Efficacy, Safety, and Tolerability of Eluxadoline in the Treatment of Participants With Diarrhea-Predominant Irritable Bowel Syndrome (IBS-d)

• Sponsor: Furiex Pharmaceuticals, Inc (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01553591
• Collaborator: (none)
• Enrollment: 1,282
• Locations: 283
• Arms: 3
• Actual Duration (Months): 26
• Patients Per Site: 4.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the efficacy, safety, and tolerability of different doses of eluxadoline (JNJ-27018966) compared with placebo in the treatment of participants with diarrhea-predominant irritable bowel syndrome.

Condition or Disease	Intervention/Treatment	Phase
Irritable Bowel Syndrome	Drug: Eluxadoline; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 1282 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blind, Placebo-controlled, Phase 3 Study to Evaluate the Efficacy, Safety, and Tolerability of JNJ-27018966 in the Treatment of Patients With Diarrhea-Predominant Irritable Bowel Syndrome
• Actual Study Start Date: May 29, 2012
• Actual Primary Completion Date: Jul 29, 2014
• Actual Study Completion Date: Jul 29, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Eluxadoline 75 mg Eluxadoline 75 mg tablets, orally, twice daily for up to 52 weeks period.	Drug: Eluxadoline; Oral tablets twice daily; Other Names: JNJ-27018966
Experimental: Eluxadoline 100 mg Eluxadoline 100 mg tablets, orally, twice daily for up to 52 weeks period.	Drug: Eluxadoline; Oral tablets twice daily; Other Names: JNJ-27018966
Placebo Comparator: Placebo Eluxadoline placebo matching tablets, orally, twice daily for up to 52 weeks period.	Drug: Placebo; Oral tablets twice daily

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Who Were Composite Responders Based on Improvements From Baseline in Daily Worst Abdominal Pain And Daily Stool Consistency Scores [Up to 12 Weeks]

   Composite responders were defined as a participant who met the daily response criteria for at least 50% of the days with diary entries during the interval of interest. A participant must had met both of the following criteria on a given day to be a daily responder: 1) Daily pain response: worst abdominal pain scores in the past 24 hours improved by ≥30% compared to baseline (average of daily worst abdominal pain the week prior to randomization). 2) Daily stool consistency response: Bristol Stool Scale (BSS) score <5 (ie, score of 1, 2, 3, or 4) or the absence of a bowel movement if accompanied by ≥30% improvement in worst abdominal pain compared to baseline pain. Bristol stool scale was defined as 7-point Scale in which a score of 1 = separate hard lumps, 2 = sausage shaped but lumpy, 3 = sausage-like with cracks on the surface, 4 = sausage-like but smooth and soft, 5 = soft blobs with clear cut edges, 6 = fluffy pieces with ragged edges, and 7 = watery with no solid pieces.

Secondary Outcome Measures

1. Percentage of Participants Who Were Composite Responders Based on Improvements From Baseline in Daily Worst Abdominal Pain And Daily Stool Consistency Scores [Up to 26 Weeks]

   Composite responders were defined as a participant who met the daily response criteria for at least 50% of the days with diary entries during the interval of interest. A participant must had met both of the following criteria on a given day to be a daily responder: 1) Daily pain response: worst abdominal pain scores in the past 24 hours improved by ≥30% compared to baseline (average of daily worst abdominal pain the week prior to randomization). 2) Daily stool consistency response: Bristol Stool Scale (BSS) score <5 (ie, score of 1, 2, 3, or 4) or the absence of a bowel movement if accompanied by ≥30% improvement in worst abdominal pain compared to baseline pain. Bristol stool scale was defined as 7-point Scale in which a score of 1 = separate hard lumps, 2 = sausage shaped but lumpy, 3 = sausage-like with cracks on the surface, 4 = sausage-like but smooth and soft, 5 = soft blobs with clear cut edges, 6 = fluffy pieces with ragged edges, and 7 = watery with no solid pieces.

2. Percentage of Participants Who Were Pain Responders In Daily Worst Abdominal Pain Scores by Intervals [12-week interval (Weeks 1-12), 26-week interval (Weeks 1-26), and 4-week interval (Weeks 1-4, 5-8, 9-12, 13-16, 17-20, and 21-24)]

   Pain responders were defined as participants who met the daily pain response criteria (ie, the worst abdominal pain score in the past 24 hours improved by ≥30% compared to baseline) for at least 50% of days with diary entries during each interval. A participant must have had a minimum of 20 days of diary entries over any 4-week interval, a minimum of 60 days of diary entries over the 12-week interval, and a minimum of 110 days of diary entries over the 26-week interval to be a responder.

3. Percentage of Participants Who Were Responders In Daily Stool Consistency Scores by Intervals [12-week interval (Weeks 1-12), 26-week interval (Weeks 1-26), and 4-week interval (Weeks 1-4, 5-8, 9-12, 13-16, 17-20, and 21-24)]

   Stool consistency responders: participants who met daily stool consistency response criterion (ie,score of 1, 2, 3, or 4 or absence of bowel movement if accompanied by ≥30% improvement in worst abdominal pain compared to baseline pain) for at least 50% of days with diary entries during each interval. BSS was defined as 7-point Scale in which score of 1= separate hard lumps, 2= sausage shaped but lumpy, 3= sausage-like with cracks on the surface, 4= sausage-like but smooth and soft, 5= soft blobs with clear cut edges, 6= fluffy pieces with ragged edges, and 7= watery with no solid pieces. A participant must have had a minimum of 20 days of diary entries over any 4-week interval, a minimum of 60 days of diary entries over 12-week interval, and a minimum of 110 days of diary entries over 26-week interval to be a responder.

4. Percentage of Participants Who Were Responders In Irritable Bowel Syndrome, Diarrhea Predominant (IBS-d) Global Symptom Scale by Intervals [12-week interval (Weeks 1-12), 26-week interval (Weeks 1-26), and 4-week interval (Weeks 1-4, 5-8, 9-12, 13-16, 17-20, and 21-24)]

   IBS-d global symptom responders were defined as those participants who met the daily IBS-d global symptom response criteria (ie, IBS-d global symptom score of 0 [none] or 1 [mild]; or a daily IBS-d global symptom score improved by ≥2.0 compared to the baseline average) for at least 50% of days with diary entries during each interval. IBS-d Global Symptom Scale was a 5 point scale, score ranging from 0 to 4. 0= no symptoms, 1= mild symptoms, 2= moderate symptoms, 3= severe symptoms and 4 = very severe symptoms. A participant must have had a minimum of 20 days of diary entries over any 4-week interval, a minimum of 60 days of diary entries over the 12-week interval, and a minimum of 110 days of diary entries over the 26-week interval to be a responder.

5. Percentage of Participants Who Were Responders to the Irritable Bowel Syndrome Quality of Life Measure (IBS-QoL) Scale [Weeks 4, 8, 12, 18, 26, 36, 44, and 52 (End of Treatment [EOT])]

   IBS-QoL responders were defined as participants who achieved at least a 14-point improvement in IBS-QoL total score from baseline to the applicable visit. The IBS-QoL consists of 34 items each with a 5-point response scale, where 1 generally represents better responses on items and 5 represents worse responses. The individual responses to the answered items were summed and standardized for a total score and then transformed to a 0- to 100-point (0= worst; 100=better) scale for ease of interpretation.

6. Percentage of Participants With Irritable Bowel Syndrome - Adequate Relief (IBS-AR) Scale [12-week interval (Weeks 1-12) and 26-week interval (Weeks 1-26)]

   Adequate relief of IBS symptoms was assessed once weekly by participants answering the IBS-AR item in the electronic diary. IBS-AR responders were defined as participants with a weekly response of "Yes" to adequate relief of their IBS symptoms for at least 50% of the total weeks during the interval. A participant must have had a positive response on ≥6 weeks for the 12-week interval and ≥13 weeks for the 26-week interval, regardless of diary compliance, to be a responder.

7. Change From Baseline in Daily Abdominal Discomfort Scores [Baseline, Weeks 4, 12 and 26]

   Symptoms of abdominal discomfort were recorded on a 0 to 10 scale, where 0 corresponded to no discomfort and 10 corresponded to worst imaginable discomfort. A negative change from Baseline indicates the discomfort decreased.

8. Change From Baseline in Daily Abdominal Bloating Scores [Baseline, Weeks 4, 12 and 26]

   Symptoms of abdominal bloating were recorded on a 0 to 10 scale, where 0 corresponded to no bloating and 10 corresponded to worst imaginable bloating. A negative change from Baseline indicates the bloating decreased.

9. Number of Bowel Movements Per Day [Weeks 4, 12 and 26]

   Participants recorded the number of bowel movements over 24 hours daily throughout the treatment.

