Clinical trial NCT01532648: Randomized Placebo-Controlled Trial of Budesonide Multi-Matrix System (MMX®) 9 Milligrams (mg) in Participants With Ulcerative Colitis Currently on a 5-Aminosalicylic Acid (5-ASA)
Official title: A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Oral Budesonide MMX® 9 mg Extended-release Tablets as Add-on Therapy in Patients With Active, Mild or Moderate Ulcerative Colitis Not Adequately Controlled on a Background Oral 5-ASA Regimen
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Ulcerative Colitis
Keywords: Ulcerative Colitis
Lead sponsor: Bausch Health Americas, Inc.
Sponsor class: INDUSTRY
First posted: 2012-02-14
Enrollment: 510
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 study is to compare the efficacy and safety of budesonide MMX 9 mg versus placebo as add-on therapy to an existing oral 5-ASA regimen for the induction of remission in participants with active mild or moderate ulcerative colitis (UC).

Detailed description: Eligible participants will be randomized to 1 of the following 2 treatment arms:

1. Budesonide MMX 9 mg (1 tablet)
2. Placebo (tablet indistinguishable from budesonide MMX 9 mg tablet)

The assigned study drug will be taken as a single oral tablet each morning after breakfast. In addition to the study drug, all participants will continue their existing background oral 5-ASA regimen during the treatment period.

Eligibility criteria: Inclusion Criteria:

1. Age 18 to 75 years, inclusive.
2. Established diagnosis of UC, based on clinical history, exclusion of infectious causes, and characteristic endoscopic and histologic findings.
3. Active mild or moderate UC with an ulcerative colitis disease activity index (UCDAI) score ≥4 and ≤10, with a mucosal appearance score of ≥1, and physician's rating of disease activity of 1 or 2.
4. Experiencing active UC (flare) despite a therapeutic dose of an oral 5-ASA (for example, mesalamine ≥2.4 g/day for ≥6 weeks prior to randomization, or equivalent). At screening, photographic evidence of active UC based on mucosal appearance must be obtained.
5. Women of childbearing potential or men of reproductive potential must be willing to use an acceptable form of contraception.
6. Able to comprehend the full nature and purpose of the study, including possible risks and side effects, and also able to comply with all requirements of the study. Must be able to understand and voluntarily sign an informed consent prior to any study procedures.

Exclusion Criteria:

1. Limited distal proctitis (from anal verge to 15 centimeters \[cm\] above the pectineal line).
2. Severe UC (UCDAI \>10 or physician global assessment \[PGA\] \>2), or non-active UC (UCDAI \<4).
3. Infectious colitis or any recent history of infectious colitis (within 30 days of Screening).
4. Active malignancy or carcinoma in situ within the last 5 years (treated non-melanoma skin cancers are not exclusionary).
5. Active ulcer or bleeding disorder that may affect evaluation of blood in the stool.
6. Evidence or history of toxic megacolon or bowel resection.
7. Crohn's disease or indeterminate colitis.
8. Known hypersensitivity to budesonide or any ingredients of the budesonide MMX tablets.
9. Active tuberculosis or other active systemic or local bacterial, fungal, or viral infection.
10. Liver cirrhosis, evident hepatic or renal disease or insufficiency, or significant impairment of the biohumoral parameters (≥2.5\*upper limit of normal \[ULN\] for alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, or ≥2\*ULN for creatinine). Elevations in bilirubin due to benign conditions such as Gilbert's syndrome are not exclusionary.
11. Severe diseases in other organs or systems.
12. Local or systemic complications or other pathological states requiring therapy with corticosteroids and/or immunosuppressive agents.
13. Type 1 diabetes.
14. Glaucoma or with a family history of glaucoma in first-degree relatives.
15. Known hepatitis B, hepatitis C, or human immunodeficiency virus (HIV), according to the local privacy policy.
16. Severe anemia (\<9 g/deciliter \[dL\] hemoglobin), leukopenia (\<2.5\*10\^9 white blood cells \[WBC\]/liter \[L\]), or granulocytopenia (\<1.2\*10\^9 cells/L).
17. Participants with a history of pancolitis (disease that extends to the hepatic flexure or beyond) for ≥8 years or left-sided colitis (disease confined to the left colon \[that is, distal to the splenic flexure\]) ≥15 years who have not yet completed a surveillance colonoscopy for dysplasia/colorectal cancer screening within the past year.
18. Prior budesonide MMX treatment.
19. Use of oral corticosteroids including other budesonide formulations within the last 4 weeks prior to randomization.
20. Use of any rectal 5-ASA or corticosteroid formulations within the last 2 weeks prior to randomization.
21. Use of immunosuppressive agents within the last 8 weeks prior to randomization.
22. Use of anti-tumor necrosis factor-alpha (TNFα) agents or other biologic therapies within the last 3 months prior to randomization.
23. Participation in experimental therapeutic studies within 30 days of randomization (or within the last 3 months if in an anti-TNFα or biologic agent study). Note: participants who participated in observational-only studies (and who did not receive study therapy) are not excluded.
24. 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 participant or obscure the interpretation of adverse events (AEs) by the appropriate independent ethics committee/institutional review board.

