Ibodutant for Relief of Irritable Bowel Syndrome With Diarrhoea (IBS-D) (IRIS-2)

Double-blind, Randomised, Placebo-controlled, Parallel-group Phase II Study to Evaluate the Effect of Oral Ibodutant in Irritable Bowel Syndrome With Diarrhoea (IBS-D).

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 the neurokinin type 2 receptor antagonist Ibodutant in improving IBS-D symptoms.

Study Overview

• Status: Completed
• Conditions: Irritable Bowel Syndrome With Diarrhea
• Intervention / Treatment: Drug: Ibodutant; Drug: Ibodutant; Drug: Ibodutant; Drug: Placebo

Detailed Description

The study evaluates the efficacy and safety of three doses of ibodutant, given once daily for 8 weeks versus placebo in IBS-D patients. Efficacy is evaluated in terms of overall symptom relief and abdominal pain/discomfort relief after 8 weeks of treatment. The clinical phase of the study comprises a 2-week run-in period (treatment-free),an 8-week double-blind treatment period and a 2-week treatment withdrawal period, resulting in a 10-week overall duration of the study for each patient.

Patients report their IBS-related symptoms daily in an electronic diary (web-and telephone based)during all periods of the study.

• Study Type: Interventional
• Enrollment (Actual): 565
• Phase: Phase 2

Contacts and Locations

Study Locations

• Bulgaria
  • Haskovo, Bulgaria, 6300
    • MHAT "Haskovo", Second Internal Department
  • Pleven, Bulgaria, 5800
    • UMHAT "Dr. Georgi Stranski", Clinic of Gastroenterology
  • Plovdiv, Bulgaria, 4000
    • MHAT "Kaspela", Department of Gastroenterology
  • Plovdiv, Bulgaria, 4000
    • UMHAT "Sveti Georgi", Internal Consultative Department
  • Ruse, Bulgaria, 7002
    • MHAT "Ruse", Clinic of Gastroenterology
  • Sofia, Bulgaria, 1233
    • Fifth City Hospital, Gastroenterology Department
  • Sofia, Bulgaria, 1431
    • UMHAT "Alexandrovska", Clinic of Propedeutic of Internal Disease
  • Sofia, Bulgaria, 1784
    • MHAT "Sveta Anna", Department of Gastroenterology, Endocrinology, and Nephrology
  • Varna, Bulgaria, 9010
    • UMHAT "St. Marina", Clinic of Gastroenterology
  • Veliko Tarnovo, Bulgaria, 5000
    • MHAT "Dr. Stefan Cherkezov", Gastroenterology Department
• Czech Republic
  • Hradec Kralove, Czech Republic, 500 12
    • Poliklinika III, Hepato-Gastroenterologie HK
  • Pardubice, Czech Republic, 530 02
    • Gastromedic s.r.o., Soukroma ordinace
  • Prague, Czech Republic, 140 21
    • IKEM, Klinika hepatogastroenterologie
  • Slany, Czech Republic, 274 51
    • Hospital Slany, Internal Department
  • Strakonice, Czech Republic, 386 29
    • District Hospital, Internal Department
  • Tabor, Czech Republic, 390 03
    • Regional Hospital Tabor, Gastroenterology
  • Zlin, Czech Republic, 76005
    • Kojecký Soukroma Ordinace
• Denmark
  • Aalborg, Denmark, 9000
    • CCBR Aalborg
  • Ballerup, Denmark, 2750
    • CCBR Ballerup
  • Hellerup, Denmark, 2900
    • Gentofte Hospital, Medicinsk Afdeling F
  • Silkeborg, Denmark, 8600
    • Regionshospitalet Silkeborg, Medicinsk Afdeling F
  • Vejle, Denmark, 7100
    • CCBR Vejle
• Germany
  • Berlin, Germany, 10787
    • Klinische Forschung Berlin
  • Cologne, Germany, 50937
    • Universitätsklinik Köln, Gastroenterologie
  • Dresden, Germany, 01307
    • ABX-CRO Clinical Research GmbH
  • Essen, Germany, 45355
    • Private Practice Dr. Schaefer
  • Hamburg, Germany, 22143
    • Clinical Research Hamburg
  • Hamburg, Germany, 22297
    • Israelitisches Krankenhaus, Innere Medizin
  • Leipzig, Germany, 04103
    • Gemeinschaftspraxis Kuchta, Wegner, Schiefke
  • Munich, Germany, 80639
    • Praxis Prof. Kellner
• Italy
  • Como, Italy, 22100
    • Ospedale Valduce, Unità Operativa Complessa di Gastroenterologia
  • Ferrara, Italy, 44100
    • Azienda Ospedaliera Sant'Anna, U.O. Di Gastroenterologia
  • Florence, Italy, 50134
    • Azienda Ospedaliero Universitaria Careggi, USOD Gastroenterologia 1
  • Genoa, Italy, 16132
    • Università degli Studi di Genova, Dipartimento di Medicina Interna e Specialità Mediche
  • Padua, Italy, 35128
    • Azienda Ospedaliera - Università di Padova, Struttura Operativa Complessa di Gastroenterologia
  • Pavia, Italy, 27100
    • IRCCS Policlinico San Matteo, Dipartimento di Medicina Interna I e Gastroenterologia
  • Pisa, Italy, 56126
    • "Ospedale Nuovo Santa Chiara-Cisanello, Dipartimento di Medicina Interna
  • Rozzano, Italy, 20089
    • IRCCS Istituto Clinico Humanitas, Dipartimento di Gastroenterologia
  • San Giovanni Rotondo, Italy, 71013
    • IRCCS Ospedale Casa Sollievo della Sofferenza, Divisione di Gastroenterologia
• Poland
  • Białystok, Poland, 15-531
    • NZOZ Specjalistyczne Centrum Gastrologii "Gastromed"
  • Bydgoszcz, Poland, 85-681
    • Gabinet Lekarski Janusz Rudzinski
  • Bydgoszcz, Poland, 85-168
    • Szpital Uniwersytecki nr 2 im dr Jana Biziela w Bydgoszczy
  • Grodzisk Mazowiecki, Poland, 05-825
    • Mazowieckie Centrum Badań Klinicznych I.Czajkowska M.Śmietańska s.c.
  • Krakov, Poland, 30-349
    • Specjalistyczne Centrum Medyczne "NOWOMED"
  • Krakov, Poland, 30-901
    • 5 Wojskowy Szpital Kliniczny z Polikliniką SPZOZ w Krakowie
  • Krakov, Poland, 31-501
    • NZOZ Krakowskie Centrum Medyczne
  • Lublin, Poland, 20-090
    • Instytut Medycyny Wsi im. Witolda Chodźki Publiczny Zakład Opieki Zdrowotnej
  • Lublin, Poland, 20-637
    • NZOZ "Centrum Alergologii"
  • Poznań, Poland, 60-539
    • NZOZ Solumed
  • Poznań, Poland, 60-547
    • NZOZ Zaspół Poradni Specjalistycznych "Artmed"
  • Sopot, Poland, 81-756
    • ENDOSKOPIA Sp. z o.o.
  • Toruń, Poland, 87-100
    • NZOZ "Nasz Lekarz" Praktyka Grupowa Lekarzy Rodzinnych
  • Toruń, Poland, 87-100
    • NZOZ Remedis Sp z o.o.
  • Warsaw, Poland, 02-507
    • Centralny Szpital Kliniczny Mswia
  • Warsaw, Poland, 03-580
    • NZOZ Vivamed
  • Warsaw, Poland, 01-377
    • Centrum Badawcze Współczesnej Terapii, Prywatny Gabinet Lekarski
  • Warsaw, Poland, 02-341
    • Centrum Medyczne "Osteomed" Sp. z o. o
• Spain
  • Badalona, Spain, 08916
    • Hospital Germans Trias i Pujol, Digestive Unit
  • Barcelona, Spain, 08022
    • Centro Medico Teknon, Gastroenteloroly Service
  • El Palmar (Murcia), Spain, 30120
    • "Hospital Universitario Virgen de la Arrixaca, Servicio de Medicina del Aparato Digestivo
  • Madrid, Spain, 28040
    • Hospital Clinico San Carlos, Digestive Diseases
  • Mataró, Spain, 08304
    • Hospital de Mataró, Unitat d'Exploracions Funcionals Digestives
  • Sabadell, Spain, 08208
    • Corporació Sanitària Parc Taulí
  • Santiago de Compostela, Spain, 15706
    • Complejo Hospitalario Universitario de Santiago, Gastroenterology
  • Sevilla, Spain, 41009
    • Hospital Virgen Macarena, Digestive Service
• Sweden
  • Gothenburg, Sweden, 413 45
    • Sahlgrenska Universitetssjukhuset, Mag-tarm lab
  • Lund, Sweden, 223 61
    • ProbarE
  • Skövde, Sweden, 541 85
    • Kärnsjukhuset
  • Stockholm, Sweden, 113 82
    • Gastrocentrum Aleris specialistvård Sabbatsberg,
  • Uppsala, Sweden, 751 85
    • Akademiska sjukhuset, Gastromottagningen
  • Örebro, Sweden, 703 62
    • Clinical Research Support, S-huset, Södra Grev Rosengatan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

