.20 bowel movements per day | Standard Deviation 2.927 |
| Eluxadoline 200 mg | Change From Baseline in the Number of Daily Bowel Movements | Change from Baseline to Week 4 | -2.03 bowel movements per day | Standard Deviation 2.519 |
| Eluxadoline 200 mg | Change From Baseline in the Number of Daily Bowel Movements | Baseline | 4.99 bowel movements per day | Standard Deviation 3.206 |
| Eluxadoline 200 mg | Change From Baseline in the Number of Daily Bowel Movements | Change from Baseline to Week 12 | -2.29 bowel movements per day | Standard Deviation 2.857 |
| Placebo | Change From Baseline in the Number of Daily Bowel Movements | Change from Baseline to Week 12 | -1.71 bowel movements per day | Standard Deviation 3.599 |
| Placebo | Change From Baseline in the Number of Daily Bowel Movements | Baseline | 4.91 bowel movements per day | Standard Deviation 3.567 |
| Placebo | Change From Baseline in the Number of Daily Bowel Movements | Change from Baseline to Week 4 | -1.39 bowel movements per day | Standard Deviation 3.096 |
| Placebo | Change From Baseline in the Number of Daily Bowel Movements | Change from Baseline to Week 8 | -1.65 bowel movements per day | Standard Deviation 3.423 |
Secondary
Change From Baseline in the Weekly Pain Scores
The participant recorded their worst daily pain score in a diary using an 11-point scale where: 0=no pain to 10=worst pain imaginable. The daily scores over the previous week were averaged. A negative change from Baseline indicates improvement.
Time frame: Baseline (Week Prior to Randomization) to Weeks 4, 8, and 12
Population: ITT analysis set was defined as the 754 participants that received at least 1 dose of study drug and had baseline and at least 1 postrandomization daily pain rating and 1 postrandomization Bristol Stool Scale (BSS) rating. Number analyzed is the number of participants with data available at the given time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eluxadoline 5 mg | Change From Baseline in the Weekly Pain Scores | Baseline | 5.75 scores on a scale | Standard Deviation 1.541 |
| Eluxadoline 5 mg | Change From Baseline in the Weekly Pain Scores | Change from Baseline to Week 4 | -1.76 scores on a scale | Standard Deviation 1.964 |
| Eluxadoline 5 mg | Change From Baseline in the Weekly Pain Scores | Change from Baseline to Week 8 | -2.35 scores on a scale | Standard Deviation 2.105 |
| Eluxadoline 5 mg | Change From Baseline in the Weekly Pain Scores | Change from Baseline to Week 12 | -2.50 scores on a scale | Standard Deviation 1.979 |
| Eluxadoline 25 mg | Change From Baseline in the Weekly Pain Scores | Baseline | 5.91 scores on a scale | Standard Deviation 1.699 |
| Eluxadoline 25 mg | Change From Baseline in the Weekly Pain Scores | Change from Baseline to Week 12 | -2.57 scores on a scale | Standard Deviation 2.22 |
| Eluxadoline 25 mg | Change From Baseline in the Weekly Pain Scores | Change from Baseline to Week 4 | -2.11 scores on a scale | Standard Deviation 1.922 |
| Eluxadoline 25 mg | Change From Baseline in the Weekly Pain Scores | Change from Baseline to Week 8 | -2.54 scores on a scale | Standard Deviation 2.2 |
| Eluxadoline 100 mg | Change From Baseline in the Weekly Pain Scores | Change from Baseline to Week 12 | -3.25 scores on a scale | Standard Deviation 2.115 |
| Eluxadoline 100 mg | Change From Baseline in the Weekly Pain Scores | Change from Baseline to Week 4 | -2.33 scores on a scale | Standard Deviation 1.945 |
| Eluxadoline 100 mg | Change From Baseline in the Weekly Pain Scores | Change from Baseline to Week 8 | -2.81 scores on a scale | Standard Deviation 1.973 |
| Eluxadoline 100 mg | Change From Baseline in the Weekly Pain Scores | Baseline | 6.11 scores on a scale | Standard Deviation 1.723 |
| Eluxadoline 200 mg | Change From Baseline in the Weekly Pain Scores | Baseline | 5.78 scores on a scale | Standard Deviation 1.477 |
| Eluxadoline 200 mg | Change From Baseline in the Weekly Pain Scores | Change from Baseline to Week 4 | -2.20 scores on a scale | Standard Deviation 1.874 |
| Eluxadoline 200 mg | Change From Baseline in the Weekly Pain Scores | Change from Baseline to Week 12 | -2.96 scores on a scale | Standard Deviation 2.138 |
| Eluxadoline 200 mg | Change From Baseline in the Weekly Pain Scores | Change from Baseline to Week 8 | -2.58 scores on a scale | Standard Deviation 2.099 |
| Placebo | Change From Baseline in the Weekly Pain Scores | Change from Baseline to Week 12 | -2.65 scores on a scale | Standard Deviation 2.339 |
| Placebo | Change From Baseline in the Weekly Pain Scores | Change from Baseline to Week 8 | -2.54 scores on a scale | Standard Deviation 2.33 |
| Placebo | Change From Baseline in the Weekly Pain Scores | Change from Baseline to Week 4 | -2.09 scores on a scale | Standard Deviation 2.085 |
| Placebo | Change From Baseline in the Weekly Pain Scores | Baseline | 5.87 scores on a scale | Standard Deviation 1.671 |
Secondary
Change From Baseline in Weekly BSS Scores
The patient recorded stool consistency in a daily diary using the BSS 7-point scale where: 1=hard stool to 7=watery diarrhea. The daily scores over the previous week were averaged. A negative change from Baseline indicates improvement.
