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)

NCT ID: NCT01532648

Last Updated: 2019-09-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 510 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-01-27
• Study Completion Date: 2013-10-02

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.

Conditions

Ulcerative Colitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Budesonide MMX

Participants will receive 1 oral tablet of budesonide MMX 9 mg for 56 days. Additionally, participants will continue to receive the same dose of their existing oral 5-ASA medication from their treating physician.

Group Type: EXPERIMENTAL

Budesonide MMX®

Intervention Type: DRUG

Oral tablet taken daily in the morning after breakfast.

5-ASA

Intervention Type: DRUG

Acceptable oral 5-ASA medications to be received during the study include:

• Asacol®, Asacol® HD, Lialda®, Pentasa® (generic: mesalamine), minimum daily dose ≥2.4 grams (g)
• Azulfidine® (generic: sulfasalazine), minimum daily dose ≥4.0 g
• Dipentum® (generic: olsalazine), minimum daily dose ≥2.0 g
• Colazal®, Colazide® (generic: balsalazide), minimum daily dose ≥6.75 g

Placebo

Participants will receive 1 oral tablet of matching budesonide MMX placebo for 56 days. Additionally, participants will continue to receive the same dose of their existing oral 5-ASA medication from their treating physician.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Matching budesonide MMX placebo oral tablet taken daily in the morning after breakfast.

5-ASA

Intervention Type: DRUG

Acceptable oral 5-ASA medications to be received during the study include:

• Asacol®, Asacol® HD, Lialda®, Pentasa® (generic: mesalamine), minimum daily dose ≥2.4 grams (g)
• Azulfidine® (generic: sulfasalazine), minimum daily dose ≥4.0 g
• Dipentum® (generic: olsalazine), minimum daily dose ≥2.0 g
• Colazal®, Colazide® (generic: balsalazide), minimum daily dose ≥6.75 g

Interventions

Budesonide MMX®

Oral tablet taken daily in the morning after breakfast.

Intervention Type: DRUG

Placebo

Matching budesonide MMX placebo oral tablet taken daily in the morning after breakfast.

Intervention Type: DRUG

5-ASA

Acceptable oral 5-ASA medications to be received during the study include:

• Asacol®, Asacol® HD, Lialda®, Pentasa® (generic: mesalamine), minimum daily dose ≥2.4 grams (g)
• Azulfidine® (generic: sulfasalazine), minimum daily dose ≥4.0 g
• Dipentum® (generic: olsalazine), minimum daily dose ≥2.0 g
• Colazal®, Colazide® (generic: balsalazide), minimum daily dose ≥6.75 g

Intervention Type: DRUG

Other Intervention Names

Budesonide Multi-Matrix System

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bausch Health Americas, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lindsey Mathew

