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: NCT01553747
• Collaborator: (none)
• Enrollment: 1,146
• Locations: 253
• Arms: 3
• Actual Duration (Months): 19.4
• 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: 1146 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: Jan 9, 2014
• Actual Study Completion Date: Jan 9, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Eluxadoline 75 mg Eluxadoline 75 mg tablets, orally, twice daily for up to 26 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 26 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 26 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 participants 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 participants 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 and 30 (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. Change From Baseline in IBS-QoL Total Scores [Baseline, Weeks 4, 8, 12, 18, 26 and 30/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 is 18 to 80 years old

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

3. 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

• 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	Birmingham	Alabama	United States	35209
2	Furiex Research Site	Birmingham	Alabama	United States	35242
3	Furiex Research Site	Decatur	Alabama	United States	35603
4	Furiex Research Site	Huntsville	Alabama	United States	35801
5	Furiex Research Site	Mobile	Alabama	United States	36608
6	Furiex Research Site	Montgomery	Alabama	United States	36109
7	Furiex Research Site	Sheffield	Alabama	United States	35660
8	Furiex Research Site	Tuscaloosa	Alabama	United States	35401
9	Furiex Research Site	Glendale	Arizona	United States	85306
10	Furiex Research Site	Glendale	Arizona	United States	85308
11	Furiex Research Site	Mesa	Arizona	United States	85206
12	Furiex Research Site	Phoenix	Arizona	United States	85023
13	Furiex Research Site	Phoenix	Arizona	United States	85032
14	Furiex Research Site	Tucson	Arizona	United States	85704
15	Furiex Research Site	Tucson	Arizona	United States	85712
16	Furiex Research Site	Jonesboro	Arkansas	United States	72401
17	Furiex Research Site	Little Rock	Arkansas	United States	72205
18	Furiex Research Site	Sherwood	Arkansas	United States	72120
19	Furiex Research Site	Anaheim	California	United States	92801
20	Furiex Research Site	Chula Vista	California	United States	91910
21	Furiex Research Site	Encinitas	California	United States	92024
22	Furiex Research Site	Garden Grove	California	United States	92840
23	Furiex Research Site	Huntington Beach	California	United States	92647
24	Furiex Research Site	Irvine	California	United States	92604
25	Furiex Research Site	La Mesa	California	United States	91942
26	Furiex Research Site	La Mirada	California	United States	90638
27	Furiex Research Site	Laguna Hills	California	United States	92653
28	Furiex Research Site	Lakewood	California	United States	90805
29	Furiex Research Site	Lincoln	California	United States	95648
30	Furiex Research Site	Loma Linda	California	United States	92354
31	Furiex Research Site	Lomita	California	United States	90717
32	Furiex Research Site	Long Beach	California	United States	90806
33	Furiex Research Site	Los Angeles	California	United States	90045
34	Furiex Research Site	Newport Beach	California	United States	92663
35	Furiex Research Site	North Hollywood	California	United States	91606
36	Furiex Research Site	Northridge	California	United States	91325
37	Furiex Research Site	Pasadena	California	United States	91105
38	Furiex Research Site	Sacramento	California	United States	95817
39	Furiex Research Site	San Diego	California	United States	92103
40	Furiex Research Site	San Diego	California	United States	92105
41	Furiex Research Site	Santa Ana	California	United States	92701
42	Furiex Research Site	Ventura	California	United States	93003
43	Furiex Research Site	Walnut Creek	California	United States	94598
44	Furiex Research Site	Denver	Colorado	United States	80211
45	Furiex Research Site	Denver	Colorado	United States	80246
46	Furiex Research Site	Boca Raton	Florida	United States	33428
47	Furiex Research Site	Boynton Beach	Florida	United States	33426
48	Furiex Research Site	Bradenton	Florida	United States	34208
49	Furiex Research Site	Brooksville	Florida	United States	34601
50	Furiex Research Site	Clearwater	Florida	United States	33759
51	Furiex Research Site	Cooper City	Florida	United States	33024
52	Furiex Research Site	Coral Springs	Florida	United States	33065
53	Furiex Research Site	Eustis	Florida	United States	32726
54	Furiex Research Site	Fort Lauderdale	Florida	United States	33308
55	Furiex Research Site	Hallandale Beach	Florida	United States	33009
56	Furiex Research Site	Hialeah	Florida	United States	33016
57	Furiex Research Site	Jacksonville	Florida	United States	32205
58	Furiex Research Site	Jupiter	Florida	United States	33458
59	Furiex Research Site	Lauderdale Lakes	Florida	United States	33319
60	Furiex Research Site	Melbourne	Florida	United States	32901
61	Furiex Research Site	Miami	Florida	United States	33015
62	Furiex Research Site	Miami	Florida	United States	33125
63	Furiex Research Site	Miami	Florida	United States	33126
64	Furiex Research Site	Miami	Florida	United States	33133
65	Furiex Research Site	Miami	Florida	United States	33135
66	Furiex Research Site	Miami	Florida	United States	33144
67	Furiex Research Site	Miami	Florida	United States	33155
68	Furiex Research Site	Miami	Florida	United States	33183
69	Furiex Research Site	Miramar	Florida	United States	33025
70	Furiex Research Site	New Port Richey	Florida	United States	34652
71	Furiex Research Site	Orlando	Florida	United States	32806
72	Furiex Research Site	Plant City	Florida	United States	33563