Time frame: Baseline (Week prior to Randomization) to Weeks 4, 8, and 12
Population: ITT analysis set was defined as the 754 participants that received at least 1 dose of study drug and had baseline and at least 1 postrandomization daily pain rating and 1 postrandomization Bristol Stool Scale (BSS) rating. Number analyzed is the number of participants with data available at the given time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eluxadoline 5 mg | Change From Baseline in Weekly BSS Scores | Change from Baseline to Week 8 | -1.19 scores on a scale | Standard Deviation 1.125 |
| Eluxadoline 5 mg | Change From Baseline in Weekly BSS Scores | Baseline | 6.19 scores on a scale | Standard Deviation 0.445 |
| Eluxadoline 5 mg | Change From Baseline in Weekly BSS Scores | Change from Baseline to Week 4 | -1.09 scores on a scale | Standard Deviation 1.095 |
| Eluxadoline 5 mg | Change From Baseline in Weekly BSS Scores | Change from Baseline to Week 12 | -1.37 scores on a scale | Standard Deviation 1.206 |
| Eluxadoline 25 mg | Change From Baseline in Weekly BSS Scores | Change from Baseline to Week 4 | -1.17 scores on a scale | Standard Deviation 1.116 |
| Eluxadoline 25 mg | Change From Baseline in Weekly BSS Scores | Baseline | 6.24 scores on a scale | Standard Deviation 0.404 |
| Eluxadoline 25 mg | Change From Baseline in Weekly BSS Scores | Change from Baseline to Week 8 | -1.39 scores on a scale | Standard Deviation 1.193 |
| Eluxadoline 25 mg | Change From Baseline in Weekly BSS Scores | Change from Baseline to Week 12 | -1.41 scores on a scale | Standard Deviation 1.225 |
| Eluxadoline 100 mg | Change From Baseline in Weekly BSS Scores | Baseline | 6.22 scores on a scale | Standard Deviation 0.429 |
| Eluxadoline 100 mg | Change From Baseline in Weekly BSS Scores | Change from Baseline to Week 12 | -1.68 scores on a scale | Standard Deviation 1.296 |
| Eluxadoline 100 mg | Change From Baseline in Weekly BSS Scores | Change from Baseline to Week 4 | -1.48 scores on a scale | Standard Deviation 1.326 |
| Eluxadoline 100 mg | Change From Baseline in Weekly BSS Scores | Change from Baseline to Week 8 | -1.64 scores on a scale | Standard Deviation 1.331 |
| Eluxadoline 200 mg | Change From Baseline in Weekly BSS Scores | Baseline | 6.23 scores on a scale | Standard Deviation 0.42 |
| Eluxadoline 200 mg | Change From Baseline in Weekly BSS Scores | Change from Baseline to Week 12 | -1.89 scores on a scale | Standard Deviation 1.317 |
| Eluxadoline 200 mg | Change From Baseline in Weekly BSS Scores | Change from Baseline to Week 8 | -1.71 scores on a scale | Standard Deviation 1.373 |
| Eluxadoline 200 mg | Change From Baseline in Weekly BSS Scores | Change from Baseline to Week 4 | -1.66 scores on a scale | Standard Deviation 1.266 |
| Placebo | Change From Baseline in Weekly BSS Scores | Change from Baseline to Week 12 | -1.27 scores on a scale | Standard Deviation 1.281 |
| Placebo | Change From Baseline in Weekly BSS Scores | Baseline | 6.20 scores on a scale | Standard Deviation 0.439 |
| Placebo | Change From Baseline in Weekly BSS Scores | Change from Baseline to Week 4 | -0.99 scores on a scale | Standard Deviation 1.179 |
| Placebo | Change From Baseline in Weekly BSS Scores | Change from Baseline to Week 8 | -1.19 scores on a scale | Standard Deviation 1.185 |
Secondary
Percentage of Participants With Response Based on Participants Achieving Prespecified Improvement in Symptoms for at Least 50% of the Time
Responders were participants that met both of the following criteria on the same week for at least 50% of time on study: 1) average of daily pain scores over the past week improved by ≥30% compared with baseline average in pain score, 2) ≥50% reduction in the number of days over the past week with a BSS score ≥5 compared with Baseline. Participants must also have had at least 5/7 days diary entry to be considered a responder for that week. Abdominal pain was assessed on an 11-point scale where a score of 0=no pain to 10=worst pain imaginable. Stool consistency was assessed using the BSS 7-point scale where: 1=separate hard lumps to 7=watery with no solid pieces. Response rates (percentage of participants) are based on model estimates from the logistic regression.
