Posaconazole Pharmacokinetics in Patients Receiving Chemotherapy or Stem Cell Transplants (POPULAR)

Pharmacokinetics Study of Posaconazole in Haematology Patients Receiving Standard of Care Treatment With Oral Posaconazole Prophylaxis for Invasive Fungal Infection

The purpose of the study is to investigate the pharmacokinetics of oral dosage of Posaconazole which is routinely administered as a standard care prophylaxis for patients undergoing cancer treatments.

Study Overview

• Status: Recruiting
• Conditions: Fungal Infection; Pharmacokinetics; Invasive Aspergillosis; Prophylaxis; Invasive Candidiases; Posaconazole; Invasive Mycosis
• Intervention / Treatment: Drug: Posaconazole pharmacokinetics

Detailed Description

Participants receiving Posaconazole prophylaxis for invasive fungal infection while undergoing cancer treatment will be required to sign an informed consent and donate blood samples for the study. Posaconazole is routinely administered as a prophylaxis using the oral tablet formulation (300mg once daily) as a standard care. Each prophylaxis course-duration will be defined according to local policy at each hospital. In general, Posaconazole prophylaxis commences prior to or with induction or consolidation chemotherapy in AML/MDS patients and continues until neutrophil recovery. In allo-HSCT setting, Posaconazole prophylaxis routinely commences on the day of transplant or with conditioning chemotherapy and continues for approximately 3 months after transplant, except in patients with initiation of intensive immunosuppression after diagnosis of acute or chronic GVHD, administration will go for at least 16 weeks or until prednisolone dose is less than 10mg per day, whichever is later. If patients are suspected or have proven malabsorption or are required to switch to an alternative antifungal agent such as in the case of suspected invasive fungal infection or Posaconazole toxicity, a switch to intravenous formulation of Posaconazole will take place.

Blood samples will be collected on Days 7, 14 and 21 from the onset of Posaconazole prophylactic treatment. If significant diarrhoea occurs, additional blood samples will be collected twice weekly until symptoms resolve, with the first sample being taken 3 days after the onset of diarrhoea. If gastrointestinal absorption is considered inadequate or invasive fungal infection is suspected and patients are switched either to IV antifungal prophylaxis or antifungal treatment as part of their standard care, a blood sample will be collected 20-24 hours after the last oral Posaconazole dose. Study participants will be followed up with respect to clinical data collection during the blood sample collection period and for up to 7 days after the last dose of Posaconazole for invasive fungal infection follow-up, and for the entire antifungal prescribing period (prophylaxis and/or treatment). Participants with diagnosed invasive fungal infection will be followed up to 30-days post-diagnosis with respect to clinical outcomes.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Monica Slavin, Prof; Phone Number: 61 3 9342 9403; Email: monica.slavin@mh.org.au
• Study Contact Backup: Name: Tseng Lau, PhD; Phone Number: 61 3 9342 8274; Email: tseng.lau@mh.org.au

Study Locations

• Australia
  • Victoria
    • Parkville, Victoria, Australia, 3050
      • Recruiting
      • Melbourne Health
      • Contact: Tseng Lau, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult (≥18 years old) haematology patients receiving Posaconazole prophylaxis in the inpatient setting as standard of care.
• Able to give informed consent.

Exclusion Criteria:

• Unable to give informed consent.

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 prophylaxis; Blood samples will be taken from participants undergoing cancer treatment and receiving Posaconazole prophylaxis. The samples will be used for Posaconazole pharmacokinetics study.	Drug: Posaconazole pharmacokinetics; Blood samples will be collected on Days 7, 14 and 21 from the onset of Posaconazole prophylactic treatment If significant diarrhoea occurs, additional blood samples will be collected twice weekly until symptoms resolve. All blood samples will be used for Posaconazole pharmacokinetics study.; Other Names: Blood sampling

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pre-dose plasma Posaconazole concentrations	The median interquartile range pre-dose plasma Posaconazole concentrations equal or greater than 0.7 mg/L will be assessed.	On days 7, 14 and 21 of Posaconazole prophylaxis course, when significant diarrhea occurs, when active gastrointestinal graft versus host disease occurs.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical symptoms affecting plasma Posaconazole concentrations.	Observed association between concurrent patient factors with change in plasma Posaconazole concentrations.	At Screening, Days 7, 14 and 21, and 72 hours after onset of diarrhoea, and when invasive fungal infection occurs.
The number/proportion of patients achieving desirable pre-dose plasma Posaconazole concentrations.	The number/proportion of patients achieving pre-dose plasma Posaconazole concentrations greater or equal to 0.7 mg/L will be assessed.	On days 7, 14 and 21 of Posaconazole prophylaxis course, when significant diarrhea occurs, when active gastrointestinal graft versus host disease occurs.
Effects of diarrhea on plasma Posaconazole concentration	Correlation between the presence/extent of diarrhea with change in plasma Posaconazole concentrations.	When diarrhea occurs during Posaconazole prophylaxis on Days 1 to 21.
Alteration in prophylaxis due to Posaconazole-attributed toxicities.	Frequency of Posaconazole-attributed toxicities resulting in dose changes or cessation of prophylaxis will be noted.	When change in or cessation of oral Posaconazole prophylaxis occurs during Day 1 to Day 21.

Collaborators and Investigators

• Sponsor: Melbourne Health
• Collaborators: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2019
• Primary Completion (Anticipated): December 30, 2023
• Study Completion (Anticipated): December 30, 2023

Study Registration Dates

• First Submitted: October 10, 2018
• First Submitted That Met QC Criteria: October 22, 2018
• First Posted (Actual): October 24, 2018

Study Record Updates

• Last Update Posted (Actual): March 29, 2023
• Last Update Submitted That Met QC Criteria: March 27, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Bacterial Infections and Mycoses; Infections; Candidiasis; Candidiasis, Invasive; Mycoses; Invasive Fungal Infections; Aspergillosis; 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: 2017.105

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes