New Tablet Formulation and Dosing Regimen of Balsalazide Disodium in Mildly to Moderately Active Ulcerative Colitis

NCT ID: NCT00269438

Last Updated: 2019-11-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 225 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-12-31
• Study Completion Date: 2007-06-30

Brief Summary

The purpose of this study is to establish the efficacy and safety of a new tablet formulation and dosing regimen of balsalazide disodium dosed twice daily in achieving clinical improvement in subjects with mildly to moderately active ulcerative colitis after 8 weeks of therapy.

Detailed Description

The primary efficacy endpoint is the proportion of subjects that achieve clinical improvement and improvement in the rectal bleeding subscale of the MMDAI at the end of eight weeks of therapy, where clinical improvement is defined as a greater than or equal to 3 point improvement from baseline in the MMDAI.

The secondary endpoints are as follows:

1. The change from baseline over the duration of treatment in total MMDAI score and in the individual MMDAI subscales.

2. The change from baseline to Weeks 1, 2, 4 and 8 in total MMDAI score and in each individual MMDAI subscale (endoscopy/sigmoidoscopy at Weeks 2 and 8 only).

3. The proportion of subjects with treatment failure, defined as withdrawal due to significant disease progression or lack of significant improvement, as determined by the Investigator.

4. The proportion of subjects with mucosal healing at Weeks 2 and 8, where mucosal healing is defined as an endoscopy/sigmoidoscopy score of 0 or 1

5. The proportion of subjects achieving complete remission at Week 2 and Week 8, where complete remission is defined as a MMDAI score of less than or equal to 1.

6. The proportion of subjects with improvement from baseline to Weeks 1, 2, 4 and 8 in total MMDAI score and in each individual MMDAI subscale (endoscopy/sigmoidoscopy at Weeks 2 and 8 only).

7. Change from baseline to Weeks 1, 2, 4 and 8 in diarrhea, abdominal discomfort, and subjective sense of well being, as recorded in the subjects' diaries.

8. The proportion of subjects achieving clinical remission at Weeks 1, 2, 4 and 8, where clinical remission is defined as a score of 0 for rectal bleeding and a combined score of less than or equal to 2 for bowel frequency and physician assessment using the MMDAI.

9. Time to clinical remission, where clinical remission is defined as in secondary endpoint number eight.

Safety endpoints are as follows:

• incidence of treatment-emergent AEs grouped by body system and evaluated by treatment group;
• changes from baseline in clinical laboratory parameters at each treatment visit by treatment group; and
• changes from baseline in vital sign measurements at each treatment visit by treatment group.

Conditions

Ulcerative Colitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Interventions

5 ASA, enemas, suppositories, corticosteroids

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

A subject will be eligible for inclusion in this study only if all of the following criteria apply:

1. An Institutional Review Board (IRB) approved informed consent is signed and dated prior to any study-related activities.

2. Subject is a male or, if the subject is female, she is eligible to enter if she is of:

Non-childbearing potential (i.e. physiologically incapable of becoming pregnant, including any female who has undergone sterilization [hysterectomy or bilateral tubal ligation] or is post-menopausal. For purposes of this study, postmenopausal is defined as 1 year without menses);

OR,

Childbearing potential, has a negative serum pregnancy test at screen and, if heterosexually active, agrees to one of the following:

• Double barrier method of contraception, specifically, use of a condom and spermicide, for 1 week prior to study drug administration, throughout the 8 week Treatment Phase.
• Oral contraceptives administered for at least 2 monthly cycles prior to study drug administration during all 6 months of study drug administration and administered for 1 monthly cycle following completion of the study.
• An intrauterine device (IUD), inserted by a qualified clinician, with published data showing that the lowest expected failure rate is less than or equal to 1% per year (not all IUDs meet this criterion).
• Medroxyprogesterone acetate (DEPO-PROVERA) administered for a minimum of 1 monthly cycle prior to the study drug administration, during all 6 months of study drug administration, and administered for 1 monthly cycle following study completion. Norelgestromin/ ethinyl estradiol transdermal system (Ortho Evra patch) administered for at least 2 monthly cycles prior to study drug administration and administered for 2 monthly cycles following study completion
• Partner has undergone vasectomy and subject is in a monogamous relationship. The investigator is responsible for determining whether the subject is using appropriate birth control for study participation.
• Subject is greater than or equal to 18 years of age.
• Subjects with mildly to moderately active ulcerative colitis experiencing symptoms of an acute flare within the past 4 weeks.

