Trial Outcomes & Findings for Efficacy, Safety, and Tolerability of JNJ-27018966 (Eluxadoline) in the Treatment of Irritable Bowel Syndrome With Diarrhea (NCT NCT01130272)

Last Updated: 2019-10-22

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

807 participants

Primary outcome timeframe

Baseline (Week prior to Randomization) to Week 4

Results posted on

2019-10-22

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	Eluxadoline 5 mg Eluxadoline 5 mg tablets, orally, twice daily for up to 12 weeks.	Eluxadoline 25 mg Eluxadoline 25 mg tablets, orally, twice daily for up to 12 weeks.	Eluxadoline 100 mg Eluxadoline 100 mg tablets, orally, twice daily for up to 12 weeks.	Eluxadoline 200 mg Eluxadoline 200 mg tablets, orally, twice daily for up to 12 weeks.	Placebo Eluxadoline placebo matching tablets, orally, twice daily for up to 12 weeks.
Overall Study STARTED	107	173	169	171	169
Overall Study Safety Analysis Set: as Randomized	105	171	166	167	162
Overall Study Safety Analysis Set: Highest Dose Level	105	170	165	172	159
Overall Study COMPLETED	48	131	121	103	117
Overall Study NOT COMPLETED	59	42	48	68	52

Reasons for withdrawal

Reasons for withdrawal
Measure	Eluxadoline 5 mg Eluxadoline 5 mg tablets, orally, twice daily for up to 12 weeks.	Eluxadoline 25 mg Eluxadoline 25 mg tablets, orally, twice daily for up to 12 weeks.	Eluxadoline 100 mg Eluxadoline 100 mg tablets, orally, twice daily for up to 12 weeks.	Eluxadoline 200 mg Eluxadoline 200 mg tablets, orally, twice daily for up to 12 weeks.	Placebo Eluxadoline placebo matching tablets, orally, twice daily for up to 12 weeks.
Overall Study Adverse Event	2	5	6	22	7
Overall Study IVRS-confirmed constipation	0	1	1	2	0
Overall Study Rescue medications due to diarrhea	3	5	8	8	6
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 Protocol Violation	0	0	3	5	5
Overall Study Lost to Follow-up	4	3	4	7	6
Overall Study Withdrawal by Subject	4	11	10	9	8
Overall Study Physician Decision	1	1	0	1	2
Overall Study Sponsor decision	6	15	16	13	16
Overall Study Study arm discontinued	38	0	0	0	0

