Pharmacokinetics of Intravenous Metamizole in Children Less Than 6 Years Old

Pain Clinical Trial

— PPMS  

Official title:

Single Center, Open-label, Prospective Study to Characterize the Pharmacokinetics of Metamizole and Its Metabolites Following Intravenous Administration in Children Less Than 6 Years Old

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02660177
• Other study ID #: 2015-00020
• Status: Completed
• Phase: Phase 2
• Start date: April 2016
• Est. completion date: December 2017

Study information

• Verified date: May 2018
• Source: University Children's Hospital Basel
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study aims to assess the PK parameters of metamizole following a single IV administration of metamizole in children less than 6 years of age.

Description:

This is an open-label pharmacokinetics (PK) study. It aims to assess the PK parameters of metamizole and its metabolites following a single IV administration of metamizole (10mg/kg) in children less than 6 years of age.

Thirty-nine children, 3-72 months of age, undergoing elective surgery at the University of Basel Children's Hospital, will receive, on the day of surgical procedure, a single dose of metamizole 10 mg/kg. After this dose, blood and saliva samples will be obtained at predetermined post-dose time points to measure concentrations of metamizole and its metabolites. The maximal duration of subject participation will be 24 hours. Plasma PK parameters (AUC, Cmax, Tmax, t1/2) of each analyte will be derived using noncompartmental methods. A population PK approach will be applied to characterize inter-subject variability and quantify the potential influence of age, sex and body weight on the PK parameters.

There are no published pharmacokinetic studies of metamizole in pediatrics. Furthermore, although Swissmedic provides no dose information for IV administration in infants with a body weight of less than 9 kg, IV is the most frequently used route of administration for direct postoperative analgesia in pediatrics, including infants with body weights of less than 9 kg. Due to the absence of data and the lack of any dosing recommendation for infants with a body weight less than 9 kg, the IV administration of metamizole in infants is "off-label" and inconsistent across hospitals and prescribing paediatricians.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: December 2017
• Est. primary completion date: December 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 3 Months to 72 Months

Eligibility

Inclusion Criteria:

• Infants and children 3-72 months of age at time of inclusion

• Body weight more than 5 kg at time of inclusion

• Children undergoing elective surgery at University of Basel Children's Hospital (UKBB) with planned administration of intravenous analgesia

• Patients who require surgical procedures that necessitate at least 24 hours in the hospital

• Parent/Legal guardian has been informed about the study and has signed Informed Consent Form

Exclusion Criteria:

• Infants and children who were born prematurely (before 37 weeks gestation), regardless of corrected gestational age

• Known kidney or liver disease

• Known neutropenia, anemia or other hematological disorders

• Known diagnosis of asthma

• Ongoing immunosuppression, except corticosteroid treatment, or primary immunodeficiency

• Treatment with strong inhibitors or inducers of CYP2C19 within 3 months prior to study

• Treatment with drugs known to induce agranulocytosis within 3 months prior to study

• Documented previous adverse reaction to metamizole

• Treatment with metamizole within 30 days prior to screening

• Any concomitant condition, which in the opinion of the investigator would preclude a subject's participation in the study

• Family members of investigators

Related Conditions & MeSH terms

• Children
• Pain
• Surgery

Intervention

Drug:
• Metamizole
metamizole IV administration

Locations

Country	Name	City	State
Switzerland	UKBB	Basel

Sponsors (1)

Lead Sponsor	Collaborator
University Children's Hospital Basel

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area under the plasma concentration-time curves (AUC0-inf, AUC0-24, AUC0-last) for metamizole and its metabolites in plasma and saliva	Time points of evaluation of these PK parameters: sampling at 1, 2, 4, 6, 10 and 24 hours after single IV metamizole dose.	0- 24 hours
Secondary	Maximum plasma concentration (Cmax) for metamizole and its metabolites in plasma and saliva	Time points of evaluation of these PK parameters: sampling at 1, 2, 4, 6, 10	0- 24 hours
Secondary	Time to reach Cmax (tmax) for metamizole and its metabolites in plasma and saliva	Time points of evaluation of these PK parameters: sampling at 1, 2, 4, 6, 10	0- 24 hours
Secondary	Terminal elimination rate constant with respective half-life time (t½) for metamizole and its metabolites in plasma and saliva	Time points of evaluation of these PK parameters: sampling at 1, 2, 4, 6, 10	0- 24 hours
Secondary	Incidence of adverse events (AEs)		0- 24 hours
Secondary	Correlation between metamizole and its metabolites in saliva and plasma		0- 24 hours