73	Furiex Research Site	Port Orange	Florida	United States	32127
74	Furiex Research Site	Saint Petersburg	Florida	United States	33705
75	Furiex Research Site	Saint Petersburg	Florida	United States	33709
76	Furiex Research Site	South Miami	Florida	United States	33143
77	Furiex Research Site	Tampa	Florida	United States	33607
78	Furiex Research Site	Wellington	Florida	United States	33414
79	Furiex Research Site	Winter Haven	Florida	United States	33880
80	Furiex Research Site	Winter Park	Florida	United States	32792
81	Furiex Research Site	Alpharetta	Georgia	United States	30005
82	Furiex Research Site	Athens	Georgia	United States	30606
83	Furiex Research Site	Atlanta	Georgia	United States	30308
84	Furiex Research Site	Atlanta	Georgia	United States	30338
85	Furiex Research Site	Dunwoody	Georgia	United States	30338
86	Furiex Research Site	Lawrenceville	Georgia	United States	30046
87	Furiex Research Site	Macon	Georgia	United States	31201
88	Furiex Research Site	Marietta	Georgia	United States	30066
89	Furiex Research Site	Norcross	Georgia	United States	30092
90	Furiex Research Site	Savannah	Georgia	United States	31404
91	Furiex Research Site	Stockbridge	Georgia	United States	30281
92	Furiex Research Site	Boise	Idaho	United States	83704
93	Furiex Research Site	Eagle	Idaho	United States	83616
94	Furiex Research Site	Idaho Falls	Idaho	United States	83404
95	Furiex Research Site	Addison	Illinois	United States	60101
96	Furiex Research Site	Chicago	Illinois	United States	60612
97	Furiex Research Site	Chicago	Illinois	United States	60622
98	Furiex Research Site	Evergreen Park	Illinois	United States	60805
99	Furiex Research Site	Hammond	Illinois	United States	46324
100	Furiex Research Site	Springfield	Illinois	United States	62703
101	Furiex Research Site	Brownsburg	Indiana	United States	46112
102	Furiex Research Site	Evansville	Indiana	United States	47714
103	Furiex Research Site	Granger	Indiana	United States	46530
104	Furiex Research Site	Clive	Iowa	United States	50325
105	Furiex Research Site	Pratt	Kansas	United States	67124
106	Furiex Research Site	Shawnee Mission	Kansas	United States	66218
107	Furiex Research Site	Topeka	Kansas	United States	66606
108	Furiex Research Site	Lexington	Kentucky	United States	40503
109	Furiex Research Site	Lexington	Kentucky	United States	40504
110	Furiex Research Site	Owensboro	Kentucky	United States	42303
111	Furiex Research Site	Paducah	Kentucky	United States	42003
112	Furiex Research Site	Lake Charles	Louisiana	United States	70601
113	Furiex Research Site	Monroe	Louisiana	United States	71201
114	Furiex Research Site	Hagerstown	Maryland	United States	21742
115	Furiex Research Site	Hollywood	Maryland	United States	20636
116	Furiex Research Site	Boston	Massachusetts	United States	02115
117	Furiex Research Site	Boston	Massachusetts	United States	02131
118	Furiex Research Site	Brockton	Massachusetts	United States	02302
119	Furiex Research Site	Watertown	Massachusetts	United States	02472
120	Furiex Research Site	Ann Arbor	Michigan	United States	48106
121	Furiex Research Site	Bay City	Michigan	United States	48706
122	Furiex Research Site	Cadillac	Michigan	United States	49601
123	Furiex Research Site	Grand Rapids	Michigan	United States	49506
124	Furiex Research Site	Kalamazoo	Michigan	United States	49009
125	Furiex Research Site	Troy	Michigan	United States	48098
126	Furiex Research Site	Ypsilanti	Michigan	United States	48197
127	Furiex Research Site	Plymouth	Minnesota	United States	55446
128	Furiex Research Site	Biloxi	Mississippi	United States	39531
129	Furiex Research Site	Hazelwood	Missouri	United States	63042
130	Furiex Research Site	Saint Louis	Missouri	United States	63122
131	Furiex Research Site	Saint Louis	Missouri	United States	63128
132	Furiex Research Site	Saint Louis	Missouri	United States	63141
133	Furiex Research Site	Saint Peters	Missouri	United States	63376
134	Furiex Research Site	Billings	Montana	United States	59101
135	Furiex Research Site	Bellevue	Nebraska	United States	68005
136	Furiex Research Site	Elkhorn	Nebraska	United States	68022
137	Furiex Research Site	Lincoln	Nebraska	United States	68510
138	Furiex Research Site	Omaha	Nebraska	United States	68134
139	Furiex Research Site	Omaha	Nebraska	United States	68144
140	Furiex Research Site	Las Vegas	Nevada	United States	89123
141	Furiex Research Site	Reno	Nevada	United States	89511
142	Furiex Research Site	Lebanon	New Hampshire	United States	03756
143	Furiex Research Site	Blackwood	New Jersey	United States	08012
144	Furiex Research Site	Edison	New Jersey	United States	08817
145	Furiex Research Site	Elizabeth	New Jersey	United States	07201
146	Furiex Research Site	Marlton	New Jersey	United States	08053
147	Furiex Research Site	Albuquerque	New Mexico	United States	87102
148	Furiex Research Site	Albuquerque	New Mexico	United States	87108
149	Furiex Research Site	Albuquerque	New Mexico	United States	87109
150	Furiex Research Site	Flushing	New York	United States	11367
151	Furiex Research Site	Hollis	New York	United States	11423
152	Furiex Research Site	Mineola	New York	United States	11501
153	Furiex Research Site	New York	New York	United States	10016
154	Furiex Research Site	Chapel Hill	North Carolina	United States	27599
155	Furiex Research Site	Dunn	North Carolina	United States	28334
156	Furiex Research Site	Greensboro	North Carolina	United States	27403
157	Furiex Research Site	Huntersville	North Carolina	United States	28078
158	Furiex Research Site	Kinston	North Carolina	United States	28501
159	Furiex Research Site	Wilmington	North Carolina	United States	28403
160	Furiex Research Site	Winston-Salem	North Carolina	United States	27103
161	Furiex Research Site	Winston-Salem	North Carolina	United States	27106
162	Furiex Research Site	Akron	Ohio	United States	44302
