Clinical trial NCT02172768: Pharmacokinetics of Micafungin Given Twice Weekly Intravenously Compared to Micafungin Given Daily to Patients at Risk for Developing an Invasive Fungal Disease
Official title: Pharmacokinetics of Micafungin (Mycamin ®) as Antifungal Prophylaxis Given Twice Weekly Intravenously Compared to Micafungin Given Daily to Patients at Risk for Developing an Invasive Fungal Disease.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Graft Versus Host Disease Grade II-IV
Allogeneic Stem Cell Transplant
Acute Myeloid Leucaemia
Myelo Dysplastic Syndrome
Keywords: pharmacokinetics
alternate dosing
micafungin
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
First posted: 2014-06-24
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: The primary objective of this trial is as follows:

To determine the pharmacokinetics of micafungin given twice weekly in patients at risk for developing an invasive fungal disease (patients who are being treated for acute or chronic graft versus host disease; patients receiving reduced intensity conditioning for Stem Cell Transplant (SCT); receiving first remission induction chemotherapy for Acute Myeloid Leucaemia (AML)/MyeloDysplasticSyndrome (MDS)) compared to the pharmacokinetics of micafungin given daily.

The secondary objective of this trial is as follows:

To determine whether adequate exposure of micafungin is attained. To determine the safety of micafungin in this patient population

Detailed description: Micafungin has been shown to be a reasonable option for treating invasive aspergillosis in hematopoietic stem cell transplantation (HSCT) recipients and has proven as effective as fluconazole for prophylaxis. Whilst micafungin has much to offer, little is known about its pharmacokinetic profile in specific patient populations, specifically concerning alternate dosing strategies with increased dosages over a prolonged dosing interval. Sufficient data are lacking up to now for twice weekly administration of micafungin as antifungal prophylaxis. Decreasing the dosing frequency to twice weekly seems a reasonable approach considering the long terminal elimination life (i.e. 10-17 h) and considering the data available from murine models that support the use of less frequent dosing with higher dosages.

It will enable us to characterize both the pharmacokinetics of micafungin in the hematology cohort and directly compare the exposure to the alternate dosing strategy.

Eligibility criteria: Inclusion Criteria:

* Patient receives immunosuppressive therapy for acute GvHD grade II-IV or reduced intensity conditioning regimens for allogeneic stem cell transplant, or patients receiving first remission induction chemotherapy for AML/MDS.
* Subject is at least 18 of age on the day of providing informed consent.
* Has no signs or symptoms of invasive fungal disease
* If a woman, is neither pregnant nor able to become pregnant and is not nursing an infant.
* Less than 1 week of immunosuppressive therapy for grade II-IV acute GvHD.
* Is managed with a central venous catheter (preferably a quadruple Arrow-Howes™ Quad-Lumen 8.5,5 French; Arrow International).
* Subject is able and willing to sign the Informed Consent before screening evaluations.

Exclusion Criteria:

* Documented history of sensitivity to medicinal products or excipients similar to those found in the micafungin preparation.
* History of or current abuse of drugs, alcohol or solvents.
* Inability to understand the nature of the trial and the procedures required.
* Has not previously participated in this trial.

Primary outcomes:
measure: area under the curve
timeFrame: day 4 and day 8
Secondary outcomes:
measure: population PK model
timeFrame: Day 4 and Day 8
measure: adverse events
timeFrame: day 1- 11
Other outcomes:
Locations:
city: Leuven
country: Belgium
facility: UZ Leuven
city: Nijmegen
country: Netherlands
facility: Radboudumc
Study officials:
affiliation: Radboud University Medical Center
name: Roger Brüggemann
role: PRINCIPAL_INVESTIGATOR
References:
citation: Muilwijk EW, Maertens JA, van der Velden WJFM, Ter Heine R, Colbers A, Burger DM, Andes D, Theunissen K, Blijlevens NMA, Bruggemann RJM. Pharmacokinetics of extended dose intervals of micafungin in haematology patients: optimizing antifungal prophylaxis. J Antimicrob Chemother. 2018 Nov 1;73(11):3095-3101. doi: 10.1093/jac/dky324.