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
Overview
- Phase
- Phase 3
- Intervention
- Eluxadoline
- Conditions
- Irritable Bowel Syndrome
- Sponsor
- Furiex Pharmaceuticals, Inc
- Enrollment
- 1146
- Locations
- 1
- Primary Endpoint
- Percentage of Participants Who Were Composite Responders Based on Improvements From Baseline in Daily Worst Abdominal Pain and Daily Stool Consistency Scores
- Status
- Completed
- Last Updated
- 7 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Participant is 18 to 80 years old
- •Participant has a diagnosis of irritable bowel syndrome (IBS) with a subtype of diarrhea defined by the Rome III criteria.
- •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).
- •Female participants must be:
Exclusion Criteria
- •Participant has a diagnosis of IBS with a subtype of constipation, mixed IBS, or unsubtyped IBS by the Rome III criteria.
- •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.
- •Participant has a history of diverticulitis within 3 months prior to Prescreening.
- •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).
- •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.
Arms & Interventions
Eluxadoline 75 mg
Eluxadoline 75 mg tablets, orally, twice daily for up to 26 weeks period.
Intervention: Eluxadoline
Eluxadoline 100 mg
Eluxadoline 100 mg tablets, orally, twice daily for up to 26 weeks period.
Intervention: Eluxadoline
Placebo
Eluxadoline placebo matching tablets, orally, twice daily for up to 26 weeks period.
Intervention: Placebo
Outcomes
Primary Outcomes
Percentage of Participants Who Were Composite Responders Based on Improvements From Baseline in Daily Worst Abdominal Pain and Daily Stool Consistency Scores
Time Frame: 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 Outcomes
- Number of Bowel Incontinence Free Days(Weeks 4, 12 and 26)
- Number of Urgency Episodes Per Day(Weeks 4, 12 and 26)
- Change From Baseline in Daily Abdominal Bloating Scores(Baseline, Weeks 4, 12 and 26)
- Number of Bowel Movements Per Day(Weeks 4, 12 and 26)
- Number of Bowel Incontinence Episodes(Weeks 4, 12 and 26)
- 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)
- 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))
- 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))
- 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]))
- 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))
- 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))
- Change From Baseline in Daily Abdominal Discomfort Scores(Baseline, Weeks 4, 12 and 26)
- Change From Baseline in IBS-QoL Total Scores(Baseline, Weeks 4, 8, 12, 18, 26 and 30/EOT)