10. Number of Bowel Incontinence Episodes [Weeks 4, 12 and 26]

    Participants recorded the number of incontinence episodes over 24 hours daily throughout the treatment.

11. Number of Bowel Incontinence Free Days [Weeks 4, 12 and 26]

    An incontinence free day was one where the participant reports zero incontinence episodes. The number of incontinence free days for a participant was assessed each week based on the number of reported days.

12. Number of Urgency Episodes Per Day [Weeks 4, 12 and 26]

    Participants recorded the number of urgency episodes over 24 hours daily throughout the treatment.

13. IBS-QoL Total Scores [Weeks 4, 8, 12, 18, 26, 36, 44, and 52 (EOT)]

    The IBS-QoL consists of 34 items each with a 5-point response scale, where 1 generally represents better responses on items and 5 represents worse responses. The individual responses to the answered items were summed and standardized for a total score and then transformed to a 0- to 100- point scale (0=worst; 100=better) for ease of interpretation.

14. Change From Baseline in IBS-QoL Total Scores [Baseline, Weeks 4, 8, 12, 18, 26, 36, 44, and 52/EOT]

    The IBS-QoL consists of 34 items each with a 5-point response scale, where 1 generally represents better responses on items and 5 represents worse responses. The individual responses to the answered items were summed and standardized for a total score and then transformed to a 0- to 100- point scale (0=worst; 100=better) for ease of interpretation. A positive change from Baseline indicates that quality of life improved.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Participant has a diagnosis of irritable bowel syndrome (IBS) with a subtype of diarrhea defined by the Rome III criteria.

2. Participant has had a colonoscopy performed:

• Within 10 years prior to Prescreening if participant is at least 50 years of age (sigmoidoscopy, double contrast barium enema, or computed tomography (CT) colonography within the past 5 years is acceptable)

• Since the onset (if applicable) of any of the following alarm features for participants of any age:

• Participant has documented weight loss within the past 6 months

• Participant has nocturnal symptoms

• Participant has a familial history of first-degree relatives with colon cancer or

• Participant has blood mixed with their stool (excluding blood from hemorrhoids).

1. Female participants must be:

• Postmenopausal, defined as 52 years or older and amenorrheic for at least 2 years at Prescreening,

• Surgically sterile (have had a hysterectomy or bilateral oophorectomy, tubal ligation, or otherwise be incapable of pregnancy),

• Abstinent, or

• If sexually active, be practicing an effective method of birth control.

Exclusion Criteria:

1. Participant has a diagnosis of IBS with a subtype of constipation, mixed IBS, or unsubtyped IBS by the Rome III criteria.

2. Participant has a history of inflammatory or immune-mediated gastrointestinal (GI) disorders including inflammatory bowel disease (ie, Crohn's disease, ulcerative colitis) and celiac disease.

3. Participant has a history of diverticulitis within 3 months prior to Prescreening.

4. Participant has a history of intestinal obstruction, stricture, toxic megacolon, GI perforation, fecal impaction, gastric banding, bariatric surgery, adhesions, ischemic colitis, or impaired intestinal circulation (eg, aortoiliac disease).

5. Participant has any of the following surgical history:

• Cholecystectomy with any history of post cholecystectomy biliary tract pain

• Any abdominal surgery within the 3 months prior to Prescreening

• Participant has a history of major gastric, hepatic, pancreatic, or intestinal surgery (appendectomy, hemorrhoidectomy, or polypectomy greater than 3 months post surgery are allowed)

