Development of a Morphine Pharmacokinetic and Pharmacodynamic Model for the Neonatal Population

NCT03035578 | Withdrawn Phase 1

• 1 other identifier: 1000053067
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This research aims to study what the baby's body does with morphine and how morphine works in the baby's body. One hundred newborn babies will be enrolled in this study. With a better understanding of the drug doctors and nurses will have more information and better administer the drug in case of pain, stress or discomfort.

Conditions

Pain; Drug Effect

Keywords

Pharmacokinetics; Pharmacodynamics; Morphine; Neonatal

Outcome Measures

Primary Outcomes (1)

• Target Morphine Plasma Concentration

  Sparse sampling coupled with population (mixed effects) method will be used to design the morphine pharmacokinetics phase. This method captures pharmacokinetics data from many subjects (learning about population), which are based on a relatively few number of samples per patient (learning about individual characteristics considering the large number of samples).Population pharmacokinetic parameters will be estimated using a non-linear mixed effects modelling with NONMEM software.

  12 months (blood sampling and modeling)

Secondary Outcomes (1)

• Brain Morphine Concentrations

  12 months (a-eeg collection and modeling)

Study Arms (1)

Morphine Blood and Saliva sampling

EXPERIMENTAL

The infants will receive a 50 mcg/kg loading dose of morphine followed by a constant infusion.Morphine Injection: 10mg/mL, 1mL ampoules.Two strengths of stock syringes: a)patients \<1.5kg, morphine 0.5mg/25mL; b)patients 1.5kg to \<5kg, morphine 1mg/25mL. Time blood samples will be collected for measurement of whole blood concentration of morphine in 24h. Total morphine, morphine-3-glucuronide and morphine-6-glucuronide concentrations; volume of blood required is 0.25 ml. Sparse sampling strategy will be used for those neonates \< 1250; total volume of blood required is 0.50 ml. Frequent sampling strategy will be used for those neonates ≥ 1250 gm; total volume of blood required is 0.50 ml.Saliva samples will be collected at 10 and 30 minutes and at 6, 12 and 24h after morphine infusion started.100 uL of saliva, captured using a collection swab.

Drug: Morphine

Interventions

Morphine DRUG

Sampling blood for development of Morphine Pharmacokinetic/Pharmacodynamic Model for Neonatal Population

Morphine Blood and Saliva sampling

Eligibility Criteria

• Age: 24 Weeks - 42 Weeks
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Gestational age \> 24 completed weeks.
• Clinically prescribed to commence a continuous morphine infusion.

You may not qualify if:

• Gestational age \< 24 completed weeks.
• Critically ill infant unlikely to survive for more than 72 hours.
• Prolonged fetal exposure to morphine, any other narcotic, or methadone, as a consequence of maternal use of the drug.
• Any postnatal exposure to morphine during the 72 hours prior to the commencement of the second morphine infusion.
• Neonates with impaired cardiac, hepatic or renal functioning as defined by clinical signs of impaired perfusion, abnormal liver function tests, or an elevated serum creatinine.
• Neonates with seizures.
• The attending neonatologist considers that participation in the study is contraindicated.

Sponsors & Collaborators

• The Hospital for Sick Children: lead

MeSH Terms

Conditions

Pain

Interventions

Morphine

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Interim Head, Division of Neonatology

Study Record Dates

• First Submitted: January 24, 2017
• First Posted: January 30, 2017
• Study Start: December 1, 2017
• Primary Completion: June 1, 2018
• Study Completion: June 1, 2019
• Last Updated: February 25, 2020

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will not share