Efficacy of Eluxadoline in the Treatment of Irritable Bowel Syndrome With Diarrhea in Patients With Inadequate Control of Symptoms With Prior Loperamide Use

• Sponsor: Allergan (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02959983
• Collaborator: (none)
• Enrollment: 346
• Locations: 83
• Arms: 2
• Actual Duration (Months): 14.9
• Patients Per Site: 4.2
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This study will evaluate the efficacy and safety of eluxadoline 100 milligrams (mg) twice a day (BID) versus placebo for the treatment of patients with Irritable Bowel Syndrome with Diarrhea (IBS-D) who report that the use of loperamide in the prior 12 months failed to provide control of their IBS-D symptoms.

Condition or Disease	Intervention/Treatment	Phase
Irritable Bowel Syndrome With Diarrhea	Drug: Eluxadoline; Drug: Placebo	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 346 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 4 Multicenter, Multinational, Prospective, Randomized, Placebo-Controlled, Double-Blinded Parallel Group Study to Assess Efficacy of Eluxadoline in the Treatment of Irritable Bowel Syndrome With Diarrhea (IBS-D) in Patients Who Report Inadequate Control of IBS-D Symptoms With Prior Loperamide Use (RELIEF)
• Actual Study Start Date: Oct 25, 2016
• Actual Primary Completion Date: Jan 22, 2018
• Actual Study Completion Date: Jan 22, 2018

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Eluxadoline Eluxadoline 100 mg oral tablets twice daily (BID) with food for 12 weeks.	Drug: Eluxadoline; Eluxadoline 100 mg oral tablets BID with food.; Other Names: VIBERZI™
Placebo Comparator: Placebo Placebo matching eluxadoline oral tablets BID with food for 12 weeks.	Drug: Placebo; Placebo matching eluxadoline oral tablets BID with food.

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 [Baseline, Weeks 1 to 12]

   Percentage of primary composite responders is defined as the percentage of participants who meet both of the following daily composite criteria for at least 50% of the days with diary entry: 1)Worst Abdominal Pain (WAP) score improved by ≥40% compared to Baseline. The participant records their WAP score in the past 24 hours each day in a daily patient diary where: 0=no pain to 10=worst imaginable pain. 2) Bristol Stool Score (BSS) <5; or the absence of a bowel movement if accompanied by ≥40% improvement in WAP compared to Baseline. The participant records their stool consistency each day in a daily patient diary using the BSS on a scale from 1 (hard stool) to 7 (watery stool).

Secondary Outcome Measures

1. Percentage of Stool Consistency Responders [Weeks 1 to 12 and 4-week intervals (Weeks 1 to 4, Weeks 5 to 8 and Weeks 9 to 12)]

   Percentage of stool consistency responders is defined as the percentage of participants who meet the daily stool consistency response criteria: BSS <5; or the absence of a bowel movement if accompanied by ≥40% improvement in WAP compared to Baseline for ≥50% of days with daily patient diary entries over a certain time period. The participant records their stool consistency each day in a daily patient diary using the BSS on a scale from 1 (hard stool) to 7 (watery stool). A participant must have had a minimum of 20 days of diary entries over any 4-week interval.

2. Percentage of Pain Responders [Baseline, Weeks 1 to 12 and 4-week intervals (Weeks 1 to 4, Weeks 5 to 8 and Weeks 9 to 12)]

   Percentage of pain responders is defined as the percentage of participants who meet the daily pain response criteria: WAP score improved by ≥40% compared to Baseline for ≥50% of days with diary entries over a certain time period. The participant records their WAP score in the past 24 hours each day in a daily diary where: 0=no pain to 10=worst imaginable pain. A participant must have had a minimum of 20 days of diary entries over any 4-week interval.

3. Percentage of Monthly Composite Responders [Weeks 1 to 4, 5 to 8, and 9 to 12]

   Percentage of monthly composite responders is defined as the percentage of participants who meet the daily composite response criteria for at least 50% of days with diary entry for a minimum of 20 days during each 4-week interval (weeks 1 to 4, 5 to 8, and 9 to 12). Composite response includes both of the following criteria: 1) WAP score improved by ≥40% compared to Baseline. The participant records their WAP score in the past 24 hours each day in a daily patient diary where: 0=no pain to 10=worst imaginable pain. 2) BSS <5; or the absence of a bowel movement if accompanied by ≥40% improvement in WAP compared to Baseline. The participant records their stool consistency each day in a daily patient diary using the BSS on a scale from 1 (hard stool) to 7 (watery stool).

