Allogeneic Stem Cell TransplantPhase 4PIRAÑANCT02805946
Pharmacokinetics of Posaconazole (Noxafil®) as Prophylaxis for Invasive Fungal Infections
A Phase 4 study testing posaconazole in people with Allogeneic Stem Cell Transplant and Acute Graft Versus Host Disease, run by Radboud University Medical Center at 2 sites in 2 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Allogeneic Stem Cell Transplant, Acute Graft Versus Host Disease, Acute Myeloid Leucaemia
- What is being tested?
- posaconazole
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 28 Apr 2017to 7 Sep 2019
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
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.
Read the 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.
- Conditions
- Allogeneic Stem Cell Transplant, Acute Graft Versus Host Disease, Acute Myeloid Leucaemia, Myelo Dysplastic Syndrome
- Being tested
- posaconazole
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
posaconazoleDrug
Also called Noxafil
iv versus oral
| Study group | Role | What they receive |
|---|---|---|
| intravenous followed by oral | Other | * 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). Receives: Drug: posaconazole |
| oral followed by intravenous | Other | * 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). Receives: Drug: posaconazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: day 7, day 12 and day 16
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.
Measured: day 7, day 12 and day 16
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jun 2016 (estimated)
- Study start28 Apr 2017
- Primary completion26 Jul 2019
- Study completion7 Sep 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Allogeneic Stem Cell TransplantStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Universitaire Ziekenhuizen KU Leuven
- Responsible party
- Sponsor
- Investigators
- Roger Brüggemann, PhD, PharmD, Principal investigator, Radboud University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02805946
- Sponsor's protocol ID
- UMCN-AKF16.01
- Other IDs
- 2016-001182-87, 2016
- Acronym
- PIRAÑA
- Status last verified
- Dec 2019
- First submitted
- 1 Jun 2016
- Last updated
- 16 Dec 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetics of Posaconazole (Noxafil®) as Prophylaxis for Invasive Fungal Infections
- ClinicalTrials.gov ID
- NCT02805946
- Acronym / sponsor ID
- PIRAÑA / UMCN-AKF16.01
- Conditions
- Allogeneic Stem Cell Transplant, Acute Graft Versus Host Disease, Acute Myeloid Leucaemia, Myelo Dysplastic Syndrome
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Collaborators
- Universitaire Ziekenhuizen KU Leuven
- Study start
- 28 Apr 2017 (actual)
- Primary completion
- 26 Jul 2019 (actual)
- Study completion
- 7 Sep 2019 (actual)
- First posted
- 20 Jun 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| intravenous followed by oral | Other | Drug: posaconazole* 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). |
| oral followed by intravenous | Other | Drug: posaconazole* 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). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| posaconazoleAlso: Noxafiliv versus oral | Drug | intravenous followed by oral, oral followed by intravenous |
Primary outcome
exposure to posaconazole (Area Under the Curve) when administered intravenously and orally (tablet formulation)
Time frame: day 7, day 12 and day 16
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.
Time frame: day 7, day 12 and day 16
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Dec 2019.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Roger Brüggemann, PhD, PharmD principal investigator
Radboud University Medical Center
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing posaconazole in people with Allogeneic Stem Cell Transplant and Acute Graft Versus Host Disease, run by Radboud University Medical Center at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Belgium, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
exposure to posaconazole (Area Under the Curve) when administered intravenously and orally (tablet formulation) (time frame: day 7, day 12 and day 16). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Dec 2019.