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

Efficacy and Safety of Oral Budesonide-MMX™ (CB-01-02) 6 mg and 9 mg Extended Release Tablets in Patients With Mild or Moderate Active Ulcerative Colitis. A Multicentre, Randomised, Double-Blind, Double-Dummy, Comparative Study Versus Placebo With an Additional Reference Arm Evaluating Entocort®EC

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.

Study Overview

• Status: Completed
• Conditions: Ulcerative Colitis
• Intervention / Treatment: Drug: Placebo; Procedure: Blood sampling, endoscopy; Drug: Budesonide MMX® 6 mg; Drug: Budesonide MMX® 9 mg; Drug: Entocort EC® 3 mg

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.

• Study Type: Interventional
• Enrollment (Actual): 514
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Adelaide, Australia, 5000
    • Royal Adelaide Hospital
  • Box Hill, Australia, VIC 3128
    • Box Hill Hospital, Department of Gastroenterology Clive Ward Centre,
  • Melbourne, Australia, 3004
    • The Alfred Hospital
  • Melbourne, Australia, 3168
    • Monash Medical Centre
  • New South Wales
    • Sydney, New South Wales, Australia, 2046
      • Centre For Digestive Diseases
• Belgium
  • Bonheiden, Belgium
    • Imelda Hospital
• Estonia
  • Kohtla-Jarve, Estonia, 30322
    • East Viru Central Hospital
  • Tallinn, Estonia, 10138
    • East Tallinn Central Hospital
  • Tallinn, Estonia, 10617
    • West Tallinn Central Hospital
  • Tartu, Estonia, 51014
    • Tartu University Hospital
• France
  • Clichy Cedex, France
    • Hopital Beaujon
  • Paris, France
    • Hôspital Saint-Louis
• Israel
  • Petach Tikva, Israel
    • Yaron Niv
• Italy
  • Aviano, Italy, 33081
    • CRO - IRCCS - Struttura Operativa Complessa di Gastroenterologia Oncologica
  • Genova, Italy, 16132
    • Dipartimento di Medicina Interna e Specialità Mediche (DIMI)
  • Milan, Italy, 20098
    • Divisione di Gastroenterologia - Istituto Clinico Humanitas IRCCS in Gastroenterologia
• Latvia
  • Daugavpils, Latvia, 5417
    • Daugavpils Regional Hospital
  • Riga, Latvia, 1002
    • Paula Stradina Clinical University Hospital
  • Riga, Latvia, 1006
    • Digestive Disease Centre Gastro
  • Riga, Latvia, 1038
    • Clinical University Hospital Gailezers
• Lithuania
  • Kaunas, Lithuania, 50009
    • Kaunas Medical University Hospital
  • Siauliai, Lithuania, 76231
    • Siauliai District Hospital
  • Vilnius, Lithuania, 08661
    • Vilnius University Hospital Santariskiu Klinikos
  • Vilnius, Lithuania, 03215
    • M.Marcinkeviciaus Hospital
• Poland
  • Bialystok, Poland, 15-842
    • Gastromed S.C.Maciej Kralisz, Andrzej Penpicki, Jacek Romatowski, Gabinet, Gastrologiczny i Pracownia Endoskopowa
  • Gdynia, Poland, 81-572
    • NZOZ Centrum Leczenia Chorob Cywilizacyjnych, oddzial Gdynia, filia Fikakw
  • Gdynia, Poland, 81-572
    • NZOZ Centrum Leczenia Chorob Cywilizacyjnych
  • Krakow, Poland, 31-531
    • Samodzielny Publiczny Zaklad Opieki Zdrowotnej, Szpital Uniwersytecki w Krakowie, Oddzial Kliniczny Kliniki Gastroenterologii, Hepatologii i Chorob Zakaznych,
  • Kraków, Poland, 31-531
    • Szpital Uniwersytecki w Krakowie,Oddział Kliniczny Kliniki Gastroenterologii Hematologii i Chorób Zakaźnych
  • Lodz, Poland, 90-302
    • Niepubliczny Zaklad Opieki Zdrowotnej POLIMEDICA