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Has a diagnosis of IBS-D, defined by the Rome III criteria as loose (mushy) or watery stools ≥25% and hard or lumpy stools ≤25% of bowel movements.

• Has had a colonoscopy performed within 5 years prior to Screening if they are at least 50 years of age, OR if they meet any of the following alarm features:

1. Has documented weight loss within the past 6 months; or

2. Has nocturnal symptoms; or

3. Has a familial history of colon cancer; or

4. Has blood mixed with their stool (excluding any blood from hemorrhoids)

• Patient reports use of loperamide in the 12 months prior to Screening for IBS-D symptoms and that loperamide did not provide adequate control of IBS-D symptoms.

• Has not used any loperamide rescue medication within 14 days prior to randomization.

Exclusion Criteria:

• Has a diagnosis of Irritable Bowel Syndrome (IBS) with a subtype of constipation IBS, mixed IBS, or unsubtyped IBS.

• Has a history of inflammatory or immune-mediated gastrointestinal (GI) disorders including inflammatory bowel disease (i.e., Crohn's disease, ulcerative colitis), microscopic colitis, or celiac disease.

• Has a history of diverticulitis within 3 months prior to screening.

• Has a documented history of lactose intolerance.

• Has a documented history of bile-acid malabsorption.

• Has a history of chronic or severe constipation or intestinal obstruction, stricture, toxic megacolon, GI perforation, fecal impaction, gastric banding, bariatric surgery, adhesions.

• Has any of the following surgical history:

1. Cholecystectomy or previously documented agenesis of gallbladder; or

2. Any abdominal surgery within the 3 months prior to screening; or

3. Major gastric, hepatic, pancreatic, or intestinal surgery (appendectomy, hemorrhoidectomy, or polypectomy greater than 3 months post-surgery are allowed).

• Has a history of cholecystitis within 6 months before screening.

• Has a history of pancreatitis or structural diseases of the pancreas, including known or suspected pancreatic duct obstruction.

• Has a history of known or suspected biliary duct obstruction or sphincter of Oddi disease or dysfunction, excluding a history of gallstones.

• Has a history or current evidence of laxative abuse within 5 years prior to screening.

• Has documented evidence of cirrhosis.

• Has a history of cardiovascular events, including stroke, myocardial infarction, congestive heart failure, or transient ischemic attack within 6 months prior to screening.

• Has an unstable renal, hepatic, metabolic, or hematologic condition.

• Has a history of malignancy within 5 years before screening (except squamous and basal cell carcinomas and cervical carcinoma in situ).

• Has a history of human immunodeficiency virus infection.

• Has a history of Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision-defined substance dependency, excluding nicotine and caffeine, within 2 years prior to screening.

• Has a history of alcohol abuse, alcohol addiction, and alcoholism or drinks more than 3 alcoholic beverages per day.

• Has used aspirin or aspirin-containing medications (>325 mg of aspirin per day) or nonsteroidal anti-inflammatory drugs, when taken specifically for the symptoms of IBS, within 14 days of randomization.

• Has current (within 14 days of randomization) or expected use of any narcotic or opioid-containing agents, tramadol, docusate, enemas, GI preparations (including antacids containing aluminum or magnesium, antidiarrheal agents [except loperamide rescue medication after randomization]), antinausea agents, antispasmodic agents, bismuth, or prokinetic agents.

• Has current (within 28 days of randomization) use of rifaximin or other antibiotics (with the exception of topical antibiotics or a 1-day course with an antibiotic). Expected use of rifaximin or other antibiotics during the course of the study that is known at the time of randomization.

• Has an elective surgery planned or expects to need elective surgery at any time during the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinical Research Associates, LLC	Huntsville	Alabama	United States	35801
2	The Center for Clinical Trials	Saraland	Alabama	United States	36571
3	Elite Clinical Studies	Phoenix	Arizona	United States	85018
4	Arkansas Gastroenterology	North Little Rock	Arkansas	United States	72117
5	Med Investigations	Carmichael	California	United States	95608
6	GW Research Inc	Chula Vista	California	United States	91910
7	Diagnamics Inc	Encinitas	California	United States	92024
8	Behavioral Research Specialists, LLC	Irvine	California	United States	92606
9	Providence Clinical Research	North Hollywood	California	United States	91606
10	Shahram Jacobs MD INC.	Sherman Oaks	California	United States	91403
11	Westlake Medical Research	Thousand Oaks	California	United States	91360
12	Upland Clinical Research	Upland	California	United States	91786
13	Advanced RX Clinicial Research Group, Inc.	Westminster	California	United States	92683
14	Connecticut Clinical Research Foundation	Bristol	Connecticut	United States	06010
15	Medical Research Center of Connecticut, LLC	Hamden	Connecticut	United States	06518
16	Innovative Research of West Florida, Inc.	Clearwater	Florida	United States	33756
17	Digestive Care of N. Broward	Coral Springs	Florida	United States	33065
18	Homestead Medical Research	Homestead	Florida	United States	33030
19	Clinical Neuroscience Solutions Inc.	Jacksonville	Florida	United States	32256
20	Health Awareness, Inc.	Jupiter	Florida	United States	33458
21	Precision Clinical Research LLC	Lauderdale Lakes	Florida	United States	33319
22	Ocean Blue Medical Research Center, Inc	Miami Springs	Florida	United States	33166
23	Pharmax Research Clinic Inc.	Miami	Florida	United States	33126
24	Well Pharma Medical Research, Corp.	Miami	Florida	United States	33143
25	Bravo Health Care Center	North Bay Village	Florida	United States	33141
26	Clinical Neuroscience Solutions Inc.	Orlando	Florida	United States	32801
27	Clinical Research of West Florida Inc.	Tampa	Florida	United States	33603
28	Meridien Research	Tampa	Florida	United States	33634
29	Emory University School of Medicine	Atlanta	Georgia	United States	30322
30	RNA America, LLC	Buford	Georgia	United States	30518
31	Northwestern University Feinbery School of Medicine	Chicago	Illinois	United States	606611
32	Pharmakon Inc	Evergreen Park	Illinois	United States	60805
33	Investigators Research	Brownsburg	Indiana	United States	46112
34	Radiant Research, Inc.	Evansville	Indiana	United States	47714
35	Clinical Research Advantage Inc/Radiant Research Inc.	Evansville	Indiana	United States	47725
36	Gtc Research	Shawnee Mission	Kansas	United States	66218
37	Investigative Clinical Research	Annapolis	Maryland	United States	21401
38	MGG Group Co. Inc. Chevy Chase Clinical Research	Chevy Chase	Maryland	United States	20815
39	MedVadis Research Corporation	Watertown	Massachusetts	United States	02472
40	Clinical Research Insititute of Michigan LLC	Chesterfield	Michigan	United States	48047
41	Gastroenterology Associates of Western Michigan, PLC	Wyoming	Michigan	United States	49519
42	The Center for Clinical Trials	Biloxi	Mississippi	United States	39531
43	Women's Clinic of Lincoln, P.C.	Lincoln	Nebraska	United States	68510
44	Quality Clinical Research Inc.	Omaha	Nebraska	United States	68114
45	Advanced Biomedical Research of America	Las Vegas	Nevada	United States	89123
46	Advanced Research Institute	Reno	Nevada	United States	89511
47	Drug Trials Brooklyn	Brooklyn	New York	United States	11230
48	NY Scientific	Brooklyn	New York	United States	11235
49	Long Island Gastrointestinal Group LLP	Great Neck	New York	United States	11023
50	IMA Medical Research, PC	Kew Gardens	New York	United States	11415
51	Charlotte Gastroenterology & Hepatology, PLLC	Charlotte	North Carolina	United States	28207
52	Peters Medical Research LLC	High Point	North Carolina	United States	27265
53	North State Clincial Research PLLC	Lenoir	North Carolina	United States	28645
54	Wake Research Associates LLC	Raleigh	North Carolina	United States	27612
55	Trial Management Associates, LLC	Wilmington	North Carolina	United States	28403
56	Clinical Inquest Center Ltd	Beavercreek	Ohio	United States	45431
57	Hometown Urgent Care and Research	Cincinnati	Ohio	United States	45215
58	Buckeye Health and Research	Columbus	Ohio	United States	43207
59	Hometown Urgent Care and Research	Columbus	Ohio	United States	43214
60	Hometown Urgent Care and Research	Huber Heights	Ohio	United States	45424
61	Central Sooner Research	Norman	Oklahoma	United States	73071
62	The Oregon Center for Clinical Investigations, INC.	Salem	Oregon	United States	97301
63	Partners in Clinical Research	Cumberland	Rhode Island	United States	02864
64	WR-ClinSearch, LLC	Chattanooga	Tennessee	United States	37421
65	New Phase Research & Development	Knoxville	Tennessee	United States	37909
66	CNS Healthcare	Memphis	Tennessee	United States	38119
67	Premier Family Physicians	Austin	Texas	United States	78735
68	Family Medicine Associate of Texas	Carrollton	Texas	United States	75010
69	Multi-Phase Trials LLC	San Antonio	Texas	United States	78217
70	Health Texas Research Institute	San Antonio	Texas	United States	78228
71	Discovery Clinical Trials - Stone Oak	San Antonio	Texas	United States	78258
72	Carl Meisner Medical Clinic	Sugar Land	Texas	United States	77478
73	Advanced Research Institute - Ogden	Ogden	Utah	United States	84405
74	Wasatch Clinical Research, LLC	Salt Lake City	Utah	United States	84107
75	Gastroenterology Associates of Northern Virginia	Fairfax	Virginia	United States	22031
76	Blue Ridge Medical Research	Lynchburg	Virginia	United States	24502
77	Corunna Medical Research Centre	Corunna	Ontario	Canada	N0N 1G0
78	Manna Research	Etobicoke	Ontario	Canada	7LM 4Y1
79	SKDS Research Inc	Newmarket	Ontario	Canada	L3Y 5G8
80	University of Calgary	Calgary		Canada	T2N 1N4
81	Viable Clinical Research Corp.	Nova Scotia		Canada	B4V 3N2
82	Centre de reserche St Louis	Quebec		Canada	G1W4R4
83	Dynamik Research Inc	Quebec		Canada	H9R 3J1

Sponsors and Collaborators

• Allergan

Investigators

• Study Director: Esther Jo, Allergan

Study Documents (Full-Text)

• Study Protocol - Aug 12, 2016
• Statistical Analysis Plan - Oct 18, 2017

More Information

Additional Information:

• More Information

Publications

None provided.

• Responsible Party: Allergan
• ClinicalTrials.gov Identifier: NCT02959983
• Other Study ID Numbers: CMO-US-GI-0429
• First Posted: Nov 9, 2016
• Last Update Posted: Feb 15, 2019
• Last Verified: Jan 1, 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Irritable Bowel Syndrome; Syndrome; Diarrhea; Eluxadoline

Study Results

Participant Flow

Pre-assignment Detail	A total of 660 participants were screened; 346 participants were randomized; 344 participants received at least 1 dose of study drug which comprises the safety population. Randomization and treatment assignment were based on a randomization scheme prepared by Allergan Biostatistics prior to the start of the study.

Arm/Group Title	Eluxadoline	Placebo
Arm/Group Description	Eluxadoline 100 mg oral tablets twice daily (BID) with food for 12 weeks.	Placebo matching eluxadoline oral tablets BID with food for 12 weeks.
Period Title: Overall Study
STARTED	172	174
COMPLETED	146	149
NOT COMPLETED	26	25

Baseline Characteristics

Arm/Group Title	Eluxadoline	Placebo	Total
Arm/Group Description	Eluxadoline 100 mg oral tablets twice daily (BID) with food for 12 weeks.	Placebo matching eluxadoline oral tablets BID with food for 12 weeks.	Total of all reporting groups
Overall Participants	172	174	346
Age, Customized (Count of Participants)
<65	158 91.9%	161 92.5%	319 92.2%
≥65	14 8.1%	13 7.5%	27 7.8%
Sex: Female, Male (Count of Participants)
Female	124 72.1%	119 68.4%	243 70.2%
Male	48 27.9%	55 31.6%	103 29.8%
Race/Ethnicity, Customized (Count of Participants)
Hispanic or Latino	33 19.2%	41 23.6%	74 21.4%
Not Hispanic or Latino	139 80.8%	133 76.4%	272 78.6%
Race/Ethnicity, Customized (Count of Participants)
Caucasian	144 83.7%	141 81%	285 82.4%
Black or African American	20 11.6%	26 14.9%	46 13.3%
Asian	7 4.1%	3 1.7%	10 2.9%
American Indian or Alaskan Native	1 0.6%	2 1.1%	3 0.9%
Native Hawaiian or Other Pacific Islander	0 0%	1 0.6%	1 0.3%
Other	0 0%	1 0.6%	1 0.3%

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	Percentage of primary composite responders is defined as the percentage of participants who meet both of the following daily composite criteria for at least 50% of the days with diary entry: 1)Worst Abdominal Pain (WAP) score improved by ≥40% compared to Baseline. The participant records their WAP score in the past 24 hours each day in a daily patient diary where: 0=no pain to 10=worst imaginable pain. 2) Bristol Stool Score (BSS) <5; or the absence of a bowel movement if accompanied by ≥40% improvement in WAP compared to Baseline. The participant records their stool consistency each day in a daily patient diary using the BSS on a scale from 1 (hard stool) to 7 (watery stool).
Time Frame	Baseline, Weeks 1 to 12

Outcome Measure Data

Analysis Population Description

The Intent-to-Treat population includes all randomized patients.

Arm/Group Title	Eluxadoline	Placebo
Arm/Group Description	Eluxadoline 100 mg oral tablets twice daily (BID) with food for 12 weeks.	Placebo matching eluxadoline oral tablets BID with food for 12 weeks.
Measure Participants	172	174
Number [percentage of participants]	22.7 13.2%	10.3 5.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Eluxadoline, Placebo
	Comments	Overall Weeks 1-12
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0022
	Comments
	Method	Chi-squared
	Comments

2. Secondary Outcome

Title	Percentage of Stool Consistency Responders
Description	Percentage of stool consistency responders is defined as the percentage of participants who meet the daily stool consistency response criteria: BSS <5; or the absence of a bowel movement if accompanied by ≥40% improvement in WAP compared to Baseline for ≥50% of days with daily patient diary entries over a certain time period. The participant records their stool consistency each day in a daily patient diary using the BSS on a scale from 1 (hard stool) to 7 (watery stool). A participant must have had a minimum of 20 days of diary entries over any 4-week interval.
Time Frame	Weeks 1 to 12 and 4-week intervals (Weeks 1 to 4, Weeks 5 to 8 and Weeks 9 to 12)

Outcome Measure Data

Analysis Population Description

The Intent-to-Treat population includes all randomized patients.

Arm/Group Title	Eluxadoline	Placebo
Arm/Group Description	Eluxadoline 100 mg oral tablets twice daily (BID) with food for 12 weeks.	Placebo matching eluxadoline oral tablets BID with food for 12 weeks.
Measure Participants	172	174
Overall Weeks 1 to 12	27.9 16.2%	16.7 9.6%
Weeks 1 to 4	24.4 14.2%	12.6 7.2%
Weeks 5 to 8	30.8 17.9%	20.1 11.6%
Weeks 9 to 12	29.7 17.3%	25.3 14.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Eluxadoline, Placebo
	Comments	Overall Weeks 1 to 12
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0119
	Comments
	Method	Chi-squared
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Eluxadoline, Placebo
	Comments	Weeks 1 to 4
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0048
	Comments
	Method	Chi-squared
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Eluxadoline, Placebo
	Comments	Weeks 5 to 8
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0207
	Comments
	Method	Chi-squared
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Eluxadoline, Placebo
	Comments	Weeks 9 to 12
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3700
	Comments
	Method	Chi-squared
	Comments

3. Secondary Outcome

Title	Percentage of Pain Responders
Description	Percentage of pain responders is defined as the percentage of participants who meet the daily pain response criteria: WAP score improved by ≥40% compared to Baseline for ≥50% of days with diary entries over a certain time period. The participant records their WAP score in the past 24 hours each day in a daily diary where: 0=no pain to 10=worst imaginable pain. A participant must have had a minimum of 20 days of diary entries over any 4-week interval.
Time Frame	Baseline, Weeks 1 to 12 and 4-week intervals (Weeks 1 to 4, Weeks 5 to 8 and Weeks 9 to 12)

Outcome Measure Data

Analysis Population Description

The Intent-to-Treat population includes all randomized patients.