Role: STUDY_DIRECTOR

Bausch Health Companies

Locations

Santarus Clinical Investigational Site 1043

Anaheim, California, United States

Santarus Clinical Investigational Site 1071

Lakewood, California, United States

Santarus Clinical Investigational Site 1003

San Diego, California, United States

Santarus Clinical Investigational Site 1063

Littleton, Colorado, United States

Santarus Clinical Investigational Site 1028

Bristol, Connecticut, United States

Santarus Clinical Investigational Site 1035

Boynton Beach, Florida, United States

Santarus Clinical Investigational Site 1045

Jacksonville, Florida, United States

Santarus Clinical Investigational Site 1001

Largo, Florida, United States

Santarus Clinical Investigational Site 1024

Maitland, Florida, United States

Santarus Clinical Investigational Site 1029

Port Orange, Florida, United States

Santarus Clinical Investigational Site 1010

Winter Park, Florida, United States

Santarus Clinical Investigational Site 1002

Zephyrhills, Florida, United States

Santarus Clinical Investigational Site 1050

Decatur, Georgia, United States

Santarus Clinical Investigational Site 1075

Chicago, Illinois, United States

Santarus Clinical Investigational Site 1065

Oak Lawn, Illinois, United States

Santarus Clinical Investigational Site 1058

Indianapolis, Indiana, United States

Santarus Clinical Investigational Site 1032

Shreveport, Louisiana, United States

Santarus Clinical Investigational Site 1044

Annapolis, Maryland, United States

Santarus Clinical Investigational Site 1016

Chesterfield, Michigan, United States

Santarus Clinical Investigational Site 1081

Novi, Michigan, United States

Santarus Clinical Investigational Site 1015

Wyoming, Michigan, United States

Santarus Clinical Investigational Site 1068

Ypsilanti, Michigan, United States

Santarus Clinical Investigational Site 1074

Rochester, Minnesota, United States

Santarus Clinical Investigational Site 1061

Lebanon, New Hampshire, United States

Santarus Clinical Investigational Site 1021

Cheektowaga, New York, United States

Santarus Clinical Investigational Site 1072

Great Neck, New York, United States

Santarus Clinical Investigational Site 1031

New York, New York, United States

Santarus Clinical Investigational Site 1073

Wilmington, North Carolina, United States

Santarus Clinical Investigational Site 1080

Cincinnati, Ohio, United States

Santarus Clinical Investigational Site 1078

Cleveland, Ohio, United States

Santarus Clinical Investigational Site 1082

Dayton, Ohio, United States

Santarus Clinical Investigational Site 1064

Lancaster, Pennsylvania, United States

Santarus Clinical Investigational Site 1006

Sayre, Pennsylvania, United States

Santarus Clinical Investigational Site 1059

Austin, Texas, United States

Santarus Clinical Investigational Site 1039

Houston, Texas, United States

Santarus Clinical Investigational Site 1005

Pasadena, Texas, United States

Santarus Clinical Investigational Site 1014

Lancaster, Utah, United States

Santarus Clinical Investigational Site 1038

Chesapeake, Virginia, United States

Santarus Clinical Investigational Site 1025

Christiansburg, Virginia, United States

Santarus Clinical Investigational Site 4003

Pleven, , Bulgaria

Santarus Clinical Investigational Site 4004

Plovdiv, , Bulgaria

Santarus Clinical Investigational Site 4009

Plovdiv, , Bulgaria

Santarus Clinical Investigational Site 4008

Rousse, , Bulgaria

Santarus Clinical Investigational Site 4001

Sofia, , Bulgaria

Santarus Clinical Investigational Site 4002

Sofia, , Bulgaria

Santarus Clinical Investigational Site 4005

Sofia, , Bulgaria

Santarus Clinical Investigational Site 4007

Sofia, , Bulgaria

Santarus Clinical Investigational Site 4010

Sofia, , Bulgaria

Santarus Clinical Investigational Site 4011

Sofia, , Bulgaria

Santarus Clinical Investigational Site 2003

Winnipeg, Manitoba, Canada

Santarus Clinical Investigational Site 2008

Halifax, Nova Scotia, Canada

Santarus Clinical Investigational Site 2004

London, Ontario, Canada

Santarus Clinical Investigational Site 2010

Ottawa, Ontario, Canada

Santarus Clinical Investigational Site 2002

Vaughan, Ontario, Canada

Santarus Clinical Investigational Site 2009