Primary outcomes:
measure: Number of Participants Who Achieved Clinical Remission at Day 56
timeFrame: Baseline up to Day 56
Secondary outcomes:
measure: Number of Participants of Who Achieved Clinical Response at Day 56
timeFrame: Baseline up to Day 56
measure: Number of Participants Who Achieved UCDAI Remission at Day 56
timeFrame: Baseline up to Day 56
measure: Number of Participants Who Achieved Endoscopic Remission at Day 56
timeFrame: Screening and Day 56
measure: Number of Participants Who Achieved Histologic Healing at Day 56
timeFrame: Baseline and Day 56
measure: Number of Participants With Treatment Failure at Day 56
timeFrame: Baseline up to Day 56
measure: Change From Baseline in Inflammatory Bowel Disease-Quality of Life (IBD-QoL) Questionnaire Scores
timeFrame: Baseline, Days 14, 28, and 56
Other outcomes:
Locations:
city: Anaheim
country: United States
facility: Santarus Clinical Investigational Site 1043
state: California
city: Lakewood
country: United States
facility: Santarus Clinical Investigational Site 1071
state: California
city: San Diego
country: United States
facility: Santarus Clinical Investigational Site 1003
state: California
city: Littleton
country: United States
facility: Santarus Clinical Investigational Site 1063
state: Colorado
city: Bristol
country: United States
facility: Santarus Clinical Investigational Site 1028
state: Connecticut
city: Boynton Beach
country: United States
facility: Santarus Clinical Investigational Site 1035
state: Florida
city: Jacksonville
country: United States
facility: Santarus Clinical Investigational Site 1045
state: Florida
city: Largo
country: United States
facility: Santarus Clinical Investigational Site 1001
state: Florida
city: Maitland
country: United States
facility: Santarus Clinical Investigational Site 1024
state: Florida
city: Port Orange
country: United States
facility: Santarus Clinical Investigational Site 1029
state: Florida
city: Winter Park
country: United States
facility: Santarus Clinical Investigational Site 1010
state: Florida
city: Zephyrhills
country: United States
facility: Santarus Clinical Investigational Site 1002
state: Florida
city: Decatur
country: United States
facility: Santarus Clinical Investigational Site 1050
state: Georgia
city: Chicago
country: United States
facility: Santarus Clinical Investigational Site 1075
state: Illinois
city: Oak Lawn
country: United States
facility: Santarus Clinical Investigational Site 1065
state: Illinois
city: Indianapolis
country: United States
facility: Santarus Clinical Investigational Site 1058
state: Indiana
city: Shreveport
country: United States
facility: Santarus Clinical Investigational Site 1032
state: Louisiana
city: Annapolis
country: United States
facility: Santarus Clinical Investigational Site 1044
state: Maryland
city: Chesterfield
country: United States
facility: Santarus Clinical Investigational Site 1016
state: Michigan
city: Novi
country: United States
facility: Santarus Clinical Investigational Site 1081
state: Michigan
city: Wyoming
country: United States
facility: Santarus Clinical Investigational Site 1015
state: Michigan
city: Ypsilanti
country: United States
facility: Santarus Clinical Investigational Site 1068
state: Michigan
city: Rochester
country: United States
facility: Santarus Clinical Investigational Site 1074
state: Minnesota
city: Lebanon
country: United States
facility: Santarus Clinical Investigational Site 1061
state: New Hampshire
city: Cheektowaga
country: United States
facility: Santarus Clinical Investigational Site 1021
state: New York
city: Great Neck
country: United States
facility: Santarus Clinical Investigational Site 1072
state: New York
city: New York
country: United States
facility: Santarus Clinical Investigational Site 1031
state: New York
city: Wilmington
country: United States
facility: Santarus Clinical Investigational Site 1073
state: North Carolina
city: Cincinnati
country: United States
facility: Santarus Clinical Investigational Site 1080
state: Ohio
city: Cleveland
country: United States
