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

NCT00679380 | Completed Phase 3 Results

• 1 other identifier: CB-01-02/02
• Study Type: interventional
• Target: 514
• Locations: 15 countries
• Sites: 71

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.

Conditions

Ulcerative Colitis

Keywords

Ulcerative colitis

Outcome Measures

Primary Outcomes (1)

• Clinical and Endoscopic Remission.

  Clinical and endoscopic remission defined as an Ulcerative Colitis Disease Activity Index (UCDAI) score ≤ 1, with subscores of 0 for rectal bleeding, stool frequency, and mucosal appearance and with a ≥ 1 point reduction in the endoscopic index score.

  8 weeks

Secondary Outcomes (2)

• Clinical Improvement.

  8 weeks

• Endoscopic Improvement.

  8 weeks

Study Arms (4)

1: budesonide-MMX® 6 mg

EXPERIMENTAL

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

Procedure: Blood sampling, endoscopy; Drug: Budesonide MMX® 6 mg

2: budesonide-MMX® 9 mg

EXPERIMENTAL

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

Procedure: Blood sampling, endoscopy; Drug: Budesonide MMX® 9 mg

3: Entocort EC® 3 mg

ACTIVE COMPARATOR

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

Procedure: Blood sampling, endoscopy; Drug: Entocort EC® 3 mg

4: Placebo

PLACEBO COMPARATOR

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

Procedure: Blood sampling, endoscopy; Drug: Placebo

Interventions

Blood sampling, endoscopy PROCEDURE

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

1: budesonide-MMX® 6 mg; 2: budesonide-MMX® 9 mg; 3: Entocort EC® 3 mg; 4: Placebo

Budesonide MMX® 6 mg DRUG

6 mg/day, 6 mg tablets

1: budesonide-MMX® 6 mg

Budesonide MMX® 9 mg DRUG

9 mg/day, 9 mg tablets

2: budesonide-MMX® 9 mg

Entocort EC® 3 mg DRUG

9 mg/day, 3 mg tablets

3: Entocort EC® 3 mg

Placebo DRUG

Placebo

4: Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Bausch Health Americas, Inc.: lead
• Cosmo Technologies Ltd: collaborator

Study Sites (71)

Centre for Digestive Diseases

Sydney, New South Wales, 2046, Australia

Location

Royal Adelaide Hospital

Adelaide, 5000, Australia

Location

Box Hill Hospital, Department of Gastroenterology Clive Ward Centre,

Box Hill, VIC 3128, Australia

Location

The Alfred Hospital

Melbourne, 3004, Australia

Location

Monash Medical Centre

Melbourne, 3168, Australia

Location

Imelda Hospital

Bonheiden, Belgium

Location

East Viru Central Hospital

Kohtla-Järve, 30322, Estonia

Location

East Tallinn Central Hospital

Tallinn, 10138, Estonia

Location

West Tallinn Central Hospital

Tallinn, 10617, Estonia

Location

Tartu University Hospital

Tartu, 51014, Estonia

Location

Hôpital Beaujon

Clichy, France

Location

Hospital Saint-Louis

Paris, France

Location

Yaron Niv

Petah Tikva, Israel

Location

CRO - IRCCS - Struttura Operativa Complessa di Gastroenterologia Oncologica

Aviano, 33081, Italy

Location

Dipartimento di Medicina Interna e Specialità Mediche (DIMI)

Genova, 16132, Italy

Location

Divisione di Gastroenterologia - Istituto Clinico Humanitas IRCCS in Gastroenterologia

Milan, 20098, Italy

Location

Daugavpils Regional Hospital

Daugavpils, 5417, Latvia

Location

Paula Stradina Clinical University Hospital

Riga, 1002, Latvia

Location

Digestive Disease Centre Gastro

Riga, 1006, Latvia

Location

Clinical University Hospital Gailezers

Riga, 1038, Latvia

Location

Kaunas Medical University Hospital

Kaunas, 50009, Lithuania

Location

Siauliai District Hospital

Šiauliai, 76231, Lithuania

Location

M.Marcinkeviciaus Hospital

Vilnius, 03215, Lithuania

Location

Vilnius University Hospital Santariskiu Klinikos

Vilnius, 08661, Lithuania

Location

Niepubliczny Zaklad Opieki Zdrowotnej VIVAMED

Warsaw, Masovian Voivodeship, 03-580, Poland

Location

Centrum Leczenia Chorób Cywilizacyjnych

Warsaw, Masovian Voivodeship, Poland

Location

Gastromed S.C.

