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)

Ulcerative Colitis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01532648
• Other study ID #: C2011-0401
• Status: Completed
• Phase: Phase 3
• Start date: January 27, 2012
• Est. completion date: October 2, 2013

Study information

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

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 510
• Est. completion date: October 2, 2013
• Est. primary completion date: October 2, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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 (TNFa) 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-TNFa 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.

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer
• Ulcerative Colitis

Intervention

Drug:
• Budesonide MMX®
Oral tablet taken daily in the morning after breakfast.
• Placebo
Matching budesonide MMX placebo oral tablet taken daily in the morning after breakfast.
• 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

Locations

Country	Name	City	State
Bulgaria	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	Ruse
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
Canada	Santarus Clinical Investigational Site 2007	Calgary
Canada	Santarus Clinical Investigational Site 2008	Halifax	Nova Scotia
Canada	Santarus Clinical Investigational Site 2004	London	Ontario
Canada	Santarus Clinical Investigational Site 2005	London
Canada	Santarus Clinical Investigational Site 2009	Montreal	Quebec
Canada	Santarus Clinical Investigational Site 2010	Ottawa	Ontario
Canada	Santarus Clinical Investigational Site 2006	Quebec
Canada	Santarus Clinical Investigational Site 2001	Sherbrooke	Quebec
Canada	Santarus Clinical Investigational Site 2002	Vaughan	Ontario
Canada	Santarus Clinical Investigational Site 2003	Winnipeg	Manitoba
Czechia	Santarus Clinical Investigational Site 3001	Hradec Kralove
Czechia	Santarus Clinical Investigational Site 3006	Hradec Kralove
Czechia	Santarus Clinical Investigational Site 3005	Labem
Czechia	Santarus Clinical Investigational Site 3003	Olomouc
Czechia	Santarus Clinical Investigational Site 3009	Prague
Czechia	Santarus Clinical Investigational Site 3004	Praha
Czechia	Santarus Clinical Investigational Site 3007	Praha
Czechia	Santarus Clinical Investigational Site 3002	Tabor
Czechia	Santarus Clinical Investigational Site 3010	Usti nad Orlici
Czechia	Santarus Clinical Investigational Site 3011	Valasske Mezirici
Estonia	Santarus Clinical Investigational Site 8001	Tallinn
Hungary	Santarus Clinical Investigational Site 5010	Bekescsaba
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	Kaposvar
Hungary	Santarus Clinical Investigational Site 5002	Miskolc
Hungary	Santarus Clinical Investigational Site 5006	Mosonmagyarovar
Hungary	Santarus Clinical Investigational Site 5011	Pecs
Hungary	Santarus Clinical Investigational Site 5005	Szeged
Hungary	Santarus Clinical Investigational Site 5007	Vac
Latvia	Santarus Clinical Investigational Site 8101	Riga
Latvia	Santarus Clinical Investigational Site 8102	Riga
Latvia	Santarus Clinical Investigational Site 8103	Riga
Lithuania	Santarus Clinical Investigational Site 8202	Kaunas
Lithuania	Santarus Clinical Investigational Site 8201	Vilnius
Lithuania	Santarus Clinical Investigational Site 8203	Vilnius
Poland	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	Warszawa
Poland	Santarus Clinical Investigational Site 6008	Warszawa
Poland	Santarus Clinical Investigational Site 6005	Warszawy
Russian Federation	Santarus Clinical Investigational Site 9016	Lipetsk
Russian Federation	Santarus Clinical Investigational Site 9005	Moscow
Russian Federation	Santarus Clinical Investigational Site 9010	Moscow