facility: Santarus Clinical Investigational Site 1078
state: Ohio
city: Dayton
country: United States
facility: Santarus Clinical Investigational Site 1082
state: Ohio
city: Lancaster
country: United States
facility: Santarus Clinical Investigational Site 1064
state: Pennsylvania
city: Sayre
country: United States
facility: Santarus Clinical Investigational Site 1006
state: Pennsylvania
city: Austin
country: United States
facility: Santarus Clinical Investigational Site 1059
state: Texas
city: Houston
country: United States
facility: Santarus Clinical Investigational Site 1039
state: Texas
city: Pasadena
country: United States
facility: Santarus Clinical Investigational Site 1005
state: Texas
city: Lancaster
country: United States
facility: Santarus Clinical Investigational Site 1014
state: Utah
city: Chesapeake
country: United States
facility: Santarus Clinical Investigational Site 1038
state: Virginia
city: Christiansburg
country: United States
facility: Santarus Clinical Investigational Site 1025
state: Virginia
city: Pleven
country: Bulgaria
facility: Santarus Clinical Investigational Site 4003
city: Plovdiv
country: Bulgaria
facility: Santarus Clinical Investigational Site 4004
city: Plovdiv
country: Bulgaria
facility: Santarus Clinical Investigational Site 4009
city: Ruse
country: Bulgaria
facility: Santarus Clinical Investigational Site 4008
city: Sofia
country: Bulgaria
facility: Santarus Clinical Investigational Site 4001
city: Sofia
country: Bulgaria
facility: Santarus Clinical Investigational Site 4002
city: Sofia
country: Bulgaria
facility: Santarus Clinical Investigational Site 4005
city: Sofia
country: Bulgaria
facility: Santarus Clinical Investigational Site 4007
city: Sofia
country: Bulgaria
facility: Santarus Clinical Investigational Site 4010
city: Sofia
country: Bulgaria
facility: Santarus Clinical Investigational Site 4011
city: Winnipeg
country: Canada
facility: Santarus Clinical Investigational Site 2003
state: Manitoba
city: Halifax
country: Canada
facility: Santarus Clinical Investigational Site 2008
state: Nova Scotia
city: London
country: Canada
facility: Santarus Clinical Investigational Site 2004
state: Ontario
city: Ottawa
country: Canada
facility: Santarus Clinical Investigational Site 2010
state: Ontario
city: Vaughan
country: Canada
facility: Santarus Clinical Investigational Site 2002
state: Ontario
city: Montreal
country: Canada
facility: Santarus Clinical Investigational Site 2009
state: Quebec
city: Sherbrooke
country: Canada
facility: Santarus Clinical Investigational Site 2001
state: Quebec
city: Calgary
country: Canada
facility: Santarus Clinical Investigational Site 2007
city: London
country: Canada
facility: Santarus Clinical Investigational Site 2005
city: Quebec
country: Canada
facility: Santarus Clinical Investigational Site 2006
city: Hradec Kralove
country: Czechia
facility: Santarus Clinical Investigational Site 3001
city: Hradec Kralove
country: Czechia
facility: Santarus Clinical Investigational Site 3006
city: Labem
country: Czechia
facility: Santarus Clinical Investigational Site 3005
city: Olomouc
country: Czechia
facility: Santarus Clinical Investigational Site 3003
city: Prague
country: Czechia
facility: Santarus Clinical Investigational Site 3009
city: Praha
country: Czechia
facility: Santarus Clinical Investigational Site 3004
city: Praha
country: Czechia
facility: Santarus Clinical Investigational Site 3007
city: Tabor
country: Czechia
facility: Santarus Clinical Investigational Site 3002
city: Usti nad Orlici
country: Czechia
facility: Santarus Clinical Investigational Site 3010
city: Valasske Mezirici
country: Czechia
facility: Santarus Clinical Investigational Site 3011
city: Tallinn
country: Estonia
facility: Santarus Clinical Investigational Site 8001
city: Bekescsaba
country: Hungary
facility: Santarus Clinical Investigational Site 5010
city: Budapest
country: Hungary
facility: Santarus Clinical Investigational Site 5008
city: Budapest
country: Hungary
facility: Santarus Clinical Investigational Site 5009
city: Debrecen
country: Hungary
