A Study of Asacol Absorption, Metabolism and Excretion in Children and Adolescents With Ulcerative Colitis.

Sponsor

Warner Chilcott (Industry)

Overall Status

Terminated

CT.gov ID

NCT00254618

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

1.5

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Ulcerative Colitis	Drug: mesalamine Drug: mesalamine Drug: mesalamine	Phase 1

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

34 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

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 Start Date :

Oct 1, 2005

Actual Primary Completion Date :

Jun 1, 2008

Actual Study Completion Date :

Jun 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 30 mg 30 mg/kg/day mesalamine	Drug: mesalamine oral tablet, 30 mg mesalamine/day for 28 days
Experimental: 60 mg 60 mg/kg/day mesalamine	Drug: mesalamine oral tablet, 60 mg mesalamine/day for 28 days
Experimental: 90 mg 90 mg/kg/day mesalamine	Drug: mesalamine oral tablet, 90 mg mesalamine/day for 28 days

Arm

Intervention/Treatment

Experimental: 30 mg

30 mg/kg/day mesalamine

Drug: mesalamine

oral tablet, 30 mg mesalamine/day for 28 days

Experimental: 60 mg

60 mg/kg/day mesalamine

Drug: mesalamine

oral tablet, 60 mg mesalamine/day for 28 days

Experimental: 90 mg

90 mg/kg/day mesalamine

Drug: mesalamine

oral tablet, 90 mg mesalamine/day for 28 days

Outcome Measures

Primary Outcome Measures

Pharmacokinetics [Days 1, 7, 14, 21, and 28]

Eligibility Criteria

Criteria

Ages Eligible for Study:

5 Years to 17 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients are eligible to participate in the study if they have/are:

male or female between the ages of 5 and 17 years, inclusive, at the time of the first dose of study medication
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
generally in good health (other than the diagnosis of ulcerative colitis), based on medical history, physical examination, and screening laboratory results
able to swallow Asacol tablets (400 mg marketed US formulation)
a body weight no less than 16 kg and no more than 90 kg
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:

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 < or =30 mL/minute at screening, estimated by serum creatinine using the Traub & Johnson equation for calculating pediatric creatinine clearance.
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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Birmingham	Alabama	United States	35203
2	Research Site	Mobile	Alabama	United States	63304
3	Research Site	Costa Mesa	California	United States	92626
4	Research Site	San Diego	California	United States	92103
5	Research Site	San Francisco	California	United States	94143
6	Research Site	Gainesville	Florida	United States	32610
7	Research Site	Jacksonville	Florida	United States	32207
8	Research Site	Park Ridge	Illinois	United States	60068
9	Research Site	Baltimore	Maryland	United States	21287
10	Research Site	Boston	Massachusetts	United States	21114
11	Research Site	Detroit	Michigan	United States	48236
12	Research Site	Omaha	Nebraska	United States	68105
13	Research Site	Morristown	New Jersey	United States	07962
14	Research Site	Buffalo	New York	United States	14222
15	Research Site	Cincinnati	Ohio	United States	45229
16	Research Site	Cleveland	Ohio	United States	44106
17	Research Site	Portland	Oregon	United States	97239
18	Research Site	Greenville	South Carolina	United States	29615
19	Research Site	Dallas	Texas	United States	75235
20	Research Site	Houston	Texas	United States	77030
21	Research Site	Pasadena	Texas	United States	77504
22	Research Site	Seattle	Washington	United States	98105