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Pharmacokinetics of Posaconazole (Noxafil®) as Prophylaxis for Invasive Fungal Infections (PIRAÑA)

Primary Purpose

Allogeneic Stem Cell Transplant, Acute Graft Versus Host Disease, Acute Myeloid Leucaemia

Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
posaconazole
Sponsored by
Radboud University Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Allogeneic Stem Cell Transplant

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Subject is able and willing to sign the Informed Consent Form prior to screening evaluations.
  2. Subject is at least 18 years of age on the day of providing informed consent.
  3. 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.
  4. In case of acute GVHD grade II-IV, patient has received less than 1 week of immunosuppressive therapy.
  5. If a woman, is neither pregnant nor able to become pregnant and is not nursing an infant.
  6. Has an ALAT <200U/L, ALAT <225U/L, alkaline phosphatase <60 U/L and a bilirubin level <50 μmol/L.
  7. Subject is capable of receiving oral tablets.
  8. Subject is managed with a central venous or arterial catheter.

Exclusion Criteria:

  1. Documented history of sensitivity to medicinal products or excipients similar to those found in the posaconazole preparation.
  2. Relevant history or presence of cardiovascular disorders (specifically QTc-time prolongation).
  3. Inability to understand the nature of the trial and the procedures required
  4. Any signs or symptoms of invasive fungal disease or the use of antifungal drugs within the previous month.
  5. Has previously participated in this trial.

Sites / Locations

  • Universitaire Ziekenhuizen Leuven
  • Radboudumc

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Other

Arm Label

intravenous followed by oral

oral followed by intravenous

Arm Description

Start with posaconazole IV 300mg BID on the first day. Posaconazole will be infused over a period of 90 minutes. Days 2-7 patients will receive posaconazole IV 300mg QD. Days 8-12 patients will receive posaconazole PO 300mg QD. Days 13-16 patients will receive posaconazole PO 200mg QD. 3 PK curves will be determined on days 7, 12 and 16 (after the 7th, 12th and 16th dosage).

Start with posaconazole PO 300mg BID on the first day. Days 2-7: patients will receive posaconazole PO 300mg QD. Days 8-12: patients will receive posaconazole IV 300mg QD. Posaconazole will be infused over a period of 90 minutes. Days 13-16 patients will receive posaconazole IV 200mg QD. 3 PK curves will be determined on days 7, 12 and 16 (after the 7th, 12th and 16th dosage).

Outcomes

Primary Outcome Measures

exposure to posaconazole (Area Under the Curve) when administered intravenously and orally (tablet formulation)
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.
impact of mucositis (determined by citrulline concentrations) on exposure (AUC) to posaconazole.
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.

Secondary Outcome Measures

Full Information

First Posted
June 1, 2016
Last Updated
December 13, 2019
Sponsor
Radboud University Medical Center
Collaborators
Universitaire Ziekenhuizen KU Leuven
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1. Study Identification

Unique Protocol Identification Number
NCT02805946
Brief Title
Pharmacokinetics of Posaconazole (Noxafil®) as Prophylaxis for Invasive Fungal Infections
Acronym
PIRAÑA
Official Title
Pharmacokinetics of Posaconazole (Noxafil®) as Prophylaxis for Invasive Fungal Infections
Study Type
Interventional

2. Study Status

Record Verification Date
December 2019
Overall Recruitment Status
Completed
Study Start Date
April 28, 2017 (Actual)
Primary Completion Date
July 26, 2019 (Actual)
Study Completion Date
September 7, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Radboud University Medical Center
Collaborators
Universitaire Ziekenhuizen KU Leuven

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Allogeneic Stem Cell Transplant, Acute Graft Versus Host Disease, Acute Myeloid Leucaemia, Myelo Dysplastic Syndrome

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
21 (Actual)

8. Arms, Groups, and Interventions

Arm Title
intravenous followed by oral
Arm Type
Other
Arm Description
Start with posaconazole IV 300mg BID on the first day. Posaconazole will be infused over a period of 90 minutes. Days 2-7 patients will receive posaconazole IV 300mg QD. Days 8-12 patients will receive posaconazole PO 300mg QD. Days 13-16 patients will receive posaconazole PO 200mg QD. 3 PK curves will be determined on days 7, 12 and 16 (after the 7th, 12th and 16th dosage).
Arm Title
oral followed by intravenous
Arm Type
Other
Arm Description
Start with posaconazole PO 300mg BID on the first day. Days 2-7: patients will receive posaconazole PO 300mg QD. Days 8-12: patients will receive posaconazole IV 300mg QD. Posaconazole will be infused over a period of 90 minutes. Days 13-16 patients will receive posaconazole IV 200mg QD. 3 PK curves will be determined on days 7, 12 and 16 (after the 7th, 12th and 16th dosage).
Intervention Type
Drug
Intervention Name(s)
posaconazole
Other Intervention Name(s)
Noxafil
Intervention Description
iv versus oral
Primary Outcome Measure Information:
Title
exposure to posaconazole (Area Under the Curve) when administered intravenously and orally (tablet formulation)
Description
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.
Time Frame
day 7, day 12 and day 16
Title
impact of mucositis (determined by citrulline concentrations) on exposure (AUC) to posaconazole.
Description
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.
Time Frame
day 7, day 12 and day 16

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Roger Brüggemann, PhD, PharmD
Organizational Affiliation
Radboud University Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Universitaire Ziekenhuizen Leuven
City
Leuven
Country
Belgium
Facility Name
Radboudumc
City
Nijmegen
ZIP/Postal Code
6500HB
Country
Netherlands

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Pharmacokinetics of Posaconazole (Noxafil®) as Prophylaxis for Invasive Fungal Infections

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