Time frame: Baseline (Week Prior to Randomization) to Weeks 1-12
Population: ITT Analysis Set; Subjects were included in the interval of Weeks 1-4, Weeks 5-8, or Weeks 9-12 if they received at least 1 dose of study medication within that interval.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Eluxadoline 5 mg | Percentage of Participants With Response Based on Participants Achieving Prespecified Improvement in Symptoms for at Least 50% of the Time | Weeks 1-12 | 16.5 percentage of participants |
| Eluxadoline 5 mg | Percentage of Participants With Response Based on Participants Achieving Prespecified Improvement in Symptoms for at Least 50% of the Time | Weeks 1-4 | 18.0 percentage of participants |
| Eluxadoline 5 mg | Percentage of Participants With Response Based on Participants Achieving Prespecified Improvement in Symptoms for at Least 50% of the Time | Weeks 9-12 | 29.7 percentage of participants |
| Eluxadoline 5 mg | Percentage of Participants With Response Based on Participants Achieving Prespecified Improvement in Symptoms for at Least 50% of the Time | Weeks 5-8 | 29.3 percentage of participants |
| Eluxadoline 25 mg | Percentage of Participants With Response Based on Participants Achieving Prespecified Improvement in Symptoms for at Least 50% of the Time | Weeks 5-8 | 34.4 percentage of participants |
| Eluxadoline 25 mg | Percentage of Participants With Response Based on Participants Achieving Prespecified Improvement in Symptoms for at Least 50% of the Time | Weeks 1-12 | 20.2 percentage of participants |
| Eluxadoline 25 mg | Percentage of Participants With Response Based on Participants Achieving Prespecified Improvement in Symptoms for at Least 50% of the Time | Weeks 1-4 | 21.0 percentage of participants |
| Eluxadoline 25 mg | Percentage of Participants With Response Based on Participants Achieving Prespecified Improvement in Symptoms for at Least 50% of the Time | Weeks 9-12 | 34.4 percentage of participants |
| Eluxadoline 100 mg | Percentage of Participants With Response Based on Participants Achieving Prespecified Improvement in Symptoms for at Least 50% of the Time | Weeks 9-12 | 49.1 percentage of participants |
| Eluxadoline 100 mg | Percentage of Participants With Response Based on Participants Achieving Prespecified Improvement in Symptoms for at Least 50% of the Time | Weeks 5-8 | 43.0 percentage of participants |
| Eluxadoline 100 mg | Percentage of Participants With Response Based on Participants Achieving Prespecified Improvement in Symptoms for at Least 50% of the Time | Weeks 1-12 | 29.7 percentage of participants |
| Eluxadoline 100 mg | Percentage of Participants With Response Based on Participants Achieving Prespecified Improvement in Symptoms for at Least 50% of the Time | Weeks 1-4 | 24.9 percentage of participants |
| Eluxadoline 200 mg | Percentage of Participants With Response Based on Participants Achieving Prespecified Improvement in Symptoms for at Least 50% of the Time | Weeks 1-12 | 30.6 percentage of participants |
| Eluxadoline 200 mg | Percentage of Participants With Response Based on Participants Achieving Prespecified Improvement in Symptoms for at Least 50% of the Time | Weeks 1-4 | 32.7 percentage of participants |
| Eluxadoline 200 mg | Percentage of Participants With Response Based on Participants Achieving Prespecified Improvement in Symptoms for at Least 50% of the Time | Weeks 5-8 | 39.3 percentage of participants |
| Eluxadoline 200 mg | Percentage of Participants With Response Based on Participants Achieving Prespecified Improvement in Symptoms for at Least 50% of the Time | Weeks 9-12 | 50.7 percentage of participants |
| Placebo | Percentage of Participants With Response Based on Participants Achieving Prespecified Improvement in Symptoms for at Least 50% of the Time | Weeks 1-4 | 20.0 percentage of participants |
| Placebo | Percentage of Participants With Response Based on Participants Achieving Prespecified Improvement in Symptoms for at Least 50% of the Time | Weeks 1-12 | 19.0 percentage of participants |
| Placebo | Percentage of Participants With Response Based on Participants Achieving Prespecified Improvement in Symptoms for at Least 50% of the Time | Weeks 9-12 | 31.0 percentage of participants |
| Placebo | Percentage of Participants With Response Based on Participants Achieving Prespecified Improvement in Symptoms for at Least 50% of the Time | Weeks 5-8 | 30.3 percentage of participants |