Clinical trial NCT01303224: Ibodutant for Relief of Irritable Bowel Syndrome With Diarrhoea (IBS-D)
Official title: 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).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Irritable Bowel Syndrome With Diarrhea
Keywords: Irritable Bowel Syndrome
Colon, irritable
Bowel disease
Lead sponsor: Menarini Group
Sponsor class: INDUSTRY
First posted: 2011-02-24
Enrollment: 565
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
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 the neurokinin type 2 receptor antagonist Ibodutant in improving IBS-D symptoms.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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).
timeFrame: Eight weeks
Secondary outcomes:
measure: 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
timeFrame: Eight weeks
measure: Quality of Life Changes (Using EuroQoL EQ-5D Questionnaire)
timeFrame: Eight weeks
Other outcomes:
measure: Subgroup Analysis: Response for Relief of Overall IBS Symptoms and of Abdominal Pain/Discomfort According to the 75% Rule in the Female ITT Population
timeFrame: Eight weeks
measure: Subgroup Analysis: Response for Relief of Overall IBS Symptoms and of Abdominal Pain/Discomfort According to the 75% Rule in the Male ITT Population
timeFrame: Eight weeks
Locations:
city: Haskovo
country: Bulgaria
facility: MHAT "Haskovo", Second Internal Department
city: Pleven
country: Bulgaria
facility: UMHAT "Dr. Georgi Stranski", Clinic of Gastroenterology
city: Plovdiv
country: Bulgaria
facility: MHAT "Kaspela", Department of Gastroenterology
city: Plovdiv
country: Bulgaria
facility: UMHAT "Sveti Georgi", Internal Consultative Department
city: Ruse
country: Bulgaria
facility: MHAT "Ruse", Clinic of Gastroenterology
city: Sofia
country: Bulgaria
facility: Fifth City Hospital, Gastroenterology Department
city: Sofia
country: Bulgaria
facility: UMHAT "Alexandrovska", Clinic of Propedeutic of Internal Disease
city: Sofia
country: Bulgaria
facility: MHAT "Sveta Anna", Department of Gastroenterology, Endocrinology, and Nephrology
city: Varna
country: Bulgaria
facility: UMHAT "St. Marina", Clinic of Gastroenterology
city: Veliko Tarnovo
country: Bulgaria
facility: MHAT "Dr. Stefan Cherkezov", Gastroenterology Department
city: Hradec Kralove
country: Czech Republic
facility: Poliklinika III, Hepato-Gastroenterologie HK
city: Pardubice
country: Czech Republic
facility: Gastromedic s.r.o., Soukroma ordinace
city: Prague
country: Czech Republic
facility: IKEM, Klinika hepatogastroenterologie
city: Slany
country: Czech Republic
facility: Hospital Slany, Internal Department
city: Strakonice
country: Czech Republic
facility: District Hospital, Internal Department
city: Tabor
country: Czech Republic
facility: Regional Hospital Tabor, Gastroenterology
city: Zlin
country: Czech Republic
facility: Kojecký Soukroma Ordinace
city: Aalborg
country: Denmark
facility: CCBR Aalborg
city: Ballerup
country: Denmark
facility: CCBR Ballerup
city: Hellerup
country: Denmark
facility: Gentofte Hospital, Medicinsk Afdeling F
city: Silkeborg
country: Denmark
facility: Regionshospitalet Silkeborg, Medicinsk Afdeling F
city: Vejle
country: Denmark
facility: CCBR Vejle
city: Berlin
country: Germany
facility: Klinische Forschung Berlin
city: Cologne
country: Germany
facility: Universitätsklinik Köln, Gastroenterologie
city: Dresden
country: Germany
facility: ABX-CRO Clinical Research GmbH
city: Essen
country: Germany
facility: Private Practice Dr. Schaefer
city: Hamburg
country: Germany
facility: Clinical Research Hamburg
city: Hamburg
country: Germany
facility: Israelitisches Krankenhaus, Innere Medizin
city: Leipzig
country: Germany
facility: Gemeinschaftspraxis Kuchta, Wegner, Schiefke
city: Munich
country: Germany
facility: Praxis Prof. Kellner
city: Como
country: Italy
facility: Ospedale Valduce, Unità Operativa Complessa di Gastroenterologia
