Back to resultsSafety and Pharmacokinetics of MMX Mesalamine in Children and Adolescents With Ulcerative Colitis
Primary Purpose
Ulcerative Colitis
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
MMX Mesalamine
MMX Mesalamine
MMX Mesalamine
Sponsored by
About this trial
This is an interventional other trial for Ulcerative Colitis
Eligibility Criteria
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.
Sites / Locations
- Arkansas Children's Hospital
- Advanced Clinical Research Institute
- University of California, San Francisco
- Connecticut Children's Medical Center
- University of Maryland Medical Center for Children
- Mayo Clinic
- Royal Children's Hospital Melbourne
- Klinika Pediatrii Gastroenterologii i Zywienia, Uniwersytecki Szpital Dzieciecy w Krakowie
- Klinika Gastroenterolofii Pediatrii, Instytut Centrum Zdrowia Matki Polki
- Klinika Pediatrii Dzieciecy Szpital Kliniczny im prof Antoniego Gebali
- Kliniczny Oddzial Pediatrii z Pododdzialem Neurologii Dzieciecej Szpital Wojewodzki
- Oddzial Gastroenterologii i Hepatologii, Instytut Pomnik-Centrum Zdrowia Dziecka
- Univerzitna nemocnica Martin
- DFNsP Banska Bystrica
- Gastroenterologicka ambulancia
- Alder Hey Children's NHS Foundation Trust
- Barts Health NHS Trust/Royal London Hospital
- Somers Clinical Research Facility/Great Ormond Street Hospital
- Southampton General Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
MMX Mesalamine (30mg/kg)
MMX Mesalamine (60 mg/kg)
MMX Mesalamine (100 mg/kg)
Arm Description
Outcomes
Primary Outcome Measures
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.
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.
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.
Total Body Clearance (CL) of MMX Mesalamine (5-ASA) at Steady State
Clearance of a substance from the blood by the kidneys.
AUC of MMX Mesalamine Major Metabolite (Ac-5-ASA) at Steady State
Cmax of MMX Mesalamine Major Metabolite (Ac-5-ASA) at Steady State
Tmax of MMX Mesalamine Major Metabolite (Ac-5-ASA) at Steady State
CL of MMX Mesalamine Major Metabolite (Ac-5-ASA) at Steady State
Secondary Outcome Measures
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.
Cumulative Amount of MMX Mesalamine (5-ASA) Recovered in Urine at Steady State
Cumulative Amount of MMX Mesalamine Major Metabolite (Ac-5-ASA) Recovered in Urine at Steady State
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01130844
Brief Title
Safety and Pharmacokinetics of MMX Mesalamine in Children and Adolescents With Ulcerative Colitis
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
Study Type
Interventional
2. Study Status
Record Verification Date
June 2021
Overall Recruitment Status
Completed
Study Start Date
October 8, 2010 (Actual)
Primary Completion Date
June 27, 2013 (Actual)
Study Completion Date
June 27, 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shire
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ulcerative Colitis
7. Study Design
Primary Purpose
Other
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
52 (Actual)
8. Arms, Groups, and Interventions
Arm Title
MMX Mesalamine (30mg/kg)
Arm Type
Experimental
Arm Title
MMX Mesalamine (60 mg/kg)
Arm Type
Experimental
Arm Title
MMX Mesalamine (100 mg/kg)
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
MMX Mesalamine
Other Intervention Name(s)
Lialda, SPD476
Intervention Description
30 mg/kg/day of MMX Mesalamine tablets, dosed once daily for 7 days.
Intervention Type
Drug
Intervention Name(s)
MMX Mesalamine
Other Intervention Name(s)
Lialda, SPD476
Intervention Description
60 mg/kg/day of MMX Mesalamine tablets, dosed once daily for 7 days.
Intervention Type
Drug
Intervention Name(s)
MMX Mesalamine
Other Intervention Name(s)
Lialda, SPD476
Intervention Description
100 mg/kg/day of MMX Mesalamine tablets, dosed once daily for 7 days.
Primary Outcome Measure Information:
Title
Area Under the Plasma Concentration Versus Time Curve (AUC) of MMX Mesalamine (5-ASA) at Steady State
Description
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.
Time Frame
2, 4, 6, 9, 12, 16, and 24 hours post-dose on day 7
Title
Maximum Plasma Concentration (Cmax) of MMX Mesalamine (5-ASA) at Steady State
Description
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.
Time Frame
Over a 24-hour period starting on day 7
Title
Time to Maximum Plasma Concentration (Tmax) of MMX Mesalamine (5-ASA) at Steady State
Description
Tmax is the time after administration of a drug when the maximum plasma concentration in the body is reached.
Time Frame
Over a 24-hour period starting on day 7
Title
Total Body Clearance (CL) of MMX Mesalamine (5-ASA) at Steady State
Description
Clearance of a substance from the blood by the kidneys.
Time Frame
Over a 24-hour period starting on day 7
Title
AUC of MMX Mesalamine Major Metabolite (Ac-5-ASA) at Steady State
Time Frame
2, 4, 6, 9, 12, 16, and 24 hours post-dose on day 7
Title
Cmax of MMX Mesalamine Major Metabolite (Ac-5-ASA) at Steady State
Time Frame
Over a 24-hour period starting on day 7
Title
Tmax of MMX Mesalamine Major Metabolite (Ac-5-ASA) at Steady State
Time Frame
Over a 24-hour period starting on day 7
Title
CL of MMX Mesalamine Major Metabolite (Ac-5-ASA) at Steady State
Time Frame
Over a 24-hour period starting on day 7
Secondary Outcome Measure Information:
Title
Percentage of Dose Absorbed For MMX Mesalamine (5-ASA) in Urine at Steady State
Description
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.
Time Frame
Over a 24-hour period starting on day 7
Title
Cumulative Amount of MMX Mesalamine (5-ASA) Recovered in Urine at Steady State
Time Frame
Over a 24-hour period starting on day 7
Title
Cumulative Amount of MMX Mesalamine Major Metabolite (Ac-5-ASA) Recovered in Urine at Steady State
Time Frame
Over a 24-hour period starting on day 7
10. Eligibility
Sex
All
Minimum Age & Unit of Time
5 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
Takeda
Official's Role
Study Director
Facility Information:
Facility Name
Arkansas Children's Hospital
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72202
Country
United States
Facility Name
Advanced Clinical Research Institute
City
Anaheim
State/Province
California
ZIP/Postal Code
92801
Country
United States
Facility Name
University of California, San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
Connecticut Children's Medical Center
City
Hartford
State/Province
Connecticut
ZIP/Postal Code
06106
Country
United States
Facility Name
University of Maryland Medical Center for Children
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Royal Children's Hospital Melbourne
City
Parkville
State/Province
Victoria
ZIP/Postal Code
3052
Country
Australia
Facility Name
Klinika Pediatrii Gastroenterologii i Zywienia, Uniwersytecki Szpital Dzieciecy w Krakowie
City
Wieliczka
State/Province
Krakow
ZIP/Postal Code
30-663
Country
Poland
Facility Name
Klinika Gastroenterolofii Pediatrii, Instytut Centrum Zdrowia Matki Polki
City
Lodz
ZIP/Postal Code
281/289
Country
Poland
Facility Name
Klinika Pediatrii Dzieciecy Szpital Kliniczny im prof Antoniego Gebali
City
Lublin
ZIP/Postal Code
20-093
Country
Poland
Facility Name
Kliniczny Oddzial Pediatrii z Pododdzialem Neurologii Dzieciecej Szpital Wojewodzki
City
Rzeszow
ZIP/Postal Code
35-301
Country
Poland
Facility Name
Oddzial Gastroenterologii i Hepatologii, Instytut Pomnik-Centrum Zdrowia Dziecka
City
Warszawa
ZIP/Postal Code
04-730
Country
Poland
Facility Name
Univerzitna nemocnica Martin
City
Martin
State/Province
Kollarova 2
ZIP/Postal Code
036 01
Country
Slovakia
Facility Name
DFNsP Banska Bystrica
City
Banska Bystrica
ZIP/Postal Code
974 09
Country
Slovakia
Facility Name
Gastroenterologicka ambulancia
City
Bratislava
ZIP/Postal Code
824 02
Country
Slovakia
Facility Name
Alder Hey Children's NHS Foundation Trust
City
Liverpool
ZIP/Postal Code
L12 2AP
Country
United Kingdom
Facility Name
Barts Health NHS Trust/Royal London Hospital
City
London
ZIP/Postal Code
E1 1BB
Country
United Kingdom
Facility Name
Somers Clinical Research Facility/Great Ormond Street Hospital
City
London
ZIP/Postal Code
WC1N 3JH
Country
United Kingdom
Facility Name
Southampton General Hospital
City
Southampton
ZIP/Postal Code
SO16 6YD
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
26893546
Citation
Cuffari C, Pierce D, Korczowski B, Fyderek K, Van Heusen H, Hossack S, Wan H, Edwards AY, Martin P. Randomized clinical trial: pharmacokinetics and safety of multimatrix mesalamine for treatment of pediatric ulcerative colitis. Drug Des Devel Ther. 2016 Feb 4;10:593-607. doi: 10.2147/DDDT.S95316. eCollection 2016.
Results Reference
derived
Learn more about this trial
Safety and Pharmacokinetics of MMX Mesalamine in Children and Adolescents With Ulcerative Colitis
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