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

Ulcerative Colitis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01130844
• Other study ID #: SPD476-112
• Secondary ID: 2011-000164-10
• Status: Completed
• Phase: Phase 1
• Start date: October 8, 2010
• Est. completion date: June 27, 2013

Study information

• Verified date: June 2021
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 52
• Est. completion date: June 27, 2013
• Est. primary completion date: June 27, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 5 Years to 17 Years

Eligibility

Inclusion Criteria:

1. Subjects aged 5-17 years, with appropriately obtained informed consent and assent.

2. Subject has a documented history of ulcerative colitis for at least 3 months.

3. 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.

4. 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.

5. Body weight of 18kg-82kg inclusive.

Exclusion Criteria:

1. 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.

2. Ulcerative Colitis known to be confined to the rectum (isolated rectal proctitis).

3. Any history of hepatic impairment or moderate to severe renal impairment.

4. 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.

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer
• Ulcerative Colitis

Intervention

Drug:
• MMX Mesalamine
30 mg/kg/day of MMX Mesalamine tablets, dosed once daily for 7 days.
• MMX Mesalamine
60 mg/kg/day of MMX Mesalamine tablets, dosed once daily for 7 days.
• MMX Mesalamine
100 mg/kg/day of MMX Mesalamine tablets, dosed once daily for 7 days.

Locations

Country	Name	City	State
Australia	Royal Children's Hospital Melbourne	Parkville	Victoria
Poland	Klinika Gastroenterolofii Pediatrii, Instytut Centrum Zdrowia Matki Polki	Lodz
Poland	Klinika Pediatrii Dzieciecy Szpital Kliniczny im prof Antoniego Gebali	Lublin
Poland	Kliniczny Oddzial Pediatrii z Pododdzialem Neurologii Dzieciecej Szpital Wojewodzki	Rzeszow
Poland	Oddzial Gastroenterologii i Hepatologii, Instytut Pomnik-Centrum Zdrowia Dziecka	Warszawa
Poland	Klinika Pediatrii Gastroenterologii i Zywienia, Uniwersytecki Szpital Dzieciecy w Krakowie	Wieliczka	Krakow
Slovakia	DFNsP Banska Bystrica	Banska Bystrica
Slovakia	Gastroenterologicka ambulancia	Bratislava
Slovakia	Univerzitna nemocnica Martin	Martin	Kollarova 2
United Kingdom	Alder Hey Children's NHS Foundation Trust	Liverpool
United Kingdom	Barts Health NHS Trust/Royal London Hospital	London
United Kingdom	Somers Clinical Research Facility/Great Ormond Street Hospital	London
United Kingdom	Southampton General Hospital	Southampton
United States	Advanced Clinical Research Institute	Anaheim	California
United States	University of Maryland Medical Center for Children	Baltimore	Maryland
United States	Connecticut Children's Medical Center	Hartford	Connecticut
United States	Arkansas Children's Hospital	Little Rock	Arkansas
United States	Mayo Clinic	Rochester	Minnesota
United States	University of California, San Francisco	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Shire

Countries where clinical trial is conducted

United States,  Australia,  Poland,  Slovakia,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	Cmax of MMX Mesalamine Major Metabolite (Ac-5-ASA) at Steady State		Over a 24-hour period starting on day 7
Primary	Tmax of MMX Mesalamine Major Metabolite (Ac-5-ASA) at Steady State		Over a 24-hour period starting on day 7
Primary	CL of MMX Mesalamine Major Metabolite (Ac-5-ASA) at Steady State		Over a 24-hour period starting on day 7
Secondary	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
Secondary	Cumulative Amount of MMX Mesalamine (5-ASA) Recovered in Urine at Steady State		Over a 24-hour period starting on day 7
Secondary	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