At start of the run-in period:

• Male or female patients aged 18 - 70 years with a clinical diagnosis of IBS-D according to the Rome III criteria:

• Recurrent abdominal pain/discomfort for at least 3 days per month in the last 3 months associated with at least 2 of the following characteristics:

  1. improvement with defecation;
  2. onset associated with a change in the frequency of stool;
  3. onset associated with a change in form (appearance) of stool.
• Symptom-onset at least 6 months prior to diagnosis.
• Loose/watery stools at least 25% of the time in the last 3 months AND hard/lumpy stools less than 25% of the time in the last 3 months.
• 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 positive family history of colorectal cancer: Normal results from colonoscopy or flexible sigmoidoscopy.
• Mentally competent, able to give written informed consent.
• For women of childbearing potential: Use of a highly effective contraceptive method throughout the entire study period and up to 30 days post-treatment.
• Normal physical examination or without clinically relevant abnormalities.

At randomisation:

-Confirmation of IBS-D severity in terms of bowel movement frequency and abdominal pain intensity along the 2-week run-in period.

Exclusion criteria:

• Organic abnormalities of the gastrointestinal tract, including history of colonic or major abdominal surgery.
• History of gluten enteropathy.
• Lactose intolerance as assessed by response to diet.
• History of positive tests for ova or parasites, or occult blood in the stool.
• Previous diagnosis of diabetes mellitus (either type 1 or 2).
• Unstable medical condition.
• Major psychiatric, neurological, or cardiovascular disorders, or uncontrolled metabolic disease.
• Relevant changes in dietary habits, lifestyle, or exercise regimen in the previous 2 months.
• Use of concurrent medication with drugs known to interfere with gastro-intestinal motility or sensitivity.
• Pregnancy or breastfeeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Ibodutant low dose; Oral tablet, to be given once daily in fasting conditions.	Drug: Ibodutant; Oral tablet, low dose, once daily, for 8 weeks; Other Names: Code: MEN 15596; Drug: Ibodutant; Oral tablet, intermediate dose, once daily, for 8 weeks; Other Names: Code: MEN 15596; Drug: Ibodutant; Oral tablet, high dose, once daily, for 8 weeks; Other Names: Code: MEN 15569
EXPERIMENTAL: Ibodutant intermediate dose; Oral tablet, to be given once daily in fasting conditions.	Drug: Ibodutant; Oral tablet, low dose, once daily, for 8 weeks; Other Names: Code: MEN 15596; Drug: Ibodutant; Oral tablet, intermediate dose, once daily, for 8 weeks; Other Names: Code: MEN 15596; Drug: Ibodutant; Oral tablet, high dose, once daily, for 8 weeks; Other Names: Code: MEN 15569
EXPERIMENTAL: Ibodutant high dose; Oral tablet, to be given once daily in fasting conditions.	Drug: Ibodutant; Oral tablet, low dose, once daily, for 8 weeks; Other Names: Code: MEN 15596; Drug: Ibodutant; Oral tablet, intermediate dose, once daily, for 8 weeks; Other Names: Code: MEN 15596; Drug: Ibodutant; Oral tablet, high dose, once daily, for 8 weeks; Other Names: Code: MEN 15569
PLACEBO_COMPARATOR: Placebo; Oral tablet, to be given once daily in fasting conditions.	Drug: Placebo; Oral tablet, (identical in appearance and weight to Ibodutant tablets), once daily, for 8 weeks; Other Names: Sugar pill

