A Study of Asacol Absorption, Metabolism and Excretion in Children and Adolescents With Ulcerative Colitis.
Information source: Procter and Gamble
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Ulcerative Colitis
Intervention: mesalamine (Drug); mesalamine (Drug); mesalamine (Drug)
Phase: Phase 1
Status: Completed
Sponsored by: Procter and Gamble Official(s) and/or principal investigator(s):
William Aronstein, MD, PhD, Study Director, Affiliation: Procter and Gamble
Summary
The purpose of this randomized, open-label, parallel-group study is to determine how the body
absorbs and eliminates mesalamine following administration of either 30 mg/kg/day, 60
mg/kg/day or 90 mg/kg/day as 400 mg delayed-release tablets given every 12 hours of 28 days
to children and adolescents with active ulcerative colitis.
Clinical Details
Official title: Study to Determine the Pharmacokinetics of Mesalamine Following Administration of 30, 60, and 90 mg/kg/Day as 400 mg Delayed-Release Tablets Given Every 12 Hours for 28 Days to Children/Adolescents With Active Ulcerative Colitis.
Study design: Other, Randomized, Open Label, Dose Comparison, Parallel Assignment, Pharmacokinetics Study
Primary outcome: Pharmacokinetics
Detailed description:
Ulcerative colitis is a type of inflammatory bowel disease characterized by diffuse,
continuous inflammation of the colon. Recent estimates suggest that approximately 17,000
children between 5 and 17 years of age in the U. S. are diagnosed with ulcerative colitis.
Estimates of average age at onset in children vary, although 80-90% of patients are 9 years
of age or older when symptoms develop.
Asacol is a delayed-release tablet formulation designed to deliver mesalamine (also known as
mesalazine) at a pH ≥ 7. 0. This property results in release of the drug in the terminal
ileum and beyond. Physiologic factors such as the pH of the surrounding medium, transit
times in the intestinal regions of interest, and the rate and extent of absorption and
metabolism govern Asacol drug release and delivery, which in turn influence the
pharmacokinetic profile of the delivered drug. These physiologic factors and their effect on
Asacol pharmacokinetics have been studied in adults, but corresponding studies in children
have not been performed. However, relevant studies describing the gastrointestinal pH;
transit times; and pharmacokinetic aspects of drug absorption, metabolism, and excretion in
pediatric patients (relative to adults) provide reasons to expect that the performance
characteristics of Asacol in the pediatric population will be similar to those measured in
adults.
In a compassionate-use study that included 66 children between the ages of 3 and 16 years,
the safety profile of long-term mesalamine therapy (10 to 93 mg/kg/day) was similar to that
observed among adult patients enrolled in the study. In addition, in a retrospective study
of 732 pediatric patients with inflammatory bowel disease (153 of whom were treated with
mesalamine), D'Agata, et al. concluded that mesalamine was safe and well tolerated when used
long term at doses ranging from 13 to 111 mg/kg/day. Although few clinical studies of
mesalamine have been performed in children, pediatric gastroenterologists use mesalamine to
treat children with inflammatory bowel disease, and doses higher than those proposed for this
study (up to 100 mg/kg/day) have been recommended.
This study will provide information about the pharmacokinetics of mesalamine and its major
metabolite in children being treated with Asacol for mildly to moderately active ulcerative
colitis. It was designed to meet the expectations outlined in a Written Request issued by
the FDA, as well as regulatory requirements to study the weight-based equivalent of 4. 8
g/day. The age-appropriate dose formulation, the 400 mg tablet, will be used, and patients
will be dosed every 12 hours, since this regimen is considered more convenient for pediatric
patients and their parents.
During this open-label, randomized, 4-week parallel-group study in pediatric patients,
patients will be stratified by age (5-8 years and 9-17 years), and randomly assigned to one
of 3 dose levels (30 mg/kg/day, 60 mg/kg/day, and 90 mg/kg/day) in the manner described in
Section 3. 5.1. Patients weighing less than 20 kg will not be assigned to the 30 mg/kg group,
and patients weighing more than 60 kg will not be assigned to the 90 mg/kg group, due to
dosing concerns. A total of 48 patients will be enrolled (8/treatment group/age stratum),
with the expectation that 36 (6/treatment group/age stratum) will complete.
Eligibility
Minimum age: 5 Years.
Maximum age: 17 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
Patients are eligible to participate in the study if they have/are:
1. male or female between the ages of 5 and 17 years, inclusive, at the time of the first
dose of study medication
2. mildly to moderately active ulcerative colitis (either newly- or
previously-diagnosed), as confirmed by their physician, for which mesalamine would be
used as part of their normal treatment
3. generally in good health (other than the diagnosis of ulcerative colitis), based on
medical history, physical examination, and screening laboratory results
4. able to swallow Asacol tablets (400 mg marketed US formulation)
5. a body weight no less than 16 kg and no more than 90 kg
6. able and willing to participate in the study and follow study procedures, as evidenced
by providing assent and having a parent/guardian-signed written informed consent.
Exclusion Criteria:
Patients will be excluded from the study if they have/are:
1. a history of cancer 2. a history of intestinal surgery or malabsorption 3. a history
of renal insufficiency 4 a history of allergy or hypersensitivity to salicylates or
aminosalicylates 5. evidence of clinically significant organic or psychiatric disease on
medical history or physical examination that, in the Investigator's opinion, would prevent
the patient from completing the study or would jeopardize the patient's safety 6. a
creatinine clearance of <30 mL/minute at screening, estimated by serum creatinine using the
Traub & Johnson equation for calculating pediatric creatinine clearance.
7. a screening BUN or creatinine value that is >1. 5 times the upper limit of normal, or
liver function tests that are >2 times the upper limit of normal 8. any other screening
laboratory test values that the Investigator or Sponsor considers clinically significant
that would impact the outcome of the study or the safety of the patient 9. using proton
pump inhibitors or antacids 10. pregnant (post-menarchal female patients should be made
aware that pregnancy testing will occur during the study, and that if they are sexually
active they must take appropriate steps to ensure they do not become pregnant during the
study) 11. a positive urine screen for drugs of abuse 12. participated in another
clinical trial involving active intervention within 30 days prior to randomization.
Locations and Contacts
Research Site, Mobile, Alabama 63304, United States
Research Site, Birmingham, Alabama 35203, United States
Research Site, San Francisco, California 94143, United States
Research Site, San Diego, California 92103, United States
Research Site, Costa Mesa, California 92626, United States
Research Site, Gainesville, Florida 32610, United States
Research Site, Jacksonville, Florida 32207, United States
Research Site, Park Ridge, Illinois 60068, United States
Research Site, Baltimore, Maryland 21287, United States
Research Site, Boston, Massachusetts 21114, United States
Research Site, Detroit, Michigan 48236, United States
Research Site, Omaha, Nebraska 68105, United States
Research Site, Morristown, New Jersey 07962, United States
Research Site, Buffalo, New York 14222, United States
Research Site, Cleveland, Ohio 44106, United States
Research Site, Cincinnati, Ohio 45229, United States
Research Site, Portland, Oregon 97239, United States
Research Site, Greenville, South Carolina 29615, United States
Research Site, Pasadena, Texas 77504, United States
Research Site, Houston, Texas 77030, United States
Research Site, Dallas, Texas 75235, United States
Research Site, Seattle, Washington 98105, United States
Additional Information
Starting date: October 2005
Ending date: August 2007
Last updated: February 5, 2008
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