163	Furiex Research Site	Beavercreek	Ohio	United States	45431
164	Furiex Research Site	Cincinnati	Ohio	United States	45224
165	Furiex Research Site	Cincinnati	Ohio	United States	45242
166	Furiex Research Site	Cincinnati	Ohio	United States	45245
167	Furiex Research Site	Cincinnati	Ohio	United States	45267
168	Furiex Research Site	Cleveland	Ohio	United States	44122
169	Furiex Research Site	Columbus	Ohio	United States	43212
170	Furiex Research Site	Columbus	Ohio	United States	43214
171	Furiex Research Site	Columbus	Ohio	United States	43235
172	Furiex Research Site	Dayton	Ohio	United States	45432
173	Furiex Research Site	Dayton	Ohio	United States	45439
174	Furiex Research Site	Groveport	Ohio	United States	43125
175	Furiex Research Site	Kettering	Ohio	United States	45429
176	Furiex Research Site	Lima	Ohio	United States	45806
177	Furiex Research Site	Tiffin	Ohio	United States	44883
178	Furiex Research Site	Toledo	Ohio	United States	43615
179	Furiex Research Site	Norman	Oklahoma	United States	73071
180	Furiex Research Site	Oklahoma City	Oklahoma	United States	73102
181	Furiex Research Site	Oklahoma City	Oklahoma	United States	73112
182	Furiex Research Site	Portland	Oregon	United States	97210
183	Furiex Research Site	Salem	Oregon	United States	97301
184	Furiex Research Site	Carnegie	Pennsylvania	United States	15106
185	Furiex Research Site	Philadelphia	Pennsylvania	United States	19107
186	Furiex Research Site	Pittsburgh	Pennsylvania	United States	15206
187	Furiex Research Site	Pittsburgh	Pennsylvania	United States	15243
188	Furiex Research Site	Scottdale	Pennsylvania	United States	15683
189	Furiex Research Site	Uniontown	Pennsylvania	United States	15401
190	Furiex Research Site	Warwick	Rhode Island	United States	02888
191	Furiex Research Site	Anderson	South Carolina	United States	29621
192	Furiex Research Site	Columbia	South Carolina	United States	29201
193	Furiex Research Site	Columbia	South Carolina	United States	29203
194	Furiex Research Site	Columbia	South Carolina	United States	29204
195	Furiex Research Site	Easley	South Carolina	United States	29640
196	Furiex Research Site	Mount Pleasant	South Carolina	United States	29464
197	Furiex Research Site	North Myrtle Beach	South Carolina	United States	29582
198	Furiex Research Site	Rapid City	South Dakota	United States	57702
199	Furiex Research Site	Athens	Tennessee	United States	37303
200	Furiex Research Site	Chattanooga	Tennessee	United States	37404
201	Furiex Research Site	Columbia	Tennessee	United States	38401
202	Furiex Research Site	Jackson	Tennessee	United States	38305
203	Furiex Research Site	Knoxville	Tennessee	United States	37919
204	Furiex Research Site	Smyrna	Tennessee	United States	37167
205	Furiex Research Site	Austin	Texas	United States	78745
206	Furiex Research Site	Beaumont	Texas	United States	77701
207	Furiex Research Site	Bedford	Texas	United States	76021
208	Furiex Research Site	Corsicana	Texas	United States	75110
209	Furiex Research Site	Dallas	Texas	United States	75218
210	Furiex Research Site	Dallas	Texas	United States	75225
211	Furiex Research Site	Fort Worth	Texas	United States	76133
212	Furiex Research Site	Frisco	Texas	United States	75035
213	Furiex Research Site	Houston	Texas	United States	77008
214	Furiex Research Site	Houston	Texas	United States	77043
215	Furiex Research Site	Houston	Texas	United States	77062
216	Furiex Research Site	Humble	Texas	United States	77338
217	Furiex Research Site	Hurst	Texas	United States	76054
218	Furiex Research Site	San Antonio	Texas	United States	78215
219	Furiex Research Site	San Antonio	Texas	United States	78229
220	Furiex Research Site	San Antonio	Texas	United States	78258
221	Furiex Research Site	Bountiful	Utah	United States	84010
222	Furiex Research Site	Salt Lake City	Utah	United States	84124
223	Furiex Research Site	West Valley City	Utah	United States	84120
224	Furiex Research Site	Burlington	Vermont	United States	05401
225	Furiex Research Site	Alexandria	Virginia	United States	22304
226	Furiex Research Site	Christiansburg	Virginia	United States	24073
227	Furiex Research Site	Midlothian	Virginia	United States	23114
228	Furiex Research Site	Norfolk	Virginia	United States	23502
229	Furiex Research Site	Richmond	Virginia	United States	23233
230	Furiex Research Site	Richmond	Virginia	United States	23235
231	Furiex Research Site	Charleston	West Virginia	United States	25304
232	Furiex Research Site	Monroe	Wisconsin	United States	53566
233	Furiex Research Site	Kelowna	British Columbia	Canada	V1Y 3G8
234	Furiex Research Site	St. John's	Newfoundland and Labrador	Canada	A1E 2E2
235	Furiex Research Site	Burlington	Ontario	Canada	L7M 4Y1
236	Furiex Research Site	Hawkesbury	Ontario	Canada	K6A 1A1
237	Furiex Research Site	London	Ontario	Canada	N5W 6A2
238	Furiex Research Site	Newmarket	Ontario	Canada	L3Y 5G8
239	Furiex Research Site	Sarnia	Ontario	Canada	N7T 4X3
240	Furiex Research Site	Sudbury	Ontario	Canada	P3E 1H5
241	Furiex Research Site	Toronto	Ontario	Canada	M6H 3M1
242	Furiex Research Site	Vaughan	Ontario	Canada	L4L 4Y7
243	Furiex Research Site	San Juan		Puerto Rico	00926-2832
244	Furiex Research Site	Chestfield	Kent	United Kingdom	CT5 3QS
245	Furiex Research Site	Blackpool	Lancashire	United Kingdom	FY4 3AD
246	Furiex Research Site	Birmingham		United Kingdom	B15 2TH
247	Furiex Research Site	County Durham		United Kingdom	DL14 6AD
248	Furiex Research Site	Coventry		United Kingdom	CV2 2DX
249	Furiex Research Site	Durham		United Kingdom	DH1 5TW
250	Furiex Research Site	Edinburgh		United Kingdom	EH4 2XH
251	Furiex Research Site	Manchester		United Kingdom	M23 9LT
252	Furiex Research Site	Sheffield		United Kingdom	S10 2JF
253	Furiex Research Site	Wigan		United Kingdom	WN1 2NN

