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

NCT02120027 | Terminated Phase 3 Results

• 2 other identifiers: NAK-072013-000895-14
• Study Type: interventional
• Target: 558
• Locations: 9 countries
• Sites: 139

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.

Conditions

Irritable Bowel Syndrome With Diarrhea

Keywords

Irritable Bowel Syndrome; Colon, irritable; Bowel disease; Diarrhea

Outcome Measures

Primary Outcomes (1)

• 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).

  The patient will be considered a weekly responder if she meets both of the following criteria in the same week: * Abdominal pain response: decrease in weekly average of worst abdominal pain score in the past 24 hours of at least 30% compared with baseline (patients reported their worst abdominal pain on a 0 to 10 NRS scale, where 0 corresponds to no pain and 10 corresponds to worst possible pain); * Stool consistency response: decrease of at least 50% in the number of days per week with at least one stool that has a consistency of Type 6 or 7 compared with baseline (patients reported their stool consistency response using the Bristol Stool Chart score based on a 1 to 7 NRS scale where 1 corresponds to hard stool and 7 corresponds to watery diarrhoea).

  24 weeks

Secondary Outcomes (4)

• 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).

  24 weeks

• 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).

  24 weeks

• 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)

  24 weeks

• Sustained Analysis of Response for Abdominal Pain AND Stool Consistency Over First 24-week Double-blind Treatment Period

  24 weeks

Study Arms (2)

Ibodutant 10 mg

EXPERIMENTAL

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 .

Drug: Ibodutant 10 mg

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

Ibodutant 10 mg DRUG

Oral tablet, to be given once daily.

Also known as: Code: MEN 15596

Ibodutant 10 mg

Placebo DRUG

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

Also known as: Sugar pill

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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.
• Symptom-onset at least 6 months prior to diagnosis.
• 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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Menarini Group: lead

Study Sites (139)

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Chandler, Arizona, 85224, United States

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Glendale, Arizona, 85308, United States

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Mesa, Arizona, 85202, United States

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Phoenix, Arizona, 85012, United States

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Little Rock, Arkansas, 72211, United States

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Little Rock, Arkansas, 72212, United States

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North Little Rock, Arkansas, 72117, United States

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Encino, California, 91436, United States

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Gold River, California, 95670, United States

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Laguna Hills, California, 92653, United States

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Lincoln, California, 95648, United States

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North Hollywood, California, 91606, United States

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Orange, California, 92868, United States

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Pasadena, California, 91105, United States

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San Diego, California, 92108, United States

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Centennial, Colorado, 80112, United States

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Colorado Springs, Colorado, 80906, United States

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Fort Myers, Florida, 33916, United States

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Hialeah, Florida, 33012, United States

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Hialeah, Florida, 33016, United States

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Inverness, Florida, 34452, United States

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Kissimmee, Florida, 34741, United States

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Lauderdale Lakes, Florida, 33319, United States

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Miami, Florida, 33135, United States

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Miami, Florida, 33165, United States

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Miami, Florida, 33173, United States

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Miami, Florida, 33185, United States

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Miami, Florida, 33186, United States

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Miami Lakes, Florida, 33014, United States

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Miami Lakes, Florida, 33016, United States

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Pinellas Park, Florida, 33782, United States

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Tamarac, Florida, 33319, United States

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Tampa, Florida, 33606, United States

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Addison, Illinois, 60101, United States

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Oak Lawn, Illinois, 60453, United States

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Rockford, Illinois, 61107, United States

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Evansville, Indiana, 47714, United States

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Clive, Iowa, 50325, United States

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Shawnee, Kansas, 66218, United States

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Metairie, Louisiana, 70006, United States

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Shreveport, Louisiana, 71103, United States

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Columbia, Maryland, 21045, United States

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Brockton, Massachusetts, 02301, United States

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Brockton, Massachusetts, 02302, United States

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Wyoming, Michigan, 49519, United States

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St Louis, Missouri, 63128, United States

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Billings, Montana, 59102, United States

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Newington, New Hampshire, 03801, United States

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Brooklyn, New York, 11235, United States

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Great Neck, New York, 11023, United States

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New York, New York, 10016, United States

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Hickory, North Carolina, 28602, United States

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High Point, North Carolina, 27262, United States

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Kinston, North Carolina, 28501-1584, United States

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Salisbury, North Carolina, 28144, United States

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Winston-Salem, North Carolina, 27103, United States

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Cincinnati, Ohio, 45224, United States

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Franklin, Ohio, 45005, United States

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Mentor, Ohio, 44060, United States

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Levittown, Pennsylvania, 19056, United States