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response for Relief of Overall IBS Symptoms and of Abdominal Pain/Discomfort at the End of 8 Weeks of Treatment, Where the Response is Defined as at Least 6 Weeks With Satisfactory Relief During 8 Weeks of Treatment (75% Rule); Intention-to-treat (ITT).	Weekly binary questions (yes/no) from Interactive Voice/Web Response (IV/WRS) diary records: "Did you have satisfactory relief of your overall IBS symptoms during the last week?" and "Did you have satisfactory relief of your abdominal pain or discomfort during the last week?" Responder: Report of satisfactory overall IBS symptom relief ="Yes" and of satisfactory abdominal pain/discomfort relief = "Yes" 6/8 weeks (75% rule)	Eight weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response for Relief of Overall IBS Symptoms and of Abdominal Pain/Discomfort at the End of 8 Weeks of Treatment, Where the Response is Defined as at Least 4 Weeks With Satisfactory Relief During 8 Weeks of Treatment (50% Rule) in the ITT Population	Weekly binary questions (yes/no) from IV/WRS diary records: "Did you have satisfactory relief of your overall IBS symptoms during the last week?" and "Did you have satisfactory relief of your abdominal pain or discomfort during the last week?" Responder: Report of satisfactory overall IBS symptom relief ="Yes" and of satisfactory abdominal pain/discomfort relief = "Yes" 4/8 weeks with at least 2 consecutive weeks of satisfactory relief during Week 5 to Week 8(50% rule)	Eight weeks
Quality of Life Changes (Using EuroQoL EQ-5D Questionnaire)	Change in EQ-5D Quality of Life (visual analogue scale) score at the end of 8 weeks of treatment versus baseline (at randomisation). EQ-5D quality of life visual analogue scale ranges from "0"= worst imaginable health state to "100"=best imaginable health state.	Eight weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subgroup Analysis: Response for Relief of Overall IBS Symptoms and of Abdominal Pain/Discomfort According to the 75% Rule in the Female ITT Population	Weekly binary questions (yes/no) from IV/WRS diary records: "Did you have satisfactory relief of your overall IBS symptoms during the last week?" and "Did you have satisfactory relief of your abdominal pain or discomfort during the last week?" Responder: Report of satisfactory overall IBS symptom relief ="Yes" and of satisfactory abdominal pain/discomfort relief = "Yes" 6/8 weeks (75% rule)	Eight weeks
Subgroup Analysis: Response for Relief of Overall IBS Symptoms and of Abdominal Pain/Discomfort According to the 75% Rule in the Male ITT Population	Weekly binary questions (yes/no) from IV/WRS diary records: "Did you have satisfactory relief of your overall IBS symptoms during the last week?" and "Did you have satisfactory relief of your abdominal pain or discomfort during the last week?" Responder: Report of satisfactory overall IBS symptom relief ="Yes" and of satisfactory abdominal pain/discomfort relief = "Yes" 6/8 weeks (75% rule)	Eight weeks

Collaborators and Investigators

• Sponsor: Menarini Group

Publications and helpful links

General Publications

• Tack J, Schumacher K, Tonini G, Scartoni S, Capriati A, Maggi CA; Iris-2 investigators. The neurokinin-2 receptor antagonist ibodutant improves overall symptoms, abdominal pain and stool pattern in female patients in a phase II study of diarrhoea-predominant IBS. Gut. 2017 Aug;66(8):1403-1413. doi: 10.1136/gutjnl-2015-310683. Epub 2016 Apr 15.

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (ACTUAL): May 1, 2012
• Study Completion (ACTUAL): July 1, 2012

Study Registration Dates

• First Submitted: February 23, 2011
• First Submitted That Met QC Criteria: February 23, 2011
• First Posted (ESTIMATE): February 24, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): October 7, 2015
• Last Update Submitted That Met QC Criteria: September 22, 2015
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Keywords: Irritable Bowel Syndrome; Colon, irritable; Bowel disease
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Disease; Signs and Symptoms, Digestive; Gastrointestinal Diseases; Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Syndrome; Irritable Bowel Syndrome; Diarrhea
• Other Study ID Numbers: NAK-04; 2010-018300-85 (EUDRACT_NUMBER)