Baseline Characteristics

Number analyzed is the number of participants with available weight data for analysis.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Eluxadoline 5 mg n=107 Participants Eluxadoline 5 mg tablets, orally, twice daily for up to 12 weeks.	Eluxadoline 25 mg n=173 Participants Eluxadoline 25 mg tablets, orally, twice daily for up to 12 weeks.	Eluxadoline 100 mg n=169 Participants Eluxadoline 100 mg tablets, orally, twice daily for up to 12 weeks.	Eluxadoline 200 mg n=171 Participants Eluxadoline 200 mg tablets, orally, twice daily for up to 12 weeks.	Placebo n=169 Participants Eluxadoline placebo matching tablets, orally, twice daily for up to 12 weeks.	Total n=789 Participants Total of all reporting groups
Age, Continuous	45.4 years STANDARD_DEVIATION 13.00 • n=107 Participants	45.5 years STANDARD_DEVIATION 11.91 • n=173 Participants	43.6 years STANDARD_DEVIATION 10.89 • n=169 Participants	45.0 years STANDARD_DEVIATION 11.65 • n=171 Participants	44.5 years STANDARD_DEVIATION 12.31 • n=169 Participants	44.8 years STANDARD_DEVIATION 11.88 • n=789 Participants
Age, Customized 18 to 25 years	13 Participants n=107 Participants	11 Participants n=173 Participants	11 Participants n=169 Participants	10 Participants n=171 Participants	11 Participants n=169 Participants	56 Participants n=789 Participants
Age, Customized 26 to 35 years	14 Participants n=107 Participants	33 Participants n=173 Participants	31 Participants n=169 Participants	32 Participants n=171 Participants	35 Participants n=169 Participants	145 Participants n=789 Participants
Age, Customized 36 to 45 years	21 Participants n=107 Participants	33 Participants n=173 Participants	45 Participants n=169 Participants	37 Participants n=171 Participants	33 Participants n=169 Participants	169 Participants n=789 Participants
Age, Customized 46 to 55 years	29 Participants n=107 Participants	54 Participants n=173 Participants	58 Participants n=169 Participants	60 Participants n=171 Participants	52 Participants n=169 Participants	253 Participants n=789 Participants
Age, Customized 56 to 65 years	30 Participants n=107 Participants	42 Participants n=173 Participants	24 Participants n=169 Participants	32 Participants n=171 Participants	38 Participants n=169 Participants	166 Participants n=789 Participants
Sex: Female, Male Female	76 Participants n=107 Participants	120 Participants n=173 Participants	117 Participants n=169 Participants	119 Participants n=171 Participants	118 Participants n=169 Participants	550 Participants n=789 Participants
Sex: Female, Male Male	31 Participants n=107 Participants	53 Participants n=173 Participants	52 Participants n=169 Participants	52 Participants n=171 Participants	51 Participants n=169 Participants	239 Participants n=789 Participants
Race/Ethnicity, Customized White	90 Participants n=107 Participants	144 Participants n=173 Participants	145 Participants n=169 Participants	147 Participants n=171 Participants	150 Participants n=169 Participants	676 Participants n=789 Participants
Race/Ethnicity, Customized Black or African American	12 Participants n=107 Participants	21 Participants n=173 Participants	18 Participants n=169 Participants	18 Participants n=171 Participants	17 Participants n=169 Participants	86 Participants n=789 Participants
Race/Ethnicity, Customized Asian	3 Participants n=107 Participants	4 Participants n=173 Participants	3 Participants n=169 Participants	4 Participants n=171 Participants	2 Participants n=169 Participants	16 Participants n=789 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	1 Participants n=107 Participants	2 Participants n=173 Participants	0 Participants n=169 Participants	0 Participants n=171 Participants	0 Participants n=169 Participants	3 Participants n=789 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=107 Participants	0 Participants n=173 Participants	0 Participants n=169 Participants	0 Participants n=171 Participants	0 Participants n=169 Participants	0 Participants n=789 Participants
Race/Ethnicity, Customized Other	1 Participants n=107 Participants	2 Participants n=173 Participants	3 Participants n=169 Participants	2 Participants n=171 Participants	0 Participants n=169 Participants	8 Participants n=789 Participants
Race/Ethnicity, Customized Hispanic or Latino	13 Participants n=107 Participants	31 Participants n=173 Participants	32 Participants n=169 Participants	22 Participants n=171 Participants	24 Participants n=169 Participants	122 Participants n=789 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	94 Participants n=107 Participants	142 Participants n=173 Participants	137 Participants n=169 Participants	149 Participants n=171 Participants	145 Participants n=169 Participants	667 Participants n=789 Participants
Height	167.05 cm STANDARD_DEVIATION 9.807 • n=107 Participants	166.26 cm STANDARD_DEVIATION 9.523 • n=173 Participants	168.38 cm STANDARD_DEVIATION 9.941 • n=169 Participants	167.82 cm STANDARD_DEVIATION 9.201 • n=171 Participants	167.40 cm STANDARD_DEVIATION 9.725 • n=169 Participants	167.40 cm STANDARD_DEVIATION 9.632 • n=789 Participants
Weight	89.10 kg STANDARD_DEVIATION 23.027 • n=107 Participants • Number analyzed is the number of participants with available weight data for analysis.	83.95 kg STANDARD_DEVIATION 23.657 • n=173 Participants • Number analyzed is the number of participants with available weight data for analysis.	86.04 kg STANDARD_DEVIATION 23.796 • n=167 Participants • Number analyzed is the number of participants with available weight data for analysis.	86.53 kg STANDARD_DEVIATION 21.584 • n=166 Participants • Number analyzed is the number of participants with available weight data for analysis.	86.28 kg STANDARD_DEVIATION 21.246 • n=162 Participants • Number analyzed is the number of participants with available weight data for analysis.	86.15 kg STANDARD_DEVIATION 22.671 • n=775 Participants • Number analyzed is the number of participants with available weight data for analysis.
Body Mass Index (BMI)	31.88 kg/m^2 STANDARD_DEVIATION 7.739 • n=107 Participants • Number analyzed is the number of participants with available BMI data for analysis.	30.41 kg/m^2 STANDARD_DEVIATION 8.398 • n=173 Participants • Number analyzed is the number of participants with available BMI data for analysis.	30.16 kg/m^2 STANDARD_DEVIATION 7.059 • n=167 Participants • Number analyzed is the number of participants with available BMI data for analysis.	30.71 kg/m^2 STANDARD_DEVIATION 7.290 • n=166 Participants • Number analyzed is the number of participants with available BMI data for analysis.	30.81 kg/m^2 STANDARD_DEVIATION 7.443 • n=162 Participants • Number analyzed is the number of participants with available BMI data for analysis.	30.71 kg/m^2 STANDARD_DEVIATION 7.595 • n=775 Participants • Number analyzed is the number of participants with available BMI data for analysis.

