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
Overview
- Phase
- Phase 3
- Intervention
- Not specified
- Conditions
- Ulcerative Colitis
- Sponsor
- Bausch Health Americas, Inc.
- Enrollment
- 225
- Locations
- 61
- Primary Endpoint
- 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.
- Status
- Completed
- Last Updated
- 6 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •A subject will be eligible for inclusion in this study only if all of the following criteria apply:
- •An Institutional Review Board (IRB) approved informed consent is signed and dated prior to any study-related activities.
- •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);
- •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.
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.):
- •Subject has a significant medical, including psychiatric, condition which in the opinion of the investigator precludes participation in the study.
- •Subject has a history of allergy or intolerance to aspirin, mesalamine, or other salicylates.
- •Subject has recently (within the past 30 days) failed therapy with balsalazide disodium
- •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.
- •Subject has received intra-rectal aminosalicylates within 14 days of screening.
- •Subject has had any prior bowel surgery, excepting appendectomy.
- •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."
- •Subject is pregnant or at risk of pregnancy, or is lactating (female subjects only).
- •Subject shows evidence of current excessive alcohol consumption or drug dependence.
Outcomes
Primary Outcomes
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 Outcomes
- The change from baseline over the duration of treatment in total MMDAI score and in the individual MMDAI subscales.