Clinical trial NCT00679380: (CB-01-02/02) Randomized Placebo Controlled Trial of Budesonide-multi-matrix System (MMX™) 6 mg and 9 mg in Patients With Ulcerative Colitis
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Ulcerative Colitis
Keywords: Ulcerative colitis
Lead sponsor: Bausch Health Americas, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Cosmo Technologies Ltd
First posted: 2008-05-16
Enrollment: 514
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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).

Primary outcomes:
measure: Clinical and Endoscopic Remission.
timeFrame: 8 weeks
Secondary outcomes:
measure: Clinical Improvement.
timeFrame: 8 weeks
measure: Endoscopic Improvement.
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Sydney
country: Australia
facility: Centre for Digestive Diseases
state: New South Wales
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
city: Box Hill
country: Australia
facility: Box Hill Hospital, Department of Gastroenterology Clive Ward Centre,
city: Melbourne
country: Australia
facility: The Alfred Hospital
city: Melbourne
country: Australia
facility: Monash Medical Centre
city: Bonheiden
country: Belgium
facility: Imelda Hospital
city: Kohtla-Jarve
country: Estonia
facility: East Viru Central Hospital
city: Tallinn
country: Estonia
facility: East Tallinn Central Hospital
city: Tallinn
country: Estonia
facility: West Tallinn Central Hospital
city: Tartu
country: Estonia
facility: Tartu University Hospital
city: Clichy Cedex
country: France
facility: Hôpital Beaujon
city: Paris
country: France
facility: Hospital Saint-Louis
city: Petach Tikva
country: Israel
facility: Yaron Niv
city: Aviano
country: Italy
facility: CRO - IRCCS - Struttura Operativa Complessa di Gastroenterologia Oncologica
city: Genova
country: Italy
facility: Dipartimento di Medicina Interna e Specialità Mediche (DIMI)
city: Milan
country: Italy
facility: Divisione di Gastroenterologia - Istituto Clinico Humanitas IRCCS in Gastroenterologia
city: Daugavpils
country: Latvia
facility: Daugavpils Regional Hospital
city: Riga
country: Latvia
facility: Paula Stradina Clinical University Hospital
city: Riga
country: Latvia
facility: Digestive Disease Centre Gastro
city: Riga
country: Latvia
facility: Clinical University Hospital Gailezers
city: Kaunas
country: Lithuania
facility: Kaunas Medical University Hospital
city: Siauliai
country: Lithuania
facility: Siauliai District Hospital
city: Vilnius
country: Lithuania
facility: M.Marcinkeviciaus Hospital
city: Vilnius
country: Lithuania
facility: Vilnius University Hospital Santariskiu Klinikos
city: Warszawa
country: Poland
facility: Niepubliczny Zaklad Opieki Zdrowotnej VIVAMED
state: Mazowieckie
city: Warszawa
country: Poland
facility: Centrum Leczenia Chorób Cywilizacyjnych
state: Mazowieckie
city: Białystok
country: Poland
facility: Gastromed S.C.
state: Podlaskie
city: Bialystok
country: Poland
facility: Gastromed S.C.Maciej Kralisz, Andrzej Penpicki, Jacek Romatowski, Gabinet, Gastrologiczny i Pracownia Endoskopowa
city: Gdynia
country: Poland
facility: NZOZ Centrum Leczenia Chorob Cywilizacyjnych, oddzial Gdynia, filia Fikakw
city: Gdynia
country: Poland
facility: NZOZ Centrum Leczenia Chorob Cywilizacyjnych
city: Krakow
country: Poland
facility: Samodzielny Publiczny Zaklad Opieki Zdrowotnej, Szpital Uniwersytecki w Krakowie, Oddzial Kliniczny Kliniki Gastroenterologii, Hepatologii i Chorob Zakaznych,
city: Kraków
country: Poland
facility: Szpital Uniwersytecki w Krakowie,Oddział Kliniczny Kliniki Gastroenterologii Hematologii i Chorób Zakaźnych
city: Lodz
country: Poland
facility: Niepubliczny Zaklad Opieki Zdrowotnej POLIMEDICA
city: Sopot
country: Poland
facility: Endoskopia Sp. z o.o.
