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

Irritable Bowel Syndrome With Diarrhea Clinical Trial

— IRIS-2  

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).

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01303224
• Other study ID #: NAK-04
• Secondary ID: 2010-018300-85
• Status: Completed
• Phase: Phase 2
• First received: February 23, 2011
• Last updated: September 22, 2015
• Start date: October 2010
• Est. completion date: July 2012

Study information

• Verified date: September 2015
• Source: Menarini Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical DevicesItaly: The Italian Medicines AgencyBulgaria: Bulgarian Drug AgencyCzech Republic: State Institute for Drug ControlDenmark: Danish Medicines AgencyPoland: Ministry of HealthSpain: Ministry of HealthSweden: Medical Products Agency
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 565
• Est. completion date: July 2012
• Est. primary completion date: May 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diarrhea
• Irritable Bowel Syndrome
• Irritable Bowel Syndrome With Diarrhea
• Syndrome

Intervention

Drug:
• Ibodutant
Oral tablet, low dose, once daily, for 8 weeks
• Ibodutant
Oral tablet, intermediate dose, once daily, for 8 weeks
• Ibodutant
Oral tablet, high dose, once daily, for 8 weeks
• Placebo
Oral tablet, (identical in appearance and weight to Ibodutant tablets), once daily, for 8 weeks