3. Subject has not taken more than 2.4 grams of mesalamine or equivalent for a continuous period of 4 weeks preceding the screening visit

4. Subjects must have a baseline Modified Mayo Disease Activity Index (MMDAI) score between 6 and 10, inclusive. Additionally, subjects must score greater than or equal to 2 on Bleeding and greater than or equal to 2 on Endoscopy/Sigmoidoscopy.

5. Subject is capable and willing to comply with all study procedures.

6. Disease extends at least 20 cm from the rectum on screening sigmoidoscopy.

Exclusion Criteria

1. Subject has a significant medical, including psychiatric, condition which in the opinion of the investigator precludes participation in the study.

2. Subject has a history of allergy or intolerance to aspirin, mesalamine, or other salicylates.

3. Subject has recently (within the past 30 days) failed therapy with balsalazide disodium

4. Subject has received immunosuppressive therapy (e.g. azothioprine, 6 mercaptopurine) within 30 days, or corticosteroids (oral, intravenous [IV] or topical rectal) within 30 days prior to screening.

5. Subject has received intra-rectal aminosalicylates within 14 days of screening.

6. Subject has had any prior bowel surgery, excepting appendectomy.

7. Subject has participated in an investigational drug or device study within the 30 days prior to study screening, with the exception of Salix protocols 3003 & 3004 entitled: "A multicenter, randomized, double-blind, placebo controlled trial to evaluate the use of mesalamine pellet formulation 1.5G QD to maintain remission from mildly to moderate ulcerative colitis."

8. Subject is pregnant or at risk of pregnancy, or is lactating (female subjects only).

9. Subject shows evidence of current excessive alcohol consumption or drug dependence.

10. Subject has a history of human immunodeficiency virus (HIV) or hepatitis (B and C).

11. Subject has other infectious, ischemic, or immunologic diseases with GI involvement.

12. Subject has twice the upper limit of normal (ULN) for any of the following LFTs: alanine aminotransferase (ALT/SGPT), aspartate aminotransferase (AST/SGOT), alkaline phosphatase, or total bilirubin (except isolated elevation of unconjugated bilirubin).

13. Subject has uncontrolled, clinically significant renal disease manifested by 1.5 × ULN of serum creatinine or blood urea nitrogen (BUN) levels.

14. Subject has calculated creatinine clearance level of less than or equal to 60 mL/min.

15. Subject has unstable cardiovascular, coagulopathy or pulmonary disease.

16. Subject has active malignancy within the last 5 years, except basal cell carcinoma of the skin, or if female, in situ cervical carcinoma that has been surgically excised.

17. Subject has any condition or circumstance that would, in the opinion of the investigator, prevent completion of the study or interfere with analysis of study results, including history of noncompliance with treatments or visits.

18. Subject has sclerosing cholangitis.

19. Subject has positive stool culture for ovum and parasites (O and P) or C. difficile.

20. Subject has been treated with infliximab, cyclosporine, natalizumab, or methotrexate for ulcerative colitis within the last 30 days prior to screening.

21. Regular use of NSAIDS except cardioprotective ASA (i.e., less than or equal to 162 mg ASA per day).

22. Subject has received cell-depleting therapies such as the Adacolumn.

23. Subject requires antidiarrheal therapy during screening.

24. Subject has clinical or radiographic findings suggestive of serious UC complications such as toxic megacolon or colonic perforation.

Females of Reproductive Potential:

If a female subject becomes pregnant while on this study, the study drug will be discontinued immediately and the subject followed until the outcome of the pregnancy is known. If a pregnancy occurs, it will be reported in the same manner as an unexpected AE using the guidelines provided in Section 6.4.1.9.

Premature Subject Discontinuation:

A subject may be discontinued from the study for the following medical or administrative reasons:

• Occurrence of an AE, which in the judgment of the investigator suggests an unacceptable risk to the subject (The investigator will follow the subject until satisfactory resolution of the AE or the AE is determined to be stable);
• Development on-study of any condition which, in the opinion of the investigator or the study sponsor, places the subject at an unacceptable medical risk if he/she continues;
• Pregnancy;
• Subject request;
• Institution of additional medical (rescue) therapy for UC. The investigator may discontinue individual subjects from the study at any time. Subjects will be encouraged to complete the study; however they may voluntarily withdraw at any time. The investigator must provide written documentation of the reason for discontinuation on the CRF. Regardless of the reason for withdrawal, all subjects will be asked to undergo an end of therapy evaluation. Every attempt will be made to obtain all the end of study assessments, including all of the subscales of the MMDAI (i.e., bowel frequency, bleeding, physician's assessment, and endoscopy/sigmoidoscopy score).

Subjects who withdraw or are withdrawn will not be replaced under this protocol.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Bausch Health Americas, Inc.

