(CB-01-02/02) Randomized Placebo Controlled Trial of Budesonide-multi-matrix System (MMX™) 6 mg and 9 mg in Patients With Ulcerative Colitis

NCT ID: NCT00679380

Last Updated: 2019-12-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 514 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-06-30
• Study Completion Date: 2010-04-30

Brief Summary

This will be a multicentre, randomised, double-blind, double-dummy, parallel group comparative study in patients with mild or moderate, active ulcerative colitis. The study will compare budesonide-MMX™ 6 mg and budesonide-MMX™ 9 mg tablets to placebo and to Entocort® 3 x 3 mg capsules, in four parallel groups of patients over an 8 week treatment period.

After the screening visit, patients will enter a washout period of 2 days, then they will be randomised to the following four treatment groups: budesonide-MMX™ tablets (6 mg), budesonide-MMX™ tablets (9 mg), Entocort® capsules (3 x 3 mg) and placebo (tablets and capsules), all administered once a day after breakfast. Hence, each patient will receive, in the morning after breakfast, either one budesonide-MMX™ 6 mg or budesonide MMX™ 9 mg tablet and 3 placebo Entocort® matching capsules, or three Entocort® 3 mg capsules and one placebo budesonide-MMX™ matching tablet, or one placebo budesonide-MMX™ matching tablet and three placebo Entocort® matching capsules.

Detailed Description

Each patient will receive one of the following regimens in the morning after breakfast:

1. One budesonide MMX® 6 mg tablet plus three placebo Entocort enteric-coated (EC®) overencapsulated capsules, or

2. One budesonide MMX® 9 mg tablet plus three placebo Entocort EC® overencapsulated capsules, or

3. Three placebo Entocort EC® overencapsulated capsules plus one placebo budesonide MMX® tablet, or

4. Three Entocort EC® 3 mg overencapsulated capsules plus one placebo budesonide MMX® tablet, daily for eight weeks.

Hence, each patient is to take four tablets/capsules per day of active or placebo study medication as per the randomization schedule. Placebo tablets of Budesonide MMX® and placebo overencapsulated capsules of Entocort EC® will be used to maintain the study blind using a double-dummy technique.

During the study, five visits to the clinical center are scheduled: one at Screening and three in the double-blind treatment period (Day 1, Day 14, Day 28 and Day 56). A safety follow-up visit will take place about 2 weeks after the final study visit. If a patient is withdrawn from the study before Day 56, they will be asked to attend the study center as soon as possible thereafter so that the Final visit assessments can be conducted.

Conditions

Ulcerative Colitis

Keywords

Ulcerative colitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

1: budesonide-MMX® 6 mg

One budesonide-MMX® 6 mg plus three placebo Entocort EC® overencapsulated capsules daily in the morning after breakfast.

Group Type: EXPERIMENTAL

Blood sampling, endoscopy

Intervention Type: PROCEDURE

Blood sampling for hematology and biochemistry and endoscopy with biopsy for histological and endoscopic assessment scores

Budesonide MMX® 6 mg

Intervention Type: DRUG

6 mg/day, 6 mg tablets

2: budesonide-MMX® 9 mg

One budesonide-MMX® 9 mg plus three placebo Entocort EC® overencapsulated capsules daily in the morning after breakfast.

Group Type: EXPERIMENTAL

Blood sampling, endoscopy

Intervention Type: PROCEDURE

Blood sampling for hematology and biochemistry and endoscopy with biopsy for histological and endoscopic assessment scores

Budesonide MMX® 9 mg

Intervention Type: DRUG

9 mg/day, 9 mg tablets

3: Entocort EC® 3 mg

Three Entocort EC® 3 mg overencapsulated capsules plus one placebo budesonide MMX® tablet daily in the morning after breakfast.

Group Type: ACTIVE_COMPARATOR

Blood sampling, endoscopy

Intervention Type: PROCEDURE

Blood sampling for hematology and biochemistry and endoscopy with biopsy for histological and endoscopic assessment scores

Entocort EC® 3 mg

Intervention Type: DRUG

9 mg/day, 3 mg tablets

4: Placebo

Three placebo Entocort EC® overencapsulated capsules plus one placebo Budesonide MMX® tablet daily in the morning after breakfast.

Group Type: PLACEBO_COMPARATOR

Blood sampling, endoscopy

Intervention Type: PROCEDURE

Blood sampling for hematology and biochemistry and endoscopy with biopsy for histological and endoscopic assessment scores

Placebo

Intervention Type: DRUG

Placebo

Interventions

Blood sampling, endoscopy

Blood sampling for hematology and biochemistry and endoscopy with biopsy for histological and endoscopic assessment scores

Intervention Type: PROCEDURE

Budesonide MMX® 6 mg

6 mg/day, 6 mg tablets

Intervention Type: DRUG

Budesonide MMX® 9 mg

9 mg/day, 9 mg tablets

Intervention Type: DRUG

Entocort EC® 3 mg

9 mg/day, 3 mg tablets

Intervention Type: DRUG

Placebo

Placebo

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Patients fulfilling the following criteria at the screening visit are eligible for participation in the study:

