Clinical trial NCT02120027: 52-Week Efficacy and Safety Study of Ibodutant in Women With Irritable Bowel Syndrome With Diarrhea (IBS-D)
Official title: A 52-Week, Double-blind, Randomised, Placebo-controlled, Parallel-group Phase III Study With Re-randomisations at Week 25 to Evaluate the Efficacy and Safety of Oral Ibodutant 10 mg Once Daily in Female Patients With Irritable Bowel Syndrome With Diarrhoea (IBS-D)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Irritable Bowel Syndrome With Diarrhea
Keywords: Irritable Bowel Syndrome
Colon, irritable
Bowel disease
Diarrhea
Lead sponsor: Menarini Group
Sponsor class: INDUSTRY
First posted: 2014-04-22
Enrollment: 558
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Irritable Bowel Syndrome with diarrhoea (IBS-D) is a functional gastrointestinal disorder characterised by chronic or recurrent abdominal pain or discomfort and diarrhoea. This trial aims at the evaluation of the efficacy and safety of oral ibodutant 10 mg once daily as compared to placebo in women with IBS-D over a 24-week treatment period.

Detailed description: The study evaluates the efficacy and safety of ibodutant 10 mg, given once daily for 24 weeks in comparison with placebo in female IBS-D patients. Randomisation to ibodutant and placebo will be 1:1. Efficacy is evaluated in terms of weekly response for abdominal pain intensity and stool consistency over 24 weeks of treatment in at least 50% of the weeks of treatment.

The clinical phase of the study comprises up to 2 weeks of screening for patient's eligibility, a 2-week run-in period (treatment-free) for IBS severity assessment, a first 24-week double-blind treatment period, a second 28-week re-randomised double-blind treatment period and a 2-week safety follow-up, resulting in a maximum 58-week overall duration of the study for each patient.

Patients report their IBS-related symptoms daily in a telephone-based electronic diary from run-in until end of treatment.

Eligibility criteria: Inclusion Criteria:

* At screening:

  * Female patients aged 18 years or older.
  * Clinical diagnosis of IBS-D according to the following symptoms-based criteria as per Rome III modular questionnaire criteria:

    1. Recurrent abdominal pain or discomfort for at least 3 days per month in the last 3 months associated with at least 2 of the following characteristics: a) improvement with defecation; b) onset associated with a change in the frequency of stool; c) onset associated with a change in form (appearance) of stool.
    2. Symptom-onset at least 6 months prior to diagnosis.
    3. Loose or watery stools at least 25% of the time in the last 3 months AND hard or lumpy stools less than 25% of the time in the last 3 months.
    4. Additional criterion: more than 3 bowel movements per day at least 25% of the time in the last 3 months.
  * For patients older than 50 years OR patients with a positive family history of colorectal cancer: normal results from colonoscopy/flexible sigmoidoscopy performed within the last 5 years.
  * For patients aged 65 years or older: absence of ischaemic colitis, microscopy colitis or any other organic gastrointestinal disease as evidenced by the results of a colonoscopy/flexible sigmoidoscopy with biopsy performed within 6 months.
  * For women of childbearing potential: Use of a highly effective contraceptive method with a failure rate \<1% per year throughout the entire study period.
  * Physical examination without clinically relevant abnormalities during screening.
  * No clinically relevant abnormalities in 12-Lead ECG or in laboratory findings.
  * Mentally competent, able to give written informed consent, and compliant to undergo all visits and procedures.
  * Unrestricted access to a touch-tone telephone.
  * Willingness to refrain from using loperamide within 3 days prior to run-in visit and during the run-in period.

Additional criteria at randomisation:

* During both weeks of the run-in period:

  1. A weekly average of worst abdominal pain in the past 24 hours with a score of ≥3.0 on a 0 to 10 point scale.
  2. At least one bowel movement on each day.
  3. A weekly average of at least 3 bowel movements per day.
  4. At least one stool with a consistency of Type 6 or Type 7 according to the Bristol Stool Scale (BSS) on at least 2 days per week.
  5. Less than 2 bowel movements with a consistency of Type 1 or Type 2 according to the BSS per week.
  6. Adequate compliance with the e-diary recording procedure defined as at least 11 of 14 days (≥75%) of the nominal daily data entry.

