Use of Rectal Dialysis Technique to Measure Rectal 5-ASA Levels in Healthy Volunteers Receiving Asacol

Study Overview
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Brief Summary
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The investigators plan to develop a novel method of estimating 5-ASA levels in the rectum at a mucosal level using in vivo rectal dialysis technique towards the eventual goal of determining the optimal dosing of Asacol® that would provide therapeutic levels of 5-ASA in the left colon.

Detailed Description
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Asacol® is mesalazine in a pH-dependent tablet (Eudragit S) that remains intact until reaching the terminal ileum. The tablet dissolves at a pH 7 or greater, allowing mesalazine release in the terminal ileum and throughout the colon; hence, it would be anticipated that this form of 5-ASA will produce higher concentrations in the left colon in patients with active ulcerative colitis compared to other immediate release forms of 5-ASA. However, preliminary research using dynamic computer modeling and simulation predicted that patients with active ulcerative colitis (characterized by an increased stool frequency) treated with Asacol® and Lialda (another delayed release formulation) will achieve very low 5-ASA levels in the sigmoid colon and rectum. The model predicts that these 5-ASA preparations will be relatively ineffective in treating the left side of the colon in active ulcerative colitis.

Official Title
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Measurement of Rectal Levels of 5-aminosalicylic Acid (5-ASA) Using a Novel In-vivo Rectal Dialysis Technique in Healthy Volunteers on Asacol

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Procedure: Rectal dialysis
* Drug: Rectal dialysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eligible subjects would be healthy males and females 18-45 years of age (inclusive) Within 20% of normal body weight at screening Who are able to give written informed consent. Exclusion Criteria: History of any chronic illness Evidence of significant organic or psychiatric disease on a brief health questionnaire A history or presence of any condition causing malabsorption or an effect on gastrointestinal motility A history of any gastrointestinal surgery A history of acute or chronic renal insufficiency Pre existing liver disease A history of severe allergic reaction to salicylates, aminosalicylates or any of the ingredients of Asacol® tablets or a history of multiple food/drug allergies or if they are pregnant or lactating. Subjects will be required to refrain from any prescription or nonprescription drug or herbal products except their birth control medications for gastrointestinal disorders for 7 days prior to dosing and during the study, till its completion at the end of the fifth visit.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1200 mg Asacol once daily for 1 week<br>Rectal dialysis will be done after 1 week on 1200 mg asacol | Procedure: Rectal dialysis<br>* Rectal dialysis done after 1 week on either 1200/2400 mg Asacol dose to test rectal mucosal 5-ASA levels<br>Drug: Rectal dialysis<br>* Rectal dialysis done after 1 week on either 1200/2400 mg Asacol dose to test rectal mucosal 5-ASA levels<br>|
| Active Comparator: 2400 mg Asacol once daily for 1 week<br>Rectal dialysis will be done after 1 week on 2400 mg asacol | Procedure: Rectal dialysis<br>* Rectal dialysis done after 1 week on either 1200/2400 mg Asacol dose to test rectal mucosal 5-ASA levels<br>Drug: Rectal dialysis<br>* Rectal dialysis done after 1 week on either 1200/2400 mg Asacol dose to test rectal mucosal 5-ASA levels<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Detection of 5-ASA | 5-ASA to be measured using rectal dialysis technique in-vivo | 2 weeks after starting Asacol | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Detected 5-ASA With Change in Ingested Asacol Dose | Comparison of 2-week and 5-week 5-ASA as measured thorugh rectal dialysis | 5 weeks after starting study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pharmacokinetics, Aminosalicylates, Mucosal levels, Rectal dialysis