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Efficacy, Safety, and Tolerability of Eluxadoline in the Treatment of Participants With Diarrhea-Predominant Irritable Bowel Syndrome (IBS-d)

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ClinicalTrials.gov Identifier: NCT01553747
Recruitment Status : Completed
First Posted : March 14, 2012
Results First Posted : July 30, 2018
Last Update Posted : July 30, 2018
Sponsor:
Information provided by (Responsible Party):
Furiex Pharmaceuticals, Inc

Tracking Information
First Submitted Date  ICMJE March 8, 2012
First Posted Date  ICMJE March 14, 2012
Results First Submitted Date  ICMJE June 11, 2018
Results First Posted Date  ICMJE July 30, 2018
Last Update Posted Date July 30, 2018
Actual Study Start Date  ICMJE May 29, 2012
Actual Primary Completion Date January 9, 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 27, 2018)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: March 13, 2012)
  • Composite response based on improvements from baseline in daily abdominal pain scores. [ Time Frame: Daily response determined to evaluate composite response over 12 weeks ]
  • Composite response based on improvements from baseline in daily stool consistency scores. [ Time Frame: Daily response determined to evaluate composite response over 12 weeks ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 27, 2018)
  • 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 26 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.
  • Percentage of Participants Who Were Pain Responders In Daily Worst Abdominal Pain Scores by Intervals [ Time Frame: 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) ]
    Pain responders were defined as participants who met the daily pain response criteria (ie, the worst abdominal pain score in the past 24 hours improved by ≥30% compared to baseline) for at least 50% of days with diary entries during each interval. A participant must have had a minimum of 20 days of diary entries over any 4-week interval, a minimum of 60 days of diary entries over the 12-week interval, and a minimum of 110 days of diary entries over the 26-week interval to be a responder.
  • Percentage of Participants Who Were Responders In Daily Stool Consistency Scores by Intervals [ Time Frame: 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) ]
    Stool consistency responders: Participants who met daily stool consistency response criterion (ie,score of 1, 2, 3, or 4 or absence of bowel movement if accompanied by ≥30% improvement in worst abdominal pain compared to baseline pain) for at least 50% of days with diary entries during each interval. BSS was defined as 7-point Scale in which 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. A participant must have had a minimum of 20 days of diary entries over any 4-week interval, a minimum of 60 days of diary entries over 12-week interval, and a minimum of 110 days of diary entries over 26-week interval to be a responder.
  • Percentage of Participants Who Were Responders In Irritable Bowel Syndrome, Diarrhea Predominant (IBS-d) Global Symptom Scale by Intervals [ Time Frame: 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) ]
    IBS-d global symptom responders were defined as those participants who met the daily IBS-d global symptom response criteria (ie, IBS-d global symptom score of 0 [none] or 1 [mild]; or a daily IBS-d global symptom score improved by ≥2.0 compared to the baseline average) for at least 50% of days with diary entries during each interval. IBS-d Global Symptom Scale was a 5-point scale, score ranging from 0 to 4. 0= no symptoms, 1= mild symptoms, 2= moderate symptoms, 3= severe symptoms and 4 = very severe symptoms. A participant must have had a minimum of 20 days of diary entries over any 4-week interval, a minimum of 60 days of diary entries over the 12-week interval, and a minimum of 110 days of diary entries over the 26-week interval to be a responder.
  • Percentage of Participants Who Were Responders to the Irritable Bowel Syndrome Quality of Life Measure (IBS-QoL) Scale [ Time Frame: Weeks 4, 8, 12, 18, 26 and 30 (End of Treatment [EOT]) ]
    IBS-QoL responders were defined as participants who achieved at least a 14-point improvement in IBS-QoL total score from baseline to the applicable visit. The IBS-QoL consists of 34 items each with a 5-point response scale, where 1 generally represents better responses on items and 5 represents worse responses. The individual responses to the answered items were summed and standardized for a total score and then transformed to a 0- to 100-point (0= worst; 100=better) scale for ease of interpretation.
  • Percentage of Participants With Irritable Bowel Syndrome - Adequate Relief (IBS-AR) Scale [ Time Frame: 12-week interval (Weeks 1-12) and 26-week interval (Weeks 1-26) ]
    Adequate relief of IBS symptoms was assessed once weekly by participants answering the IBS-AR item in the electronic diary. IBS-AR responders were defined as participants with a weekly response of "Yes" to adequate relief of their IBS symptoms for at least 50% of the total weeks during the interval. A participant must have had a positive response on ≥6 weeks for the 12-week interval and ≥13 weeks for the 26-week interval, regardless of diary compliance, to be a responder.
