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

NCT ID: NCT02107196

Last Updated: 2017-01-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 535 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-03-31
• Study Completion Date: 2015-06-30

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 12-week treatment period.

Detailed Description

The study evaluates the efficacy and safety of ibodutant 10 mg, given once daily for 12 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 12 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 12-week double-blind treatment period, a 4-week randomised withdrawal (RW) period and a 2-week safety follow-up, resulting in a maximum 22-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 12 weeks of treatment. Patients randomised to the ibodutant 10 mg arm will be re-randomised at week 13 in a 1:1 ratio to either ibodutant 10 mg or placebo for additional 4 weeks of treatment.

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 12 weeks of treatment. Patients randomised to the placebo arm will be mock-re-randomised (switch in blinded conditions) to ibodutant at week 13 for additional 4 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.

• 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 F 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

Brandon, Florida, United States

Brooksville, Florida, United States

Coral Gables, Florida, United States

Gainesville, Florida, United States

Hialeah, Florida, United States

Jupiter, Florida, United States

Miami, Florida, United States

Miami, Florida, United States

Miami, Florida, United States

Addison, Illinois, United States

Chicago, Illinois, United States

Augusta, Kansas, United States

Newton, Kansas, United States

Wichita, Kansas, United States

Lexington, Kentucky, United States

Miami, Florida, United States

Miami Lakes, Florida, United States

Madisonville, Kentucky, United States

Owensboro, Kentucky, United States

Crowley, Louisiana, United States

Baltimore, Maryland, United States

Ann Arbor, Michigan, United States

Chesterfield, Michigan, United States

Saginaw, Michigan, United States

Troy, Michigan, United States

Las Vegas, Nevada, United States

Hartsdale, New York, United States

Fayetteville, North Carolina, United States

Greensboro, North Carolina, United States

Fargo, North Dakota, United States

Akron, Ohio, United States

Cincinnati, Ohio, United States

Cincinnati, Ohio, United States

Cleveland, Ohio, United States

Columbus, Ohio, United States

Dayton, Ohio, United States

Reading, Pennsylvania, United States

Greer, South Carolina, United States

Simpsonville, South Carolina, United States

Chattanooga, Tennessee, United States

Knoxville, Tennessee, United States

Knoxville, Tennessee, United States

Nashville, Tennessee, United States

Smyrna, Tennessee, United States

Beaumont, Texas, United States

Houston, Texas, United States

Houston, Texas, United States

Hurst, Texas, United States

San Antonio, Texas, United States

Ste. Channelview, Texas, United States

West Jordan, Utah, United States

Morgantown, West Virginia, United States

Haskovo, , Bulgaria

Plovdiv, , Bulgaria

Rousse, , Bulgaria

Sofia, , Bulgaria

Sofia, , Bulgaria

Veliko Tarnovo, , Bulgaria

Karlovy Vary, , Czechia

Prague, , Czechia

Prague, , Czechia

Ústí nad Labem, , Czechia

Ústí nad Orlicí, , Czechia

Bordeaux, , France

Nantes, , France

Nice, , France

Rouen, , France

Bobigny, Île-de-France Region, France

Stuttgart, Baden-Wurttemberg, Germany

Berlin, , Germany

Berlin, , Germany

Essen, , Germany

Hamburg, , Germany

Hamburg, , Germany

Bari, , Italy

Bari, , Italy

Bologna, , Italy

Florence, , Italy

Pavia, , Italy

Rome, , Italy

Bydgoszcz, , Poland

Częstochowa, , Poland

Krakow, , Poland

Lublin, , Poland

Wroclaw, , Poland

Târgu Mureş, Jud. Mures, Romania

Târgu Mureş, Mureș County, Romania

Timișoara, Timiș County, Romania

Timișoara, Timiș County, Romania

Brasov, , Romania

Brasov, , Romania

Bucharest, , Romania

Bucharest, , Romania

Kaluga, , Russia

Moscow, , Russia

Saint Petersburg, , Russia

Saint Petersburg, , Russia

Saint Petersburg, , Russia

Smolensk, , Russia

Yaroslavl, , Russia

Badalona, Barcelona, Spain

Mataró, Barcelona, Spain

Sabadell, Barcelona, Spain

Barcelona, , Spain

Barcelona, , Spain

Madrid, , Spain

Seville, , Spain

Penzance, Cornwall, United Kingdom

Chesterfield, Derbyshire, United Kingdom

Inverness, Scotland, United Kingdom

Doncaster, South Yorkshire, United Kingdom

Leicestershire, , United Kingdom

Manchester, , United Kingdom

Plymouth, Devon, , United Kingdom

San Diego, California, United States

Upland, California, United States

Littleton, Colorado, United States

Bristol, Connecticut, United States

Boynton Beach, Florida, United States

Huntsville, Alabama, United States

Sherwood, Arizona, United States

Little Rock, Arkansas, United States

Artesia, California, United States

Chula Vista, California, United States

Encino, California, United States

Mission Hills, California, United States

Sacramento, California, United States

Countries

United States; Bulgaria; Czechia; France; Germany; Italy; Poland; Romania; Russia; Spain; United Kingdom

Other Identifiers

2013-000894-56

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

NAK-06

Identifier Type: -

Identifier Source: org_study_id