Bialystok, Podlaskie Voivodeship, 15-842, Poland

Location

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

Bialystok, 15-842, Poland

Location

NZOZ Centrum Leczenia Chorob Cywilizacyjnych, oddzial Gdynia, filia Fikakw

Gdynia, 81-572, Poland

Location

NZOZ Centrum Leczenia Chorob Cywilizacyjnych

Gdynia, 81-572, Poland

Location

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

Krakow, 31-531, Poland

Location

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

Krakow, 31-531, Poland

Location

Niepubliczny Zaklad Opieki Zdrowotnej POLIMEDICA

Lodz, 90-302, Poland

Location

NZOZ Polimedica

Lodz, 90-302, Poland

Location

Endoskopia Sp. z o.o.

Sopot, 81-756, Poland

Location

Endoskopia Sp.z o.o.

Sopot, 81-756, Poland

Location

Indywidualna Specjalistyczna Praktyka Lekarska

Wejherowo, 84-200, Poland

Location

Spitalul Clinic Colentina Sectia Gastroenterologie

Bucharest, 020125, Romania

Location

Cabinet Medical

Oradea, Romania

Location

Spitalul Judetean Sibiu

Sibiu, Romania

Location

Centrul de Gastroenterologie Dr. Goldis Adrian

Timișoara, Romania

Location

Federal State Institution ?National Medical Surgical Center

Moscow, 105203, Russia

Location

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, 121309, Russia

Location

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

Moscow, 123423, Russia

Location

GUZ of Moscow "City Clinical Hospital #24"

Moscow, 127006, Russia

Location

Rostov State Medical University

Rostov-on-Don, 344022, Russia

Location

Saint-Petersburg GUZ City polyclinic #38 28

Saint Petersburg, 193015, Russia

Location

Krestovsky Ireland Medical Institute

Saint Petersburg, 197110, Russia

Location

FGU North-West DIstrict Medical Center of Roszdrav

Saint Petersburg, 199004, Russia

Location

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

Saint Petersburg, Russia

Location

ZAO Clinic Dvizhenie

Volgograd, 400107, Russia

Location

Yaroslavl Region Clinical Hospital

Yaroslavl, Russia

Location

FNsP Bratislava, Nemocnica Stare Mesto 1st Internal Clinic Mickiewiczova

Bratislava, 813 69, Slovakia

Location

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

Bratislava, 826 06, Slovakia

Location

Gastroenterologické a Hepatologické centrum

Nitra, 94901, Slovakia

Location

NsP Nove Mesto nad Vahom n.o.

Nové Mesto nad Váhom, Slovakia

Location

Sahlgrenska Univerity Hospital

Gothenburg, 416 85, Sweden

Location

Lund University Hospital

Lund, 221 85, Sweden

Location

IBD-Unit, Sophiahemmet

Stockholm, 11486, Sweden

Location

Div. of Gastroenterology and Hepatology

Stockholm, 118 83, Sweden

Location

Dept. of Gastroenerology and Hepatology

Stockholm, 171 76, Sweden

Location

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

Dnipro, 49074, Ukraine

Location

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

Kharkiv, 61018, Ukraine

Location

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

Lviv, 79013, Ukraine

Location

Odessa city Polyclinic #20, Therapeutic Dept. 6

Odesa, 65114, Ukraine

Location

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

Uzhhorod, Ukraine

Location

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

Uzhhorod, Ukraine

Location

John Radcliffe Hospital

Headington, Oxford, OX3 9DU, United Kingdom

Location

University Hospital of Coventry and Warwickshire

Coventry, CV2 2DX, United Kingdom

Location

Gastrointestinal Unit

Edinburgh, EH4 2XU, United Kingdom

Location

St Marks Hospital

Harrow, HA1 3UJ, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 23436336 DERIVED

MeSH Terms

Conditions

Colitis, Ulcerative

Interventions

Blood Specimen Collection; Endoscopy; Budesonide

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Inflammatory Bowel Diseases; Colonic Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Diagnostic Techniques, Surgical; Minimally Invasive Surgical Procedures; Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Michael Huang, M.D., Senior Medical Director
• Organization: Santarus, Inc.

contact@santarus.com

858-314-5700

Study Officials

• Simon Travis

  Oxford University Hospitals NHS Trust

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

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: May 14, 2008
• First Posted: May 16, 2008
• Study Start: June 1, 2008
• Primary Completion: February 1, 2010
• Study Completion: April 1, 2010
• Last Updated: December 10, 2019
• Results First Posted: August 1, 2014

Record last verified: 2019-11

Locations

PL (13); IT (3); SL (4); IL (1); GB (4); LA (4); LI (4); FR (2); RO (4); BE (1); AU (5); ES (4); RU (11); SE (5); UA (6)