Other protocol-specific eligibility criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Furiex Research Site	Athens	Alabama	United States	35611
2	Furiex Research Site	Birmingham	Alabama	United States	35213
3	Furiex Research Site	Foley	Alabama	United States	36535
4	Furiex Research Site	Huntsville	Alabama	United States	35802
5	Furiex Research Site	Ozark	Alabama	United States	36360
6	Furiex Research Site	Chandler	Arizona	United States	85224
7	Furiex Research Site	Glendale	Arizona	United States	85306
8	Furiex Research Site	Mesa	Arizona	United States	85213
9	Furiex Research Site	Phoenix	Arizona	United States	85018
10	Furiex Research Site	Tucson	Arizona	United States	85712
11	Furiex Research Site	Little Rock	Arkansas	United States	72211
12	Furiex Research Site	Little Rock	Arkansas	United States	72212
13	Furiex Research Site	North Little Rock	Arkansas	United States	72117
14	Furiex Research Site	Azusa	California	United States	91702
15	Furiex Research Site	Bell Gardens	California	United States	90201
16	Furiex Research Site	Beverly Hills	California	United States	90211
17	Furiex Research Site	Carson	California	United States	91105
18	Furiex Research Site	Chula Vista	California	United States	91910
19	Furiex Research Site	Corona	California	United States	92880
20	Furiex Research Site	El Cajon	California	United States	92020
21	Furiex Research Site	Encino	California	United States	91436
22	Furiex Research Site	Garden Grove	California	United States	92843
23	Furiex Research Site	Lomita	California	United States	90717
24	Furiex Research Site	Los Angeles	California	United States	90022
25	Furiex Research Site	Monterey Park	California	United States	91754
26	Furiex Research Site	Murrieta	California	United States	92562
27	Furiex Research Site	Newport Beach	California	United States	92663
28	Furiex Research Site	North Hollywood	California	United States	91606
29	Furiex Research Site	Oakland	California	United States	94612
30	Furiex Research Site	Oxnard	California	United States	93030
31	Furiex Research Site	Pismo Beach	California	United States	93449
32	Furiex Research Site	Poway	California	United States	92064
33	Furiex Research Site	Riverside	California	United States	92501
34	Furiex Research Site	Roseville	California	United States	95661
35	Furiex Research Site	Sacramento	California	United States	95825
36	Furiex Research Site	San Diego	California	United States	92103
37	Furiex Research Site	San Diego	California	United States	92114
38	Furiex Research Site	Santa Monica	California	United States	90404
39	Furiex Research Site	Thousand Oaks	California	United States	91360
40	Furiex Research Site	Colorado Springs	Colorado	United States	80904
41	Furiex Research Site	Colorado Springs	Colorado	United States	80907
42	Furiex Research Site	Lafayette	Colorado	United States	80026
43	Furiex Research Site	Lakewood	Colorado	United States	80215
44	Furiex Research Site	Longmont	Colorado	United States	80501
45	Furiex Research Site	Norwalk	Connecticut	United States	06851
46	Furiex Research Site	Ridgefield	Connecticut	United States	06877
47	Furiex Research Site	Boca Raton	Florida	United States	33428
48	Furiex Research Site	Brandon	Florida	United States	33511
49	Furiex Research Site	Clearwater	Florida	United States	33765
50	Furiex Research Site	Cooper City	Florida	United States	33024
51	Furiex Research Site	Coral Springs	Florida	United States	33065
52	Furiex Research Site	Crystal River	Florida	United States	34429
53	Furiex Research Site	Doral	Florida	United States	33172
54	Furiex Research Site	Eustis	Florida	United States	32726
55	Furix Research Site	Hialeah	Florida	United States	33013
56	Furiex Research Site	Hialeah	Florida	United States	33016
57	Furiex Research Site	Inverness	Florida	United States	34452
58	Furiex Research Site	Jacksonville	Florida	United States	32216
59	Furiex Research Site	Kissimmee	Florida	United States	34741
60	Furiex Research Site	Maitland	Florida	United States	32751
61	Furiex Research Site	Melbourne	Florida	United States	32935
62	Furiex Research Site	Miami Springs	Florida	United States	33166
63	Furiex Research Site	Miami	Florida	United States	33015
64	Furiex Research Site	Miami	Florida	United States	33125
65	Furiex Research Site	Miami	Florida	United States	33126
66	Furiex Research Site	Miami	Florida	United States	33133
67	Furiex Research Site	Miami	Florida	United States	33135
68	Furiex Research Site	Miami	Florida	United States	33144
69	Furiex Research Site	Miami	Florida	United States	33155
70	Furiex Research Site	Miami	Florida	United States	33175
71	Furiex Research Site	Miramar	Florida	United States	33025
72	Furiex Research Site	Naples	Florida	United States	34102
73	Furiex Research Site	New Port Richey	Florida	United States	34653
74	Furiex Research Site	New Smyrna Beach	Florida	United States	32168
75	Furiex Research Site	Orlando	Florida	United States	32801
76	Furiex Research Site	Orlando	Florida	United States	32806
77	Furiex Research Site	Orlando	Florida	United States	32819
78	Furiex Research Site	Ormond Beach	Florida	United States	32174
79	Furiex Research Site	Oviedo	Florida	United States	32765
80	Furiex Research Site	Palm Beach	Florida	United States	33472
81	Furiex Research Site	Pinellas Park	Florida	United States	33781
82	Furiex Research Site	Pinellas Park	Florida	United States	33782
83	Furiex Research Site	Port Orange	Florida	United States	32129
84	Furiex Research Site	Sanford	Florida	United States	32771
85	Furiex Research Site	Sebastian	Florida	United States	32958
86	Furiex Research Site	South Miami	Florida	United States	33143
87	Furiex Research Site	Tampa	Florida	United States	33606
88	Furiex Research Site	Tampa	Florida	United States	33607
89	Furiex Research Site	Venice	Florida	United States	34292
90	Furiex Research Site	Wellington	Florida	United States	33414
91	Furiex Research Site	Winter Haven	Florida	United States	33880
92	Furiex Research Site	Winter Park	Florida	United States	32792
93	Furiex Research Site	Atlanta	Georgia	United States	30338
94	Furiex Research Site	Blue Ridge	Georgia	United States	30513
95	Furiex Research Site	Johns Creek	Georgia	United States	30097
96	Furiex Research Site	Lilburn	Georgia	United States	30047
97	Furiex Research Site	Oakwood	Georgia	United States	30566
98	Furiex Research Site	Perry	Georgia	United States	31069
99	Furiex Research Site	Snellville	Georgia	United States	30078
100	Furiex Research Site	Eagle	Idaho	United States	83616
101	Furiex Research Site	Addison	Illinois	United States	60101
102	Furiex Research Site	Chicago	Illinois	United States	60611
103	Furiex Research Site	Morton	Illinois	United States	61550
104	Furiex Research Site	Brownsburg	Indiana	United States	46112
105	Furiex Research Site	Evansville	Indiana	United States	47714
106	Furiex Research Site	Indianapolis	Indiana	United States	46202
107	Furiex Research Site	Clive	Iowa	United States	50325
108	Furiex Research Site	Davenport	Iowa	United States	52807
109	Furiex Research Site	Iowa City	Iowa	United States	52242
110	Furiex Research Site	West Des Moines	Iowa	United States	50266
111	Furiex Research Site	Newton	Kansas	United States	67114
112	Furiex Research Site	Prairie Village	Kansas	United States	66206
113	Furiex Research Site	Shawnee Mission	Kansas	United States	66218
114	Furiex Research Site	Wichita	Kansas	United States	67203
115	Furiex Research Site	Wichita	Kansas	United States	67205
116	Furiex Research Site	Crestview Hills	Kentucky	United States	41017
117	Furiex Research Site	Hawesville	Kentucky	United States	42348
118	Furiex Research Site	Lexington	Kentucky	United States	40509
119	Furiex Research Site	Lexington	Kentucky	United States	40536
120	Furiex Research Site	Louisville	Kentucky	United States	40202
121	Furiex Research Site	Madisonville	Kentucky	United States	42431
122	Furiex Research Site	Owensboro	Kentucky	United States	42303
123	Furiex Research Site	Baker	Louisiana	United States	70794
124	Furiex Research Site	Covington	Louisiana	United States	70435
125	Furiex Research Site	Hammond	Louisiana	United States	70403
126	Furiex Research Site	Metairie	Louisiana	United States	70006
127	Furiex Research Site	New Orleans	Louisiana	United States	70124
128	Furiex Research Site	Opelousas	Louisiana	United States	70570
129	Furiex Research Site	Shreveport	Louisiana	United States	71101
130	Furiex Research Site	Shreveport	Louisiana	United States	71105
131	Furiex Research Site	Bangor	Maine	United States	04401
132	Furiex Research Site	Annapolis	Maryland	United States	21401
133	Furiex Research Site	Chevy Chase	Maryland	United States	20815
134	Furiex Research Site	Brockton	Massachusetts	United States	02301
135	Furiex Research Site	Watertown	Massachusetts	United States	02472
136	Furiex Research Site	Ann Arbor	Michigan	United States	48106
137	Furiex Research Site	Southfield	Michigan	United States	48034
138	Furiex Research Site	Stevensville	Michigan	United States	49127
139	Furiex Research Site	Chaska	Minnesota	United States	55318
140	Furiex Research Site	Jackson	Mississippi	United States	39202
141	Furiex Research Site	Jefferson City	Missouri	United States	65109
142	Furiex Research Site	Saint Louis	Missouri	United States	63128
143	Furiex Research Site	Saint Louis	Missouri	United States	63141
144	Furiex Research Site	Saint Peters	Missouri	United States	63376
145	Furiex Research Site	Billings	Montana	United States	59102
146	Furiex Research Site	Bellevue	Nebraska	United States	68005
147	Furiex Research Site	Omaha	Nebraska	United States	68114
148	Furiex Research Site	Omaha	Nebraska	United States	68134
149	Furiex Research Site	Las Vegas	Nevada	United States	89106
150	Furiex Research Site	Las Vegas	Nevada	United States	89119
151	Furiex Research Site	Collingswood	New Jersey	United States	08108
152	Furiex Research Site	Edison	New Jersey	United States	08817
153	Furiex Research Site	Albuquerque	New Mexico	United States	87106
154	Furiex Research Site	Brooklyn	New York	United States	11230
155	Furiex Research Site	Endwell	New York	United States	13760
156	Furiex Research Site	Great Neck	New York	United States	11023
157	Furiex Research Site	Hartsdale	New York	United States	10530
158	Furiex Research Site	Kew Gardens	New York	United States	11415
159	Furiex Research Site	New Windsor	New York	United States	12553
160	Furiex Research Site	New York	New York	United States	10016
161	Furiex Research Site	North Massapequa	New York	United States	11758
162	Furiex Research Site	Poughkeepsie	New York	United States	12601
163	Furiex Research Site	Asheville	North Carolina	United States	28801
164	Furiex Research Site	Asheville	North Carolina	United States	28803
165	Furiex Research Site	Charlotte	North Carolina	United States	28211
166	Furiex Research Site	Durham	North Carolina	United States	27713
167	Furiex Research Site	Fayetteville	North Carolina	United States	28304
168	Furiex Research Site	Greensboro	North Carolina	United States	27403
169	Furiex Research Site	Hickory	North Carolina	United States	28602
170	Furiex Research Site	High Point	North Carolina	United States	27262
171	Furiex Research Site	Kinston	North Carolina	United States	28501
172	Furiex Research Site	Lenoir	North Carolina	United States	28645
173	Furiex Research Site	Raleigh	North Carolina	United States	27609
174	Furiex Research Site	Raleigh	North Carolina	United States	27612
175	Furiex Research Site	Salisbury	North Carolina	United States	28144
176	Furiex Research Site	Winston-Salem	North Carolina	United States	27103
177	Furiex Research Site	Fargo	North Dakota	United States	58103
178	Furiex Research Site	Fargo	North Dakota	United States	58104
179	Furiex Research Site	Beavercreek	Ohio	United States	45432
180	Furiex Research Site	Berea	Ohio	United States	44017
181	Furiex Research Site	Centerville	Ohio	United States	45459
182	Furiex Research Site	Cincinnati	Ohio	United States	45212
183	Furiex Research Site	Cincinnati	Ohio	United States	45219
184	Furiex Research Site	Columbus	Ohio	United States	43215
185	Furiex Research Site	Dayton	Ohio	United States	45415
186	Furiex Research Site	Dayton	Ohio	United States	45419
187	Furiex Research Site	Englewood	Ohio	United States	45322
188	Furiex Research Site	Franklin	Ohio	United States	45005
189	Furiex Research Site	Marion	Ohio	United States	43302
190	Furiex Research Site	Miamisburg	Ohio	United States	45342
191	Furiex Research Site	Middleburg Heights	Ohio	United States	44130
192	Furiex Research Site	Wadsworth	Ohio	United States	44281
193	Furiex Research Site	Zanesville	Ohio	United States	43701
194	Furiex Research Site	Tulsa	Oklahoma	United States	74104
195	Furiex Research Site	Tulsa	Oklahoma	United States	74135
196	Furiex Research Site	Tulsa	Oklahoma	United States	74136
197	Furiex Research Site	Belle Vernon	Pennsylvania	United States	15012
198	Furiex Research Site	Jenkintown	Pennsylvania	United States	19046
199	Furiex Research Site	Johnstown	Pennsylvania	United States	15905
200	Furiex Research Site	Lansdale	Pennsylvania	United States	19446
201	Furiex Research Site	Philadelphia	Pennsylvania	United States	19142
202	Furiex Research Site	Philadelphia	Pennsylvania	United States	19152
203	Furiex Research Site	Pittsburgh	Pennsylvania	United States	15236
204	Furiex Research Site	Pittsburgh	Pennsylvania	United States	15243
205	Furiex Research Site	Uniontown	Pennsylvania	United States	15401
206	Furiex Research Site	Upper Saint Clair	Pennsylvania	United States	15241
207	Furiex Research Site	Cumberland	Rhode Island	United States	02864
208	Furiex Research Site	East Providence	Rhode Island	United States	02914
209	Furiex Research Site	Anderson	South Carolina	United States	29621
210	Furiex Research Site	Charleston	South Carolina	United States	29406
211	Furiex Research Site	Fort Mill	South Carolina	United States	29707
212	Furiex Research Site	Greenville	South Carolina	United States	29615
213	Furiex Research Site	Greer	South Carolina	United States	29650
214	Furiex Research Site	Greer	South Carolina	United States	29651
215	Furiex Research Site	Myrtle Beach	South Carolina	United States	29588
216	Furiex Research Site	Myrtle Beach	South Carolina	United States	29752
217	Furiex Research Site	Simpsonville	South Carolina	United States	29681
218	Furiex Research Site	Summerville	South Carolina	United States	29485
219	Furiex Research Site	Bristol	Tennessee	United States	37620
220	Furiex Research Site	Chattanooga	Tennessee	United States	37421
221	Furiex Research Site	Clarksville	Tennessee	United States	37043
222	Furiex Research Site	Columbia	Tennessee	United States	38401
223	Furiex Research Site	Franklin	Tennessee	United States	37064
224	Furiex Research Site	Johnson City	Tennessee	United States	37604
225	Furiex Research Site	Memphis	Tennessee	United States	38119
226	Furiex Research Site	Smyrna	Tennessee	United States	37167
227	Furiex Research Site	Austin	Texas	United States	78745
228	Furiex Research Site	Austin	Texas	United States	78756
229	Furiex Research Site	Baytown	Texas	United States	77521
230	Furiex Research Site	Beaumont	Texas	United States	77701
231	Furiex Research Site	Dallas	Texas	United States	75224
232	Furiex Research Site	El Paso	Texas	United States	79905
233	Furiex Research Site	Houston	Texas	United States	77074
234	Furiex Research Site	Houston	Texas	United States	77079
235	Furiex Research Site	Houston	Texas	United States	77089
236	Furiex Research Site	Houston	Texas	United States	77098
237	Furiex Research Site	Marshall	Texas	United States	75670
238	Furiex Research Site	Plano	Texas	United States	75024
239	Furiex Research Site	San Antonio	Texas	United States	78209
240	Furiex Research Site	San Antonio	Texas	United States	78229
241	Furiex Research Site	San Antonio	Texas	United States	78258
242	Furiex Research Site	Sugar Land	Texas	United States	77478
243	Furiex Research Site	Clinton	Utah	United States	84015
244	Furiex Research Site	Draper	Utah	United States	84020
245	Furiex Research Site	Logan	Utah	United States	84341
246	Furiex Research Site	Ogden	Utah	United States	84405
247	Furiex Research Site	Salt Lake City	Utah	United States	84102
248	Furiex Research Site	West Jordan	Utah	United States	84088
249	Furiex Research Site	Lynchburg	Virginia	United States	24502
250	Furiex Research Site	Richmond	Virginia	United States	23219
251	Furiex Research Site	Williamsburg	Virginia	United States	23185
252	Furiex Research Site	Spokane	Washington	United States	99202
253	Furiex Research Site	Spokane	Washington	United States	99204
254	Furiex Research Site	Spokane	Washington	United States	99208
255	Furiex Research Site	Wenatchee	Washington	United States	98801
256	Furiex Research Site	Morgantown	West Virginia	United States	26505
257	Furiex Research Site	Wauwatosa	Wisconsin	United States	53226
258	Furiex Research Site	Kamloops	British Columbia	Canada	V2C 1K7
259	Furiex Research Site	Kelowna	British Columbia	Canada	V1Y 1Z9
260	Furiex Research Site	Winnipeg	Manitoba	Canada	R3A 1R9
261	Furiex Research Site	Bridgewater	Nova Scotia	Canada	B4V 3N2
262	Furiex Research Site	Halifax	Nova Scotia	Canada	B3K 2M5
263	Furiex Research Site	Cambridge	Ontario	Canada	N1S 2M6
264	Furiex Research Site	London	Ontario	Canada	N6A 5R8
265	Furiex Research Site	Niagara Falls	Ontario	Canada	L2G 1J4
266	Furiex Research Site	Oshawa	Ontario	Canada	L1H 1B9
267	Furiex Research Site	Chesterfield	Derbyshire	United Kingdom	S40 4AA
268	Furiex Research Site	Blackpool	Lancashire	United Kingdom	FY3 7EN
269	Furiex Research Site	Thornton-Cleveleys	Lancashire	United Kingdom	FY5 3LF
270	Furiex Research Site	Burbage	Leicestershire	United Kingdom	LE10 2SE
271	Furiex Research Site	Leamington Spa	Warwickshire	United Kingdom	CV32 4RA
272	Furiex Research Site	Chippenham	Wiltshire	United Kingdom	SN14 6GT
273	Furiex Research Site	Bath		United Kingdom	BA2 3HT
274	Furiex Research Site	Bath		United Kingdom	BA2 4BY
275	Furiex Research Site	Coventry		United Kingdom	CV6 4DD
276	Furiex Research Site	Dorking		United Kingdom	RH4 1SD
277	Furiex Research Site	Haxey		United Kingdom	DN9 2HY
278	Furiex Research Site	London		United Kingdom	E11 1NR
279	Furiex Research Site	Shrewsbury		United Kingdom	SY3 8XQ
280	Furiex Research Site	Southampton		United Kingdom	SO16 6YD
281	Furiex Research Site	Strensall		United Kingdom	YO32 5UA
282	Furiex Research Site	Thornton		United Kingdom	FY5 2TZ
283	Furiex Research Site	Torpoint		United Kingdom	PL11 2JW