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: NCT01553747
• Other Study ID Numbers: 27018966IBS3002; 2012-001601-24
• First Posted: Mar 14, 2012
• Last Update Posted: Jul 30, 2018
• Last Verified: Jul 1, 2018

• Keywords provided by Furiex Pharmaceuticals, Inc: Irritable bowel syndrome with diarrhea; Irritable bowel syndrome; Diarrhea predominant irritable bowel syndrome; Colonic diseases; Colonic diseases, functional; Digestive system disease; Gastrointestinal disease; Intestinal disease; Colonic pseudo-obstruction; Diarrhea; Signs and symptoms, Digestive
• Additional relevant MeSH terms: Irritable Bowel Syndrome; Syndrome; Diarrhea; Eluxadoline

Study Results

Participant Flow

Pre-assignment Detail	3356 participants were prescreened and entered into interactive voice response system for participation in the study. 1146 participants were randomized. One participant was unintentionally randomized twice and was assigned 2 different participant identification numbers due to participant trying to participate at more than 1 study center at once.

Arm/Group Title	Eluxadoline 75 mg	Eluxadoline 100 mg	Placebo
Arm/Group Description	Eluxadoline 75 mg tablets, orally, twice daily for up to 26 weeks treatment period followed by placebo orally, twice daily for next 4 weeks of blinded-placebo period.	Eluxadoline 100 mg tablets, orally, twice daily for up to 26 weeks treatment period followed by placebo orally, twice daily for next 4 weeks of blinded-placebo period.	Eluxadoline placebo matching tablets, orally, twice daily for up to 26 weeks treatment period followed by placebo orally, twice daily for next 4 weeks of blinded-placebo period.
Period Title: Overall Study
STARTED	381	383	382
Attended Week 12 Visit	296	301	312
Attended Week 26 Visit	259	271	278
Participated in Blinded-Placebo Period	246	253	272
COMPLETED	250	264	273
NOT COMPLETED	131	119	109

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 26 weeks treatment period followed by placebo orally, twice daily for next 4 weeks of blinded-placebo period.	Eluxadoline 100 mg tablets, orally, twice daily for up to 26 weeks treatment period followed by placebo orally, twice daily for next 4 weeks of blinded-placebo period.	Eluxadoline placebo matching tablets, orally, twice daily for up to 26 weeks treatment period followed by placebo orally, twice daily for next 4 weeks of blinded-placebo period.	Total of all reporting groups
Overall Participants	381	383	382	1146
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	45.0 (13.17)	45.7 (13.31)	47.1 (13.82)	45.9 (13.45)
Age, Customized (Count of Participants)
18-40 years	139 36.5%	146 38.1%	133 34.8%	418 36.5%
41-64 years	206 54.1%	198 51.7%	198 51.8%	602 52.5%
≥65 years	36 9.4%	39 10.2%	51 13.4%	126 11%
Sex: Female, Male (Count of Participants)
Female	261 68.5%	257 67.1%	250 65.4%	768 67%
Male	120 31.5%	126 32.9%	132 34.6%	378 33%

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 participants 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

