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

• ClinicalTrials.gov Identifier: NCT03717623
• Recruitment Status: Recruiting
• First Posted: October 24, 2018
• Last Update Posted: August 27, 2019
• Sponsor: Melbourne Health
• Collaborator: Merck Sharp & Dohme Corp.
• Information provided by (Responsible Party): Melbourne Health

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Posaconazole; Pharmacokinetics; Invasive Candidiases; Invasive Aspergillosis; Invasive Mycosis; Fungal Infection; Prophylaxis	Drug: Posaconazole pharmacokinetics	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 100 participants
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Pharmacokinetics Study of Posaconazole in Haematology Patients Receiving Standard of Care Treatment With Oral Posaconazole Prophylaxis for Invasive Fungal Infection
• Actual Study Start Date: August 1, 2019
• Estimated Primary Completion Date: June 30, 2020
• Estimated Study Completion Date: December 31, 2020

Arms and Interventions

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 Name: Blood sampling

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Contacts

Contact: Monica Slavin, Prof; 61 3 9342 9403; monica.slavin@mh.org.au

Contact: Tseng Lau, PhD; 61 3 9342 8274; tseng.lau@mh.org.au

Locations

Australia, Victoria

Melbourne Health; Recruiting

Parkville, Victoria, Australia, 3050

Contact: Tseng Lau, PhD

Sponsors and Collaborators

Melbourne Health

Merck Sharp & Dohme Corp.

More Information

• Responsible Party: Melbourne Health
• ClinicalTrials.gov Identifier: NCT03717623 History of Changes
• Other Study ID Numbers: 2017.105
• First Posted: October 24, 2018
• Last Update Posted: August 27, 2019
• Last Verified: August 2019

• 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

Additional relevant MeSH terms:

Infection; Mycoses; Candidiasis; Aspergillosis; Candidiasis, Invasive; Invasive Fungal Infections; Posaconazole; Antifungal Agents; Anti-Infective Agents; Trypanocidal Agents; Antiprotozoal Agents; Antiparasitic Agents; 14-alpha Demethylase Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Steroid Synthesis Inhibitors; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs