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

Last updated: November 21, 2019
Sponsor: Bausch Health Americas, Inc.
Overall Status: Completed

Phase

3

Condition

Ulcerative Colitis

Crohn's Disease

Inflammatory Bowel Disease

Treatment

N/A

Clinical Study ID

NCT00269438
BZUC3002
  • Ages 18-80
  • All Genders
  • Accepts Healthy Volunteers

Study 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.

Eligibility Criteria

Inclusion

Inclusion Criteria: A subject will be eligible for inclusion in this study only if all of the followingcriteria apply:

  1. An Institutional Review Board (IRB) approved informed consent is signed and datedprior 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 tuballigation] or is post-menopausal. For purposes of this study, postmenopausal is definedas 1 year without menses); OR, Childbearing potential, has a negative serum pregnancy test at screen and, ifheterosexually active, agrees to one of the following:

  • Double barrier method of contraception, specifically, use of a condom andspermicide, for 1 week prior to study drug administration, throughout the 8 weekTreatment Phase.

  • Oral contraceptives administered for at least 2 monthly cycles prior to studydrug administration during all 6 months of study drug administration andadministered for 1 monthly cycle following completion of the study.

  • An intrauterine device (IUD), inserted by a qualified clinician, with publisheddata 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 1monthly cycle prior to the study drug administration, during all 6 months ofstudy drug administration, and administered for 1 monthly cycle following studycompletion. Norelgestromin/ ethinyl estradiol transdermal system (Ortho Evrapatch) administered for at least 2 monthly cycles prior to study drugadministration and administered for 2 monthly cycles following study completion

  • Partner has undergone vasectomy and subject is in a monogamous relationship. Theinvestigator is responsible for determining whether the subject is usingappropriate birth control for study participation.

  • Subject is greater than or equal to 18 years of age.

  • Subjects with mildly to moderately active ulcerative colitis experiencingsymptoms of an acute flare within the past 4 weeks.

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

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

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

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

Exclusion

Exclusion Criteria: A subject will not be eligible for inclusion in this study if any of the following criteriaapply (Note: Development of any of the following exclusion criteria on-study will beconsidered a basis for subject discontinuation.):

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

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

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

  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 daysprior to study screening, with the exception of Salix protocols 3003 & 3004 entitled: "A multicenter, randomized, double-blind, placebo controlled trial to evaluate the useof mesalamine pellet formulation 1.5G QD to maintain remission from mildly to moderateulcerative 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), alkalinephosphatase, or total bilirubin (except isolated elevation of unconjugated bilirubin).

  13. Subject has uncontrolled, clinically significant renal disease manifested by 1.5 × ULNof 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 ofthe 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 theinvestigator, prevent completion of the study or interfere with analysis of studyresults, 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 methotrexatefor 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 mgASA 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 complicationssuch as toxic megacolon or colonic perforation. Females of Reproductive Potential: If a female subject becomes pregnant while on this study, the study drug will bediscontinued immediately and the subject followed until the outcome of the pregnancy isknown. If a pregnancy occurs, it will be reported in the same manner as an unexpected AEusing 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 administrativereasons:

  • Occurrence of an AE, which in the judgment of the investigator suggests anunacceptable risk to the subject (The investigator will follow the subject untilsatisfactory 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 thestudy 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 maydiscontinue individual subjects from the study at any time. Subjects will beencouraged to complete the study; however they may voluntarily withdraw at any time.The investigator must provide written documentation of the reason for discontinuationon the CRF. Regardless of the reason for withdrawal, all subjects will be asked toundergo an end of therapy evaluation. Every attempt will be made to obtain all the endof study assessments, including all of the subscales of the MMDAI (i.e., bowelfrequency, bleeding, physician's assessment, and endoscopy/sigmoidoscopy score). Subjects who withdraw or are withdrawn will not be replaced under this protocol.

Study Design

Total Participants: 225
Study Start date:
December 01, 2005
Estimated Completion Date:
June 30, 2007

Study 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.

Connect with a study center

  • Birmingham Gastroenterology Associates

    Birmingham, Alabama 35209
    United States

    Site Not Available

  • Spring Memorial Hospital

    Mobile, Alabama 36608
    United States

    Site Not Available

  • Little Rock Diagnostic Clinic

    Little Rock, Arkansas 72205
    United States

    Site Not Available

  • Advanced Clinical Research Institute

    Anaheim, California 92801
    United States

    Site Not Available

  • Lovelace Scientific Resources

    Beverly Hills, California 90211
    United States

    Site Not Available

  • Digestive Liver Disease Specialists, Medical Group

    Garden Grove, California 92840
    United States

    Site Not Available

  • Therapeutic Research Institute of Orange County

    Laguna Hills, California 92653
    United States

    Site Not Available

  • Long Beach VA Medical Center

    Long Beach, California 90822
    United States

    Site Not Available

  • Facey Medical Group

    Mission Hills, California 91345
    United States

    Site Not Available

  • Community Clinical Trials

    Orange, California 92868
    United States

    Site Not Available

  • Rider Research Group

    San Francisco, California 94117
    United States

    Site Not Available

  • John Jolley, M.D.

    San Rafael, California 94901
    United States

    Site Not Available

  • Lovelace Scientific Resources

    Santa Ana, California 92704
    United States

    Site Not Available

  • Santa Barbara Clinical Research

    Santa Barbara, California 93108
    United States

    Site Not Available

  • Connecticut Gastroenterology Institute

    Bristol, Connecticut 06010
    United States

    Site Not Available

  • Stamford Therapeutic Consortium

    Stamford, Connecticut 06905
    United States

    Site Not Available

  • Medical Research Unlimited

    Hialeah, Florida 33013
    United States

    Site Not Available

  • Mark Lamet, M.D.