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Eluxadoline 5 mg n=105 Participants Eluxadoline 5 mg tablets, orally, twice daily for up to 12 weeks.	Eluxadoline 25 mg n=167 Participants Eluxadoline 25 mg tablets, orally, twice daily for up to 12 weeks.	Eluxadoline 100 mg n=163 Participants Eluxadoline 100 mg tablets, orally, twice daily for up to 12 weeks.	Eluxadoline 200 mg n=160 Participants Eluxadoline 200 mg tablets, orally, twice daily for up to 12 weeks.	Placebo n=159 Participants Eluxadoline placebo matching tablets, orally, twice daily for up to 12 weeks.
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	12.0 percentage of participants	11.0 percentage of participants	13.8 percentage of participants	5.7 percentage of participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Eluxadoline 5 mg n=105 Participants Eluxadoline 5 mg tablets, orally, twice daily for up to 12 weeks.	Eluxadoline 25 mg n=167 Participants Eluxadoline 25 mg tablets, orally, twice daily for up to 12 weeks.	Eluxadoline 100 mg n=163 Participants Eluxadoline 100 mg tablets, orally, twice daily for up to 12 weeks.	Eluxadoline 200 mg n=160 Participants Eluxadoline 200 mg tablets, orally, twice daily for up to 12 weeks.	Placebo n=159 Participants Eluxadoline placebo matching tablets, orally, twice daily for up to 12 weeks.
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	13.2 percentage of participants	20.2 percentage of participants	15.0 percentage of participants	11.3 percentage of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Eluxadoline 5 mg n=105 Participants Eluxadoline 5 mg tablets, orally, twice daily for up to 12 weeks.	Eluxadoline 25 mg n=167 Participants Eluxadoline 25 mg tablets, orally, twice daily for up to 12 weeks.	Eluxadoline 100 mg n=163 Participants Eluxadoline 100 mg tablets, orally, twice daily for up to 12 weeks.	Eluxadoline 200 mg n=160 Participants Eluxadoline 200 mg tablets, orally, twice daily for up to 12 weeks.	Placebo n=159 Participants Eluxadoline placebo matching tablets, orally, twice daily for up to 12 weeks.
Change From Baseline in the Weekly Pain Scores Baseline	5.75 scores on a scale Standard Deviation 1.541	5.91 scores on a scale Standard Deviation 1.699	6.11 scores on a scale Standard Deviation 1.723	5.78 scores on a scale Standard Deviation 1.477	5.87 scores on a scale Standard Deviation 1.671
Change From Baseline in the Weekly Pain Scores Change from Baseline to Week 4	-1.76 scores on a scale Standard Deviation 1.964	-2.11 scores on a scale Standard Deviation 1.922	-2.33 scores on a scale Standard Deviation 1.945	-2.20 scores on a scale Standard Deviation 1.874	-2.09 scores on a scale Standard Deviation 2.085
Change From Baseline in the Weekly Pain Scores Change from Baseline to Week 8	-2.35 scores on a scale Standard Deviation 2.105	-2.54 scores on a scale Standard Deviation 2.200	-2.81 scores on a scale Standard Deviation 1.973	-2.58 scores on a scale Standard Deviation 2.099	-2.54 scores on a scale Standard Deviation 2.330
Change From Baseline in the Weekly Pain Scores Change from Baseline to Week 12	-2.50 scores on a scale Standard Deviation 1.979	-2.57 scores on a scale Standard Deviation 2.220	-3.25 scores on a scale Standard Deviation 2.115	-2.96 scores on a scale Standard Deviation 2.138	-2.65 scores on a scale Standard Deviation 2.339