Russian Federation	Santarus Clinical Investigational Site 9004	Nizhny Novgorod
Russian Federation	Santarus Clinical Investigational Site 9003	Ryazan
Russian Federation	Santarus Clinical Investigational Site 9008	Saint Petersburg
Russian Federation	Santarus Clinical Investigational Site 9013	Saint Petersburg
Russian Federation	Santarus Clinical Investigational Site 9014	Saint Petersburg
Russian Federation	Santarus Clinical Investigational Site 9009	Saratov
Russian Federation	Santarus Clinical Investigational Site 9001	St Petersburg
Russian Federation	Santarus Clinical Investigational Site 9007	Stavropol
Russian Federation	Santarus Clinical Investigational Site 9006	Ufa
Russian Federation	Santarus Clinical Investigational Site 9017	Volgograd
Ukraine	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
United States	Santarus Clinical Investigational Site 1043	Anaheim	California
United States	Santarus Clinical Investigational Site 1044	Annapolis	Maryland
United States	Santarus Clinical Investigational Site 1059	Austin	Texas
United States	Santarus Clinical Investigational Site 1035	Boynton Beach	Florida
United States	Santarus Clinical Investigational Site 1028	Bristol	Connecticut
United States	Santarus Clinical Investigational Site 1021	Cheektowaga	New York
United States	Santarus Clinical Investigational Site 1038	Chesapeake	Virginia
United States	Santarus Clinical Investigational Site 1016	Chesterfield	Michigan
United States	Santarus Clinical Investigational Site 1075	Chicago	Illinois
United States	Santarus Clinical Investigational Site 1025	Christiansburg	Virginia
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 1050	Decatur	Georgia
United States	Santarus Clinical Investigational Site 1072	Great Neck	New York
United States	Santarus Clinical Investigational Site 1039	Houston	Texas
United States	Santarus Clinical Investigational Site 1058	Indianapolis	Indiana
United States	Santarus Clinical Investigational Site 1045	Jacksonville	Florida
United States	Santarus Clinical Investigational Site 1071	Lakewood	California
United States	Santarus Clinical Investigational Site 1014	Lancaster	Utah
United States	Santarus Clinical Investigational Site 1064	Lancaster	Pennsylvania
United States	Santarus Clinical Investigational Site 1001	Largo	Florida
United States	Santarus Clinical Investigational Site 1061	Lebanon	New Hampshire
United States	Santarus Clinical Investigational Site 1063	Littleton	Colorado
United States	Santarus Clinical Investigational Site 1024	Maitland	Florida
United States	Santarus Clinical Investigational Site 1031	New York	New York
United States	Santarus Clinical Investigational Site 1081	Novi	Michigan
United States	Santarus Clinical Investigational Site 1065	Oak Lawn	Illinois
United States	Santarus Clinical Investigational Site 1005	Pasadena	Texas
United States	Santarus Clinical Investigational Site 1029	Port Orange	Florida
United States	Santarus Clinical Investigational Site 1074	Rochester	Minnesota
United States	Santarus Clinical Investigational Site 1003	San Diego	California
United States	Santarus Clinical Investigational Site 1006	Sayre	Pennsylvania
United States	Santarus Clinical Investigational Site 1032	Shreveport	Louisiana
United States	Santarus Clinical Investigational Site 1073	Wilmington	North Carolina
United States	Santarus Clinical Investigational Site 1010	Winter Park	Florida
United States	Santarus Clinical Investigational Site 1015	Wyoming	Michigan
United States	Santarus Clinical Investigational Site 1068	Ypsilanti	Michigan
United States	Santarus Clinical Investigational Site 1002	Zephyrhills	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Bausch Health Americas, Inc.

