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

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

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

Study Overview

• Status: Completed
• Conditions: Ulcerative Colitis
• Intervention / Treatment: Drug: MMX Mesalamine; Drug: MMX Mesalamine; Drug: MMX Mesalamine

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Parkville, Victoria, Australia, 3052
      • Royal Children's Hospital Melbourne
• Poland
  • Lodz, Poland, 281/289
    • Klinika Gastroenterolofii Pediatrii, Instytut Centrum Zdrowia Matki Polki
  • Lublin, Poland, 20-093
    • Klinika Pediatrii Dzieciecy Szpital Kliniczny im prof Antoniego Gebali
  • Rzeszow, Poland, 35-301
    • Kliniczny Oddzial Pediatrii z Pododdzialem Neurologii Dzieciecej Szpital Wojewodzki
  • Warszawa, Poland, 04-730
    • Oddzial Gastroenterologii i Hepatologii, Instytut Pomnik-Centrum Zdrowia Dziecka
  • Krakow
    • Wieliczka, Krakow, Poland, 30-663
      • Klinika Pediatrii Gastroenterologii i Zywienia, Uniwersytecki Szpital Dzieciecy w Krakowie
• Slovakia
  • Banska Bystrica, Slovakia, 974 09
    • DFNsP Banska Bystrica
  • Bratislava, Slovakia, 824 02
    • Gastroenterologická ambulancia
  • Kollarova 2
    • Martin, Kollarova 2, Slovakia, 036 01
      • Univerzitna nemocnica Martin
• United Kingdom
  • Liverpool, United Kingdom, L12 2AP
    • Alder Hey Children's NHS Foundation Trust
  • London, United Kingdom, E1 1BB
    • Barts Health NHS Trust/Royal London Hospital
  • London, United Kingdom, WC1N 3JH
    • Somers Clinical Research Facility/Great Ormond Street Hospital
  • Southampton, United Kingdom, SO16 6YD
    • Southampton General Hospital
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Arkansas Children's Hospital
  • California
    • Anaheim, California, United States, 92801
      • Advanced Clinical Research Institute
    • San Francisco, California, United States, 94143
      • University of California, San Francisco
  • Connecticut
    • Hartford, Connecticut, United States, 06106
      • Connecticut Children's Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Medical Center for Children
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 17 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: MMX Mesalamine (30mg/kg)	Drug: MMX Mesalamine; 30 mg/kg/day of MMX Mesalamine tablets, dosed once daily for 7 days.; Other Names: Lialda, SPD476; Drug: MMX Mesalamine; 60 mg/kg/day of MMX Mesalamine tablets, dosed once daily for 7 days.; Other Names: Lialda, SPD476; Drug: MMX Mesalamine; 100 mg/kg/day of MMX Mesalamine tablets, dosed once daily for 7 days.; Other Names: Lialda, SPD476
EXPERIMENTAL: MMX Mesalamine (60 mg/kg)	Drug: MMX Mesalamine; 30 mg/kg/day of MMX Mesalamine tablets, dosed once daily for 7 days.; Other Names: Lialda, SPD476; Drug: MMX Mesalamine; 60 mg/kg/day of MMX Mesalamine tablets, dosed once daily for 7 days.; Other Names: Lialda, SPD476; Drug: MMX Mesalamine; 100 mg/kg/day of MMX Mesalamine tablets, dosed once daily for 7 days.; Other Names: Lialda, SPD476
EXPERIMENTAL: MMX Mesalamine (100 mg/kg)	Drug: MMX Mesalamine; 30 mg/kg/day of MMX Mesalamine tablets, dosed once daily for 7 days.; Other Names: Lialda, SPD476; Drug: MMX Mesalamine; 60 mg/kg/day of MMX Mesalamine tablets, dosed once daily for 7 days.; Other Names: Lialda, SPD476; Drug: MMX Mesalamine; 100 mg/kg/day of MMX Mesalamine tablets, dosed once daily for 7 days.; Other Names: Lialda, SPD476

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Shire

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 8, 2010
• Primary Completion (ACTUAL): June 27, 2013
• Study Completion (ACTUAL): June 27, 2013

Study Registration Dates

• First Submitted: May 20, 2010
• First Submitted That Met QC Criteria: May 25, 2010
• First Posted (ESTIMATE): May 26, 2010

Study Record Updates

• Last Update Posted (ACTUAL): June 14, 2021
• Last Update Submitted That Met QC Criteria: June 8, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Mesalamine
• Other Study ID Numbers: SPD476-112; 2011-000164-10 (EUDRACT_NUMBER)