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Eluxadoline 5 mg n=105 Participants Eluxadoline 5 mg tablets, orally, twice daily for up to 12 weeks.	Eluxadoline 25 mg n=167 Participants Eluxadoline 25 mg tablets, orally, twice daily for up to 12 weeks.	Eluxadoline 100 mg n=163 Participants Eluxadoline 100 mg tablets, orally, twice daily for up to 12 weeks.	Eluxadoline 200 mg n=160 Participants Eluxadoline 200 mg tablets, orally, twice daily for up to 12 weeks.	Placebo n=159 Participants Eluxadoline placebo matching tablets, orally, twice daily for up to 12 weeks.
Change From Baseline in Weekly BSS Scores Baseline	6.19 scores on a scale Standard Deviation 0.445	6.24 scores on a scale Standard Deviation 0.404	6.22 scores on a scale Standard Deviation 0.429	6.23 scores on a scale Standard Deviation 0.420	6.20 scores on a scale Standard Deviation 0.439
Change From Baseline in Weekly BSS Scores Change from Baseline to Week 4	-1.09 scores on a scale Standard Deviation 1.095	-1.17 scores on a scale Standard Deviation 1.116	-1.48 scores on a scale Standard Deviation 1.326	-1.66 scores on a scale Standard Deviation 1.266	-0.99 scores on a scale Standard Deviation 1.179
Change From Baseline in Weekly BSS Scores Change from Baseline to Week 8	-1.19 scores on a scale Standard Deviation 1.125	-1.39 scores on a scale Standard Deviation 1.193	-1.64 scores on a scale Standard Deviation 1.331	-1.71 scores on a scale Standard Deviation 1.373	-1.19 scores on a scale Standard Deviation 1.185
Change From Baseline in Weekly BSS Scores Change from Baseline to Week 12	-1.37 scores on a scale Standard Deviation 1.206	-1.41 scores on a scale Standard Deviation 1.225	-1.68 scores on a scale Standard Deviation 1.296	-1.89 scores on a scale Standard Deviation 1.317	-1.27 scores on a scale Standard Deviation 1.281