Sponsors and Collaborators

• Furiex Pharmaceuticals, Inc

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Furiex Pharmaceuticals, Inc
• ClinicalTrials.gov Identifier: NCT01553591
• Other Study ID Numbers: 27018966IBS3001; 2012-001600-38
• First Posted: Mar 14, 2012
• Last Update Posted: Sep 4, 2018
• Last Verified: Aug 1, 2018

• Additional relevant MeSH terms: Irritable Bowel Syndrome; Syndrome; Diarrhea; Eluxadoline

Study Results

Participant Flow

Arm/Group Title	Eluxadoline 75 mg	Eluxadoline 100 mg	Placebo
Arm/Group Description	Eluxadoline 75 mg tablets, orally, twice daily for up to 52 weeks period.	Eluxadoline 100 mg tablets, orally, twice daily for up to 52 weeks period.	Eluxadoline placebo matching tablets, orally, twice daily for up to 52 weeks period.
Period Title: Overall Study
STARTED	429	426	427
Attended Week 12 Visit	341	330	342
Attended Week 26 Visit	289	291	290
COMPLETED	257	257	269
NOT COMPLETED	172	169	158

Baseline Characteristics

Arm/Group Title	Eluxadoline 75 mg	Eluxadoline 100 mg	Placebo	Total
Arm/Group Description	Eluxadoline 75 mg tablets, orally, twice daily for up to 52 weeks period.	Eluxadoline 100 mg tablets, orally, twice daily for up to 52 weeks period.	Eluxadoline placebo matching tablets, orally, twice daily for up to 52 weeks period.	Total of all reporting groups
Overall Participants	429	426	427	1282
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	44.5 (13.18)	44.4 (13.91)	45.8 (14.10)	44.9 (13.74)
Age, Customized (Count of Participants)
18-40 years	173 40.3%	166 39%	159 37.2%	498 38.8%
41-64 years	227 52.9%	225 52.8%	217 50.8%	669 52.2%
≥65 years	29 6.8%	35 8.2%	51 11.9%	115 9%
Sex: Female, Male (Count of Participants)
Female	278 64.8%	283 66.4%	277 64.9%	838 65.4%
Male	151 35.2%	143 33.6%	150 35.1%	444 34.6%
Race/Ethnicity, Customized (Count of Participants)
White	374 87.2%	368 86.4%	370 86.7%	1112 86.7%
Black	46 10.7%	48 11.3%	46 10.8%	140 10.9%
Asian	3 0.7%	3 0.7%	4 0.9%	10 0.8%
American Indian or Alaska Native	1 0.2%	2 0.5%	1 0.2%	4 0.3%
Native Hawaiian or Other Pacific Islander	0 0%	1 0.2%	0 0%	1 0.1%
Other	5 1.2%	4 0.9%	6 1.4%	15 1.2%
Race/Ethnicity, Customized (Count of Participants)
Hispanic or Latino	119 27.7%	117 27.5%	125 29.3%	361 28.2%
Not Hispanic or Latino	310 72.3%	309 72.5%	302 70.7%	921 71.8%
Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	30.70 (7.421)	31.22 (7.858)	30.63 (7.253)	30.85 (7.513)