city: Ferrara
country: Italy
facility: Azienda Ospedaliera Sant'Anna, U.O. Di Gastroenterologia
city: Florence
country: Italy
facility: Azienda Ospedaliero Universitaria Careggi, USOD Gastroenterologia 1
city: Genoa
country: Italy
facility: Università degli Studi di Genova, Dipartimento di Medicina Interna e Specialità Mediche
city: Padua
country: Italy
facility: Azienda Ospedaliera - Università di Padova, Struttura Operativa Complessa di Gastroenterologia
city: Pavia
country: Italy
facility: IRCCS Policlinico San Matteo, Dipartimento di Medicina Interna I e Gastroenterologia
city: Pisa
country: Italy
facility: "Ospedale Nuovo Santa Chiara-Cisanello, Dipartimento di Medicina Interna
city: Rozzano
country: Italy
facility: IRCCS Istituto Clinico Humanitas, Dipartimento di Gastroenterologia
city: San Giovanni Rotondo
country: Italy
facility: IRCCS Ospedale Casa Sollievo della Sofferenza, Divisione di Gastroenterologia
city: Białystok
country: Poland
facility: NZOZ Specjalistyczne Centrum Gastrologii "Gastromed"
city: Bydgoszcz
country: Poland
facility: Szpital Uniwersytecki nr 2 im dr Jana Biziela w Bydgoszczy
city: Bydgoszcz
country: Poland
facility: Gabinet Lekarski Janusz Rudziński
city: Grodzisk Mazowiecki
country: Poland
facility: Mazowieckie Centrum Badań Klinicznych I.Czajkowska M.Śmietańska s.c.
city: Krakov
country: Poland
facility: Specjalistyczne Centrum Medyczne "NOWOMED"
city: Krakov
country: Poland
facility: 5 Wojskowy Szpital Kliniczny z Polikliniką SPZOZ w Krakowie
city: Krakov
country: Poland
facility: NZOZ Krakowskie Centrum Medyczne
city: Lublin
country: Poland
facility: Instytut Medycyny Wsi im. Witolda Chodźki Publiczny Zakład Opieki Zdrowotnej
city: Lublin
country: Poland
facility: NZOZ "Centrum Alergologii"
city: Poznań
country: Poland
facility: NZOZ Solumed
city: Poznań
country: Poland
facility: NZOZ Zaspół Poradni Specjalistycznych "Artmed"
city: Sopot
country: Poland
facility: Endoskopia Sp. z o.o.
city: Toruń
country: Poland
facility: NZOZ "Nasz Lekarz" Praktyka Grupowa Lekarzy Rodzinnych
city: Toruń
country: Poland
facility: NZOZ Remedis Sp z o.o.
city: Warsaw
country: Poland
facility: Centrum Badawcze Współczesnej Terapii, Prywatny Gabinet Lekarski
city: Warsaw
country: Poland
facility: Centrum Medyczne "Osteomed" Sp. z o. o
city: Warsaw
country: Poland
facility: Centralny Szpital Kliniczny MSWiA
city: Warsaw
country: Poland
facility: NZOZ Vivamed
city: Badalona
country: Spain
facility: Hospital Germans Trias i Pujol, Digestive Unit
city: Barcelona
country: Spain
facility: Centro Medico Teknon, Gastroenteloroly Service
city: El Palmar (Murcia)
country: Spain
facility: "Hospital Universitario Virgen de la Arrixaca, Servicio de Medicina del Aparato Digestivo
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos, Digestive Diseases
city: Mataró
country: Spain
facility: Hospital de Mataró, Unitat d'Exploracions Funcionals Digestives
city: Sabadell
country: Spain
facility: Corporació Sanitària Parc Tauli
city: Santiago de Compostela
country: Spain
facility: Complejo Hospitalario Universitario de Santiago, Gastroenterology
city: Sevilla
country: Spain
facility: Hospital Virgen Macarena, Digestive Service
city: Gothenburg
country: Sweden
facility: Sahlgrenska Universitetssjukhuset, Mag-tarm lab
city: Lund
country: Sweden
facility: Probare
city: Skövde
country: Sweden
facility: Kärnsjukhuset
city: Stockholm
country: Sweden
facility: Gastrocentrum Aleris specialistvård Sabbatsberg,
city: Uppsala
country: Sweden
facility: Akademiska sjukhuset, Gastromottagningen
city: Örebro
country: Sweden
facility: Clinical Research Support, S-huset, Södra Grev Rosengatan
Study officials:
affiliation: Department of Gastroenterology, University Hospital Gasthuisberg, Katholieke Universiteit Leuven, Leuven, Belgium
name: Jan Tack, Professor
role: STUDY_CHAIR
References:
citation: 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.