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Eluxadoline 5 mg n=105 Participants Eluxadoline 5 mg tablets, orally, twice daily for up to 12 weeks.	Eluxadoline 25 mg n=167 Participants Eluxadoline 25 mg tablets, orally, twice daily for up to 12 weeks.	Eluxadoline 100 mg n=163 Participants Eluxadoline 100 mg tablets, orally, twice daily for up to 12 weeks.	Eluxadoline 200 mg n=160 Participants Eluxadoline 200 mg tablets, orally, twice daily for up to 12 weeks.	Placebo n=159 Participants Eluxadoline placebo matching tablets, orally, twice daily for up to 12 weeks.
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	-1.31 bowel movements per day Standard Deviation 1.607	-1.85 bowel movements per day Standard Deviation 1.944	-2.20 bowel movements per day Standard Deviation 2.927	-1.65 bowel movements per day Standard Deviation 3.423
Change From Baseline in the Number of Daily Bowel Movements Baseline	4.55 bowel movements per day Standard Deviation 2.474	4.43 bowel movements per day Standard Deviation 3.155	5.13 bowel movements per day Standard Deviation 3.590	4.99 bowel movements per day Standard Deviation 3.206	4.91 bowel movements per day Standard Deviation 3.567
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	-1.19 bowel movements per day Standard Deviation 1.673	-1.71 bowel movements per day Standard Deviation 1.989	-2.03 bowel movements per day Standard Deviation 2.519	-1.39 bowel movements per day Standard Deviation 3.096
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	-1.38 bowel movements per day Standard Deviation 1.727	-2.13 bowel movements per day Standard Deviation 2.139	-2.29 bowel movements per day Standard Deviation 2.857	-1.71 bowel movements per day Standard Deviation 3.599

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Eluxadoline 5 mg n=105 Participants Eluxadoline 5 mg tablets, orally, twice daily for up to 12 weeks.	Eluxadoline 25 mg n=167 Participants Eluxadoline 25 mg tablets, orally, twice daily for up to 12 weeks.	Eluxadoline 100 mg n=163 Participants Eluxadoline 100 mg tablets, orally, twice daily for up to 12 weeks.	Eluxadoline 200 mg n=160 Participants Eluxadoline 200 mg tablets, orally, twice daily for up to 12 weeks.	Placebo n=159 Participants Eluxadoline placebo matching tablets, orally, twice daily for up to 12 weeks.
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	34.4 percentage of participants	43.0 percentage of participants	39.3 percentage of participants	30.3 percentage of participants
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	20.2 percentage of participants	29.7 percentage of participants	30.6 percentage of participants	19.0 percentage of participants
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	21.0 percentage of participants	24.9 percentage of participants	32.7 percentage of participants	20.0 percentage of participants
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	34.4 percentage of participants	49.1 percentage of participants	50.7 percentage of participants	31.0 percentage of participants

Adverse Events

Placebo

Serious events: 1 serious events

Other events: 25 other events

Deaths: 0 deaths

Eluxadoline 5 mg

Serious events: 1 serious events

Other events: 20 other events

Deaths: 0 deaths

Eluxadoline 25 mg

Serious events: 3 serious events

Other events: 34 other events

Deaths: 0 deaths

Eluxadoline 100 mg

Serious events: 1 serious events

Other events: 27 other events

Deaths: 0 deaths

Eluxadoline 200 mg

Serious events: 3 serious events

Other events: 43 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=159 participants at risk Eluxadoline placebo matching tablets, orally, twice daily for up to 12 weeks.	Eluxadoline 5 mg n=105 participants at risk Eluxadoline 5 mg tablets, orally, twice daily for up to 12 weeks.	Eluxadoline 25 mg n=170 participants at risk Eluxadoline 25 mg tablets, orally, twice daily for up to 12 weeks.	Eluxadoline 100 mg n=165 participants at risk Eluxadoline 100 mg tablets, orally, twice daily for up to 12 weeks.	Eluxadoline 200 mg n=172 participants at risk Eluxadoline 200 mg tablets, orally, twice daily for up to 12 weeks.
Psychiatric disorders Anxiety	0.63% 1/159 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.	0.00% 0/105 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.	0.00% 0/170 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.	0.00% 0/165 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.	0.00% 0/172 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.
Psychiatric disorders Depression	0.63% 1/159 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.	0.00% 0/105 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.	0.00% 0/170 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.	0.00% 0/165 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.	0.00% 0/172 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.
Gastrointestinal disorders Pancreatitis	0.00% 0/159 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.	0.00% 0/105 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.	0.59% 1/170 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.	0.00% 0/165 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.	0.00% 0/172 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.
General disorders Noncardiac chest pain	0.00% 0/159 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.	0.95% 1/105 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.	0.00% 0/170 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.	0.00% 0/165 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.	0.00% 0/172 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.
Gastrointestinal disorders Alcoholic pancreatitis	0.00% 0/159 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.	0.00% 0/105 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.	0.00% 0/170 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.	0.00% 0/165 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.	0.58% 1/172 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.
Infections and infestations Pneumonia	0.00% 0/159 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.	0.00% 0/105 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.	0.59% 1/170 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.	0.00% 0/165 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.	0.00% 0/172 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.
Psychiatric disorders Major depression	0.00% 0/159 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.	0.00% 0/105 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.	0.59% 1/170 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.	0.00% 0/165 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.	0.00% 0/172 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.
Psychiatric disorders Affective disorder	0.00% 0/159 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.	0.00% 0/105 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.	0.59% 1/170 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.	0.00% 0/165 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.	0.00% 0/172 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.
Gastrointestinal disorders Pancreatitis acute	0.00% 0/159 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.	0.00% 0/105 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.	0.00% 0/170 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.	0.61% 1/165 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.	0.58% 1/172 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.
Gastrointestinal disorders Appendicitis perforated	0.00% 0/159 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.	0.00% 0/105 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.	0.00% 0/170 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.	0.00% 0/165 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.	0.58% 1/172 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.