Locations

Country	Name	City	State
Bulgaria	MHAT "Haskovo", Second Internal Department	Haskovo
Bulgaria	UMHAT "Dr. Georgi Stranski", Clinic of Gastroenterology	Pleven
Bulgaria	MHAT "Kaspela", Department of Gastroenterology	Plovdiv
Bulgaria	UMHAT "Sveti Georgi", Internal Consultative Department	Plovdiv
Bulgaria	MHAT "Ruse", Clinic of Gastroenterology	Ruse
Bulgaria	Fifth City Hospital, Gastroenterology Department	Sofia
Bulgaria	MHAT "Sveta Anna", Department of Gastroenterology, Endocrinology, and Nephrology	Sofia
Bulgaria	UMHAT "Alexandrovska", Clinic of Propedeutic of Internal Disease	Sofia
Bulgaria	UMHAT "St. Marina", Clinic of Gastroenterology	Varna
Bulgaria	MHAT "Dr. Stefan Cherkezov", Gastroenterology Department	Veliko Tarnovo
Czech Republic	Poliklinika III, Hepato-Gastroenterologie HK	Hradec Kralove
Czech Republic	Gastromedic s.r.o., Soukroma ordinace	Pardubice
Czech Republic	IKEM, Klinika hepatogastroenterologie	Prague
Czech Republic	Hospital Slany, Internal Department	Slany
Czech Republic	District Hospital, Internal Department	Strakonice
Czech Republic	Regional Hospital Tabor, Gastroenterology	Tabor
Czech Republic	Kojecký Soukroma Ordinace	Zlin
Denmark	CCBR Aalborg	Aalborg
Denmark	CCBR Ballerup	Ballerup
Denmark	Gentofte Hospital, Medicinsk Afdeling F	Hellerup
Denmark	Regionshospitalet Silkeborg, Medicinsk Afdeling F	Silkeborg
Denmark	CCBR Vejle	Vejle
Germany	Klinische Forschung Berlin	Berlin
Germany	Universitätsklinik Köln, Gastroenterologie	Cologne
Germany	ABX-CRO Clinical Research GmbH	Dresden
Germany	Private Practice Dr. Schaefer	Essen
Germany	Clinical Research Hamburg	Hamburg
Germany	Israelitisches Krankenhaus, Innere Medizin	Hamburg
Germany	Gemeinschaftspraxis Kuchta, Wegner, Schiefke	Leipzig
Germany	Praxis Prof. Kellner	Munich
Italy	Ospedale Valduce, Unità Operativa Complessa di Gastroenterologia	Como
Italy	Azienda Ospedaliera Sant'Anna, U.O. Di Gastroenterologia	Ferrara
Italy	Azienda Ospedaliero Universitaria Careggi, USOD Gastroenterologia 1	Florence
Italy	Università degli Studi di Genova, Dipartimento di Medicina Interna e Specialità Mediche	Genoa
Italy	Azienda Ospedaliera - Università di Padova, Struttura Operativa Complessa di Gastroenterologia	Padua
Italy	IRCCS Policlinico San Matteo, Dipartimento di Medicina Interna I e Gastroenterologia	Pavia
Italy	"Ospedale Nuovo Santa Chiara-Cisanello, Dipartimento di Medicina Interna	Pisa
Italy	IRCCS Istituto Clinico Humanitas, Dipartimento di Gastroenterologia	Rozzano
Italy	IRCCS Ospedale Casa Sollievo della Sofferenza, Divisione di Gastroenterologia	San Giovanni Rotondo
Poland	NZOZ Specjalistyczne Centrum Gastrologii "Gastromed"	Bialystok
Poland	Gabinet Lekarski Janusz Rudzinski	Bydgoszcz
Poland	Szpital Uniwersytecki nr 2 im dr Jana Biziela w Bydgoszczy	Bydgoszcz
Poland	Mazowieckie Centrum Badan Klinicznych I.Czajkowska M.Smietanska s.c.	Grodzisk Mazowiecki
Poland	5 Wojskowy Szpital Kliniczny z Poliklinika SPZOZ w Krakowie	Krakov
Poland	NZOZ Krakowskie Centrum Medyczne	Krakov
Poland	Specjalistyczne Centrum Medyczne "NOWOMED"	Krakov
Poland	Instytut Medycyny Wsi im. Witolda Chodzki Publiczny Zaklad Opieki Zdrowotnej	Lublin
Poland	NZOZ "Centrum Alergologii"	Lublin
Poland	NZOZ Solumed	Poznan
Poland	NZOZ Zaspól Poradni Specjalistycznych "Artmed"	Poznan
Poland	Endoskopia Sp. z o.o.	Sopot
Poland	NZOZ "Nasz Lekarz" Praktyka Grupowa Lekarzy Rodzinnych	Torun
Poland	NZOZ Remedis Sp z o.o.	Torun
Poland	Centralny Szpital Kliniczny MSWiA	Warsaw
Poland	Centrum Badawcze Wspólczesnej Terapii, Prywatny Gabinet Lekarski	Warsaw
Poland	Centrum Medyczne "Osteomed" Sp. z o. o	Warsaw
Poland	NZOZ Vivamed	Warsaw
Spain	Hospital Germans Trias i Pujol, Digestive Unit	Badalona
Spain	Centro Medico Teknon, Gastroenteloroly Service	Barcelona
Spain	"Hospital Universitario Virgen de la Arrixaca, Servicio de Medicina del Aparato Digestivo	El Palmar (Murcia)
Spain	Hospital Clinico San Carlos, Digestive Diseases	Madrid
Spain	Hospital de Mataró, Unitat d'Exploracions Funcionals Digestives	Mataró
Spain	Corporació Sanitària Parc Tauli	Sabadell
Spain	Complejo Hospitalario Universitario de Santiago, Gastroenterology	Santiago de Compostela
Spain	Hospital Virgen Macarena, Digestive Service	Sevilla
Sweden	Sahlgrenska Universitetssjukhuset, Mag-tarm lab	Gothenburg
Sweden	Probare	Lund
Sweden	Clinical Research Support, S-huset, Södra Grev Rosengatan	Örebro
Sweden	Kärnsjukhuset	Skövde
Sweden	Gastrocentrum Aleris specialistvård Sabbatsberg,	Stockholm
Sweden	Akademiska sjukhuset, Gastromottagningen	Uppsala

Sponsors (1)

Lead Sponsor	Collaborator
Menarini Group

Countries where clinical trial is conducted

Bulgaria,  Czech Republic,  Denmark,  Germany,  Italy,  Poland,  Spain,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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	No
Other	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	No
Primary	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	No
Secondary	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	No
Secondary	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	No