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Who Were Composite Responders Based on Improvements From Baseline in Daily Worst Abdominal Pain And Daily Stool Consistency Scores
Description	Composite responders were defined as a participant who met the daily response criteria for at least 50% of the days with diary entries during the interval of interest. A participant must had met both of the following criteria on a given day to be a daily responder: 1) Daily pain response: worst abdominal pain scores in the past 24 hours improved by ≥30% compared to baseline (average of daily worst abdominal pain the week prior to randomization). 2) Daily stool consistency response: Bristol Stool Scale (BSS) score <5 (ie, score of 1, 2, 3, or 4) or the absence of a bowel movement if accompanied by ≥30% improvement in worst abdominal pain compared to baseline pain. Bristol stool scale was defined as 7-point Scale in which a score of 1 = separate hard lumps, 2 = sausage shaped but lumpy, 3 = sausage-like with cracks on the surface, 4 = sausage-like but smooth and soft, 5 = soft blobs with clear cut edges, 6 = fluffy pieces with ragged edges, and 7 = watery with no solid pieces.
Time Frame	Up to 12 Weeks

Outcome Measure Data

Analysis Population Description

Intent to Treat (ITT) analysis set included all participants who were randomized into a treatment group and presents data for participants according to their randomization assignment.

Arm/Group Title	Eluxadoline 75 mg	Eluxadoline 100 mg	Placebo
Arm/Group Description	Eluxadoline 75 mg tablets, orally, twice daily for up to 52 weeks period.	Eluxadoline 100 mg tablets, orally, twice daily for up to 52 weeks period.	Eluxadoline placebo matching tablets, orally, twice daily for up to 52 weeks period.
Measure Participants	427	426	427
Number [percentage of participants]	23.9 5.6%	25.1 5.9%	17.1 4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Eluxadoline 75 mg, Placebo
	Comments	The family-wise error rate was controlled by Bonferroni adjustment for each active dose versus placebo.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.014
	Comments	Significance level of 0.025
	Method	Chi-square test statistic
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Eluxadoline 100 mg, Placebo
	Comments	The family-wise error rate was controlled by Bonferroni adjustment for each active dose versus placebo.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.004
	Comments	Significance level of 0.025
	Method	Chi-square test statistic
	Comments

2. Secondary Outcome

Title	Percentage of Participants Who Were Composite Responders Based on Improvements From Baseline in Daily Worst Abdominal Pain And Daily Stool Consistency Scores
Description	Composite responders were defined as a participant who met the daily response criteria for at least 50% of the days with diary entries during the interval of interest. A participant must had met both of the following criteria on a given day to be a daily responder: 1) Daily pain response: worst abdominal pain scores in the past 24 hours improved by ≥30% compared to baseline (average of daily worst abdominal pain the week prior to randomization). 2) Daily stool consistency response: Bristol Stool Scale (BSS) score <5 (ie, score of 1, 2, 3, or 4) or the absence of a bowel movement if accompanied by ≥30% improvement in worst abdominal pain compared to baseline pain. Bristol stool scale was defined as 7-point Scale in which a score of 1 = separate hard lumps, 2 = sausage shaped but lumpy, 3 = sausage-like with cracks on the surface, 4 = sausage-like but smooth and soft, 5 = soft blobs with clear cut edges, 6 = fluffy pieces with ragged edges, and 7 = watery with no solid pieces.
Time Frame	Up to 26 Weeks

Outcome Measure Data

Analysis Population Description

ITT analysis set included all participants who were randomized into a treatment group and presents data for participants according to their randomization assignment.

Arm/Group Title	Eluxadoline 75 mg	Eluxadoline 100 mg	Placebo
Arm/Group Description	Eluxadoline 75 mg tablets, orally, twice daily for up to 52 weeks period.	Eluxadoline 100 mg tablets, orally, twice daily for up to 52 weeks period.	Eluxadoline placebo matching tablets, orally, twice daily for up to 52 weeks period.
Measure Participants	427	426	427
Number [percentage of participants]	23.4 5.5%	29.3 6.9%	19.0 4.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Eluxadoline 75 mg, Placebo
	Comments	The family-wise error rate was controlled by Bonferroni adjustment for each active dose versus placebo.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.112
	Comments	Significance level of 0.025
	Method	Chi-square test statistic
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Eluxadoline 100 mg, Placebo
	Comments	The family-wise error rate was controlled by Bonferroni adjustment for each active dose versus placebo.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Significance level of 0.025
	Method	Chi-square test statistic
	Comments

3. Secondary Outcome

Title	Percentage of Participants Who Were Pain Responders In Daily Worst Abdominal Pain Scores by Intervals
Description	Pain responders were defined as participants who met the daily pain response criteria (ie, the worst abdominal pain score in the past 24 hours improved by ≥30% compared to baseline) for at least 50% of days with diary entries during each interval. A participant must have had a minimum of 20 days of diary entries over any 4-week interval, a minimum of 60 days of diary entries over the 12-week interval, and a minimum of 110 days of diary entries over the 26-week interval to be a responder.
Time Frame	12-week interval (Weeks 1-12), 26-week interval (Weeks 1-26), and 4-week interval (Weeks 1-4, 5-8, 9-12, 13-16, 17-20, and 21-24)

Outcome Measure Data

Analysis Population Description

ITT analysis set included all participants who were randomized into a treatment group and presents data for participants according to their randomization assignment.

Arm/Group Title	Eluxadoline 75 mg	Eluxadoline 100 mg	Placebo
Arm/Group Description	Eluxadoline 75 mg tablets, orally, twice daily for up to 52 weeks period.	Eluxadoline 100 mg tablets, orally, twice daily for up to 52 weeks period.	Eluxadoline placebo matching tablets, orally, twice daily for up to 52 weeks period.
Measure Participants	427	426	427
Responders during Weeks 1-12	42.4 9.9%	43.2 10.1%	39.6 9.3%
Responders during Weeks 1-26	45.2 10.5%	46.5 10.9%	43.3 10.1%
Responders during Weeks 1-4	40.5 9.4%	44.4 10.4%	37.5 8.8%
Responders during Weeks 5-8	44.5 10.4%	47.2 11.1%	45.4 10.6%
Responders during Weeks 9-12	44.5 10.4%	45.8 10.8%	43.8 10.3%
Responders during Weeks 13-16	44.3 10.3%	44.1 10.4%	45.4 10.6%
Responders during Weeks 17-20	44.7 10.4%	43.2 10.1%	41.5 9.7%
Responders during Weeks 21-24	44.7 10.4%	42.0 9.9%	38.4 9%

4. Secondary Outcome

Title	Percentage of Participants Who Were Responders In Daily Stool Consistency Scores by Intervals
Description	Stool consistency responders: participants who met daily stool consistency response criterion (ie,score of 1, 2, 3, or 4 or absence of bowel movement if accompanied by ≥30% improvement in worst abdominal pain compared to baseline pain) for at least 50% of days with diary entries during each interval. BSS was defined as 7-point Scale in which score of 1= separate hard lumps, 2= sausage shaped but lumpy, 3= sausage-like with cracks on the surface, 4= sausage-like but smooth and soft, 5= soft blobs with clear cut edges, 6= fluffy pieces with ragged edges, and 7= watery with no solid pieces. A participant must have had a minimum of 20 days of diary entries over any 4-week interval, a minimum of 60 days of diary entries over 12-week interval, and a minimum of 110 days of diary entries over 26-week interval to be a responder.
Time Frame	12-week interval (Weeks 1-12), 26-week interval (Weeks 1-26), and 4-week interval (Weeks 1-4, 5-8, 9-12, 13-16, 17-20, and 21-24)

Outcome Measure Data

Analysis Population Description

ITT analysis set included all participants who were randomized into a treatment group and presents data for participants according to their randomization assignment.