Intention-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 26 weeks treatment period followed by placebo orally, twice daily for next 4 weeks of blinded-placebo period.	Eluxadoline 100 mg tablets, orally, twice daily for up to 26 weeks treatment period followed by placebo orally, twice daily for next 4 weeks of blinded-placebo period.	Eluxadoline placebo matching tablets, orally, twice daily for up to 26 weeks treatment period followed by placebo orally, twice daily for next 4 weeks of blinded-placebo period.
Measure Participants	381	382	382
Number [percentage of participants]	28.9 7.6%	29.6 7.7%	16.2 4.2%

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	<0.001
	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

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 participants 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 26 weeks treatment period followed by placebo orally, twice daily for next 4 weeks of blinded-placebo period.	Eluxadoline 100 mg tablets, orally, twice daily for up to 26 weeks treatment period followed by placebo orally, twice daily for next 4 weeks of blinded-placebo period.	Eluxadoline placebo matching tablets, orally, twice daily for up to 26 weeks treatment period followed by placebo orally, twice daily for next 4 weeks of blinded-placebo period.
Measure Participants	381	382	382
Number [percentage of participants]	30.4 8%	32.7 8.5%	20.2 5.3%

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	0.001
	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 26 weeks treatment period followed by placebo orally, twice daily for next 4 weeks of blinded-placebo period.	Eluxadoline 100 mg tablets, orally, twice daily for up to 26 weeks treatment period followed by placebo orally, twice daily for next 4 weeks of blinded-placebo period.	Eluxadoline placebo matching tablets, orally, twice daily for up to 26 weeks treatment period followed by placebo orally, twice daily for next 4 weeks of blinded-placebo period.
Measure Participants	381	382	382
Responders during Weeks 1-12	48.0 12.6%	51.0 13.3%	45.3 11.9%
Responders during Weeks 1-26	47.5 12.5%	50.0 13.1%	44.8 11.7%
Responders during Weeks 1-4	46.7 12.3%	46.6 12.2%	41.9 11%
Responders during Weeks 5-8	53.0 13.9%	52.9 13.8%	49.2 12.9%
Responders during Weeks 9-12	48.0 12.6%	50.3 13.1%	46.9 12.3%
Responders during Weeks 13-16	47.2 12.4%	49.0 12.8%	43.5 11.4%
Responders during Weeks 17-20	45.1 11.8%	47.4 12.4%	42.7 11.2%
Responders during Weeks 21-24	41.7 10.9%	46.9 12.2%	40.6 10.6%

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 26 weeks treatment period followed by placebo orally, twice daily for next 4 weeks of blinded-placebo period.	Eluxadoline 100 mg tablets, orally, twice daily for up to 26 weeks treatment period followed by placebo orally, twice daily for next 4 weeks of blinded-placebo period.	Eluxadoline placebo matching tablets, orally, twice daily for up to 26 weeks treatment period followed by placebo orally, twice daily for next 4 weeks of blinded-placebo period.
Measure Participants	381	382	382
Responders during Weeks 1-12	37.0 9.7%	35.6 9.3%	20.9 5.5%
Responders during Weeks 1-26	34.4 9%	39.8 10.4%	23.6 6.2%
Responders during Weeks 1-4	34.6 9.1%	37.2 9.7%	18.1 4.7%
Responders during Weeks 5-8	37.5 9.8%	38.2 10%	23.3 6.1%
Responders during Weeks 9-12	37.5 9.8%	39.3 10.3%	26.4 6.9%
Responders during Weeks 13-16	36.2 9.5%	41.4 10.8%	24.9 6.5%
Responders during Weeks 17-20	33.9 8.9%	36.1 9.4%	24.9 6.5%
Responders during Weeks 21-24	32.5 8.5%	38.2 10%	22.8 6%

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 26 weeks treatment period followed by placebo orally, twice daily for next 4 weeks of blinded-placebo period.	Eluxadoline 100 mg tablets, orally, twice daily for up to 26 weeks treatment period followed by placebo orally, twice daily for next 4 weeks of blinded-placebo period.	Eluxadoline placebo matching tablets, orally, twice daily for up to 26 weeks treatment period followed by placebo orally, twice daily for next 4 weeks of blinded-placebo period.
Measure Participants	381	382	382
Responders during Weeks 1-12	43.6 11.4%	42.4 11.1%	29.6 7.7%
Responders during Weeks 1-26	45.1 11.8%	43.2 11.3%	34.3 9%
Responders during Weeks 1-4	40.2 10.6%	36.9 9.6%	25.7 6.7%
Responders during Weeks 5-8	45.1 11.8%	45.0 11.7%	35.1 9.2%
Responders during Weeks 9-12	44.9 11.8%	43.5 11.4%	34.0 8.9%
Responders during Weeks 13-16	43.8 11.5%	42.9 11.2%	33.0 8.6%
Responders during Weeks 17-20	42.5 11.2%	40.8 10.7%	33.2 8.7%
Responders during Weeks 21-24	41.7 10.9%	41.6 10.9%	33.8 8.8%

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 and 30 (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 26 weeks treatment period followed by placebo orally, twice daily for next 4 weeks of blinded-placebo period.	Eluxadoline 100 mg tablets, orally, twice daily for up to 26 weeks treatment period followed by placebo orally, twice daily for next 4 weeks of blinded-placebo period.	Eluxadoline placebo matching tablets, orally, twice daily for up to 26 weeks treatment period followed by placebo orally, twice daily for next 4 weeks of blinded-placebo period.
Measure Participants	381	382	382
Responders at Week 4	45.1 11.8%	45.5 11.9%	40.1 10.5%
Responders at Week 8	48.8 12.8%	50.0 13.1%	43.7 11.4%
Responders at Week 12	48.3 12.7%	49.5 12.9%	45.0 11.8%
Responders at Week 18	45.1 11.8%	45.0 11.7%	41.9 11%
Responders at Week 26	45.4 11.9%	44.8 11.7%	41.4 10.8%
Responders at Week 30 /EOT	54.3 14.3%	53.9 14.1%	52.6 13.8%