Other adverse events

Other adverse events
Measure	Placebo n=159 participants at risk Eluxadoline placebo matching tablets, orally, twice daily for up to 12 weeks.	Eluxadoline 5 mg n=105 participants at risk Eluxadoline 5 mg tablets, orally, twice daily for up to 12 weeks.	Eluxadoline 25 mg n=170 participants at risk Eluxadoline 25 mg tablets, orally, twice daily for up to 12 weeks.	Eluxadoline 100 mg n=165 participants at risk Eluxadoline 100 mg tablets, orally, twice daily for up to 12 weeks.	Eluxadoline 200 mg n=172 participants at risk Eluxadoline 200 mg tablets, orally, twice daily for up to 12 weeks.
Gastrointestinal disorders Nausea	4.4% 7/159 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.	5.7% 6/105 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.	6.5% 11/170 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.	5.5% 9/165 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.	10.5% 18/172 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.
Gastrointestinal disorders Abdominal pain	1.9% 3/159 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.	2.9% 3/105 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.	3.5% 6/170 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.	2.4% 4/165 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.	7.6% 13/172 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.
Gastrointestinal disorders Vomiting	0.63% 1/159 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.	0.95% 1/105 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.	4.1% 7/170 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.	4.2% 7/165 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.	7.0% 12/172 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.
Gastrointestinal disorders Constipation	2.5% 4/159 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.	1.9% 2/105 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.	2.9% 5/170 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.	6.1% 10/165 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.	3.5% 6/172 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.
Infections and infestations Sinusitis	5.7% 9/159 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.	4.8% 5/105 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.	2.4% 4/170 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.	1.8% 3/165 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.	0.58% 1/172 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.
Nervous system disorders Dizziness	2.5% 4/159 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.	3.8% 4/105 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.	2.4% 4/170 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.	3.0% 5/165 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.	6.4% 11/172 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.
Nervous system disorders Headache	3.8% 6/159 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.	2.9% 3/105 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.	7.1% 12/170 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.	3.0% 5/165 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.	4.1% 7/172 • First dose of study drug and up to and including 7 days after date of the last dose of study drug (Up to 114 days) Safety population: all patients enrolled who received at least 1 dose of study drug. Nine patients were identified as having been randomized more than once in the study, enrolling at a second (or third) site after discontinuation from the first site. All available data for each patient was included in the Safety Analysis Set and was analyzed according to the highest dose level of treatment received.

Additional Information

Therapeutic Area Head

Allergan

Phone: 714-246-4500

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee All data generated in this study will be the property of Forest Research Institute, Inc. An integrated clinical and statistical report will be prepared at the completion of the study. Publication of the results by the Investigator will be subject to mutual agreement between the Investigator and Forest Research Institute, Inc.
Publication restrictions are in place

Restriction type: OTHER