    Hollywood, Florida 33021
    United States

    Site Not Available

  • Southern Clinical Research Consultants

    Hollywood, Florida 33021
    United States

    Site Not Available

  • United Medical Research

    New Smyrna Beach, Florida 32168
    United States

    Site Not Available

  • Venture Research Institute, LLC

    North Miami Beach, Florida 33162
    United States

    Site Not Available

  • Advanced Gastroenterology Associates

    Palm Harbor, Florida 34684
    United States

    Site Not Available

  • Advent Clinical Research

    Sarasota, Florida 34239
    United States

    Site Not Available

  • Lovelace Scientific Resources

    Sarasota, Florida 34233
    United States

    Site Not Available

  • Clinical Research of Tampa Bay, Inc.

    Spring Hill, Florida 34609
    United States

    Site Not Available

  • Metabolic Research Institute, Inc.

    West Palm Beach, Florida 33401
    United States

    Site Not Available

  • Gary Richter, M.D.

    Atlanta, Georgia 30308
    United States

    Site Not Available

  • The Atlanta Center for Gastroenterology

    Decatur, Georgia 30033
    United States

    Site Not Available

  • Gastroenterology Associates of Central Georgia

    Macon, Georgia 31201
    United States

    Site Not Available

  • Northwest Gastroenterologists S.C.

    Arlington Heights, Illinois 60005
    United States

    Site Not Available

  • University Digestive Health Center

    Oak Forest, Illinois 60452
    United States

    Site Not Available

  • Covenent Clinic

    Waterloo, Iowa 50702
    United States

    Site Not Available

  • Digestive Health Center

    Topeka, Kansas 66606
    United States

    Site Not Available

  • University of Louisville

    Louisville, Kentucky 40202
    United States

    Site Not Available

  • Digestive Health Center of Louisiana

    Baton Rouge, Louisiana 70809
    United States

    Site Not Available

  • Sinai Medical Office Building

    Baltimore, Maryland 21215
    United States

    Site Not Available

  • Woodholme Gastroenterology Associates, PA

    Baltimore, Maryland 21208
    United States

    Site Not Available

  • Mid Atlantic Medical Research Centers

    Hollywood, Maryland 20636
    United States

    Site Not Available

  • Clinical Research Institute of Michigan, LLC

    Chesterfield, Michigan 48047
    United States

    Site Not Available

  • Kansas City, Missouri 67131
    United States

    Site Not Available

  • Center for Digestive & Liver Diseases

    Mexico, Missouri 65265
    United States

    Site Not Available

  • St. Louis Center for Clinical Research

    Saint Louis, Missouri 63128
    United States

    Site Not Available

  • St. Louis Center for Clinical Research

    St. Louis, Missouri 63128
    United States

    Site Not Available

  • Central Jersey Primary Care Inc.

    Elizabeth, New Jersey 07202
    United States

    Site Not Available

  • empty

    Ocean, New Jersey 07712
    United States

    Site Not Available

  • Ocean City, New Jersey 07712
    United States

    Site Not Available

  • New York, New York 10128
    United States

    Site Not Available

  • VA Medical Center

    Syracuse, New York 13210
    United States

    Site Not Available

  • Upstate Gastroenterology Associates, PC

    Troy, New York 12180
    United States

    Site Not Available

  • LeBauer Research Associates, PA

    Greensboro, North Carolina 27265
    United States

    Site Not Available

  • Bethany Medical Center

    High Point, North Carolina 27262
    United States

    Site Not Available

  • Boice-Willis Clinic

    Rocky Mount, North Carolina 27804
    United States

    Site Not Available

  • Consultants for Clinical Research, Inc.

    Cincinnati, Ohio 45219
    United States

    Site Not Available

  • Avamar Center for Gastroenterology, Inc.

    Warren, Ohio 44484
    United States

    Site Not Available

  • Charleston Gastroenterology Specialists, LLC

    Charleston, South Carolina 29414
    United States

    Site Not Available

  • Hillcrest Clinical Research LLC

    Simpsonville, South Carolina 29681
    United States

    Site Not Available

  • Gastroenterology Associates

    Kingsport, Tennessee 37660
    United States

    Site Not Available

  • Gastrointestinal Associates

    Knoxville, Tennessee 37909
    United States

    Site Not Available

  • Memphis Gastroenterology Group

    Memphis, Tennessee 38210
    United States

    Site Not Available

  • Nashville Medical Research Institute

    Nashville, Tennessee 37205
    United States

    Site Not Available

  • Clinical Trial Network

    Houston, Texas 77030
    United States

    Site Not Available

  • Houston Digestive Disease Clinic

    Houston, Texas 77090
    United States

    Site Not Available

  • NationsMed Clinical Research

    Houston, Texas 77034
    United States

    Site Not Available

  • Gastroenterology Associates of Tidewater

    Chesapeake, Virginia 23320
    United States

    Site Not Available

  • Seattle Gastroenterology Associates

    Seattle, Washington 98133
    United States

    Site Not Available

  • Eastern Washington Clinical Research Center

    Spokane, Washington 99204
    United States

    Site Not Available

  • Spokane Digestive Disease Center Research

    Spokane, Washington 99204
    United States

    Site Not Available

  • Tacoma Digestive Disease Research Center

    Tacoma, Washington 98405
    United States

    Site Not Available

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