  • Sopot, Poland, 81-756
    • ENDOSKOPIA Sp. z o.o.
  • Sopot, Poland, 81-756
    • Endoskopia Sp.z o.o.
  • Wejherowo, Poland, 84-200
    • Indywidualna Specjalistyczna Praktyka Lekarska
  • Łódź, Poland, 90-302
    • NZOZ Polimedica
  • Mazowieckie
    • Warszawa, Mazowieckie, Poland, 03-580
      • Niepubliczny Zaklad Opieki Zdrowotnej VIVAMED
    • Warszawa, Mazowieckie, Poland
      • Centrum Leczenia Chorob Cywilizacyjnych
  • Podlaskie
    • Białystok, Podlaskie, Poland, 15-842
      • GASTROMED s.c.
• Romania
  • Bucuresti, Romania, 020125
    • Spitalul Clinic Colentina Sectia Gastroenterologie
  • Oradea, Romania
    • Cabinet Médical
  • Sibiu, Romania
    • Spitalul Judetean Sibiu
  • Timisoara, Romania
    • Centrul de Gastroenterologie Dr. Goldis Adrian
• Russian Federation
  • Moscow, Russian Federation, 105203
    • Federal State Institution ?National Medical Surgical Center
  • Moscow, Russian Federation, 121309
    • 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, Russian Federation, 123423
    • State Scientific Centre of Coloproctology of the Federal Agency for High-Technology Medical Care
  • Moscow, Russian Federation, 127006
    • GUZ of Moscow "City Clinical Hospital #24"
  • Rostov-on-Don, Russian Federation, 344022
    • Rostov State Medical University
  • St Petersburg, Russian Federation, 193015
    • Saint-Petersburg GUZ City polyclinic #38 28
  • St Petersburg, Russian Federation
    • St. Petersburg State Medical Academy n.a. I.I. Mechnikov
  • St-Petersburg, Russian Federation, 197110
    • Krestovsky Ireland Medical Institute
  • St-Petersburg, Russian Federation, 199004
    • FGU North-West DIstrict Medical Center of Roszdrav
  • Volgograd, Russian Federation, 400107
    • ZAO Clinic Dvizhenie
  • Yaroslavl, Russian Federation
    • Yaroslavl Region Clinical Hospital
• Slovakia
  • Bratislava, Slovakia, 813 69
    • FNsP Bratislava, Nemocnica Stare Mesto 1st Internal Clinic Mickiewiczova
  • Bratislava, Slovakia, 826 06
    • FNsP Bratislava, Nemocnica Ruzinov V. Interna klinika, Gastroenterohepatologicke oddelenie Ruzinovska
  • Nitra, Slovakia, 94901
    • Gastroenterologické a Hepatologické centrum
  • Nové Mesto nad Váhom, Slovakia
    • NsP Nove Mesto nad Vahom n.o.
• Sweden
  • Göteborg, Sweden, 416 85
    • Sahlgrenska Univerity Hospital
  • Lund, Sweden, 221 85
    • Lund University Hospital
  • Stockholm, Sweden, 11486
    • IBD-Unit, Sophiahemmet
  • Stockholm, Sweden, 118 83
    • Div. of Gastroenterology and Hepatology
  • Stockholm, Sweden, 171 76
    • Dept. of Gastroenerology and Hepatology
• Ukraine
  • Dnepropetrovsk, Ukraine, 49074
    • Chair of Gastroenterology and therapy of Dnipropetrovsk State Medical Academy based on Institute of gastroenterology
  • Kharkov, Ukraine, 61018
    • City Clinical Emergency Hospital named after O.I.Meschaninov,
  • Lviv, Ukraine, 79013
    • Lviv National Medical University after name Danylo Halytsky based on Communal Clinical City hospital No 5, Department of Propedeutic of Internal Disease
  • Odessa, Ukraine, 65114
    • Odessa city Polyclinic #20, Therapeutic Dept. 6
  • Uzhorod, Ukraine
    • Uzhgorod National University, Hospital surgery chair on the base of Uzhgorod Regional Clinical Hospital
  • Uzhorod, Ukraine