• Male and female patients, 18-75 years old, suffering from ulcerative colitis for at least 6 months.
• Diagnosis of ulcerative colitis in active phase, of mild or moderate entity with Ulcerative Colitis Disease Activity Index (UCDAI) ≥ 4 and ≤ 10 according to Sutherland.
• All females of child-bearing potential must have a negative serum pregnancy test immediately prior to enrollment. In addition, all females of child-bearing potential must agree to be completely abstinent or be using an accepted form of contraception throughout the entire study period. Accepted forms of contraception are defined as those with a failure rate <1% when properly applied and include: combination oral pill, some intra-uterine devices, and a sterilised partner in a stable relationship. Female subjects must also not be actively breast-feeding through the entire study period.
• Ability to comprehend the full nature and purpose of the study, including possible risks and side effects.
• Ability to co-operate with the investigator and to comply with the requirements of the entire study.
• Must be able to understand and voluntarily sign written informed consent prior to inclusion in the study.

Exclusion Criteria

• Patients who meet any of the following criteria at screening visit are to be excluded from study participation:

• Patients with limited distal proctitis (from anal verge up to 15 cm above the pectineal line).
• Patients with severe ulcerative colitis (UCDAI >10).
• Patients with infectious colitis.
• Evidence or history of toxic megacolon.
• Severe anaemia, leucopaenia or granulocytopaenia.
• Use of oral or rectal steroids in the last 4 weeks.
• Use of immuno-suppressive agents in the last 8 weeks before the study.
• Use of anti tumour necrosis factor alpha (anti-TNFα) agents in the last 3 months.
• Concomitant use of any rectal preparation.
• Concomitant use of antibiotics.
• Concurrent use of cytochrome P450 3A4 (CYP3A4) inducers or CYP3A4 inhibitors.
• Patients with verified, presumed or expected pregnancy or ongoing lactation.
• Patients with liver cirrhosis, or evident hepatic or renal disease or insufficiency, and/or severe impairment of the bio-humoural parameters (i.e. 2 x upper limit of normal for alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT) or creatinine).
• Patient with severe diseases in other organs and systems.
• Patients with local or systemic complications or other pathological states requiring a therapy with corticosteroids and/or immuno-suppressive agents.
• Patients diagnosed with type 1 diabetes.
• Patients diagnosed with, or with a family history of, glaucoma.
• All patients with known hepatitis B, hepatitis C or with human immunodeficiency virus (HIV), according to the local privacy policy.
• Participation in experimental therapeutic studies in the last 3 months. (Note: patients who participated in observational only studies are not excluded).
• Any other medical condition that in the principal investigator's opinion would make the administration of the study drug or study procedures hazardous to the subject or obscure the interpretation of adverse events (AEs).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cosmo Technologies Ltd

INDUSTRY

Sponsor Role: collaborator

Bausch Health Americas, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Simon Travis

Role: PRINCIPAL_INVESTIGATOR

Oxford University Hospitals NHS Trust

Locations

Centre for Digestive Diseases

Sydney, New South Wales, Australia

Royal Adelaide Hospital

Adelaide, , Australia

Box Hill Hospital, Department of Gastroenterology Clive Ward Centre,

Box Hill, , Australia

The Alfred Hospital

Melbourne, , Australia

Monash Medical Centre

Melbourne, , Australia

Imelda Hospital

Bonheiden, , Belgium

East Viru Central Hospital

Kohtla-Järve, , Estonia

East Tallinn Central Hospital

Tallinn, , Estonia

West Tallinn Central Hospital

Tallinn, , Estonia

Tartu University Hospital

Tartu, , Estonia

Hôpital Beaujon

Clichy, , France

Hospital Saint-Louis

Paris, , France

Yaron Niv

Petah Tikva, , Israel

CRO - IRCCS - Struttura Operativa Complessa di Gastroenterologia Oncologica

Aviano, , Italy

Dipartimento di Medicina Interna e Specialità Mediche (DIMI)

Genova, , Italy

Divisione di Gastroenterologia - Istituto Clinico Humanitas IRCCS in Gastroenterologia

Milan, , Italy

Daugavpils Regional Hospital

Daugavpils, , Latvia

Paula Stradina Clinical University Hospital

Riga, , Latvia

Digestive Disease Centre Gastro

Riga, , Latvia

Clinical University Hospital Gailezers

Riga, , Latvia

Kaunas Medical University Hospital

Kaunas, , Lithuania

Siauliai District Hospital

Šiauliai, , Lithuania

M.Marcinkeviciaus Hospital

Vilnius, , Lithuania

Vilnius University Hospital Santariskiu Klinikos

Vilnius, , Lithuania

Niepubliczny Zaklad Opieki Zdrowotnej VIVAMED

Warsaw, Masovian Voivodeship, Poland

Centrum Leczenia Chorób Cywilizacyjnych

Warsaw, Masovian Voivodeship, Poland

Gastromed S.C.

Bialystok, Podlaskie Voivodeship, Poland

Gastromed S.C.Maciej Kralisz, Andrzej Penpicki, Jacek Romatowski, Gabinet, Gastrologiczny i Pracownia Endoskopowa

Bialystok, , Poland

NZOZ Centrum Leczenia Chorob Cywilizacyjnych, oddzial Gdynia, filia Fikakw

Gdynia, , Poland

NZOZ Centrum Leczenia Chorob Cywilizacyjnych

Gdynia, , Poland

Samodzielny Publiczny Zaklad Opieki Zdrowotnej, Szpital Uniwersytecki w Krakowie, Oddzial Kliniczny Kliniki Gastroenterologii, Hepatologii i Chorob Zakaznych,

Krakow, , Poland

Szpital Uniwersytecki w Krakowie,Oddział Kliniczny Kliniki Gastroenterologii Hematologii i Chorób Zakaźnych

Krakow, , Poland

Niepubliczny Zaklad Opieki Zdrowotnej POLIMEDICA

Lodz, , Poland

NZOZ Polimedica

Lodz, , Poland

Endoskopia Sp. z o.o.

Sopot, , Poland

Endoskopia Sp.z o.o.

Sopot, , Poland

Indywidualna Specjalistyczna Praktyka Lekarska

Wejherowo, , Poland

Spitalul Clinic Colentina Sectia Gastroenterologie

Bucharest, , Romania

Cabinet Medical

Oradea, , Romania

Spitalul Judetean Sibiu

Sibiu, , Romania

Centrul de Gastroenterologie Dr. Goldis Adrian

Timișoara, , Romania

Federal State Institution ?National Medical Surgical Center

Moscow, , Russia

GU research educational medical centre of the administration of the affairs of the president of Russian Federation on the basis of State Healthcare Institution "State Clinical Hospital # 51"

Moscow, , Russia

State Scientific Centre of Coloproctology of the Federal Agency for High-Technology Medical Care

Moscow, , Russia

GUZ of Moscow "City Clinical Hospital #24"

Moscow, , Russia

Rostov State Medical University

Rostov-on-Don, , Russia

Saint-Petersburg GUZ City polyclinic #38 28

Saint Petersburg, , Russia

Krestovsky Ireland Medical Institute

Saint Petersburg, , Russia

FGU North-West DIstrict Medical Center of Roszdrav

Saint Petersburg, , Russia

St. Petersburg State Medical Academy n.a. I.I. Mechnikov

Saint Petersburg, , Russia

ZAO Clinic Dvizhenie

Volgograd, , Russia

Yaroslavl Region Clinical Hospital

Yaroslavl, , Russia

FNsP Bratislava, Nemocnica Stare Mesto 1st Internal Clinic Mickiewiczova

Bratislava, , Slovakia

FNsP Bratislava, Nemocnica Ruzinov V. Interna klinika, Gastroenterohepatologicke oddelenie Ruzinovska

Bratislava, , Slovakia

Gastroenterologické a Hepatologické centrum

Nitra, , Slovakia

NsP Nove Mesto nad Vahom n.o.

Nové Mesto nad Váhom, , Slovakia

Sahlgrenska Univerity Hospital

Gothenburg, , Sweden

Lund University Hospital

Lund, , Sweden

IBD-Unit, Sophiahemmet

Stockholm, , Sweden

Div. of Gastroenterology and Hepatology

Stockholm, , Sweden

Dept. of Gastroenerology and Hepatology

Stockholm, , Sweden

Chair of Gastroenterology and therapy of Dnipropetrovsk State Medical Academy based on Institute of gastroenterology

Dnipro, , Ukraine

City Clinical Emergency Hospital named after O.I.Meschaninov,

Kharkiv, , Ukraine

Lviv National Medical University after name Danylo Halytsky based on Communal Clinical City hospital No 5, Department of Propedeutic of Internal Disease

Lviv, , Ukraine

Odessa city Polyclinic #20, Therapeutic Dept. 6

Odesa, , Ukraine

Uzhgorod National University, Hospital surgery chair on the base of Uzhgorod Regional Clinical Hospital

Uzhhorod, , Ukraine

Uzhgorod State Medical University, chair of therapy and family medicine, district clinical hospitalof station "Uzhgorod"

Uzhhorod, , Ukraine

John Radcliffe Hospital

Headington, Oxford, United Kingdom

University Hospital of Coventry and Warwickshire

Coventry, , United Kingdom

Gastrointestinal Unit

Edinburgh, , United Kingdom

St Marks Hospital

Harrow, , United Kingdom

Countries

Australia; Belgium; Estonia; France; Israel; Italy; Latvia; Lithuania; Poland; Romania; Russia; Slovakia; Sweden; Ukraine; United Kingdom

References

Travis SP, Danese S, Kupcinskas L, Alexeeva O, D'Haens G, Gibson PR, Moro L, Jones R, Ballard ED, Masure J, Rossini M, Sandborn WJ. Once-daily budesonide MMX in active, mild-to-moderate ulcerative colitis: results from the randomised CORE II study. Gut. 2014 Mar;63(3):433-41. doi: 10.1136/gutjnl-2012-304258. Epub 2013 Feb 22.

Reference Type: DERIVED

PMID: 23436336 (View on PubMed)

Other Identifiers

CB-01-02/02

Identifier Type: -

Identifier Source: org_study_id