     Exclusion Criteria:
* Male gender.
* Diagnosis of IBS with a subtype of constipation, mixed IBS, or un-subtyped IBS.
* Colonic or major abdominal surgery, any other major abdominal surgery or elective major surgery planned or expected during the study.
* History of organic GI abnormalities, inflammatory bowel diseases, complicated diverticulosis, ischaemic colitis, microscopic colitis.
* History of pancreatitis, active biliary duct disease, cholecystitis or symptomatic gallbladder stone disease in the previous 6 months.
* History of gluten enteropathy or lactose intolerance.
* Current or previous diagnosis of neoplasia.
* History of endometriosis.
* History of positive tests for ova or parasites, or clostridium difficile toxin or occult blood in the stool in the previous 6 months.
* History of human immunodeficiency virus infection.
* History of major cardiovascular events in the previous 6 months.
* Uncontrolled hypertension, insulin-dependent diabetes mellitus or abnormal thyroid function.
* Major psychiatric or neurological disorders or unstable medical condition which may compromise the efficacy and safety assessments.
* Evidence of clinically significant hepatic disease, severe renal insufficiency or anemia.
* Relevant changes in dietary habits, lifestyle, or exercise regimen in the previous 2 months.
* Use of prohibited concurrent medication within the previous month such as antibiotics, antimuscarinic drugs, drugs enhancing GI motility and analgesics.
* Pregnancy or breastfeeding.
* Inability to understand or collaborate throughout the study.
* Participation in other clinical studies in the previous 4 weeks or concurrent enrollment in a clinical study.
* Any condition that would compromise the well-being of the patient.