    • Uzhgorod State Medical University, chair of therapy and family medicine, district clinical hospitalof station "Uzhgorod"
• United Kingdom
  • Coventry, United Kingdom, CV2 2DX
    • University Hospital of Coventry and Warwickshire
  • Edinburgh, United Kingdom, EH4 2XU
    • Gastrointestinal Unit
  • Harrow, United Kingdom, HA1 3UJ
    • St Marks Hospital
  • Oxford
    • Headington, Oxford, United Kingdom, OX3 9DU
      • John Radcliffe Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1: budesonide-MMX® 6 mg; One budesonide-MMX® 6 mg plus three placebo Entocort EC® overencapsulated capsules daily in the morning after breakfast.	Procedure: Blood sampling, endoscopy; Blood sampling for hematology and biochemistry and endoscopy with biopsy for histological and endoscopic assessment scores; Drug: Budesonide MMX® 6 mg; 6 mg/day, 6 mg tablets
Experimental: 2: budesonide-MMX® 9 mg; One budesonide-MMX® 9 mg plus three placebo Entocort EC® overencapsulated capsules daily in the morning after breakfast.	Procedure: Blood sampling, endoscopy; Blood sampling for hematology and biochemistry and endoscopy with biopsy for histological and endoscopic assessment scores; Drug: Budesonide MMX® 9 mg; 9 mg/day, 9 mg tablets
Active Comparator: 3: Entocort EC® 3 mg; Three Entocort EC® 3 mg overencapsulated capsules plus one placebo budesonide MMX® tablet daily in the morning after breakfast.	Procedure: Blood sampling, endoscopy; Blood sampling for hematology and biochemistry and endoscopy with biopsy for histological and endoscopic assessment scores; Drug: Entocort EC® 3 mg; 9 mg/day, 3 mg tablets
Placebo Comparator: 4: Placebo; Three placebo Entocort EC® overencapsulated capsules plus one placebo Budesonide MMX® tablet daily in the morning after breakfast.	Drug: Placebo; Placebo; Procedure: Blood sampling, endoscopy; Blood sampling for hematology and biochemistry and endoscopy with biopsy for histological and endoscopic assessment scores

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Improvement.	Clinical improvement, defined as a ≥ 3-point improvement in UCDAI from baseline to the end of Week 8.	8 weeks
Endoscopic Improvement.	Greater or equal to a 1 point improvement in the mucosal appearance subscore of the UCDAI, from baseline to week 8. As per the hierarchical testing procedure for secondary endpoints, because clinical improvement was not statistically significant in the ITT population, formal statistical comparisons for endoscopic improvement between the 2 budesonide MMX groups and placebo were not conducted.	8 weeks

Collaborators and Investigators

• Sponsor: Bausch Health Americas, Inc.
• Collaborators: Cosmo Technologies Ltd
• Investigators: Principal Investigator: Simon Travis, Oxford University Hospitals NHS Trust

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: June 1, 2008
• Primary Completion (Actual): February 1, 2010
• Study Completion (Actual): April 1, 2010

Study Registration Dates

• First Submitted: May 14, 2008
• First Submitted That Met QC Criteria: May 15, 2008
• First Posted (Estimate): May 16, 2008

Study Record Updates

• Last Update Posted (Actual): December 10, 2019
• Last Update Submitted That Met QC Criteria: November 26, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: Ulcerative colitis
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Budesonide
• Other Study ID Numbers: CB-01-02/02