Ulcerative ColitisPhase 1NCT00254618
A Study of Asacol Absorption, Metabolism and Excretion in Children and Adolescents With Ulcerative Colitis.
A Phase 1 study testing mesalamine in people with Ulcerative Colitis, run by Warner Chilcott at 22 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 5 to 17 years
- Conditions the study is for
- Ulcerative Colitis
- What is being tested?
- mesalamine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 22 sitesUnited States
- Study dates
- Oct 2005to Jun 2008
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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 < or =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.
Trial locations and contacts
22 sites in 1 country.
22 sites in 1 country
United States22 sites
Research Site
Baltimore, Maryland, 21287
Research Site
Birmingham, Alabama, 35203
Research Site
Boston, Massachusetts, 21114
Research Site
Buffalo, New York, 14222
Research Site
Cincinnati, Ohio, 45229
Research Site
Cleveland, Ohio, 44106
Research Site
Costa Mesa, California, 92626
Research Site
Dallas, Texas, 75235
Research Site
Detroit, Michigan, 48236
Research Site
Gainesville, Florida, 32610
Research Site
Greenville, South Carolina, 29615
Research Site
Houston, Texas, 77030
Research Site
Jacksonville, Florida, 32207
Research Site
Mobile, Alabama, 63304
Research Site
Morristown, New Jersey, 07962
Research Site
Omaha, Nebraska, 68105
Research Site
Park Ridge, Illinois, 60068
Research Site
Pasadena, Texas, 77504
Research Site
Portland, Oregon, 97239
Research Site
San Diego, California, 92103
Research Site
San Francisco, California, 94143
Research Site
Seattle, Washington, 98105
About this study
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.
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.
Read the 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.
- Conditions
- Ulcerative Colitis
- Being tested
- mesalamine
- Keywords
- ulcerative colitis; pharmacokinetics; pediatrics
- Medical subject headings
- Colitis, Ulcerative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
mesalamineDrug
oral tablet, 30 mg mesalamine/day for 28 days
mesalamineDrug
oral tablet, 60 mg mesalamine/day for 28 days
mesalamineDrug
oral tablet, 90 mg mesalamine/day for 28 days
| Study group | Role | What they receive |
|---|---|---|
| 30 mg | Experimental | 30 mg/kg/day mesalamine Receives: Drug: mesalamine |
| 60 mg | Experimental | 60 mg/kg/day mesalamine Receives: Drug: mesalamine |
| 90 mg | Experimental | 90 mg/kg/day mesalamine Receives: Drug: mesalamine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pharmacokinetics
Measured: Days 1, 7, 14, 21, and 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Nov 2005 (estimated)
- Study startOct 2005
- Primary completionJun 2008
- Study completionJun 2008
Why it stopped: Slow enrollment.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ulcerative ColitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- Warner Chilcott
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- William Aronstein, MD, PhD, Study director, Procter and Gamble
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00254618
- Sponsor's protocol ID
- 2005018
- Status last verified
- Apr 2013
- First submitted
- 14 Nov 2005
- Last updated
- 17 Apr 2013
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Apr 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT00254618
- Acronym / sponsor ID
- 2005018
- Conditions
- Ulcerative Colitis
- Keywords
- ulcerative colitis; pharmacokinetics; pediatrics
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow enrollment.
- Enrolment
- 34 participants (actual)
- Lead sponsor
- Warner ChilcottIndustry (pharma, biotech, devices)
- Study start
- Oct 2005
- Primary completion
- Jun 2008 (actual)
- Study completion
- Jun 2008 (actual)
- First posted
- 16 Nov 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 30 mg | Experimental | Drug: mesalamine30 mg/kg/day mesalamine |
| 60 mg | Experimental | Drug: mesalamine60 mg/kg/day mesalamine |
| 90 mg | Experimental | Drug: mesalamine90 mg/kg/day mesalamine |
Who may qualify
- Ages
- 5 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (3 listed)
- 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 < or =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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| mesalamineoral tablet, 30 mg mesalamine/day for 28 days | Drug | 30 mg |
| mesalamineoral tablet, 60 mg mesalamine/day for 28 days | Drug | 60 mg |
| mesalamineoral tablet, 90 mg mesalamine/day for 28 days | Drug | 90 mg |
Primary outcome
Pharmacokinetics
Time frame: Days 1, 7, 14, 21, and 28
Results and safety
The study was stopped early (reason given: Slow enrollment.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Apr 2013.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
William Aronstein, MD, PhD study director
Procter and Gamble
22 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing mesalamine in people with Ulcerative Colitis, run by Warner Chilcott at 22 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 17 Apr 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 22 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Slow enrollment.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pharmacokinetics (time frame: Days 1, 7, 14, 21, and 28). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Apr 2013.