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Anderson, South Carolina, 29621, United States

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Germantown, Tennessee, 38138, United States

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Jackson, Tennessee, 38305, United States

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Kingsport, Tennessee, 37660, United States

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Arlington, Texas, 76012, United States

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Houston, Texas, 77074, United States

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San Antonio, Texas, 78229, United States

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Logan, Utah, 84341, United States

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Ogden, Utah, 84405, United States

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Sandy City, Utah, 84094, United States

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Lynchburgh, Virginia, 24502, United States

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Seattle, Washington, 98105, United States

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Spokane, Washington, 99208, United States

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České Budějovice, 37001, Czechia

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Hradec Králové, 500 02, Czechia

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Kralove, 50012, Czechia

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Prague, 130 00, Czechia

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Příbram, 26126, Czechia

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Slaný, 274 51, Czechia

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Zlín, 76001, Czechia

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Berlin, 10117, Germany

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Berlin, 12627, Germany

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Bochum, 44787, Germany

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Frankfurt, 60596, Germany

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Hamburg, 22297, Germany

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Hanover, 30159, Germany

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Karlsruhe, 76199, Germany

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Leipzig, 04103, Germany

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Mainz, 55116, Germany

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Schwerin, 19055, Germany

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Budapest, 1088, Hungary

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Budapest, 1136, Hungary

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Budapest, H 1032, Hungary

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Debrecen, 4032, Hungary

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Debrecen, 4043, Hungary

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Gyula, 5703, Hungary

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Mátészalka, 4700, Hungary

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Pécs, 7624, Hungary

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Szekszárd, 7100, Hungary

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Vác, 2600, Hungary

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Daugavpils, 5417, Latvia

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Riga, 1002, Latvia

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Riga, 1005, Latvia

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Riga III, 1006, Latvia

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Valmiera, 4201, Latvia

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Katowice, 40772, Poland

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Lodz, 90153, Poland

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Poznan, 60355, Poland

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Poznan, 61606, Poland

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Sopot, 81756, Poland

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Staszów, 28100, Poland

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Warsaw, 01231, Poland

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Warsaw, 02018, Poland

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Warsaw, 02679, Poland

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Warsaw, 03580, Poland

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Wroclaw, 50556, Poland

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Wroclaw, 54144, Poland

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Bratislava, 82107, Slovakia

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Bratislava, 83104, Slovakia

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Bratislava, 85101, Slovakia

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Ilava, 01901, Slovakia

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Nitra, 94901, Slovakia

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Trenčín, 91101, Slovakia

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Trnava, 91701, Slovakia

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Gothenburg, 41345, Sweden

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Lund, 22222, Sweden

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Stockholm, 14186, Sweden

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Uppsala, 75185, Sweden

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Bexhill-on-Sea, TN40 1JJ, United Kingdom

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Chorley, PR7 7NA, United Kingdom

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Coventry, CV2 2DX, United Kingdom

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Edgbaston, B15 2SQ, United Kingdom

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Glasgow, G20 0SP, United Kingdom

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Llanishen, CF14 5GJ, United Kingdom

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North Manchester, M15 6SX, United Kingdom

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Northumberland, NE46 1QJ, United Kingdom

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Norwich, NR4 7UY, United Kingdom

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Reading, RG2 0TG, United Kingdom

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Waterloo, L22 0LG, United Kingdom

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MeSH Terms

Conditions

Irritable Bowel Syndrome; Intestinal Diseases; Diarrhea

Interventions

ibodutant; Sugars

Condition Hierarchy (Ancestors)

Colonic Diseases, Functional; Colonic Diseases; Gastrointestinal Diseases; Digestive System Diseases; Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Carbohydrates

Limitations and Caveats

The Sponsor decided on 03 September 2015 to prematurely terminate the study because of negative results of the contemporaneous sister study NAK-06 and the definitely lower than expected overall (ibodutant/placebo) response rate at week 24.

Results Point of Contact

• Title: Angela Capriati, MD PhD - Corporate Director Clinical Research
• Organization: MENARINI Group

acapriati@menarini-ricerche.it

+39 055 5680

Study Officials

• Jan Tack, Professor

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

  STUDY CHAIR

• Lin Chang, Professor

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

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 17, 2014
• First Posted: April 22, 2014
• Study Start: February 1, 2014
• Primary Completion: November 1, 2015
• Study Completion: November 1, 2015
• Last Updated: March 3, 2017
• Results First Posted: January 18, 2017

Record last verified: 2017-01

Locations

US (73); SE (4); LA (5); SL (7); HU (10); DE (10); CZ (7); GB (11); PL (12)