facility: Santarus Clinical Investigational Site 5001
city: Gyula
country: Hungary
facility: Santarus Clinical Investigational Site 5003
city: Kaposvar
country: Hungary
facility: Santarus Clinical Investigational Site 5004
city: Miskolc
country: Hungary
facility: Santarus Clinical Investigational Site 5002
city: Mosonmagyarovar
country: Hungary
facility: Santarus Clinical Investigational Site 5006
city: Pecs
country: Hungary
facility: Santarus Clinical Investigational Site 5011
city: Szeged
country: Hungary
facility: Santarus Clinical Investigational Site 5005
city: Vac
country: Hungary
facility: Santarus Clinical Investigational Site 5007
city: Riga
country: Latvia
facility: Santarus Clinical Investigational Site 8101
city: Riga
country: Latvia
facility: Santarus Clinical Investigational Site 8102
city: Riga
country: Latvia
facility: Santarus Clinical Investigational Site 8103
city: Kaunas
country: Lithuania
facility: Santarus Clinical Investigational Site 8202
city: Vilnius
country: Lithuania
facility: Santarus Clinical Investigational Site 8201
city: Vilnius
country: Lithuania
facility: Santarus Clinical Investigational Site 8203
city: Elblag
country: Poland
facility: Santarus Clinical Investigational Site 6003
city: Krakow
country: Poland
facility: Santarus Clinical Investigational Site 6001
city: Sopot
country: Poland
facility: Santarus Clinical Investigational Site 6002
city: Szczecin
country: Poland
facility: Santarus Clinical Investigational Site 6006
city: Warszawa
country: Poland
facility: Santarus Clinical Investigational Site 6004
city: Warszawa
country: Poland
facility: Santarus Clinical Investigational Site 6008
city: Warszawy
country: Poland
facility: Santarus Clinical Investigational Site 6005
city: Lipetsk
country: Russian Federation
facility: Santarus Clinical Investigational Site 9016
city: Moscow
country: Russian Federation
facility: Santarus Clinical Investigational Site 9005
city: Moscow
country: Russian Federation
facility: Santarus Clinical Investigational Site 9010
city: Nizhny Novgorod
country: Russian Federation
facility: Santarus Clinical Investigational Site 9004
city: Ryazan
country: Russian Federation
facility: Santarus Clinical Investigational Site 9003
city: Saint Petersburg
country: Russian Federation
facility: Santarus Clinical Investigational Site 9008
city: Saint Petersburg
country: Russian Federation
facility: Santarus Clinical Investigational Site 9013
city: Saint Petersburg
country: Russian Federation
facility: Santarus Clinical Investigational Site 9014
city: Saratov
country: Russian Federation
facility: Santarus Clinical Investigational Site 9009
city: St Petersburg
country: Russian Federation
facility: Santarus Clinical Investigational Site 9001
city: Stavropol
country: Russian Federation
facility: Santarus Clinical Investigational Site 9007
city: Ufa
country: Russian Federation
facility: Santarus Clinical Investigational Site 9006
city: Volgograd
country: Russian Federation
facility: Santarus Clinical Investigational Site 9017
city: Crimea
country: Ukraine
facility: Santarus Clinical Investigational Site 7010
city: Donetsk
country: Ukraine
facility: Santarus Clinical Investigational Site 7002
city: Kharkiv
country: Ukraine
facility: Santarus Clinical Investigational Site 7001
city: Kharkiv
country: Ukraine
facility: Santarus Clinical Investigational Site 7004
city: Kyiv
country: Ukraine
facility: Santarus Clinical Investigational Site 7006
city: Kyiv
country: Ukraine
facility: Santarus Clinical Investigational Site 7008
city: Vinnytsia
country: Ukraine
facility: Santarus Clinical Investigational Site 7005
Study officials:
affiliation: Bausch Health Companies
name: Lindsey Mathew
role: STUDY_DIRECTOR
References:
citation: Rubin DT, Cohen RD, Sandborn WJ, Lichtenstein GR, Axler J, Riddell RH, Zhu C, Barrett AC, Bortey E, Forbes WP. Budesonide Multimatrix Is Efficacious for Mesalamine-refractory, Mild to Moderate Ulcerative Colitis: A Randomised, Placebo-controlled Trial. J Crohns Colitis. 2017 Jul 1;11(7):785-791. doi: 10.1093/ecco-jcc/jjx032.