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

Phase 3

Completed

• Conditions: Ulcerative Colitis
• Interventions: Procedure: Blood sampling, endoscopy; Drug: Budesonide MMX® 6 mg; Drug: Budesonide MMX® 9 mg; Drug: Entocort EC® 3 mg; Drug: Placebo

• Registration Number: NCT00679380
• Lead Sponsor: Bausch Health Americas, Inc.

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.

Study Timeline

• Study First Submitted: 2008-05-14
• Study First Submitted QC: 2008-05-15
• Study First Posted: 2008-05-16
• Study Start: 2008-06
• Primary Completion: 2010-02
• Study Completion: 2010-04
• Disposition First Submitted: 2011-12-01
• Disposition First Submitted QC: 2012-02-09
• Disposition First Posted: 2012-02-13
• Results First Submitted: 2014-04-25
• Results First Submitted QC: 2014-07-03
• Results First Posted: 2014-08-01
• Status Verified: 2019-11
• Last Update Submitted: 2019-11-26
• Last Update Posted: 2019-12-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 514

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
4: Placebo	Blood sampling, endoscopy	Three placebo Entocort EC® overencapsulated capsules plus one placebo Budesonide MMX® tablet daily in the morning after breakfast.
1: budesonide-MMX® 6 mg	Blood sampling, endoscopy	One budesonide-MMX® 6 mg plus three placebo Entocort EC® overencapsulated capsules daily in the morning after breakfast.
1: budesonide-MMX® 6 mg	Budesonide MMX® 6 mg	One budesonide-MMX® 6 mg plus three placebo Entocort EC® overencapsulated capsules daily in the morning after breakfast.
2: budesonide-MMX® 9 mg	Blood sampling, endoscopy	One budesonide-MMX® 9 mg plus three placebo Entocort EC® overencapsulated capsules daily in the morning after breakfast.
2: budesonide-MMX® 9 mg	Budesonide MMX® 9 mg	One budesonide-MMX® 9 mg plus three placebo Entocort EC® overencapsulated capsules daily in the morning after breakfast.
3: Entocort EC® 3 mg	Blood sampling, endoscopy	Three Entocort EC® 3 mg overencapsulated capsules plus one placebo budesonide MMX® tablet daily in the morning after breakfast.
3: Entocort EC® 3 mg	Entocort EC® 3 mg	Three Entocort EC® 3 mg overencapsulated capsules plus one placebo budesonide MMX® tablet daily in the morning after breakfast.
4: Placebo	Placebo	Three placebo Entocort EC® overencapsulated capsules plus one placebo Budesonide MMX® tablet daily in the morning after breakfast.

Primary Outcome Measures

Name	Time	Method
Clinical and Endoscopic Remission.	8 weeks	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.

Secondary Outcome Measures

Name	Time	Method
Endoscopic Improvement.	8 weeks	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.
Clinical Improvement.	8 weeks	Clinical improvement, defined as a ≥ 3-point improvement in UCDAI from baseline to the end of Week 8.

Trial Locations

Locations (71)

Imelda Hospital; 🇧🇪 Bonheiden, Belgium

The Alfred Hospital; 🇦🇺 Melbourne, Australia

East Viru Central Hospital; 🇪🇪 Kohtla-Jarve, Estonia

Niepubliczny Zaklad Opieki Zdrowotnej POLIMEDICA; 🇵🇱 Lodz, Poland

Hospital Saint-Louis; 🇫🇷 Paris, France

GUZ of Moscow "City Clinical Hospital #24"; 🇷🇺 Moscow, Russian Federation

Gastromed S.C.Maciej Kralisz, Andrzej Penpicki, Jacek Romatowski, Gabinet, Gastrologiczny i Pracownia Endoskopowa; 🇵🇱 Bialystok, Poland

FGU North-West DIstrict Medical Center of Roszdrav; 🇷🇺 St-Petersburg, Russian Federation

Yaron Niv; 🇮🇱 Petach Tikva, Israel

Monash Medical Centre; 🇦🇺 Melbourne, Australia

Daugavpils Regional Hospital; 🇱🇻 Daugavpils, Latvia

NZOZ Centrum Leczenia Chorob Cywilizacyjnych, oddzial Gdynia, filia Fikakw; 🇵🇱 Gdynia, Poland

NZOZ Polimedica; 🇵🇱 Łódź, Poland

Saint-Petersburg GUZ City polyclinic #38 28; 🇷🇺 St Petersburg, Russian Federation

Hôpital Beaujon; 🇫🇷 Clichy Cedex, France

Box Hill Hospital, Department of Gastroenterology Clive Ward Centre,; 🇦🇺 Box Hill, Australia

Royal Adelaide Hospital; 🇦🇺 Adelaide, Australia

Centrum Leczenia Chorób Cywilizacyjnych; 🇵🇱 Warszawa, Mazowieckie, Poland

NZOZ Centrum Leczenia Chorob Cywilizacyjnych; 🇵🇱 Gdynia, Poland

Dipartimento di Medicina Interna e Specialità Mediche (DIMI); 🇮🇹 Genova, Italy

FNsP Bratislava, Nemocnica Stare Mesto 1st Internal Clinic Mickiewiczova; 🇸🇰 Bratislava, Slovakia

Endoskopia Sp. z o.o.; 🇵🇱 Sopot, Poland

Endoskopia Sp.z o.o.; 🇵🇱 Sopot, Poland

ZAO Clinic Dvizhenie; 🇷🇺 Volgograd, Russian Federation

Chair of Gastroenterology and therapy of Dnipropetrovsk State Medical Academy based on Institute of gastroenterology; 🇺🇦 Dnepropetrovsk, Ukraine

Odessa city Polyclinic #20, Therapeutic Dept. 6; 🇺🇦 Odessa, Ukraine

St Marks Hospital; 🇬🇧 Harrow, United Kingdom

Lund University Hospital; 🇸🇪 Lund, Sweden

John Radcliffe Hospital; 🇬🇧 Headington, Oxford, United Kingdom

City Clinical Emergency Hospital named after O.I.Meschaninov,; 🇺🇦 Kharkov, Ukraine

IBD-Unit, Sophiahemmet; 🇸🇪 Stockholm, Sweden

Gastrointestinal Unit; 🇬🇧 Edinburgh, United Kingdom

Dept. of Gastroenerology and Hepatology; 🇸🇪 Stockholm, Sweden

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

State Scientific Centre of Coloproctology of the Federal Agency for High-Technology Medical Care; 🇷🇺 Moscow, Russian Federation

Rostov State Medical University; 🇷🇺 Rostov-on-Don, Russian Federation

St. Petersburg State Medical Academy n.a. I.I. Mechnikov; 🇷🇺 St Petersburg, Russian Federation

Krestovsky Ireland Medical Institute; 🇷🇺 St-Petersburg, Russian Federation

Centre for Digestive Diseases; 🇦🇺 Sydney, New South Wales, Australia

Divisione di Gastroenterologia - Istituto Clinico Humanitas IRCCS in Gastroenterologia; 🇮🇹 Milan, Italy

Digestive Disease Centre Gastro; 🇱🇻 Riga, Latvia

Niepubliczny Zaklad Opieki Zdrowotnej VIVAMED; 🇵🇱 Warszawa, Mazowieckie, Poland

CRO - IRCCS - Struttura Operativa Complessa di Gastroenterologia Oncologica; 🇮🇹 Aviano, Italy

Gastromed S.C.; 🇵🇱 Białystok, Podlaskie, 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; 🇵🇱 Kraków, Poland

Spitalul Judetean Sibiu; 🇷🇴 Sibiu, Romania

Federal State Institution ?National Medical Surgical Center; 🇷🇺 Moscow, Russian Federation

Yaroslavl Region Clinical Hospital; 🇷🇺 Yaroslavl, Russian Federation

FNsP Bratislava, Nemocnica Ruzinov V. Interna klinika, Gastroenterohepatologicke oddelenie Ruzinovska; 🇸🇰 Bratislava, Slovakia

NsP Nove Mesto nad Vahom n.o.; 🇸🇰 Nové Mesto nad Váhom, Slovakia

Gastroenterologické a Hepatologické centrum; 🇸🇰 Nitra, Slovakia

Sahlgrenska Univerity Hospital; 🇸🇪 Göteborg, Sweden

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

Div. of Gastroenterology and Hepatology; 🇸🇪 Stockholm, Sweden

University Hospital of Coventry and Warwickshire; 🇬🇧 Coventry, United Kingdom

Kaunas Medical University Hospital; 🇱🇹 Kaunas, Lithuania

Vilnius University Hospital Santariskiu Klinikos; 🇱🇹 Vilnius, Lithuania

Spitalul Clinic Colentina Sectia Gastroenterologie; 🇷🇴 Bucuresti, Romania

Centrul de Gastroenterologie Dr. Goldis Adrian; 🇷🇴 Timisoara, Romania

East Tallinn Central Hospital; 🇪🇪 Tallinn, Estonia

West Tallinn Central Hospital; 🇪🇪 Tallinn, Estonia

Clinical University Hospital Gailezers; 🇱🇻 Riga, Latvia

M.Marcinkeviciaus Hospital; 🇱🇹 Vilnius, Lithuania

Tartu University Hospital; 🇪🇪 Tartu, Estonia

Paula Stradina Clinical University Hospital; 🇱🇻 Riga, Latvia

Cabinet Medical; 🇷🇴 Oradea, Romania

Siauliai District Hospital; 🇱🇹 Siauliai, Lithuania

Indywidualna Specjalistyczna Praktyka Lekarska; 🇵🇱 Wejherowo, Poland

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"; 🇺🇦 Uzhorod, Ukraine