- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02805946
Pharmacokinetics of Posaconazole (Noxafil®) as Prophylaxis for Invasive Fungal Infections (PIRAÑA)
December 13, 2019 updated by: Radboud University Medical Center
This study evaluates the the pharmacokinetics of posaconazole (new solid oral and IV) given as prophylaxis to patients who are at risk for developing fungal infections after receiving conditioning therapy (except strictly non-myeloablative (NMA)) for allogeneic Stem Cell Transplant (SCT), remission induction chemotherapy for acute myeloid leukemia (AML) or myelo dysplastic syndrome (MDS) or being treated for severe graft versus host disease (GvHD) and determines the impact of mucositis on the pharmacokinetics of posaconazole new solid oral.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
In 2014, the new intravenous and solid oral formulation of posaconazole were marketed.
This offers new treatment possibilities, specifically in patients previously unable to attain adequate exposure to posaconazole solution.
To the opinion of the researchers, only limited data are available on the pharmacokinetics (PK) of the new formulations of posaconazole, however, these use strictly selected patients or healthy volunteers, but more importantly, specific aspects related to the PK remain unsolved.
Despite the fact that adequate exposure is attained using the new solid oral formulation, it is hypothesized that oral bioavailability of posaconazole may be impacted during mucositis.
Whether mucosal barrier injury impacts the absorption of posaconazole or alters presystemic clearance is still unknown.
Therefore, it seems prudent to conduct a trial in a group of patients that will experience a severe degree of mucositis to identify changes in absorption of posaconazole and resolving the impact of various stages of mucositis on the PK of posaconazole by linking PK of posaconazole to markers of mucositis (citrulline).
This research may also serve as a model for other drugs and allows for direct translations in improving patient care.
For this purpose it is needed to determine the PK using both IV and PO dosing of posaconazole.
Study Type
Interventional
Enrollment (Actual)
21
Phase
- Phase 4
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Leuven, Belgium
- Universitaire Ziekenhuizen Leuven
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Nijmegen, Netherlands, 6500HB
- Radboudumc
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
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:
- Subject is able and willing to sign the Informed Consent Form prior to screening evaluations.
- Subject is at least 18 years of age on the day of providing informed consent.
- Patient receives immunosuppressive therapy for acute or chronic GVHD grade II-IV, reduced intensity conditioning regimens for allogeneic stem cell transplant, or first remission induction chemotherapy for AML/MDS.
- In case of acute GVHD grade II-IV, patient has received less than 1 week of immunosuppressive therapy.
- If a woman, is neither pregnant nor able to become pregnant and is not nursing an infant.
- Has an ALAT <200U/L, ALAT <225U/L, alkaline phosphatase <60 U/L and a bilirubin level <50 μmol/L.
- Subject is capable of receiving oral tablets.
- Subject is managed with a central venous or arterial catheter.
Exclusion Criteria:
- Documented history of sensitivity to medicinal products or excipients similar to those found in the posaconazole preparation.
- Relevant history or presence of cardiovascular disorders (specifically QTc-time prolongation).
- Inability to understand the nature of the trial and the procedures required
- Any signs or symptoms of invasive fungal disease or the use of antifungal drugs within the previous month.
- Has previously participated in this trial.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Other: intravenous followed by oral
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iv versus oral
Other Names:
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Other: oral followed by intravenous
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iv versus oral
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
exposure to posaconazole (Area Under the Curve) when administered intravenously and orally (tablet formulation)
Time Frame: day 7, day 12 and day 16
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Plasma samples drawn on t=0 (pre-dose), 0.5, 1 (just prior to end of infusion), 2, 3, 4, 6, 8, 10, 12, 18 and 24 hours post infusion or post intake will be taken op day 7, day 12 and day 16 to determine posaconazole concentrations.
Area Under the Curve of two routes of administration and two dosing regimens will be determined.
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day 7, day 12 and day 16
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impact of mucositis (determined by citrulline concentrations) on exposure (AUC) to posaconazole.
Time Frame: day 7, day 12 and day 16
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Full pharmacokinetic curve (plasma samples drawn on t=0 (pre-dose), 0.5, 1 (just prior to end of infusion), 2, 3, 4, 6, 8, 10, 12, 18 and 24 hours post infusion or post intake) will be taken op day 7, day 12 and day 16 (posaconazole).
Impact of mucositis on oral absorption will be determined by comparing AUCs after intravenous administration with oral (tablet) administration in patients with mucositis.
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day 7, day 12 and day 16
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Investigators
- Principal Investigator: Roger Brüggemann, PhD, PharmD, Radboud University Medical Center
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
April 28, 2017
Primary Completion (Actual)
July 26, 2019
Study Completion (Actual)
September 7, 2019
Study Registration Dates
First Submitted
June 1, 2016
First Submitted That Met QC Criteria
June 15, 2016
First Posted (Estimate)
June 20, 2016
Study Record Updates
Last Update Posted (Actual)
December 16, 2019
Last Update Submitted That Met QC Criteria
December 13, 2019
Last Verified
December 1, 2019
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Infections
- Immune System Diseases
- Neoplasms
- Bone Marrow Diseases
- Hematologic Diseases
- Bacterial Infections and Mycoses
- Precancerous Conditions
- Myelodysplastic Syndromes
- Preleukemia
- Mycoses
- Invasive Fungal Infections
- Graft vs Host Disease
- 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
- UMCN-AKF16.01
- 2016-001182-87 (EudraCT Number)
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
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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