Overview

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

Status:
Completed
Trial end date:
2007-06-01
Target enrollment:
0
Participant gender:
All
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.
Phase:
Phase 3
Accepts Healthy Volunteers?
Accepts Healthy Volunteers
Details
Lead Sponsor:
Bausch Health Americas, Inc.
Valeant Pharmaceuticals International, Inc.
Treatments:
Balsalazide
Mesalamine
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.