Population Pharmacokinetics and Safety of Oral Posaconazole in Children With Leukemia

This study is designed to evaluate the safety, efficacy and Population Pharmacokinetics of Oral Posaconazole in Children with leukemia.

Study Overview

• Status: Completed
• Conditions: Leukemia, Acute
• Intervention / Treatment: Drug: posaconazole oral suspensions

Detailed Description

Posaconazole as a new triazole antifungal agent with broad spectrum coverage, was recommended for prophylaxis of invasive fungal disease in adults. Some studies have demonstrated the relationship between posaconazole plasma concentration and efficacy and few data have been published in children with leukemia.The purpose of this study is to describe the off-label use of posaconazole oral suspensions in children;to figure out the relationship between concentration and clinical outcomes/ adverse events;to identify factors that influence plasma concentration.

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guanzhou, Guangdong, China
      • Zhujiang Hospital of Southern Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 14 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 1、Patients age 2-14 years with acute leukemia (AML, ALL) undergoing chemotherapy and neutropenia expected to last at least 7 days.

  2、Karnofsky/Lansky score of 60% or greater. 3、defined as alanine transaminase (ALT) <3 x upper limit of normal (ULN),aspartate aminotransferase (AST) <3 x ULN; serum bilirubin and alkaline phosphatase <2 x ULN.

  4、No other treatment and combination of triazoles antifungals and drugs like vincristine, sirolimus, cyclosporine etc.

  5、Able to take oral medication or take medication via enteral feeding tube. 6、Ability to give informed consent. 7、No history of anaphylaxis attributed to the azole class of antifungal agents.

Exclusion Criteria:

• 1、Existing severe illness (e.g. significant cardiac, pulmonary, hepatic diseases, etc.) or major organ dysfunction.

  2、Subject is not considered eligible for this clinical research program with posaconazole.

  3、Use of medications that are known to interact with posaconazole and that may lead to life-threatening side to effects.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: posaconazole as antifungal prophylaxis	Drug: posaconazole oral suspensions; posaconazole oral suspensions（5mg/kg/d,tid) will be administered specially febrile neutropenia patients four times a day and blood samples will be taken any hours after the first dose at least Day 7.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number, type and grade of adverse events of posaconazole assessed by CTCAE v4.0	Number, type and grade of adverse events of posaconazole oral suspensions to children with leukemia assessed by CTCAE v4.0.	1 year
Plasma posaconazole concentration monitoring and its pharmacokinetic	Blood samples for determination of plasma posaconazole concentration will be collected predoses (just prior to a daily dose) on days 3, 7, 14 and 21. Anther concentration (include peak concentraton) will also be collected at least 7days after the first dose.	1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
Serious Adverse events and drug-related adverse events monitoring	2 years

Collaborators and Investigators

• Sponsor: Zhujiang Hospital
• Collaborators: Guangdong Provincial People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2018
• Primary Completion (Actual): July 1, 2021
• Study Completion (Actual): July 30, 2021

Study Registration Dates

• First Submitted: October 19, 2019
• First Submitted That Met QC Criteria: December 8, 2019
• First Posted (Actual): December 11, 2019

Study Record Updates

• Last Update Posted (Actual): August 3, 2021
• Last Update Submitted That Met QC Criteria: August 2, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; 14-alpha Demethylase Inhibitors; Trypanocidal Agents; Posaconazole
• Other Study ID Numbers: 2018-EKZX-003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No