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 26 weeks treatment period followed by placebo orally, twice daily for next 4 weeks of blinded-placebo period.	Eluxadoline 100 mg tablets, orally, twice daily for up to 26 weeks treatment period followed by placebo orally, twice daily for next 4 weeks of blinded-placebo period.	Eluxadoline placebo matching tablets, orally, twice daily for up to 26 weeks treatment period followed by placebo orally, twice daily for next 4 weeks of blinded-placebo period.
Measure Participants	381	382	382
Responders during Weeks 1-12	60.1 15.8%	58.4 15.2%	49.2 12.9%
Responders during Weeks 1-26	52.8 13.9%	53.7 14%	43.7 11.4%

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

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 26 weeks treatment period followed by placebo orally, twice daily for next 4 weeks of blinded-placebo period.	Eluxadoline 100 mg tablets, orally, twice daily for up to 26 weeks treatment period followed by placebo orally, twice daily for next 4 weeks of blinded-placebo period.	Eluxadoline placebo matching tablets, orally, twice daily for up to 26 weeks treatment period followed by placebo orally, twice daily for next 4 weeks of blinded-placebo period.
Measure Participants	381	382	382
Change at Week 4	-2.44 (2.219)	-2.19 (2.120)	-2.06 (2.063)
Change at Week 12	-2.88 (2.417)	-2.90 (2.175)	-2.56 (2.461)
Change at Week 26	-3.19 (2.454)	-3.16 (2.362)	-2.76 (2.582)

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

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 26 weeks treatment period followed by placebo orally, twice daily for next 4 weeks of blinded-placebo period.	Eluxadoline 100 mg tablets, orally, twice daily for up to 26 weeks treatment period followed by placebo orally, twice daily for next 4 weeks of blinded-placebo period.	Eluxadoline placebo matching tablets, orally, twice daily for up to 26 weeks treatment period followed by placebo orally, twice daily for next 4 weeks of blinded-placebo period.
Measure Participants	381	382	382
Change at Week 4	-1.89 (2.170)	-1.80 (2.204)	-1.73 (2.081)
Change at Week 12	-2.24 (2.445)	-2.41 (2.396)	-2.08 (2.492)
Change at Week 26	-2.38 (2.619)	-2.68 (2.673)	-2.17 (2.682)

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

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 26 weeks treatment period followed by placebo orally, twice daily for next 4 weeks of blinded-placebo period.	Eluxadoline 100 mg tablets, orally, twice daily for up to 26 weeks treatment period followed by placebo orally, twice daily for next 4 weeks of blinded-placebo period.	Eluxadoline placebo matching tablets, orally, twice daily for up to 26 weeks treatment period followed by placebo orally, twice daily for next 4 weeks of blinded-placebo period.
Measure Participants	381	382	382
Week 4	3.03 (2.021)	3.05 (1.962)	3.38 (1.856)
Week 12	2.89 (2.057)	2.80 (1.685)	3.15 (1.991)
Week 26	2.57 (1.637)	2.66 (1.625)	2.96 (1.931)

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

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 26 weeks treatment period followed by placebo orally, twice daily for next 4 weeks of blinded-placebo period.	Eluxadoline 100 mg tablets, orally, twice daily for up to 26 weeks treatment period followed by placebo orally, twice daily for next 4 weeks of blinded-placebo period.	Eluxadoline placebo matching tablets, orally, twice daily for up to 26 weeks treatment period followed by placebo orally, twice daily for next 4 weeks of blinded-placebo period.
Measure Participants	381	382	382
Week 4	0.47 (1.304)	0.41 (1.230)	0.50 (1.195)
Week 12	0.40 (1.083)	0.28 (0.875)	0.46 (1.269)
Week 26	0.30 (0.982)	0.27 (0.844)	0.50 (1.503)

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

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 26 weeks treatment period followed by placebo orally, twice daily for next 4 weeks of blinded-placebo period.	Eluxadoline 100 mg tablets, orally, twice daily for up to 26 weeks treatment period followed by placebo orally, twice daily for next 4 weeks of blinded-placebo period.	Eluxadoline placebo matching tablets, orally, twice daily for up to 26 weeks treatment period followed by placebo orally, twice daily for next 4 weeks of blinded-placebo period.
Measure Participants	381	382	382
Week 4	5.53 (2.282)	5.46 (2.264)	5.31 (2.444)
Week 12	5.38 (2.320)	5.56 (2.164)	5.28 (2.364)
Week 26	5.53 (2.129)	5.59 (2.216)	5.29 (2.322)

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

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 26 weeks treatment period followed by placebo orally, twice daily for next 4 weeks of blinded-placebo period.	Eluxadoline 100 mg tablets, orally, twice daily for up to 26 weeks treatment period followed by placebo orally, twice daily for next 4 weeks of blinded-placebo period.	Eluxadoline placebo matching tablets, orally, twice daily for up to 26 weeks treatment period followed by placebo orally, twice daily for next 4 weeks of blinded-placebo period.
Measure Participants	381	382	382
Week 4	1.62 (1.948)	1.58 (1.732)	2.00 (1.779)
Week 12	1.37 (1.884)	1.32 (1.675)	1.73 (1.785)
Week 26	1.13 (1.580)	1.12 (1.576)	1.54 (1.826)

