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

• ClinicalTrials.gov Identifier: NCT01130272
• Recruitment Status: Completed
• First Posted: May 25, 2010
• Results First Posted: October 22, 2019
• Last Update Posted: October 22, 2019
• Sponsor: Furiex Pharmaceuticals, Inc
• Information provided by (Responsible Party): Furiex Pharmaceuticals, Inc

Tracking Information

• First Submitted Date: May 24, 2010
• First Posted Date: May 25, 2010
• Results First Submitted Date: August 22, 2019
• Results First Posted Date: October 22, 2019
• Last Update Posted Date: October 22, 2019
• Actual Study Start Date: April 28, 2010
• Actual Primary Completion Date: July 14, 2011 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 30, 2019)

• 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.

Original Primary Outcome Measures (submitted: May 24, 2010)

• Clinical response to treatment based upon improvement from baseline in both of the following co-primary endpoints: pain intensity as assessed by average daily pain scores; and stool consistency as assessed by Bristol Stool Scores. [ Time Frame: 4 weeks ]
  The patient-reported daily pain score is based on a 0- to 10-point scale, where 0 corresponds to no pain and 10 corresponds to worst imaginable pain. The patient-reported BSS consistency score is based on a 1- to 7-point scale where 1 corresponds to a hard stool and 7 corresponds to watery diarrhea.
• Clinical response to treatment based upon improvement from baseline in both of the following co-primary endpoints: pain intensity as assessed by average daily pain scores; and stool consistency as assessed by Bristol Stool Scores. [ Time Frame: 8 weeks ]
  The patient-reported daily pain score is based on a 0- to 10-point scale, where 0 corresponds to no pain and 10 corresponds to worst imaginable pain. The patient-reported BSS consistency score is based on a 1- to 7-point scale where 1 corresponds to a hard stool and 7 corresponds to watery diarrhea.
• Clinical response to treatment based upon improvement from baseline in both of the following co-primary endpoints: pain intensity as assessed by average daily pain scores; and stool consistency as assessed by Bristol Stool Scores. [ Time Frame: 12 weeks ]
  The patient-reported daily pain score is based on a 0- to 10-point scale, where 0 corresponds to no pain and 10 corresponds to worst imaginable pain. The patient-reported BSS consistency score is based on a 1- to 7-point scale where 1 corresponds to a hard stool and 7 corresponds to watery diarrhea.

Current Secondary Outcome Measures (submitted: September 30, 2019)

• 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.

Original Secondary Outcome Measures (submitted: May 24, 2010)

• Average daily pain scores [ Time Frame: 4, 8, and 12 weeks ]
• Stool consistency [ Time Frame: 4, 8, and 12 weeks ]
• Stool frequency [ Time Frame: 4, 8, and 12 weeks ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Efficacy, Safety, and Tolerability of JNJ-27018966 (Eluxadoline) in the Treatment of Irritable Bowel Syndrome With Diarrhea
• Official Title: 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
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Irritable Bowel Syndrome

Intervention

• Drug: Eluxadoline
  Tablets, orally, twice daily.
  Other Name: JNJ-27018966
• Drug: Placebo
  Matching placebo oral tablets twice daily.

Study Arms

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

Publications *

• Fant RV, Henningfield JE, Cash BD, Dove LS, Covington PS. Eluxadoline Demonstrates a Lack of Abuse Potential in Phase 2 and 3 Studies of Patients With Irritable Bowel Syndrome With Diarrhea. Clin Gastroenterol Hepatol. 2017 Jul;15(7):1021-1029.e6. doi: 10.1016/j.cgh.2017.01.026. Epub 2017 Feb 3.
• Andrae DA, Covington PS, Patrick DL. Item-level assessment of the irritable bowel syndrome quality of life questionnaire in patients with diarrheal irritable bowel syndrome. Clin Ther. 2014 May;36(5):663-79. doi: 10.1016/j.clinthera.2014.04.009. Epub 2014 May 9.
• Dove LS, Lembo A, Randall CW, Fogel R, Andrae D, Davenport JM, McIntyre G, Almenoff JS, Covington PS. Eluxadoline benefits patients with irritable bowel syndrome with diarrhea in a phase 2 study. Gastroenterology. 2013 Aug;145(2):329-38.e1. doi: 10.1053/j.gastro.2013.04.006. Epub 2013 Apr 9.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 9, 2011): 807
• Original Estimated Enrollment (submitted: May 24, 2010): 850
• Actual Study Completion Date: July 14, 2011
• Actual Primary Completion Date: July 14, 2011 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01130272
• Other Study ID Numbers: 27018966IBS2001
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Furiex Pharmaceuticals, Inc
• Original Responsible Party: June Almenoff, MD, President/Chief Medical Officer, Furiex Pharmaceuticals, Inc
• Current Study Sponsor: Furiex Pharmaceuticals, Inc
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Furiex Pharmaceuticals, Inc
• Verification Date: September 2019