52-Week Efficacy and Safety Study of Ibodutant in Women With Irritable Bowel Syndrome With Diarrhea (IBS-D)

NCT ID: NCT02120027

Last Updated: 2017-03-03

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 558 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-02-28
• Study Completion Date: 2015-11-30

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.

Conditions

Irritable Bowel Syndrome With Diarrhea

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Ibodutant 10 mg

Oral tablet to be given once daily for 24 weeks of treatment. Patients randomised to the ibodutant 10 mg arm will continue on ibodutant 10 mg for additional 28 weeks of treatment via mock-re-randomisation at week 25 .

Group Type: EXPERIMENTAL

Ibodutant 10 mg

Intervention Type: DRUG

Oral tablet, to be given once daily.

Placebo

Oral tablet to be given once daily for 24 weeks of treatment. Patients randomised to the placebo arm will be re-randomised at week 25 in a 1:1 ratio to ibodutant or placebo for additional 28 weeks of treatment.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Oral tablet (identical in appearance and weight to ibodutant tablets) to be given once daily.

Interventions

Ibodutant 10 mg

Oral tablet, to be given once daily.

Intervention Type: DRUG

Placebo

Oral tablet (identical in appearance and weight to ibodutant tablets) to be given once daily.

Intervention Type: DRUG

Other Intervention Names

Code: MEN 15596; Sugar pill

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Menarini Group

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jan Tack, Professor

Role: STUDY_CHAIR

Department of Gastroenterology, University Hospital Gasthuisberg, Katholieke Universiteit Leuven, Leuven, Belgium

Lin Chang, Professor

Role: STUDY_CHAIR

Digestive Health and Nutrition Clinic. University of California, Los Angeles, CA, USA

Locations

Chandler, Arizona, United States

Glendale, Arizona, United States

Mesa, Arizona, United States

Phoenix, Arizona, United States

Little Rock, Arkansas, United States

Little Rock, Arkansas, United States

North Little Rock, Arkansas, United States

Encino, California, United States

Gold River, California, United States

Laguna Hills, California, United States

Lincoln, California, United States

North Hollywood, California, United States

Orange, California, United States

Pasadena, California, United States

San Diego, California, United States

Centennial, Colorado, United States

Colorado Springs, Colorado, United States

Fort Myers, Florida, United States

Hialeah, Florida, United States

Hialeah, Florida, United States

Inverness, Florida, United States

Kissimmee, Florida, United States

Lauderdale Lakes, Florida, United States

Miami, Florida, United States

Miami, Florida, United States

Miami, Florida, United States

Miami, Florida, United States

Miami, Florida, United States

Miami Lakes, Florida, United States

Miami Lakes, Florida, United States

Pinellas Park, Florida, United States

Tamarac, Florida, United States

Tampa, Florida, United States

Addison, Illinois, United States

Oak Lawn, Illinois, United States

Rockford, Illinois, United States

Evansville, Indiana, United States

Clive, Iowa, United States

Shawnee, Kansas, United States

Metairie, Louisiana, United States

Shreveport, Louisiana, United States

Columbia, Maryland, United States

Brockton, Massachusetts, United States

Brockton, Massachusetts, United States

Wyoming, Michigan, United States

St Louis, Missouri, United States

Billings, Montana, United States

Newington, New Hampshire, United States

Brooklyn, New York, United States

Great Neck, New York, United States

New York, New York, United States

Hickory, North Carolina, United States

High Point, North Carolina, United States

Kinston, North Carolina, United States

Salisbury, North Carolina, United States

Winston-Salem, North Carolina, United States

Cincinnati, Ohio, United States

Franklin, Ohio, United States

Mentor, Ohio, United States

Levittown, Pennsylvania, United States

Anderson, South Carolina, United States

Germantown, Tennessee, United States

Jackson, Tennessee, United States

Kingsport, Tennessee, United States

Arlington, Texas, United States

Houston, Texas, United States

San Antonio, Texas, United States

Logan, Utah, United States

Ogden, Utah, United States

Sandy City, Utah, United States

Lynchburgh, Virginia, United States

Seattle, Washington, United States

Spokane, Washington, United States

České Budějovice, , Czechia

Hradec Králové, , Czechia

Kralove, , Czechia

Prague, , Czechia

Příbram, , Czechia

Slaný, , Czechia

Zlín, , Czechia

Berlin, , Germany

Berlin, , Germany

Bochum, , Germany

Frankfurt, , Germany

Hamburg, , Germany

Hanover, , Germany

Karlsruhe, , Germany

Leipzig, , Germany

Mainz, , Germany

Schwerin, , Germany

Budapest, , Hungary

Budapest, , Hungary

Budapest, , Hungary

Debrecen, , Hungary

Debrecen, , Hungary

Gyula, , Hungary

Mátészalka, , Hungary

Pécs, , Hungary

Szekszárd, , Hungary

Vác, , Hungary

Daugavpils, , Latvia

Riga, , Latvia

Riga, , Latvia

Riga III, , Latvia

Valmiera, , Latvia

Katowice, , Poland

Lodz, , Poland

Poznan, , Poland

Poznan, , Poland

Sopot, , Poland

Staszów, , Poland

Warsaw, , Poland

Warsaw, , Poland

Warsaw, , Poland

Warsaw, , Poland

Wroclaw, , Poland

Wroclaw, , Poland

Bratislava, , Slovakia

Bratislava, , Slovakia

Bratislava, , Slovakia

Ilava, , Slovakia

Nitra, , Slovakia

Trenčín, , Slovakia

Trnava, , Slovakia

Gothenburg, , Sweden

Lund, , Sweden

Stockholm, , Sweden

Uppsala, , Sweden

Bexhill-on-Sea, , United Kingdom

Chorley, , United Kingdom

Coventry, , United Kingdom

Edgbaston, , United Kingdom

Glasgow, , United Kingdom

Llanishen, , United Kingdom

North Manchester, , United Kingdom

Northumberland, , United Kingdom

Norwich, , United Kingdom

Reading, , United Kingdom

Waterloo, , United Kingdom

Countries

United States; Czechia; Germany; Hungary; Latvia; Poland; Slovakia; Sweden; United Kingdom

Other Identifiers

2013-000895-14

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

NAK-07

Identifier Type: -

Identifier Source: org_study_id