Arm/Group Title	Eluxadoline	Placebo
Arm/Group Description	Eluxadoline 100 mg oral tablets twice daily (BID) with food for 12 weeks.	Placebo matching eluxadoline oral tablets BID with food for 12 weeks.
Measure Participants	172	174
Overall Weeks 1 to 12	43.6 25.3%	31.0 17.8%
Weeks 1 to 4	30.2 17.6%	25.9 14.9%
Weeks 5 to 8	45.9 26.7%	31.6 18.2%
Weeks 9 to 12	44.8 26%	35.1 20.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Eluxadoline, Placebo
	Comments	Overall Weeks 1 to 12
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0174
	Comments
	Method	Chi-squared
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Eluxadoline, Placebo
	Comments	Weeks 1 to 4
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3832
	Comments
	Method	Chi-squared
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Eluxadoline, Placebo
	Comments	Weeks 5 to 8
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0052
	Comments
	Method	Chi-squared
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Eluxadoline, Placebo
	Comments	Weeks 9 to 12
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0619
	Comments
	Method	Chi-squared
	Comments

4. Secondary Outcome

Title	Percentage of Monthly Composite Responders
Description	Percentage of monthly composite responders is defined as the percentage of participants who meet the daily composite response criteria for at least 50% of days with diary entry for a minimum of 20 days during each 4-week interval (weeks 1 to 4, 5 to 8, and 9 to 12). Composite response includes both of the following criteria: 1) WAP score improved by ≥40% compared to Baseline. The participant records their WAP score in the past 24 hours each day in a daily patient diary where: 0=no pain to 10=worst imaginable pain. 2) BSS <5; or the absence of a bowel movement if accompanied by ≥40% improvement in WAP compared to Baseline. The participant records their stool consistency each day in a daily patient diary using the BSS on a scale from 1 (hard stool) to 7 (watery stool).
Time Frame	Weeks 1 to 4, 5 to 8, and 9 to 12

Outcome Measure Data

Analysis Population Description

The Intent-to-Treat population includes all randomized patients.

Arm/Group Title	Eluxadoline	Placebo
Arm/Group Description	Eluxadoline 100 mg oral tablets twice daily (BID) with food for 12 weeks.	Placebo matching eluxadoline oral tablets BID with food for 12 weeks.
Measure Participants	172	174
Weeks 1-4	14 8.1%	6.9 4%
Weeks 5-8	26.7 15.5%	14.9 8.6%
Weeks 9-12	30.8 17.9%	16.7 9.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Eluxadoline, Placebo
	Comments	Weeks 1-4
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0330
	Comments
	Method	Chi-squared
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Eluxadoline, Placebo
	Comments	Weeks 5 to 8
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0063
	Comments
	Method	Chi-squared
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Eluxadoline, Placebo
	Comments	Weeks 9 to 12
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0018
	Comments
	Method	Chi-squared
	Comments

Adverse Events

Time Frame	Up to 12 weeks
Adverse Event Reporting Description	The Safety Population will include all patients enrolled who received at least 1 dose of study drug. Safety data will be analyzed using the safety population.
Arm/Group Title	Eluxadoline		Placebo
Arm/Group Description	Eluxadoline 100 mg oral tablets twice daily (BID) with food for 12 weeks.		Placebo matching eluxadoline oral tablets BID with food for 12 weeks.
All Cause Mortality
	Eluxadoline		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/171 (0%)		0/173 (0%)
Serious Adverse Events
	Eluxadoline		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/171 (0.6%)		3/173 (1.7%)
Cardiac disorders
Cardiac failure congestive	0/171 (0%)		1/173 (0.6%)
Gastrointestinal disorders
Pancreatic mass	1/171 (0.6%)		0/173 (0%)
Infections and infestations
Cellulitis	0/171 (0%)		1/173 (0.6%)
Pneumonia	0/171 (0%)		1/173 (0.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine leiomyoma	0/171 (0%)		1/173 (0.6%)
Reproductive system and breast disorders
Dysmenorrhea	0/171 (0%)		1/173 (0.6%)
Endometriosis	0/171 (0%)		1/173 (0.6%)
Ovarian cyst	0/171 (0%)		1/173 (0.6%)
Pelvic pain	0/171 (0%)		1/173 (0.6%)
Other (Not Including Serious) Adverse Events
	Eluxadoline		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/171 (5.8%)		5/173 (2.9%)
Gastrointestinal disorders
Nausea	10/171 (5.8%)		5/173 (2.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

A disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 90 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.