Arm/Group Title	Eluxadoline 75 mg	Eluxadoline 100 mg	Placebo
Arm/Group Description	Eluxadoline 75 mg tablets, orally, twice daily for up to 52 weeks period.	Eluxadoline 100 mg tablets, orally, twice daily for up to 52 weeks period.	Eluxadoline placebo matching tablets, orally, twice daily for up to 52 weeks period.
Measure Participants	427	426	427
Responders during Weeks 1-12	30.0 7%	34.3 8.1%	22.0 5.2%
Responders during Weeks 1-26	28.1 6.6%	34.0 8%	24.1 5.6%
Responders during Weeks 1-4	28.8 6.7%	31.5 7.4%	19.0 4.4%
Responders during Weeks 5-8	31.1 7.2%	35.2 8.3%	24.1 5.6%
Responders during Weeks 9-12	29.0 6.8%	35.2 8.3%	24.6 5.8%
Responders during Weeks 13-16	27.6 6.4%	32.9 7.7%	24.4 5.7%
Responders during Weeks 17-20	31.9 7.4%	31.5 7.4%	23.7 5.6%
Responders during Weeks 21-24	30.2 7%	30.3 7.1%	24.4 5.7%

5. Secondary Outcome

Title	Percentage of Participants Who Were Responders In Irritable Bowel Syndrome, Diarrhea Predominant (IBS-d) Global Symptom Scale by Intervals
Description	IBS-d global symptom responders were defined as those participants who met the daily IBS-d global symptom response criteria (ie, IBS-d global symptom score of 0 [none] or 1 [mild]; or a daily IBS-d global symptom score improved by ≥2.0 compared to the baseline average) for at least 50% of days with diary entries during each interval. IBS-d Global Symptom Scale was a 5 point scale, score ranging from 0 to 4. 0= no symptoms, 1= mild symptoms, 2= moderate symptoms, 3= severe symptoms and 4 = very severe symptoms. A participant must have had a minimum of 20 days of diary entries over any 4-week interval, a minimum of 60 days of diary entries over the 12-week interval, and a minimum of 110 days of diary entries over the 26-week interval to be a responder.
Time Frame	12-week interval (Weeks 1-12), 26-week interval (Weeks 1-26), and 4-week interval (Weeks 1-4, 5-8, 9-12, 13-16, 17-20, and 21-24)

Outcome Measure Data

Analysis Population Description

ITT analysis set included all participants who were randomized into a treatment group and presents data for participants according to their randomization assignment.

Arm/Group Title	Eluxadoline 75 mg	Eluxadoline 100 mg	Placebo
Arm/Group Description	Eluxadoline 75 mg tablets, orally, twice daily for up to 52 weeks period.	Eluxadoline 100 mg tablets, orally, twice daily for up to 52 weeks period.	Eluxadoline placebo matching tablets, orally, twice daily for up to 52 weeks period.
Measure Participants	427	426	427
Responders during Weeks 1-12	35.1 8.2%	34.7 8.1%	28.8 6.7%
Responders during Weeks 1-26	36.3 8.5%	37.1 8.7%	32.3 7.6%
Responders during Weeks 1-4	32.6 7.6%	31.9 7.5%	26.9 6.3%
Responders during Weeks 5-8	37.0 8.6%	38.7 9.1%	32.8 7.7%
Responders during Weeks 9-12	35.6 8.3%	36.6 8.6%	34.0 8%
Responders during Weeks 13-16	35.8 8.3%	35.9 8.4%	35.4 8.3%
Responders during Weeks 17-20	37.5 8.7%	36.4 8.5%	33.3 7.8%
Responders during Weeks 21-24	36.8 8.6%	35.2 8.3%	29.5 6.9%

6. Secondary Outcome

Title	Percentage of Participants Who Were Responders to the Irritable Bowel Syndrome Quality of Life Measure (IBS-QoL) Scale
Description	IBS-QoL responders were defined as participants who achieved at least a 14-point improvement in IBS-QoL total score from baseline to the applicable visit. The IBS-QoL consists of 34 items each with a 5-point response scale, where 1 generally represents better responses on items and 5 represents worse responses. The individual responses to the answered items were summed and standardized for a total score and then transformed to a 0- to 100-point (0= worst; 100=better) scale for ease of interpretation.
Time Frame	Weeks 4, 8, 12, 18, 26, 36, 44, and 52 (End of Treatment [EOT])

Outcome Measure Data

Analysis Population Description

ITT analysis set included all participants who were randomized into a treatment group and presents data for participants according to their randomization assignment.

Arm/Group Title	Eluxadoline 75 mg	Eluxadoline 100 mg	Placebo
Arm/Group Description	Eluxadoline 75 mg tablets, orally, twice daily for up to 52 weeks period.	Eluxadoline 100 mg tablets, orally, twice daily for up to 52 weeks period.	Eluxadoline placebo matching tablets, orally, twice daily for up to 52 weeks period.
Measure Participants	427	426	427
Responders at Week 4	42.6 9.9%	44.1 10.4%	37.0 8.7%
Responders at Week 8	43.8 10.2%	49.8 11.7%	41.7 9.8%
Responders at Week 12	44.3 10.3%	48.1 11.3%	44.0 10.3%
Responders at Week 18	44.5 10.4%	45.1 10.6%	43.3 10.1%
Responders at Week 26	45.4 10.6%	45.1 10.6%	40.0 9.4%
Responders at Week 36	41.0 9.6%	43.2 10.1%	39.6 9.3%
Responders at Week 44	39.6 9.2%	40.1 9.4%	37.5 8.8%
Responders at Week 52/EOT	49.4 11.5%	54.9 12.9%	47.8 11.2%

7. Secondary Outcome

Title	Percentage of Participants With Irritable Bowel Syndrome - Adequate Relief (IBS-AR) Scale
Description	Adequate relief of IBS symptoms was assessed once weekly by participants answering the IBS-AR item in the electronic diary. IBS-AR responders were defined as participants with a weekly response of "Yes" to adequate relief of their IBS symptoms for at least 50% of the total weeks during the interval. A participant must have had a positive response on ≥6 weeks for the 12-week interval and ≥13 weeks for the 26-week interval, regardless of diary compliance, to be a responder.
Time Frame	12-week interval (Weeks 1-12) and 26-week interval (Weeks 1-26)

Outcome Measure Data

Analysis Population Description

ITT analysis set included all participants who were randomized into a treatment group and presents data for participants according to their randomization assignment.

Arm/Group Title	Eluxadoline 75 mg	Eluxadoline 100 mg	Placebo
Arm/Group Description	Eluxadoline 75 mg tablets, orally, twice daily for up to 52 weeks period.	Eluxadoline 100 mg tablets, orally, twice daily for up to 52 weeks period.	Eluxadoline placebo matching tablets, orally, twice daily for up to 52 weeks period.
Measure Participants	427	426	427
Responders during Weeks 1-12	52.9 12.3%	54.2 12.7%	43.8 10.3%
Responders during Weeks 1-26	45.7 10.7%	49.5 11.6%	40.0 9.4%

8. Secondary Outcome

Title	Change From Baseline in Daily Abdominal Discomfort Scores
Description	Symptoms of abdominal discomfort were recorded on a 0 to 10 scale, where 0 corresponded to no discomfort and 10 corresponded to worst imaginable discomfort. A negative change from Baseline indicates the discomfort decreased.
Time Frame	Baseline, Weeks 4, 12 and 26

Outcome Measure Data

Analysis Population Description

Intent to Treat (ITT) analysis set included all participants who were randomized into a treatment group and presents data for participants according to their randomization assignment. Here, number analyzed is the participants who were evaluable at specific time point.

Arm/Group Title	Eluxadoline 75 mg	Eluxadoline 100 mg	Placebo
Arm/Group Description	Eluxadoline 75 mg tablets, orally, twice daily for up to 52 weeks period.	Eluxadoline 100 mg tablets, orally, twice daily for up to 52 weeks period.	Eluxadoline placebo matching tablets, orally, twice daily for up to 52 weeks period.
Measure Participants	427	426	427
Change at Week 4	-2.24 (2.204)	-2.41 (2.326)	-2.01 (2.156)
Change at Week 12	-2.75 (2.534)	-2.97 (2.526)	-2.61 (2.444)
Change at Week 26	-3.27 (2.578)	-3.52 (2.543)	-3.00 (2.579)

9. Secondary Outcome

Title	Change From Baseline in Daily Abdominal Bloating Scores
Description	Symptoms of abdominal bloating were recorded on a 0 to 10 scale, where 0 corresponded to no bloating and 10 corresponded to worst imaginable bloating. A negative change from Baseline indicates the bloating decreased.
Time Frame	Baseline, Weeks 4, 12 and 26

Outcome Measure Data

Analysis Population Description

Intent to Treat (ITT) analysis set included all participants who were randomized into a treatment group and presents data for participants according to their randomization assignment. Here, number analyzed is the participants who were evaluable at specific time point.

Arm/Group Title	Eluxadoline 75 mg	Eluxadoline 100 mg	Placebo
Arm/Group Description	Eluxadoline 75 mg tablets, orally, twice daily for up to 52 weeks period.	Eluxadoline 100 mg tablets, orally, twice daily for up to 52 weeks period.	Eluxadoline placebo matching tablets, orally, twice daily for up to 52 weeks period.
Measure Participants	427	426	427
Change at Week 4	-1.84 (2.303)	-2.03 (2.333)	-1.72 (2.303)
Change at Week 12	-2.42 (2.616)	-2.49 (2.533)	-2.16 (2.544)
Change at Week 26	-2.76 (2.823)	-2.94 (2.576)	-2.47 (2.562)

10. Secondary Outcome

Title	Number of Bowel Movements Per Day
Description	Participants recorded the number of bowel movements over 24 hours daily throughout the treatment.
Time Frame	Weeks 4, 12 and 26

Outcome Measure Data

Analysis Population Description

Intent to Treat (ITT) analysis set included all participants who were randomized into a treatment group and presents data for participants according to their randomization assignment. Here, number analyzed is the participants who were evaluable at specific time point.