INDUSTRY

Sponsor Role: lead

Locations

Birmingham Gastroenterology Associates

Birmingham, Alabama, United States

Spring Memorial Hospital

Mobile, Alabama, United States

Little Rock Diagnostic Clinic

Little Rock, Arkansas, United States

Advanced Clinical Research Institute

Anaheim, California, United States

Lovelace Scientific Resources

Beverly Hills, California, United States

Digestive Liver Disease Specialists, Medical Group

Garden Grove, California, United States

Therapeutic Research Institute of Orange County

Laguna Hills, California, United States

Long Beach VA Medical Center

Long Beach, California, United States

Facey Medical Group

Mission Hills, California, United States

Community Clinical Trials

Orange, California, United States

Rider Research Group

San Francisco, California, United States

John Jolley, M.D.

San Rafael, California, United States

Lovelace Scientific Resources

Santa Ana, California, United States

Santa Barbara Clinical Research

Santa Barbara, California, United States

Connecticut Gastroenterology Institute

Bristol, Connecticut, United States

Stamford Therapeutic Consortium

Stamford, Connecticut, United States

Medical Research Unlimited

Hialeah, Florida, United States

Mark Lamet, M.D.

Hollywood, Florida, United States

Southern Clinical Research Consultants

Hollywood, Florida, United States

United Medical Research

New Smyrna Beach, Florida, United States

Venture Research Institute, LLC

North Miami Beach, Florida, United States

Advanced Gastroenterology Associates

Palm Harbor, Florida, United States

Lovelace Scientific Resources

Sarasota, Florida, United States

Advent Clinical Research

Sarasota, Florida, United States

Clinical Research of Tampa Bay, Inc.

Spring Hill, Florida, United States

Metabolic Research Institute, Inc.

West Palm Beach, Florida, United States

Gary Richter, M.D.

Atlanta, Georgia, United States

The Atlanta Center for Gastroenterology

Decatur, Georgia, United States

Gastroenterology Associates of Central Georgia

Macon, Georgia, United States

Northwest Gastroenterologists S.C.

Arlington Heights, Illinois, United States

University Digestive Health Center

Oak Forest, Illinois, United States

Covenent Clinic

Waterloo, Iowa, United States

Digestive Health Center

Topeka, Kansas, United States

University of Louisville

Louisville, Kentucky, United States

Digestive Health Center of Louisiana

Baton Rouge, Louisiana, United States

Woodholme Gastroenterology Associates, PA

Baltimore, Maryland, United States

Sinai Medical Office Building

Baltimore, Maryland, United States

Mid Atlantic Medical Research Centers

Hollywood, Maryland, United States

Clinical Research Institute of Michigan, LLC

Chesterfield, Michigan, United States

Kansas City, Missouri, United States

Center for Digestive & Liver Diseases

Mexico, Missouri, United States

St. Louis Center for Clinical Research

St Louis, Missouri, United States

Central Jersey Primary Care Inc.

Elizabeth, New Jersey, United States

Ocean City, New Jersey, United States

New York, New York, United States

VA Medical Center

Syracuse, New York, United States

Upstate Gastroenterology Associates, PC

Troy, New York, United States

LeBauer Research Associates, PA

Greensboro, North Carolina, United States

Bethany Medical Center

High Point, North Carolina, United States

Boice-Willis Clinic

Rocky Mount, North Carolina, United States

Consultants for Clinical Research, Inc.

Cincinnati, Ohio, United States

Avamar Center for Gastroenterology, Inc.

Warren, Ohio, United States

Charleston Gastroenterology Specialists, LLC

Charleston, South Carolina, United States

Hillcrest Clinical Research LLC

Simpsonville, South Carolina, United States

Gastroenterology Associates

Kingsport, Tennessee, United States

Gastrointestinal Associates

Knoxville, Tennessee, United States

Memphis Gastroenterology Group

Memphis, Tennessee, United States

Nashville Medical Research Institute

Nashville, Tennessee, United States

Clinical Trial Network

Houston, Texas, United States

NationsMed Clinical Research

Houston, Texas, United States

Houston Digestive Disease Clinic

Houston, Texas, United States

Gastroenterology Associates of Tidewater

Chesapeake, Virginia, United States

Seattle Gastroenterology Associates

Seattle, Washington, United States

Eastern Washington Clinical Research Center

Spokane, Washington, United States

Spokane Digestive Disease Center Research

Spokane, Washington, United States

Tacoma Digestive Disease Research Center

Tacoma, Washington, United States

Countries

United States

Other Identifiers

BZUC3002

Identifier Type: -

Identifier Source: org_study_id