Safety and Pharmacokinetics of MMX Mesalamine in Children and Adolescents With Ulcerative Colitis

Study Overview
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Brief Summary
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The purpose of this study is to determine the safety and pharmacokinetics of MMX mesalamine following administration in children and adolescents with ulcerative colitis.

Official Title
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A Phase 1, Multicenter, Open-label Study to Determine the Safety and Pharmacokinetics of MMX Mesalamine Following Administration in Children and Adolescents With Ulcerative Colitis

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Drug: MMX Mesalamine
* Drug: MMX Mesalamine
* Drug: MMX Mesalamine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects aged 5-17 years, with appropriately obtained informed consent and assent. Subject has a documented history of ulcerative colitis for at least 3 months. Subjects who are currently on 5-ASA or product(s) containing or metabolized to mesalamine must have been on a stable regimen for at least 4 weeks prior to first dose of investigational medicinal product. Subjects who are not currently on a drug regimen, or on a 5-ASA or product containing or metabolized to mesalamine, must have been on a stable regimen for at least 4 weeks prior to first dose at least 4 weeks prior first dose of investigational medicinal product. Body weight of 18kg-82kg inclusive. Exclusion Criteria: Current or recurrent disease (eg cardiovascular, renal, liver, malignancy or other conditions) that could affect the colon, the action, absorption or disposition of the IMP, or clinical or laboratory assessments with the exception of their existing ulcerative colitis. Ulcerative Colitis known to be confined to the rectum (isolated rectal proctitis). Any history of hepatic impairment or moderate to severe renal impairment. The use of systemic or rectal steroids within the last 4 weeks, immunomodulators within the last 6 weeks, biologics within 6 months, antibiotic use within the last 7 days prior to the first dose of investigational medicinal product.

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MMX Mesalamine (30mg/kg)<br> | Drug: MMX Mesalamine<br>* 30 mg/kg/day of MMX Mesalamine tablets, dosed once daily for 7 days.<br>* Other names: Lialda, SPD476;|
| Experimental: MMX Mesalamine (60 mg/kg)<br> | Drug: MMX Mesalamine<br>* 60 mg/kg/day of MMX Mesalamine tablets, dosed once daily for 7 days.<br>* Other names: Lialda, SPD476;|
| Experimental: MMX Mesalamine (100 mg/kg)<br> | Drug: MMX Mesalamine<br>* 100 mg/kg/day of MMX Mesalamine tablets, dosed once daily for 7 days.<br>* Other names: Lialda, SPD476;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Plasma Concentration Versus Time Curve (AUC) of MMX Mesalamine (5-ASA) at Steady State | AUC can be used as a measure of drug exposure. It is derived from drug concentration and time so it gives a measure how much and how long a drug stays in a body. | 2, 4, 6, 9, 12, 16, and 24 hours post-dose on day 7 | 
| Maximum Plasma Concentration (Cmax) of MMX Mesalamine (5-ASA) at Steady State | Cmax is a term that refers to the maximum (or peak) concentration that a drug achieves in the body after the drug has been administrated. | Over a 24-hour period starting on day 7 | 
| Time to Maximum Plasma Concentration (Tmax) of MMX Mesalamine (5-ASA) at Steady State | Tmax is the time after administration of a drug when the maximum plasma concentration in the body is reached. | Over a 24-hour period starting on day 7 | 
| Total Body Clearance (CL) of MMX Mesalamine (5-ASA) at Steady State | Clearance of a substance from the blood by the kidneys. | Over a 24-hour period starting on day 7 | 
| AUC of MMX Mesalamine Major Metabolite (Ac-5-ASA) at Steady State |  | 2, 4, 6, 9, 12, 16, and 24 hours post-dose on day 7 | 
| Cmax of MMX Mesalamine Major Metabolite (Ac-5-ASA) at Steady State |  | Over a 24-hour period starting on day 7 | 
| Tmax of MMX Mesalamine Major Metabolite (Ac-5-ASA) at Steady State |  | Over a 24-hour period starting on day 7 | 
| CL of MMX Mesalamine Major Metabolite (Ac-5-ASA) at Steady State |  | Over a 24-hour period starting on day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Dose Absorbed For MMX Mesalamine (5-ASA) in Urine at Steady State | The percentage of the dose absorbed was calculated as: 100 x (Xu0-24h 5-ASA + [0.7847* Xu0-24h Ac-5-ASA])/dose, where 0.7847 is the ratio of the molecular weight of 5-ASA (153.14) to the molecular weight of Ac-5-ASA (195.15). Xu0-24h is equal to the cumulative amount recovered in urine in the time interval of 0 to 24 hours. | Over a 24-hour period starting on day 7 | 
| Cumulative Amount of MMX Mesalamine (5-ASA) Recovered in Urine at Steady State |  | Over a 24-hour period starting on day 7 | 
| Cumulative Amount of MMX Mesalamine Major Metabolite (Ac-5-ASA) Recovered in Urine at Steady State |  | Over a 24-hour period starting on day 7 |