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

Phase 2

Completed

Conditions: Irritable Bowel Syndrome

Interventions: Drug: Placebo
Drug: Eluxadoline

Registration Number: NCT01130272

Lead Sponsor: Furiex Pharmaceuticals, Inc

Brief Summary: 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).

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 807

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Eluxadoline placebo matching tablets, orally, twice daily for up to 12 weeks.
Eluxadoline 5 mg	Eluxadoline	Eluxadoline 5 mg tablets, orally, twice daily for up to 12 weeks.
Eluxadoline 25 mg	Eluxadoline	Eluxadoline 25 mg tablets, orally, twice daily for up to 12 weeks. .
Eluxadoline 200 mg	Eluxadoline	Eluxadoline 200 mg tablets, orally, twice daily for up to 12 weeks.
Eluxadoline 100 mg	Eluxadoline	Eluxadoline 100 mg tablets, orally, twice daily for up to 12 weeks.

Primary Outcome Measures

Name	Time	Method
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	Baseline (Week prior to Randomization) to 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.
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	Baseline (Week prior to Randomization) to 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.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in the Number of Daily Bowel Movements	Baseline (Week prior to Randomization) to Weeks 4, 8, and 12	Participants recorded the number of bowel movements in a daily diary at the same time each day. The number of daily bowel movements over the previous week were averaged. A negative change from Baseline indicates improvement.
Change From Baseline in the Weekly Pain Scores	Baseline (Week Prior to Randomization) to Weeks 4, 8, and 12	The participant recorded their worst daily pain score in a diary using an 11-point scale where: 0=no pain to 10=worst pain imaginable. The daily scores over the previous week were averaged. A negative change from Baseline indicates improvement.
Change From Baseline in Weekly BSS Scores	Baseline (Week prior to Randomization) to Weeks 4, 8, and 12	The patient recorded stool consistency in a daily diary using the BSS 7-point scale where: 1=hard stool to 7=watery diarrhea. The daily scores over the previous week were averaged. A negative change from Baseline indicates improvement.
Percentage of Participants With Response Based on Participants Achieving Prespecified Improvement in Symptoms for at Least 50% of the Time	Baseline (Week Prior to Randomization) to Weeks 1-12	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.