Arm/Group Title	Eluxadoline 75 mg	Eluxadoline 100 mg	Placebo
Arm/Group Description	Eluxadoline 75 mg tablets, orally, twice daily for up to 52 weeks period.	Eluxadoline 100 mg tablets, orally, twice daily for up to 52 weeks period.	Eluxadoline placebo matching tablets, orally, twice daily for up to 52 weeks period.
Measure Participants	427	426	427
Week 4	3.20 (2.090)	3.20 (2.236)	3.72 (2.100)
Week 12	3.12 (2.143)	3.09 (2.318)	3.44 (1.987)
Week 26	2.83 (2.158)	2.79 (2.270)	3.12 (1.831)

11. Secondary Outcome

Title	Number of Bowel Incontinence Episodes
Description	Participants recorded the number of incontinence episodes over 24 hours daily throughout the treatment.
Time Frame	Weeks 4, 12 and 26

Outcome Measure Data

Analysis Population Description

Intent to Treat (ITT) analysis set included all participants who were randomized into a treatment group and presents data for participants according to their randomization assignment. Here, number analyzed is the participants who were evaluable at specific time point.

Arm/Group Title	Eluxadoline 75 mg	Eluxadoline 100 mg	Placebo
Arm/Group Description	Eluxadoline 75 mg tablets, orally, twice daily for up to 52 weeks period.	Eluxadoline 100 mg tablets, orally, twice daily for up to 52 weeks period.	Eluxadoline placebo matching tablets, orally, twice daily for up to 52 weeks period.
Measure Participants	427	426	427
Week 4	0.74 (1.603)	0.72 (1.534)	0.93 (2.140)
Week 12	0.63 (1.542)	0.71 (1.663)	0.94 (3.612)
Week 26	0.46 (1.298)	0.58 (1.358)	0.69 (1.500)

12. Secondary Outcome

Title	Number of Bowel Incontinence Free Days
Description	An incontinence free day was one where the participant reports zero incontinence episodes. The number of incontinence free days for a participant was assessed each week based on the number of reported days.
Time Frame	Weeks 4, 12 and 26

Outcome Measure Data

Analysis Population Description

Intent to Treat (ITT) analysis set included all participants who were randomized into a treatment group and presents data for participants according to their randomization assignment. Here, number analyzed is the participants who were evaluable at specific time point.

Arm/Group Title	Eluxadoline 75 mg	Eluxadoline 100 mg	Placebo
Arm/Group Description	Eluxadoline 75 mg tablets, orally, twice daily for up to 52 weeks period.	Eluxadoline 100 mg tablets, orally, twice daily for up to 52 weeks period.	Eluxadoline placebo matching tablets, orally, twice daily for up to 52 weeks period.
Measure Participants	427	426	427
Week 4	4.83 (2.745)	4.95 (2.618)	4.63 (2.741)
Week 12	4.96 (2.672)	4.79 (2.671)	4.64 (2.704)
Week 26	4.39 (2.465)	4.35 (2.449)	4.00 (2.539)

13. Secondary Outcome

Title	Number of Urgency Episodes Per Day
Description	Participants recorded the number of urgency episodes over 24 hours daily throughout the treatment.
Time Frame	Weeks 4, 12 and 26

Outcome Measure Data

Analysis Population Description

Intent to Treat (ITT) analysis set included all participants who were randomized into a treatment group and presents data for participants according to their randomization assignment. Here, number analyzed is the participants who were evaluable at specific time point.

Arm/Group Title	Eluxadoline 75 mg	Eluxadoline 100 mg	Placebo
Arm/Group Description	Eluxadoline 75 mg tablets, orally, twice daily for up to 52 weeks period.	Eluxadoline 100 mg tablets, orally, twice daily for up to 52 weeks period.	Eluxadoline placebo matching tablets, orally, twice daily for up to 52 weeks period.
Measure Participants	427	426	427
Week 4	1.75 (1.840)	1.74 (1.879)	2.19 (2.082)
Week 12	1.55 (1.777)	1.60 (1.995)	1.81 (1.883)
Week 26	1.25 (1.773)	1.45 (2.113)	1.55 (1.853)

14. Secondary Outcome

Title	IBS-QoL Total Scores
Description	The IBS-QoL consists of 34 items each with a 5-point response scale, where 1 generally represents better responses on items and 5 represents worse responses. The individual responses to the answered items were summed and standardized for a total score and then transformed to a 0- to 100- point scale (0=worst; 100=better) for ease of interpretation.
Time Frame	Weeks 4, 8, 12, 18, 26, 36, 44, and 52 (EOT)

Outcome Measure Data

Analysis Population Description

Intent to Treat (ITT) analysis set included all participants who were randomized into a treatment group and presents data for participants according to their randomization assignment. Here, number analyzed is the participants who were evaluable at specific time point.

Arm/Group Title	Eluxadoline 75 mg	Eluxadoline 100 mg	Placebo
Arm/Group Description	Eluxadoline 75 mg tablets, orally, twice daily for up to 52 weeks period.	Eluxadoline 100 mg tablets, orally, twice daily for up to 52 weeks period.	Eluxadoline placebo matching tablets, orally, twice daily for up to 52 weeks period.
Measure Participants	427	426	427
Responders at Week 4	62.37 (23.747)	64.34 (24.049)	57.13 (24.318)
Responders at Week 8	66.22 (23.919)	67.73 (23.421)	59.46 (24.323)
Responders at Week 12	66.80 (24.131)	68.93 (23.938)	61.72 (25.545)
Responders at Week 18	68.75 (23.902)	70.05 (23.662)	63.60 (24.618)
Responders at Week 26	70.74 (23.312)	71.34 (23.106)	64.83 (24.380)
Responders at Week 36	70.53 (23.043)	72.37 (23.246)	66.47 (24.034)
Responders at Week 44	70.30 (24.408)	72.15 (24.398)	65.59 (25.045)
Responders at Week 52/EOT	68.85 (24.754)	71.02 (24.294)	63.93 (26.359)

15. Secondary Outcome

Title	Change From Baseline in IBS-QoL Total Scores
Description	The IBS-QoL consists of 34 items each with a 5-point response scale, where 1 generally represents better responses on items and 5 represents worse responses. The individual responses to the answered items were summed and standardized for a total score and then transformed to a 0- to 100- point scale (0=worst; 100=better) for ease of interpretation. A positive change from Baseline indicates that quality of life improved.
Time Frame	Baseline, Weeks 4, 8, 12, 18, 26, 36, 44, and 52/EOT

Outcome Measure Data

Analysis Population Description

Intent to Treat (ITT) analysis set included all participants who were randomized into a treatment group and presents data for participants according to their randomization assignment. Here, number analyzed is the participants who were evaluable at specific time point.

Arm/Group Title	Eluxadoline 75 mg	Eluxadoline 100 mg	Placebo
Arm/Group Description	Eluxadoline 75 mg tablets, orally, twice daily for up to 52 weeks period.	Eluxadoline 100 mg tablets, orally, twice daily for up to 52 weeks period.	Eluxadoline placebo matching tablets, orally, twice daily for up to 52 weeks period.
Measure Participants	427	426	427
Change at Week 4	16.49 (20.693)	17.86 (20.191)	13.25 (18.475)
Change at Week 8	19.88 (21.855)	21.08 (21.347)	15.76 (19.398)
Change at Week 12	20.26 (23.412)	22.76 (22.592)	17.76 (21.523)
Change at Week 18	23.09 (23.846)	24.18 (23.025)	19.80 (22.368)
Change at Week 26	25.28 (23.679)	25.80 (23.998)	20.62 (22.306)
Change at Week 36	25.37 (24.603)	27.18 (24.201)	22.64 (23.414)
Change at Week 44	25.13 (24.948)	26.64 (25.017)	21.77 (23.977)
Change at Week 52/EOT	23.30 (23.959)	25.86 (23.854)	20.66 (23.956)