Primary outcomes:
measure: Weekly Response for Abdominal Pain Intensity AND Stool Consistency Over the First 24 Weeks of Treatment in at Least 50% of the Weeks of Treatment (12 Out of 24 Weeks).
timeFrame: 24 weeks
Secondary outcomes:
measure: Weekly Response for Abdominal Pain Intensity Over the First 24 Weeks of Treatment in at Least 50% of the Weeks of Treatment (12 Out of 24 Weeks).
timeFrame: 24 weeks
measure: Weekly Response for Stool Consistency Over the First 24 Weeks of Treatment in at Least 50% of the Weeks of Treatment (12 Out of 24 Weeks).
timeFrame: 24 weeks
measure: Weekly Response for Relief of Overall IBS Signs and Symptoms Over the First 24 Weeks of Treatment in at Least 50% of the Weeks (12 Out of 24)
timeFrame: 24 weeks
measure: Sustained Analysis of Response for Abdominal Pain AND Stool Consistency Over First 24-week Double-blind Treatment Period
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Chandler
country: United States
state: Arizona
city: Glendale
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state: Arizona
city: Mesa
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state: Arizona
city: Phoenix
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state: Arizona
city: Little Rock
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state: Arkansas
city: Little Rock
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state: Arkansas
city: North Little Rock
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state: Arkansas
city: Encino
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state: California
city: Gold River
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state: California
city: Laguna Hills
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state: California
city: Lincoln
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state: California
city: North Hollywood
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state: California
city: Orange
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state: California
city: Pasadena
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state: California
city: San Diego
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state: California
city: Centennial
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state: Colorado
city: Colorado Springs
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state: Colorado
city: Fort Myers
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state: Florida
city: Hialeah
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state: Florida
city: Hialeah
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state: Florida
city: Inverness
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city: Lauderdale Lakes
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city: Miami Lakes
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city: Miami Lakes
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city: Miami
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city: Miami
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city: Pinellas Park
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city: Tamarac
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city: Tampa
country: United States
state: Florida
city: Addison
country: United States
state: Illinois
city: Oak Lawn
country: United States
state: Illinois
city: Rockford
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state: Illinois
city: Evansville
country: United States
state: Indiana
city: Clive
country: United States
state: Iowa
city: Shawnee
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state: Kansas
city: Metairie
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state: Louisiana
city: Shreveport
country: United States
state: Louisiana
city: Columbia
country: United States
state: Maryland
city: Brockton
country: United States
state: Massachusetts
city: Brockton
country: United States
state: Massachusetts
city: Wyoming
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state: Michigan
city: St. Louis
country: United States
state: Missouri
city: Billings
country: United States
state: Montana
city: Newington
country: United States
state: New Hampshire
city: Brooklyn
country: United States
state: New York
city: Great Neck
country: United States
state: New York
city: New York
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state: New York
city: Hickory
country: United States
state: North Carolina
city: High Point
country: United States
state: North Carolina
city: Kinston
country: United States
state: North Carolina
city: Salisbury
country: United States
state: North Carolina
city: Winston-Salem
country: United States
state: North Carolina
city: Cincinnati
country: United States
state: Ohio
city: Franklin
country: United States
state: Ohio
city: Mentor
country: United States
state: Ohio
city: Levittown
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state: Pennsylvania
city: Anderson
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state: South Carolina
city: Germantown
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state: Tennessee
city: Jackson
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state: Tennessee
city: Kingsport
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state: Tennessee
city: Arlington
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state: Texas
city: Houston
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state: Texas
city: San Antonio
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state: Texas
city: Logan
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state: Utah
city: Ogden
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city: Sandy
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state: Utah
city: Lynchburgh
country: United States
state: Virginia
city: Seattle
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state: Washington
city: Spokane
country: United States
state: Washington
city: Ceske Budejovice
country: Czech Republic
city: Hradec Kralove
country: Czech Republic
city: Kralove
country: Czech Republic
city: Prague
country: Czech Republic
city: Pribram
country: Czech Republic
city: Slany
country: Czech Republic
city: Zlin
country: Czech Republic
city: Berlin
country: Germany
city: Berlin
country: Germany
city: Bochum
country: Germany
city: Frankfurt
country: Germany
city: Hamburg
country: Germany
city: Hannover
country: Germany
city: Karlsruhe
country: Germany
city: Leipzig
country: Germany
city: Mainz
country: Germany
city: Schwerin
country: Germany
city: Budapest
country: Hungary
city: Budapest
country: Hungary
city: Budapest
country: Hungary
city: Debrecen
country: Hungary
city: Debrecen
country: Hungary
city: Gyula
country: Hungary
city: Mateszalka
country: Hungary
city: Pécs
country: Hungary
city: Szekszard
country: Hungary
city: Vac
country: Hungary
city: Daugavpils
country: Latvia
city: Riga III
country: Latvia
city: Riga
country: Latvia
city: Riga
country: Latvia
city: Valmiera
country: Latvia
city: Katowice
country: Poland
city: Lodz
country: Poland
city: Poznan
country: Poland
city: Poznan
country: Poland
city: Sopot
country: Poland
city: Staszow
country: Poland
city: Warszawa
country: Poland
city: Warszawa
country: Poland
city: Warszawa
country: Poland
city: Warszawa
country: Poland
city: Wroclaw
country: Poland
city: Wroclaw
country: Poland
city: Bratislava
country: Slovakia
city: Bratislava
country: Slovakia
city: Bratislava
country: Slovakia
city: Ilava
country: Slovakia
city: Nitra
country: Slovakia
city: Trencin
country: Slovakia
city: Trnava
country: Slovakia
city: Goteborg
country: Sweden
city: Lund
country: Sweden
city: Stockholm
country: Sweden
city: Uppsala
country: Sweden
city: Bexhill-on-Sea
country: United Kingdom
city: Chorley
country: United Kingdom
city: Coventry
country: United Kingdom
city: Edgbaston
country: United Kingdom
city: Glasgow
country: United Kingdom
city: Llanishen
country: United Kingdom
city: North Manchester
country: United Kingdom
city: Northumberland
country: United Kingdom
city: Norwich
country: United Kingdom
city: Reading
country: United Kingdom
city: Waterloo
country: United Kingdom
Study officials:
affiliation: Department of Gastroenterology, University Hospital Gasthuisberg, Katholieke Universiteit Leuven, Leuven, Belgium
name: Jan Tack, Professor
role: STUDY_CHAIR
affiliation: Digestive Health and Nutrition Clinic. University of California, Los Angeles, CA, USA
name: Lin Chang, Professor
role: STUDY_CHAIR
References: