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

Overview

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).

Full Title of Study: “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”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: July 14, 2011

Interventions

  • Drug: Eluxadoline
    • Tablets, orally, twice daily.
  • Drug: Placebo
    • Matching placebo oral tablets twice daily.

Arms, Groups and Cohorts

  • Experimental: Eluxadoline 5 mg
    • Eluxadoline 5 mg tablets, orally, twice daily for up to 12 weeks.
  • Experimental: Eluxadoline 25 mg
    • Eluxadoline 25 mg tablets, orally, twice daily for up to 12 weeks. .
  • Experimental: Eluxadoline 100 mg
    • Eluxadoline 100 mg tablets, orally, twice daily for up to 12 weeks.
  • Experimental: Eluxadoline 200 mg
    • Eluxadoline 200 mg tablets, orally, twice daily for up to 12 weeks.
  • Placebo Comparator: Placebo
    • Eluxadoline placebo matching tablets, orally, twice daily for up to 12 weeks.

Clinical Trial Outcome Measures

Primary Measures

  • 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
    • Time Frame: 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.
  • 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
    • Time Frame: 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.

Secondary Measures

  • Change From Baseline in the Weekly Pain Scores
    • Time Frame: 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
    • Time Frame: 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.
  • Change From Baseline in the Number of Daily Bowel Movements
    • Time Frame: 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.
  • Percentage of Participants With Response Based on Participants Achieving Prespecified Improvement in Symptoms for at Least 50% of the Time
    • Time Frame: 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.

Participating in This Clinical Trial

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.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 65 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Furiex Pharmaceuticals, Inc
  • Provider of Information About this Clinical Study
    • Sponsor

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