Efficacy, Safety, and Tolerability of JNJ-27018966 (Eluxadoline) in the Treatment of Irritable Bowel Syndrome With Diarrhea

Study Overview
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Brief Summary
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The purpose of this study is to determine the efficacy, safety, and tolerability of different doses of JNJ-27018966 (eluxadoline) compared with placebo in the treatment of patients with irritable bowel syndrome with diarrhea (IBS-d).

Official Title
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A Randomized, Double-blind, Placebo-controlled, Parallel Group, Dose Ranging, Multicenter Study to Evaluate the Efficacy, Safety, and Tolerability of JNJ-27018966 in the Treatment of Patients With Irritable Bowel Syndrome With Diarrhea

Conditions
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Irritable Bowel Syndrome

Intervention / Treatment
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* Drug: Eluxadoline
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Patient has a diagnosis of IBS by Rome III criteria with a subtype of diarrhea Female patients must be: postmenopausal, defined as amenorrhea for at least 2 years at Prescreening, surgically sterile (have had a hysterectomy or bilateral oophorectomy, tubal ligation, or otherwise be incapable of pregnancy), abstinent, or if sexually active, be practicing an effective method of birth control. Key Exclusion Criteria: Patient has a diagnosis of IBS by Rome III criteria with a subtype of constipation, mixed IBS, or unsubtyped IBS Patient has a history of inflammatory or immune-mediated gastrointestinal (GI) disorders including inflammatory bowel disease (ie, Crohn's disease, ulcerative colitis) and celiac disease Patient has a history of diverticulitis within 6 months prior to Prescreening Patient has a history of intestinal obstruction, stricture, toxic megacolon, GI perforation, fecal impaction, gastric banding, bariatric surgery, adhesions, ischemic colitis, impaired intestinal circulation (eg, aortoiliac disease), thrombophlebitis of a major vein, or hypercoagulable states. Other protocol-specific eligibility criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Eluxadoline 5 mg<br>Eluxadoline 5 mg tablets, orally, twice daily for up to 12 weeks. | Drug: Eluxadoline<br>* Tablets, orally, twice daily.<br>* Other names: JNJ-27018966;|
| Experimental: Eluxadoline 25 mg<br>Eluxadoline 25 mg tablets, orally, twice daily for up to 12 weeks. . | Drug: Eluxadoline<br>* Tablets, orally, twice daily.<br>* Other names: JNJ-27018966;|
| Experimental: Eluxadoline 100 mg<br>Eluxadoline 100 mg tablets, orally, twice daily for up to 12 weeks. | Drug: Eluxadoline<br>* Tablets, orally, twice daily.<br>* Other names: JNJ-27018966;|
| Experimental: Eluxadoline 200 mg<br>Eluxadoline 200 mg tablets, orally, twice daily for up to 12 weeks. | Drug: Eluxadoline<br>* Tablets, orally, twice daily.<br>* Other names: JNJ-27018966;|
| Placebo Comparator: Placebo<br>Eluxadoline placebo matching tablets, orally, twice daily for up to 12 weeks. | Drug: Placebo<br>* Matching placebo oral tablets twice daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Were Composite Responders Based on Improvements From Baseline in Daily Worst Abdominal Pain and Daily Stool Consistency Scores at Week 4 | Composite responders were defined as participants who completed at least 5 out of 7 days with diary entries during the interval of interest and met both of the following criteria: 1) Average daily pain response scores over the past week improved by ≥30% and at least 2 points as compared with the baseline average pain score (average of daily worst abdominal pain the week prior to randomization), 2) Bristol Stool Scale (BSS) score of 3 or 4 on 66% of reported days in the past week. Abdominal pain was assessed on an 11-point scale where: 0=no pain to 10=worst pain imaginable. Stool consistency was assessed using the BSS 7-point scale where: 1=separate hard lumps, 2=sausage shaped but lumpy, 3=sausage-like with cracks on the surface, 4=sausage-like but smooth and soft, 5=soft blobs with clear cut edges, 6=fluffy pieces with ragged edges, and 7=watery with no solid pieces. | Baseline (Week prior to Randomization) to Week 4 | 
| Percentage of Participants Who Were Composite Responders Based on Improvements From Baseline in Daily Worst Abdominal Pain and Daily Stool Consistency Scores at Week 12 | Composite responders were defined as participants who completed at least 5 out of 7 days with diary entries during the interval of interest and met both of the following criteria: 1) Average daily pain response scores over the past week improved by ≥30% and at least 2 points as compared with the baseline average pain score (average of daily worst abdominal pain the week prior to randomization), 2) Bristol Stool Scale (BSS) score of 3 or 4 on 66% of reported days in the past week. The participant recorded their abdominal pain in a daily diary using an 11-point scale where: 0=no pain to 10=worst pain imaginable. The participant recorded stool consistency in a daily diary using the BSS 7-point scale where: 1=separate hard lumps, 2=sausage shaped but lumpy, 3=sausage-like with cracks on the surface, 4=sausage-like but smooth and soft, 5=soft blobs with clear cut edges, 6=fluffy pieces with ragged edges, and 7=watery with no solid pieces. | Baseline (Week prior to Randomization) to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Weekly Pain Scores | The participant recorded their worst daily pain score in a diary using an 11-point scale where: 0=no pain to 10=worst pain imaginable. The daily scores over the previous week were averaged. A negative change from Baseline indicates improvement. | Baseline (Week Prior to Randomization) to Weeks 4, 8, and 12 | 
| Change From Baseline in Weekly BSS Scores | The patient recorded stool consistency in a daily diary using the BSS 7-point scale where: 1=hard stool to 7=watery diarrhea. The daily scores over the previous week were averaged. A negative change from Baseline indicates improvement. | Baseline (Week prior to Randomization) to Weeks 4, 8, and 12 | 
| Change From Baseline in the Number of Daily Bowel Movements | Participants recorded the number of bowel movements in a daily diary at the same time each day. The number of daily bowel movements over the previous week were averaged. A negative change from Baseline indicates improvement. | Baseline (Week prior to Randomization) to Weeks 4, 8, and 12 | 
| Percentage of Participants With Response Based on Participants Achieving Prespecified Improvement in Symptoms for at Least 50% of the Time | Responders were participants that met both of the following criteria on the same week for at least 50% of time on study: 1) average of daily pain scores over the past week improved by ≥30% compared with baseline average in pain score, 2) ≥50% reduction in the number of days over the past week with a BSS score ≥5 compared with Baseline. Participants must also have had at least 5/7 days diary entry to be considered a responder for that week. Abdominal pain was assessed on an 11-point scale where a score of 0=no pain to 10=worst pain imaginable. Stool consistency was assessed using the BSS 7-point scale where: 1=separate hard lumps to 7=watery with no solid pieces. Response rates (percentage of participants) are based on model estimates from the logistic regression. | Baseline (Week Prior to Randomization) to Weeks 1-12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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