Montreal, Quebec, Canada

Santarus Clinical Investigational Site 2001

Sherbrooke, Quebec, Canada

Santarus Clinical Investigational Site 2007

Calgary, , Canada

Santarus Clinical Investigational Site 2005

London, , Canada

Santarus Clinical Investigational Site 2006

Québec, , Canada

Santarus Clinical Investigational Site 3001

Hradec Králové, , Czechia

Santarus Clinical Investigational Site 3006

Hradec Králové, , Czechia

Santarus Clinical Investigational Site 3005

Labem, , Czechia

Santarus Clinical Investigational Site 3003

Olomouc, , Czechia

Santarus Clinical Investigational Site 3004

Prague, , Czechia

Santarus Clinical Investigational Site 3007

Prague, , Czechia

Santarus Clinical Investigational Site 3009

Prague, , Czechia

Santarus Clinical Investigational Site 3002

Tábor, , Czechia

Santarus Clinical Investigational Site 3010

Ústí nad Orlicí, , Czechia

Santarus Clinical Investigational Site 3011

Valašské Meziříčí, , Czechia

Santarus Clinical Investigational Site 8001

Tallinn, , Estonia

Santarus Clinical Investigational Site 5010

Békéscsaba, , Hungary

Santarus Clinical Investigational Site 5008

Budapest, , Hungary

Santarus Clinical Investigational Site 5009

Budapest, , Hungary

Santarus Clinical Investigational Site 5001

Debrecen, , Hungary

Santarus Clinical Investigational Site 5003

Gyula, , Hungary

Santarus Clinical Investigational Site 5004

Kaposvár, , Hungary

Santarus Clinical Investigational Site 5002

Miskolc, , Hungary

Santarus Clinical Investigational Site 5006

Mosonmagyaróvár, , Hungary

Santarus Clinical Investigational Site 5011

Pécs, , Hungary

Santarus Clinical Investigational Site 5005

Szeged, , Hungary

Santarus Clinical Investigational Site 5007

Vác, , Hungary

Santarus Clinical Investigational Site 8101

Riga, , Latvia

Santarus Clinical Investigational Site 8102

Riga, , Latvia

Santarus Clinical Investigational Site 8103

Riga, , Latvia

Santarus Clinical Investigational Site 8202

Kaunas, , Lithuania

Santarus Clinical Investigational Site 8201

Vilnius, , Lithuania

Santarus Clinical Investigational Site 8203

Vilnius, , Lithuania

Santarus Clinical Investigational Site 6003

Elblag, , Poland

Santarus Clinical Investigational Site 6001

Krakow, , Poland

Santarus Clinical Investigational Site 6002

Sopot, , Poland

Santarus Clinical Investigational Site 6006

Szczecin, , Poland

Santarus Clinical Investigational Site 6004

Warsaw, , Poland

Santarus Clinical Investigational Site 6008

Warsaw, , Poland

Santarus Clinical Investigational Site 6005

Warszawy, , Poland

Santarus Clinical Investigational Site 9016

Lipetsk, , Russia

Santarus Clinical Investigational Site 9005

Moscow, , Russia

Santarus Clinical Investigational Site 9010

Moscow, , Russia

Santarus Clinical Investigational Site 9004

Nizhny Novgorod, , Russia

Santarus Clinical Investigational Site 9003

Ryazan, , Russia

Santarus Clinical Investigational Site 9001

Saint Petersburg, , Russia

Santarus Clinical Investigational Site 9008

Saint Petersburg, , Russia

Santarus Clinical Investigational Site 9013

Saint Petersburg, , Russia

Santarus Clinical Investigational Site 9014

Saint Petersburg, , Russia

Santarus Clinical Investigational Site 9009

Saratov, , Russia

Santarus Clinical Investigational Site 9007

Stavropol, , Russia

Santarus Clinical Investigational Site 9006

Ufa, , Russia

Santarus Clinical Investigational Site 9017

Volgograd, , Russia

Santarus Clinical Investigational Site 7010

Crimea, , Ukraine

Santarus Clinical Investigational Site 7002

Donetsk, , Ukraine

Santarus Clinical Investigational Site 7001

Kharkiv, , Ukraine

Santarus Clinical Investigational Site 7004

Kharkiv, , Ukraine

Santarus Clinical Investigational Site 7006

Kyiv, , Ukraine

Santarus Clinical Investigational Site 7008

Kyiv, , Ukraine

Santarus Clinical Investigational Site 7005

Vinnytsia, , Ukraine

Countries

United States; Bulgaria; Canada; Czechia; Estonia; Hungary; Latvia; Lithuania; Poland; Russia; Ukraine

References

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.

Reference Type: DERIVED

PMID: 28333362 (View on PubMed)

Other Identifiers

C2011-0401

Identifier Type: -

Identifier Source: org_study_id