  • Change From Baseline in Daily Abdominal Discomfort Scores [ Time Frame: Baseline, Weeks 4, 12 and 26 ]
    Symptoms of abdominal discomfort were recorded on a 0 to 10 scale, where 0 corresponded to no discomfort and 10 corresponded to worst imaginable discomfort. A negative change from Baseline indicates the discomfort decreased.
  • Change From Baseline in Daily Abdominal Bloating Scores [ Time Frame: Baseline, Weeks 4, 12 and 26 ]
    Symptoms of abdominal bloating were recorded on a 0 to 10 scale, where 0 corresponded to no bloating and 10 corresponded to worst imaginable bloating. A negative change from Baseline indicates the bloating decreased.
  • Number of Bowel Movements Per Day [ Time Frame: Weeks 4, 12 and 26 ]
    Participants recorded the number of bowel movements over 24 hours daily throughout the treatment.
  • Number of Bowel Incontinence Episodes [ Time Frame: Weeks 4, 12 and 26 ]
    Participants recorded the number of incontinence episodes over 24 hours daily throughout the treatment.
  • Number of Bowel Incontinence Free Days [ Time Frame: Weeks 4, 12 and 26 ]
    An incontinence free day was one where the participant reports zero incontinence episodes. The number of incontinence free days for a participant was assessed each week based on the number of reported days.
  • Number of Urgency Episodes Per Day [ Time Frame: Weeks 4, 12 and 26 ]
    Participants recorded the number of urgency episodes over 24 hours daily throughout the treatment.
  • Change From Baseline in IBS-QoL Total Scores [ Time Frame: Baseline, Weeks 4, 8, 12, 18, 26 and 30/EOT ]
    The IBS-QoL consists of 34 items each with a 5-point response scale, where 1 generally represents better responses on items and 5 represents worse responses. The individual responses to the answered items were summed and standardized for a total score and then transformed to a 0- to 100- point scale (0=worst; 100=better) for ease of interpretation. A positive change from Baseline indicates that quality of life improved.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 13, 2012)
  • Pain response based on improvement from baseline in daily abdominal pain scores [ Time Frame: Daily pain response determined to evaluate response rates over 12 weeks ]
  • Stool consistency response based on improvement from baseline in daily stool consistency scores. [ Time Frame: Daily stool consistency response determined to evaluate response over 12 weeks ]
  • Abdominal bloating [ Time Frame: Daily for 12 weeks ]
  • Bowel movement frequency [ Time Frame: Daily for 12 weeks ]
  • Urgency episodes [ Time Frame: Daily for 12 weeks ]
  • Incontinence episodes [ Time Frame: Daily for 12 weeks ]
  • Irritable Bowel Syndrome global symptom severity [ Time Frame: Daily for 12 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy, Safety, and Tolerability of Eluxadoline in the Treatment of Participants With Diarrhea-Predominant Irritable Bowel Syndrome (IBS-d)
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Irritable Bowel Syndrome
Intervention  ICMJE
  • Drug: Eluxadoline
    Oral tablets twice daily
    Other Name: JNJ-27018966
  • Drug: Placebo
    Oral tablets twice daily
Study Arms  ICMJE
  • Experimental: Eluxadoline 75 mg
    Eluxadoline 75 mg tablets, orally, twice daily for up to 26 weeks period.
    Intervention: Drug: Eluxadoline
  • Experimental: Eluxadoline 100 mg
    Eluxadoline 100 mg tablets, orally, twice daily for up to 26 weeks period.
    Intervention: Drug: Eluxadoline
  • Placebo Comparator: Placebo
    Eluxadoline placebo matching tablets, orally, twice daily for up to 26 weeks period.
    Intervention: Drug: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 27, 2018)
1146
Original Estimated Enrollment  ICMJE
 (submitted: March 13, 2012)
1125
Actual Study Completion Date  ICMJE January 9, 2014
Actual Primary Completion Date January 9, 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Participant is 18 to 80 years old
  2. Participant has a diagnosis of irritable bowel syndrome (IBS) with a subtype of diarrhea defined by the Rome III criteria.

2. 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).

      3. Female participants must be:

  • Postmenopausal, defined as 52 years or older and amenorrheic 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.

Exclusion Criteria:

  1. Participant has a diagnosis of IBS with a subtype of constipation, mixed IBS, or unsubtyped IBS by the Rome III criteria.
  2. 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.
  3. Participant has a history of diverticulitis within 3 months prior to Prescreening.
  4. 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).
  5. 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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   Puerto Rico,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01553747
Other Study ID Numbers  ICMJE 27018966IBS3002
2012-001601-24 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Furiex Pharmaceuticals, Inc
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Furiex Pharmaceuticals, Inc
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Furiex Pharmaceuticals, Inc
Verification Date July 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP