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

Ulcerative Colitis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00679380
• Other study ID #: CB-01-02/02
• Status: Completed
• Phase: Phase 3
• Start date: June 2008
• Est. completion date: April 2010

Study information

• Verified date: November 2019
• Source: Bausch Health Americas, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 514
• Est. completion date: April 2010
• Est. primary completion date: February 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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-TNFa) 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).

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer
• Ulcerative Colitis

Intervention

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
• Budesonide MMX® 9 mg
9 mg/day, 9 mg tablets
• Entocort EC® 3 mg
9 mg/day, 3 mg tablets
• Placebo
Placebo

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide
Australia	Box Hill Hospital, Department of Gastroenterology Clive Ward Centre,	Box Hill
Australia	Monash Medical Centre	Melbourne
Australia	The Alfred Hospital	Melbourne
Australia	Centre for Digestive Diseases	Sydney	New South Wales
Belgium	Imelda Hospital	Bonheiden
Estonia	East Viru Central Hospital	Kohtla-Jarve
Estonia	East Tallinn Central Hospital	Tallinn
Estonia	West Tallinn Central Hospital	Tallinn
Estonia	Tartu University Hospital	Tartu
France	Hôpital Beaujon	Clichy Cedex
France	Hospital Saint-Louis	Paris
Israel	Yaron Niv	Petach Tikva
Italy	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
Latvia	Daugavpils Regional Hospital	Daugavpils
Latvia	Clinical University Hospital Gailezers	Riga
Latvia	Digestive Disease Centre Gastro	Riga
Latvia	Paula Stradina Clinical University Hospital	Riga
Lithuania	Kaunas Medical University Hospital	Kaunas
Lithuania	Siauliai District Hospital	Siauliai
Lithuania	M.Marcinkeviciaus Hospital	Vilnius
Lithuania	Vilnius University Hospital Santariskiu Klinikos	Vilnius
Poland	Gastromed S.C.	Bialystok	Podlaskie
Poland	Gastromed S.C.Maciej Kralisz, Andrzej Penpicki, Jacek Romatowski, Gabinet, Gastrologiczny i Pracownia Endoskopowa	Bialystok
Poland	NZOZ Centrum Leczenia Chorob Cywilizacyjnych	Gdynia
Poland	NZOZ Centrum Leczenia Chorob Cywilizacyjnych, oddzial Gdynia, filia Fikakw	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,Oddzial Kliniczny Kliniki Gastroenterologii Hematologii i Chorób Zakaznych	Kraków
Poland	Niepubliczny Zaklad Opieki Zdrowotnej POLIMEDICA	Lodz
Poland	NZOZ Polimedica	Lódz
Poland	Endoskopia Sp. z o.o.	Sopot
Poland	Endoskopia Sp.z o.o.	Sopot
Poland	Centrum Leczenia Chorób Cywilizacyjnych	Warszawa	Mazowieckie
Poland	Niepubliczny Zaklad Opieki Zdrowotnej VIVAMED	Warszawa	Mazowieckie
Poland	Indywidualna Specjalistyczna Praktyka Lekarska	Wejherowo
Romania	Spitalul Clinic Colentina Sectia Gastroenterologie	Bucuresti
Romania	Cabinet Medical	Oradea
Romania	Spitalul Judetean Sibiu	Sibiu
Romania	Centrul de Gastroenterologie Dr. Goldis Adrian	Timisoara
Russian Federation	Federal State Institution ?National Medical Surgical Center	Moscow
Russian Federation	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	GUZ of Moscow "City Clinical Hospital #24"	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	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	FGU North-West DIstrict Medical Center of Roszdrav	St-Petersburg
Russian Federation	Krestovsky Ireland Medical Institute	St-Petersburg
Russian Federation	ZAO Clinic Dvizhenie	Volgograd
Russian Federation	Yaroslavl Region Clinical Hospital	Yaroslavl
Slovakia	FNsP Bratislava, Nemocnica Ruzinov V. Interna klinika, Gastroenterohepatologicke oddelenie Ruzinovska	Bratislava
Slovakia	FNsP Bratislava, Nemocnica Stare Mesto 1st Internal Clinic Mickiewiczova	Bratislava
Slovakia	Gastroenterologické a Hepatologické centrum	Nitra
Slovakia	NsP Nove Mesto nad Vahom n.o.	Nové Mesto nad Váhom
Sweden	Sahlgrenska Univerity Hospital	Göteborg
Sweden	Lund University Hospital	Lund
Sweden	Dept. of Gastroenerology and Hepatology	Stockholm
Sweden	Div. of Gastroenterology and Hepatology	Stockholm
Sweden	IBD-Unit, Sophiahemmet	Stockholm
Ukraine	Chair of Gastroenterology and therapy of Dnipropetrovsk State Medical Academy based on Institute of gastroenterology	Dnepropetrovsk
Ukraine	City Clinical Emergency Hospital named after O.I.Meschaninov,	Kharkov
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	Odessa
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"	Uzhorod
United Kingdom	University Hospital of Coventry and Warwickshire	Coventry
United Kingdom	Gastrointestinal Unit	Edinburgh
United Kingdom	St Marks Hospital	Harrow
United Kingdom	John Radcliffe Hospital	Headington	Oxford

Sponsors (2)

Lead Sponsor	Collaborator
Bausch Health Americas, Inc.	Cosmo Technologies Ltd

Countries where clinical trial is conducted

Australia,  Belgium,  Estonia,  France,  Israel,  Italy,  Latvia,  Lithuania,  Poland,  Romania,  Russian Federation,  Slovakia,  Sweden,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Clinical Improvement.	Clinical improvement, defined as a = 3-point improvement in UCDAI from baseline to the end of Week 8.	8 weeks
Secondary	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