14. 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 and 30/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. 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 26 weeks treatment period followed by placebo orally, twice daily for next 4 weeks of blinded-placebo period.	Eluxadoline 100 mg tablets, orally, twice daily for up to 26 weeks treatment period followed by placebo orally, twice daily for next 4 weeks of blinded-placebo period.	Eluxadoline placebo matching tablets, orally, twice daily for up to 26 weeks treatment period followed by placebo orally, twice daily for next 4 weeks of blinded-placebo period.
Measure Participants	381	382	382
Change at Week 4	17.51 (19.755)	17.26 (18.980)	14.07 (18.787)
Change at Week 8	21.60 (20.762)	21.10 (21.925)	16.62 (20.856)
Change at Week 12	22.69 (21.723)	22.62 (24.017)	19.50 (21.636)
Change at Week 18	24.17 (22.761)	23.52 (24.029)	20.64 (23.268)
Change at Week 26	24.91 (22.638)	24.19 (24.599)	21.50 (23.709)
Change at Week 30/EOT	22.79 (22.329)	20.92 (23.724)	21.63 (23.376)

Adverse Events

Time Frame	From first dose of study drug up to 30 weeks
Adverse Event Reporting Description	Safety Set: all participants who received at least 1 dose of drug per actual treatment received. 1 participant in 100 mg arm received 75 mg, 2 participants in Placebo arm received eluxadoline 75 mg and 100 mg. AEs for each period were analyzed separately. In the Other AE section, a result of 0 in an arm means the ≥5% threshold was not met.
Arm/Group Title	Eluxadoline 75 mg (Treatment Period)		Eluxadoline 100 mg (Treatment Period)		Placebo (Treatment Period)		Eluxadoline 75 mg (Blinded-Placebo Period)		Eluxadoline 100 mg (Blinded-Placebo Period)		Placebo (Blinded-Placebo Period)
Arm/Group Description	Eluxadoline 75 mg tablets, orally, twice daily for up to 26 weeks period.		Eluxadoline 100 mg tablets, orally, twice daily for up to 26 weeks period.		Eluxadoline placebo matching tablets, orally, twice daily for up to 26 weeks period.		Participants who received eluxadoline 75 mg in treatment period were administered with placebo orally, twice daily for next 4 weeks.		Participants who received eluxadoline 100 mg in treatment period were administered with placebo orally, twice daily for next 4 weeks.		Participants who received placebo matching tablets in treatment period were administered with placebo orally, twice daily for next 4 weeks.
All Cause Mortality
	Eluxadoline 75 mg (Treatment Period)		Eluxadoline 100 mg (Treatment Period)		Placebo (Treatment Period)		Eluxadoline 75 mg (Blinded-Placebo Period)		Eluxadoline 100 mg (Blinded-Placebo Period)		Placebo (Blinded-Placebo Period)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/379 (0%)		0/380 (0%)		0/381 (0%)		0/246 (0%)		0/253 (0%)		0/272 (0%)
Serious Adverse Events
	Eluxadoline 75 mg (Treatment Period)		Eluxadoline 100 mg (Treatment Period)		Placebo (Treatment Period)		Eluxadoline 75 mg (Blinded-Placebo Period)		Eluxadoline 100 mg (Blinded-Placebo Period)		Placebo (Blinded-Placebo Period)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/379 (2.4%)		14/380 (3.7%)		8/381 (2.1%)		0/246 (0%)		0/253 (0%)		0/272 (0%)
Cardiac disorders
Acute coronary syndrome	0/379 (0%)		0/380 (0%)		1/381 (0.3%)		0/246 (0%)		0/253 (0%)		0/272 (0%)
Angina pectoris	1/379 (0.3%)		0/380 (0%)		0/381 (0%)		0/246 (0%)		0/253 (0%)		0/272 (0%)
Coronary artery disease	0/379 (0%)		0/380 (0%)		1/381 (0.3%)		0/246 (0%)		0/253 (0%)		0/272 (0%)
Gastrointestinal disorders
Abdominal discomfort	1/379 (0.3%)		0/380 (0%)		0/381 (0%)		0/246 (0%)		0/253 (0%)		0/272 (0%)
Colitis ischemic	0/379 (0%)		1/380 (0.3%)		0/381 (0%)		0/246 (0%)		0/253 (0%)		0/272 (0%)
Dyspepsia	0/379 (0%)		1/380 (0.3%)		0/381 (0%)		0/246 (0%)		0/253 (0%)		0/272 (0%)
