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

NCT01130844 | Completed Phase 1 Results

• 2 other identifiers: SPD476-1122011-000164-10
• Study Type: interventional
• Target: 52
• Locations: 5 countries
• Sites: 19

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.

Conditions

Ulcerative Colitis

Outcome Measures

Primary Outcomes (8)

• 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 Outcomes (3)

• Percentage of Dose Absorbed For MMX Mesalamine (5-ASA) in Urine at Steady State

  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

Study Arms (3)

MMX Mesalamine (30mg/kg)

EXPERIMENTAL

Drug: MMX Mesalamine

MMX Mesalamine (60 mg/kg)

EXPERIMENTAL

Drug: MMX Mesalamine

MMX Mesalamine (100 mg/kg)

EXPERIMENTAL

Drug: MMX Mesalamine

Interventions

MMX Mesalamine DRUG

30 mg/kg/day of MMX Mesalamine tablets, dosed once daily for 7 days.

Also known as: Lialda, SPD476

MMX Mesalamine (30mg/kg)

Eligibility Criteria

• Age: 5 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Shire: lead

Study Sites (19)

Arkansas Children's Hospital

Little Rock, Arkansas, 72202, United States

Location

Advanced Clinical Research Institute

Anaheim, California, 92801, United States

Location

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Connecticut Children's Medical Center

Hartford, Connecticut, 06106, United States

Location

University of Maryland Medical Center for Children

Baltimore, Maryland, 21201, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Royal Children's Hospital Melbourne

Parkville, Victoria, 3052, Australia

Location

Klinika Pediatrii Gastroenterologii i Zywienia, Uniwersytecki Szpital Dzieciecy w Krakowie

Wieliczka, Krakow, 30-663, Poland

Location

Klinika Gastroenterolofii Pediatrii, Instytut Centrum Zdrowia Matki Polki

Lodz, 281/289, Poland

Location

Klinika Pediatrii Dzieciecy Szpital Kliniczny im prof Antoniego Gebali

Lublin, 20-093, Poland

Location

Kliniczny Oddzial Pediatrii z Pododdzialem Neurologii Dzieciecej Szpital Wojewodzki

Rzeszów, 35-301, Poland

Location

Oddzial Gastroenterologii i Hepatologii, Instytut Pomnik-Centrum Zdrowia Dziecka

Warsaw, 04-730, Poland

Location

Univerzitna nemocnica Martin

Martin, Kollarova 2, 036 01, Slovakia

Location

DFNsP Banska Bystrica

Banská Bystrica, 974 09, Slovakia

Location

Gastroenterologicka ambulancia

Bratislava, 824 02, Slovakia

Location

Alder Hey Children's NHS Foundation Trust

Liverpool, L12 2AP, United Kingdom

Location

Barts Health NHS Trust/Royal London Hospital

London, E1 1BB, United Kingdom

Location

Somers Clinical Research Facility/Great Ormond Street Hospital

London, WC1N 3JH, United Kingdom

Location

Southampton General Hospital

Southampton, SO16 6YD, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 26893546 DERIVED

MeSH Terms

Conditions

Colitis, Ulcerative

Interventions

Mesalamine

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Inflammatory Bowel Diseases; Colonic Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

meta-Aminobenzoates; Aminobenzoates; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Aminosalicylic Acids; Salicylates; Hydroxybenzoates; Hydroxy Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phenols

Results Point of Contact

• Title: Study Director
• Organization: Shire

ClinicalTransparency@shire.com

+1 866 842 5335

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 20, 2010
• First Posted: May 26, 2010
• Study Start: October 8, 2010
• Primary Completion: June 27, 2013
• Study Completion: June 27, 2013
• Last Updated: June 14, 2021
• Results First Posted: July 9, 2015

Record last verified: 2021-06

Locations

US (6); AU (1); SL (3); PL (5); GB (4)