Countries where clinical trial is conducted

United States,  Bulgaria,  Canada,  Czechia,  Estonia,  Hungary,  Latvia,  Lithuania,  Poland,  Russian Federation,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants Who Achieved Clinical Remission at Day 56	Clinical remission defined as a score of 0 for rectal bleeding and 0 for stool frequency components from the Ulcerative Colitis Disease Activity Index (UCDAI). UCDAI is the sum (0 to 12) of 4 severity scores (0 to 3). Stool frequency and rectal bleeding were based on information recorded in daily participant diaries. The diary entries were averaged for rectal bleeding and stool frequency for 3 days prior to (and closest to) Day 56 with non-missing diary data, within 5 days prior to (and closest to) Day 56. The 5 days did not include any days of the flexible sigmoidoscopy (or colonoscopy) or the preparation for the flexible sigmoidoscopy (or colonoscopy). These averages were rounded to integer values. If either subscore could not be calculated because of missing data, the score for that UCDAI component was set to missing. Participants with insufficient data at Day 56 were excluded from the analysis. Participants who had clinical remission at Baseline were classified as non-responders.	Baseline up to Day 56
Secondary	Number of Participants of Who Achieved Clinical Response at Day 56	Clinical response defined as an improvement in UCDAI from Baseline of =3 points with a rectal bleeding score =1. UCDAI is the sum (0 to 12) of 4 severity scores (0 to 3). Rectal bleeding was based on information recorded in daily participant diaries. The diary entries were averaged for rectal bleeding for 3 days prior to (and closest to) Day 56 with non-missing diary data, within 5 days prior to (and closest to) Day 56. The 5 days did not include any days of the flexible sigmoidoscopy (or colonoscopy) or the preparation for the flexible sigmoidoscopy (or colonoscopy). These averages were rounded to integer values. If either subscore could not be calculated because of missing data, the score for that UCDAI component was set to missing. Participants with insufficient data at Day 56 were excluded from the analysis.	Baseline up to Day 56
Secondary	Number of Participants Who Achieved UCDAI Remission at Day 56	UCDAI remission was defined as a total UCDAI score =1 with subscores of 0 for rectal bleeding, stool frequency, and mucosal appearance of the colon. UCDAI is the sum (0 to 12) of 4 severity scores (0 to 3). Stool frequency and rectal bleeding were based on information recorded in daily participant diaries and mucosal appearance was based on endoscopy results. The diary entries were averaged for rectal bleeding and stool frequency for 3 days prior to (and closest to) Day 56 with non-missing diary data, within 5 days prior to (and closest to) Day 56. The 5 days did not include any days of the flexible sigmoidoscopy (or colonoscopy) or the preparation for the flexible sigmoidoscopy (or colonoscopy). These averages were rounded to integer values. If the subscore could not be calculated because of missing data, the score for that UCDAI component was set to missing. Participants with insufficient data at Day 56 were excluded from the analysis.	Baseline up to Day 56
Secondary	Number of Participants Who Achieved Endoscopic Remission at Day 56	Endoscopic remission was defined as a score of 0 in the mucosal appearance component subscore of the UCDAI at Day 56. UCDAI is the sum (0 to 12) of 4 severity scores (0 to 3). Mucosal appearance was based on endoscopy results. If the mucosal appearance subscore could not be calculated because of missing data, endoscopic remission was set to missing. Participants with insufficient data at Day 56 were excluded from the analysis.	Screening and Day 56
Secondary	Number of Participants Who Achieved Histologic Healing at Day 56	Participants achieved histologic healing if histologic assessments of all biopsy specimens were graded as 0 (normal mucosa). If the score for =1 sample was missing, the overall score at that visit was set to missing. Participants with insufficient data at Day 56 were excluded from analysis.	Baseline and Day 56
Secondary	Number of Participants With Treatment Failure at Day 56	Treatment failure was defined as an unchanged, worsened, or missing UCDAI score at Day 56. UCDAI is the sum (0 to 12) of 4 severity scores (0 to 3). Stool frequency and rectal bleeding was based on information recorded in daily participant diaries and mucosal appearance was based on endoscopy results. The diary entries were averaged for rectal bleeding and stool frequency for 3 days prior to (and closest to) Day 56 with non-missing diary data, within 5 days prior to (and closest to) Day 56. The 5 days did not include any days of the flexible sigmoidoscopy (or colonoscopy) or the preparation for the flexible sigmoidoscopy (or colonoscopy). These averages were rounded to integer values. If the subscore could not be calculated because of missing data, the score for that UCDAI component was set to missing. Participants with insufficient data at Day 56 were excluded from the analysis.	Baseline up to Day 56
Secondary	Change From Baseline in Inflammatory Bowel Disease-Quality of Life (IBD-QoL) Questionnaire Scores	The IBD-QoL questionnaire was self-completed by the participant. The IBD-QoL is a disease-specific instrument to evaluate the quality of life of participants with UC. This 32-item questionnaire has 4 dimensions: bowel function, emotional function, systemic symptoms, and social function. The total score is presented, which ranges from 32 to 224, with higher scores indicating a better quality of life. The scores of participants in remission usually range from 170 to 190. If >50% of the questionnaire answers for a particular dimension were missing, this dimension score was set to missing. The total score for the IBD-QoL was the sum of the domain scores, however, if any dimension score was missing, the total IBD-QoL score was set to missing.	Baseline, Days 14, 28, and 56