Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study has been completed.
Sponsor:
Information provided by:
Salix Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00269438
First received: December 22, 2005
Last updated: December 21, 2009
Last verified: December 2009
  Purpose

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.


Condition Intervention Phase
Ulcerative Colitis
Drug: 5 ASA, enemas, suppositories, corticosteroids
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: Phase 3 Study 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

Resource links provided by NLM:


Further study details as provided by Salix Pharmaceuticals:

Primary Outcome Measures:
  • 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 >3 point improvement from baseline in the MMDAI.

Secondary Outcome Measures:
  • The change from baseline over the duration of treatment in total MMDAI score and in the individual MMDAI subscales.

Estimated Enrollment: 225
Study Start Date: December 2005
Study Completion Date: June 2007
Primary Completion Date: March 2007 (Final data collection date for primary outcome measure)
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.
  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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:

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

  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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00269438

  Hide Study Locations
Locations
United States, Alabama
Birmingham Gastroenterology Associates
Birmingham, Alabama, United States, 35209
Spring Memorial Hospital
Mobile, Alabama, United States, 36608
United States, Arkansas
Little Rock Diagnostic Clinic
Little Rock, Arkansas, United States, 72205
United States, California
Advanced Clinical Research Institute
Anaheim, California, United States, 92801
Lovelace Scientific Resources
Beverly Hills, California, United States, 90211
Digestive Liver Disease Specialists, Medical Group
Garden Grove, California, United States, 92840
Therapeutic Research Institute of Orange County
Laguna Hills, California, United States, 92653
Long Beach VA Medical Center
Long Beach, California, United States, 90822
Facey Medical Group
Mission Hills, California, United States, 91345
Community Clinical Trials
Orange, California, United States, 92868
Rider Research Group
San Francisco, California, United States, 94117
John Jolley, M.D.
San Rafael, California, United States, 94901
Lovelace Scientific Resources
Santa Ana, California, United States, 92704
Santa Barbara Clinical Research
Santa Barbara, California, United States, 93108
United States, Connecticut
Connecticut Gastroenterology Institute
Bristol, Connecticut, United States, 06010
Stamford Therapeutic Consortium
Stamford, Connecticut, United States, 06905
United States, Florida
Medical Research Unlimited
Hialeah, Florida, United States, 33013
Mark Lamet, M.D.
Hollywood, Florida, United States, 33021
Southern Clinical Research Consultants
Hollywood, Florida, United States, 33021
United Medical Research
New Smyrna Beach, Florida, United States, 32168
Venture Research Institute, LLC
North Miami Beach, Florida, United States, 33162
Advanced Gastroenterology Associates
Palm Harbor, Florida, United States, 34684
Advent Clinical Research
Sarasota, Florida, United States, 34239
Lovelace Scientific Resources
Sarasota, Florida, United States, 34233
Clinical Research of Tampa Bay, Inc.
Spring Hill, Florida, United States, 34609
Metabolic Research Institute, Inc.
West Palm Beach, Florida, United States, 33401
United States, Georgia
Gary Richter, M.D.
Atlanta, Georgia, United States, 30308
The Atlanta Center for Gastroenterology
Decatur, Georgia, United States, 30033
Gastroenterology Associates of Central Georgia
Macon, Georgia, United States, 31201
United States, Illinois
Northwest Gastroenterologists S.C.
Arlington Heights, Illinois, United States, 60005
University Digestive Health Center
Oak Forest, Illinois, United States, 60452
United States, Iowa
Covenent Clinic
Waterloo, Iowa, United States, 50702
United States, Kansas
Digestive Health Center
Topeka, Kansas, United States, 66606
United States, Kentucky
University of Louisville
Louisville, Kentucky, United States, 40202
United States, Louisiana
Digestive Health Center of Louisiana
Baton Rouge, Louisiana, United States, 70809
United States, Maryland
Sinai Medical Office Building
Baltimore, Maryland, United States, 21215
Woodholme Gastroenterology Associates, PA
Baltimore, Maryland, United States, 21208
Mid Atlantic Medical Research Centers
Hollywood, Maryland, United States, 20636
United States, Michigan
Clinical Research Institute of Michigan, LLC
Chesterfield, Michigan, United States, 48047
United States, Missouri
Kansas City, Missouri, United States, 67131
Center for Digestive & Liver Diseases
Mexico, Missouri, United States, 65265
St. Louis Center for Clinical Research
St. Louis, Missouri, United States, 63128
United States, New Jersey
Central Jersey Primary Care Inc.
Elizabeth, New Jersey, United States, 07202
Ocean, New Jersey, United States, 07712
United States, New York
New York, New York, United States, 10128
VA Medical Center
Syracuse, New York, United States, 13210
Upstate Gastroenterology Associates, PC
Troy, New York, United States, 12180
United States, North Carolina
LeBauer Research Associates, PA
Greensboro, North Carolina, United States, 27265
Bethany Medical Center
High Point, North Carolina, United States, 27262
Boice-Willis Clinic
Rocky Mount, North Carolina, United States, 27804
United States, Ohio
Consultants for Clinical Research, Inc.
Cincinnati, Ohio, United States, 45219
Avamar Center for Gastroenterology, Inc.
Warren, Ohio, United States, 44484
United States, South Carolina
Charleston Gastroenterology Specialists, LLC
Charleston, South Carolina, United States, 29414
Hillcrest Clinical Research LLC
Simpsonville, South Carolina, United States, 29681
United States, Tennessee
Gastroenterology Associates
Kingsport, Tennessee, United States, 37660
Gastrointestinal Associates
Knoxville, Tennessee, United States, 37909
Memphis Gastroenterology Group
Memphis, Tennessee, United States, 38210
Nashville Medical Research Institute
Nashville, Tennessee, United States, 37205
United States, Texas
Clinical Trial Network
Houston, Texas, United States, 77030
Houston Digestive Disease Clinic
Houston, Texas, United States, 77090
NationsMed Clinical Research
Houston, Texas, United States, 77034
United States, Virginia
Gastroenterology Associates of Tidewater
Chesapeake, Virginia, United States, 23320
United States, Washington
Seattle Gastroenterology Associates
Seattle, Washington, United States, 98133
Eastern Washington Clinical Research Center
Spokane, Washington, United States, 99204
Spokane Digestive Disease Center Research
Spokane, Washington, United States, 99204
Tacoma Digestive Disease Research Center
Tacoma, Washington, United States, 98405
Sponsors and Collaborators
Salix Pharmaceuticals
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00269438     History of Changes
Other Study ID Numbers: BZUC3002
Study First Received: December 22, 2005
Last Updated: December 21, 2009
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Colitis
Colitis, Ulcerative
Ulcer
Colonic Diseases
Digestive System Diseases
Gastroenteritis
Gastrointestinal Diseases
Inflammatory Bowel Diseases
Intestinal Diseases
Pathologic Processes
Balsalazide
Analgesics
Analgesics, Non-Narcotic
Anti-Inflammatory Agents
Anti-Inflammatory Agents, Non-Steroidal
Antirheumatic Agents
Central Nervous System Agents
Gastrointestinal Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sensory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014