city: Sopot
country: Poland
facility: Endoskopia Sp.z o.o.
city: Wejherowo
country: Poland
facility: Indywidualna Specjalistyczna Praktyka Lekarska
city: Łódź
country: Poland
facility: NZOZ Polimedica
city: Bucuresti
country: Romania
facility: Spitalul Clinic Colentina Sectia Gastroenterologie
city: Oradea
country: Romania
facility: Cabinet Medical
city: Sibiu
country: Romania
facility: Spitalul Judetean Sibiu
city: Timisoara
country: Romania
facility: Centrul de Gastroenterologie Dr. Goldis Adrian
city: Moscow
country: Russian Federation
facility: Federal State Institution ?National Medical Surgical Center
city: Moscow
country: Russian Federation
facility: 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"
city: Moscow
country: Russian Federation
facility: State Scientific Centre of Coloproctology of the Federal Agency for High-Technology Medical Care
city: Moscow
country: Russian Federation
facility: GUZ of Moscow "City Clinical Hospital #24"
city: Rostov-on-Don
country: Russian Federation
facility: Rostov State Medical University
city: St Petersburg
country: Russian Federation
facility: Saint-Petersburg GUZ City polyclinic #38 28
city: St Petersburg
country: Russian Federation
facility: St. Petersburg State Medical Academy n.a. I.I. Mechnikov
city: St-Petersburg
country: Russian Federation
facility: Krestovsky Ireland Medical Institute
city: St-Petersburg
country: Russian Federation
facility: FGU North-West DIstrict Medical Center of Roszdrav
city: Volgograd
country: Russian Federation
facility: ZAO Clinic Dvizhenie
city: Yaroslavl
country: Russian Federation
facility: Yaroslavl Region Clinical Hospital
city: Bratislava
country: Slovakia
facility: FNsP Bratislava, Nemocnica Stare Mesto 1st Internal Clinic Mickiewiczova
city: Bratislava
country: Slovakia
facility: FNsP Bratislava, Nemocnica Ruzinov V. Interna klinika, Gastroenterohepatologicke oddelenie Ruzinovska
city: Nitra
country: Slovakia
facility: Gastroenterologické a Hepatologické centrum
city: Nové Mesto nad Váhom
country: Slovakia
facility: NsP Nove Mesto nad Vahom n.o.
city: Göteborg
country: Sweden
facility: Sahlgrenska Univerity Hospital
city: Lund
country: Sweden
facility: Lund University Hospital
city: Stockholm
country: Sweden
facility: IBD-Unit, Sophiahemmet
city: Stockholm
country: Sweden
facility: Div. of Gastroenterology and Hepatology
city: Stockholm
country: Sweden
facility: Dept. of Gastroenerology and Hepatology
city: Dnepropetrovsk
country: Ukraine
facility: Chair of Gastroenterology and therapy of Dnipropetrovsk State Medical Academy based on Institute of gastroenterology
city: Kharkov
country: Ukraine
facility: City Clinical Emergency Hospital named after O.I.Meschaninov,
city: Lviv
country: Ukraine
facility: Lviv National Medical University after name Danylo Halytsky based on Communal Clinical City hospital No 5, Department of Propedeutic of Internal Disease
city: Odessa
country: Ukraine
facility: Odessa city Polyclinic #20, Therapeutic Dept. 6
city: Uzhorod
country: Ukraine
facility: Uzhgorod National University, Hospital surgery chair on the base of Uzhgorod Regional Clinical Hospital
city: Uzhorod
country: Ukraine
facility: Uzhgorod State Medical University, chair of therapy and family medicine, district clinical hospitalof station "Uzhgorod"
city: Headington
country: United Kingdom
facility: John Radcliffe Hospital
state: Oxford
city: Coventry
country: United Kingdom
facility: University Hospital of Coventry and Warwickshire
city: Edinburgh
country: United Kingdom
facility: Gastrointestinal Unit
city: Harrow
country: United Kingdom
facility: St Marks Hospital
Study officials:
affiliation: Oxford University Hospitals NHS Trust
name: Simon Travis
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.