Gastric ulcer	1/379 (0.3%)		0/380 (0%)		0/381 (0%)		0/246 (0%)		0/253 (0%)		0/272 (0%)
Hiatus hernia	0/379 (0%)		1/380 (0.3%)		0/381 (0%)		0/246 (0%)		0/253 (0%)		0/272 (0%)
Pancreatitis acute	1/379 (0.3%)		1/380 (0.3%)		0/381 (0%)		0/246 (0%)		0/253 (0%)		0/272 (0%)
Umbilical hernia	0/379 (0%)		1/380 (0.3%)		0/381 (0%)		0/246 (0%)		0/253 (0%)		0/272 (0%)
Upper gastrointestinal haemorrhage	0/379 (0%)		0/380 (0%)		1/381 (0.3%)		0/246 (0%)		0/253 (0%)		0/272 (0%)
General disorders
Chest pain	1/379 (0.3%)		1/380 (0.3%)		0/381 (0%)		0/246 (0%)		0/253 (0%)		0/272 (0%)
Non-cardiac pain	0/379 (0%)		1/380 (0.3%)		0/381 (0%)		0/246 (0%)		0/253 (0%)		0/272 (0%)
Hepatobiliary disorders
Hepatitis	0/379 (0%)		1/380 (0.3%)		0/381 (0%)		0/246 (0%)		0/253 (0%)		0/272 (0%)
Infections and infestations
Appendicitis	1/379 (0.3%)		0/380 (0%)		0/381 (0%)		0/246 (0%)		0/253 (0%)		0/272 (0%)
Bacterial pyelonephritis	1/379 (0.3%)		0/380 (0%)		0/381 (0%)		0/246 (0%)		0/253 (0%)		0/272 (0%)
Enterocolitis infections	0/379 (0%)		0/380 (0%)		1/381 (0.3%)		0/246 (0%)		0/253 (0%)		0/272 (0%)
Liver abscess	0/379 (0%)		0/380 (0%)		1/381 (0.3%)		0/246 (0%)		0/253 (0%)		0/272 (0%)
Pyelonephritis	1/379 (0.3%)		0/380 (0%)		0/381 (0%)		0/246 (0%)		0/253 (0%)		0/272 (0%)
Urinary tract infection	0/379 (0%)		1/380 (0.3%)		0/381 (0%)		0/246 (0%)		0/253 (0%)		0/272 (0%)
Injury, poisoning and procedural complications
Concussion	0/379 (0%)		1/380 (0.3%)		0/381 (0%)		0/246 (0%)		0/253 (0%)		0/272 (0%)
Pseudomeningocele	1/379 (0.3%)		0/380 (0%)		0/381 (0%)		0/246 (0%)		0/253 (0%)		0/272 (0%)
Investigations
ECG T wave abnormal	0/379 (0%)		1/380 (0.3%)		0/381 (0%)		0/246 (0%)		0/253 (0%)		0/272 (0%)
Hepatic enzyme increased	1/379 (0.3%)		0/380 (0%)		0/381 (0%)		0/246 (0%)		0/253 (0%)		0/272 (0%)
Musculoskeletal and connective tissue disorders
Back pain	0/379 (0%)		0/380 (0%)		1/381 (0.3%)		0/246 (0%)		0/253 (0%)		0/272 (0%)
Nervous system disorders
Headache	0/379 (0%)		1/380 (0.3%)		0/381 (0%)		0/246 (0%)		0/253 (0%)		0/272 (0%)
Myasthenia gravis	0/379 (0%)		1/380 (0.3%)		0/381 (0%)		0/246 (0%)		0/253 (0%)		0/272 (0%)
Psychiatric disorders
Suicide attempt	0/379 (0%)		1/380 (0.3%)		0/381 (0%)		0/246 (0%)		0/253 (0%)		0/272 (0%)
Renal and urinary disorders
Nephrolithiasis	0/379 (0%)		0/380 (0%)		1/381 (0.3%)		0/246 (0%)		0/253 (0%)		0/272 (0%)
Reproductive system and breast disorders
Dysfunctional uterine bleeding	0/379 (0%)		1/380 (0.3%)		0/381 (0%)		0/246 (0%)		0/253 (0%)		0/272 (0%)
Ovarian cyst ruptured	1/379 (0.3%)		0/380 (0%)		0/381 (0%)		0/246 (0%)		0/253 (0%)		0/272 (0%)
Uterine prolapse	0/379 (0%)		0/380 (0%)		1/381 (0.3%)		0/246 (0%)		0/253 (0%)		0/272 (0%)
Skin and subcutaneous tissue disorders
Dermatitis contact	0/379 (0%)		1/380 (0.3%)		0/381 (0%)		0/246 (0%)		0/253 (0%)		0/272 (0%)
Other (Not Including Serious) Adverse Events
	Eluxadoline 75 mg (Treatment Period)		Eluxadoline 100 mg (Treatment Period)		Placebo (Treatment Period)		Eluxadoline 75 mg (Blinded-Placebo Period)		Eluxadoline 100 mg (Blinded-Placebo Period)		Placebo (Blinded-Placebo Period)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	97/379 (25.6%)		97/380 (25.5%)		69/381 (18.1%)		0/246 (0%)		0/253 (0%)		0/272 (0%)
Gastrointestinal disorders
Constipation	33/379 (8.7%)		30/380 (7.9%)		8/381 (2.1%)		0/246 (0%)		0/253 (0%)		0/272 (0%)
Nausea	31/379 (8.2%)		33/380 (8.7%)		22/381 (5.8%)		0/246 (0%)		0/253 (0%)		0/272 (0%)
Infections and infestations
Nasopharyngitis	19/379 (5%)		13/380 (3.4%)		15/381 (3.9%)		0/246 (0%)		0/253 (0%)		0/272 (0%)
Upper respiratory tract infection	13/379 (3.4%)		22/380 (5.8%)		17/381 (4.5%)		0/246 (0%)		0/253 (0%)		0/272 (0%)
Nervous system disorders
Headache	14/379 (3.7%)		23/380 (6.1%)		22/381 (5.8%)		0/246 (0%)		0/253 (0%)		0/272 (0%)

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.