Adverse Events

Time Frame	Up to 54 weeks
Adverse Event Reporting Description	The Safety Analysis Set included enrolled participants who received at least one dose of study drug and presents data according to the actual treatment received. A total of 53 participants were randomized to the Eluxadoline 75 mg arm but received Eluxadoline 100 mg due to site misallocations, these participants were included in Eluxadoline 100 mg arm. Therefore, the number of participants in the Eluxadoline 100 mg arm were more than the number of participants who were randomized to this arm.
Arm/Group Title	Eluxadoline 75 mg		Eluxadoline 100 mg		Placebo
Arm/Group Description	Eluxadoline 75 mg tablets, orally, twice daily for up to 52 weeks period.		Eluxadoline 100 mg tablets, orally, twice daily for up to 52 weeks period.		Eluxadoline placebo matching tablets, orally, twice daily for up to 52 weeks period.
All Cause Mortality
	Eluxadoline 75 mg		Eluxadoline 100 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/428 (0%)		0/479 (0%)		0/427 (0%)
Serious Adverse Events
	Eluxadoline 75 mg		Eluxadoline 100 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	25/428 (5.8%)		27/479 (5.6%)		16/427 (3.7%)
Cardiac disorders
Acute myocardial infarction	0/428 (0%)		1/479 (0.2%)		0/427 (0%)
Angina pectoris	1/428 (0.2%)		2/479 (0.4%)		0/427 (0%)
Angina unstable	0/428 (0%)		1/479 (0.2%)		0/427 (0%)
Coronary artery disease	0/428 (0%)		1/479 (0.2%)		0/427 (0%)
Myocardial infarction	1/428 (0.2%)		0/479 (0%)		0/427 (0%)
Stress cardiomyopathy	0/428 (0%)		1/479 (0.2%)		0/427 (0%)
Eye disorders
Papilloedema	0/428 (0%)		0/479 (0%)		1/427 (0.2%)
Gastrointestinal disorders
Abdominal pain	1/428 (0.2%)		3/479 (0.6%)		0/427 (0%)
Abdominal pain upper	1/428 (0.2%)		0/479 (0%)		0/427 (0%)
Colitis	0/428 (0%)		1/479 (0.2%)		0/427 (0%)
Diverticulum intestinal hemorrhagic	0/428 (0%)		1/479 (0.2%)		0/427 (0%)
Hemorrhoids	0/428 (0%)		0/479 (0%)		1/427 (0.2%)
Hiatus hernia	1/428 (0.2%)		0/479 (0%)		0/427 (0%)
Irritable bowel syndrome	0/428 (0%)		0/479 (0%)		1/427 (0.2%)
Pancreatitis	1/428 (0.2%)		1/479 (0.2%)		0/427 (0%)
Pancreatitis acute	1/428 (0.2%)		2/479 (0.4%)		0/427 (0%)
Small intestinal obstruction	0/428 (0%)		1/479 (0.2%)		1/427 (0.2%)
General disorders
Chest pain	1/428 (0.2%)		0/479 (0%)		1/427 (0.2%)
Hepatobiliary disorders
Cholecystitis chronic	0/428 (0%)		1/479 (0.2%)		0/427 (0%)
Infections and infestations
Appendicitis	0/428 (0%)		0/479 (0%)		1/427 (0.2%)
Bronchitis	1/428 (0.2%)		1/479 (0.2%)		0/427 (0%)
Cellulitis	0/428 (0%)		1/479 (0.2%)		0/427 (0%)
Diverticulitis	2/428 (0.5%)		1/479 (0.2%)		0/427 (0%)
Escherichia infection	0/428 (0%)		0/479 (0%)		1/427 (0.2%)
Gastroenteritis	0/428 (0%)		1/479 (0.2%)		0/427 (0%)
Influenza	2/428 (0.5%)		0/479 (0%)		0/427 (0%)
Necrotising fasciitis	1/428 (0.2%)		0/479 (0%)		0/427 (0%)
Pneumonia	0/428 (0%)		1/479 (0.2%)		0/427 (0%)
Rectal abscess	0/428 (0%)		1/479 (0.2%)		0/427 (0%)
Injury, poisoning and procedural complications
Ankle fracture	0/428 (0%)		0/479 (0%)		1/427 (0.2%)
Joint dislocation	1/428 (0.2%)		0/479 (0%)		0/427 (0%)
Procedural complication	0/428 (0%)		0/479 (0%)		1/427 (0.2%)
Radius fracture	0/428 (0%)		1/479 (0.2%)		0/427 (0%)
Road traffic accident	1/428 (0.2%)		2/479 (0.4%)		0/427 (0%)
Skull fracture	0/428 (0%)		1/479 (0.2%)		0/427 (0%)
Spinal compression fracture	0/428 (0%)		0/479 (0%)		1/427 (0.2%)
Subdural hematoma	0/428 (0%)		1/479 (0.2%)		0/427 (0%)
Investigations
Alanine aminotransferase increased	0/428 (0%)		1/479 (0.2%)		0/427 (0%)
Aspartate aminotransferase increased	0/428 (0%)		1/479 (0.2%)		0/427 (0%)
Hepatic enzyme increased	0/428 (0%)		1/479 (0.2%)		0/427 (0%)
Metabolism and nutrition disorders
Dehydration	0/428 (0%)		1/479 (0.2%)		1/427 (0.2%)
Diabetes mellitus	0/428 (0%)		1/479 (0.2%)		0/427 (0%)
Obesity	0/428 (0%)		0/479 (0%)		1/427 (0.2%)
Musculoskeletal and connective tissue disorders
Arthritis	0/428 (0%)		1/479 (0.2%)		0/427 (0%)
Back pain	0/428 (0%)		1/479 (0.2%)		0/427 (0%)
Intervertebral disc protrusion	1/428 (0.2%)		0/479 (0%)		0/427 (0%)
Musculoskeletal pain	0/428 (0%)		0/479 (0%)		1/427 (0.2%)
Osteoarthritis	2/428 (0.5%)		0/479 (0%)		1/427 (0.2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Thyroid neoplasm	1/428 (0.2%)		0/479 (0%)		0/427 (0%)
Liposarcoma	0/428 (0%)		0/479 (0%)		1/427 (0.2%)
Nervous system disorders
Hemiparesis	0/428 (0%)		0/479 (0%)		1/427 (0.2%)
Intracranial pressure increased	0/428 (0%)		1/479 (0.2%)		0/427 (0%)
Presyncope	1/428 (0.2%)		0/479 (0%)		0/427 (0%)
Primary progressive multiple sclerosis	1/428 (0.2%)		0/479 (0%)		0/427 (0%)
Syncope	1/428 (0.2%)		0/479 (0%)		0/427 (0%)
Syncope vasovagal	1/428 (0.2%)		0/479 (0%)		0/427 (0%)
Pregnancy, puerperium and perinatal conditions
Abortion spontaneousa	1/428 (0.2%)		0/479 (0%)		0/427 (0%)
Psychiatric disorders
Anxiety	0/428 (0%)		2/479 (0.4%)		1/427 (0.2%)
Conversion disorder	1/428 (0.2%)		0/479 (0%)		0/427 (0%)
Depression	1/428 (0.2%)		0/479 (0%)		0/427 (0%)
Renal and urinary disorders
Hydronephrosis	0/428 (0%)		1/479 (0.2%)		0/427 (0%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	0/428 (0%)		1/479 (0.2%)		0/427 (0%)
Asthma	0/428 (0%)		1/479 (0.2%)		1/427 (0.2%)
Respiratory failure	0/428 (0%)		1/479 (0.2%)		0/427 (0%)
Vascular disorders
Arteriosclerosis	0/428 (0%)		1/479 (0.2%)		0/427 (0%)
Deep vein thrombosis	0/428 (0%)		1/479 (0.2%)		0/427 (0%)
Hematoma	0/428 (0%)		1/479 (0.2%)		0/427 (0%)
Hypertension	1/428 (0.2%)		0/479 (0%)		0/427 (0%)
Hypertensive crisis	1/428 (0.2%)		0/479 (0%)		0/427 (0%)
Other (Not Including Serious) Adverse Events
	Eluxadoline 75 mg		Eluxadoline 100 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	84/428 (19.6%)		89/479 (18.6%)		47/427 (11%)
Gastrointestinal disorders
Constipation	27/428 (6.3%)		44/479 (9.2%)		12/427 (2.8%)
Nausea	34/428 (7.9%)		31/479 (6.5%)		19/427 (4.4%)
Vomiting	22/428 (5.1%)		19/479 (4%)		7/427 (1.6%)
Infections and infestations
Upper respiratory tract infection	14/428 (3.3%)		25/479 (5.2%)		15/427 (3.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The sponsor will work with the Investigators to determine how any manuscript or publication in a scientific journal is written and edited, the number and order of authors, the publication to which it will be submitted, and other related issues. The sponsor has final approval authority over all such issues. Data are the property of the sponsor and cannot be published without prior authorization from the sponsor, but data and publication thereof will not be unduly withheld.