Pharmacokinetics of Micafungin Given Twice Weekly Intravenously Compared to Micafungin Given Daily to Patients at Risk for Developing an Invasive Fungal Disease

Phase 2

Completed

• Conditions: Acute Myeloid Leucaemia; Myelo Dysplastic Syndrome; Allogeneic Stem Cell Transplant; Acute Graft Versus Host Disease Grade II-IV
• Interventions: Other: daily dosing; Other: alternate dosing; Drug: micafungin

• Registration Number: NCT02172768
• Lead Sponsor: Radboud University Medical Center

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.

Study Timeline

• Study First Submitted: 2014-06-20
• Study First Submitted QC: 2014-06-23
• Study First Posted: 2014-06-24
• Study Start: 2014-10
• Primary Completion: 2016-06
• Study Completion: 2016-07
• Status Verified: 2020-12
• Last Update Submitted: 2020-12-04
• Last Update Posted: 2020-12-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
daily dosing	daily dosing	micafungin daily for 8 days
alternate dosing	alternate dosing	treatment for 8 days with intravenous micafungin twice weekly
alternate dosing	micafungin	treatment for 8 days with intravenous micafungin twice weekly
daily dosing	micafungin	micafungin daily for 8 days

Primary Outcome Measures

Name	Time	Method
area under the curve	day 4 and day 8	Full pharmacokinetic curves will be taken op Day 4 or 5 and Day 8 (micafungin). AUC of two dosing regimens will be compared.

Secondary Outcome Measures

Name	Time	Method
population PK model	Day 4 and Day 8	to perform Monte Carlo simulations to provide the scientific background for alternate dosing strategies in the prophylactic setting
adverse events	day 1- 11	number and severity of adverse events will be recorded during the study and both treatment regimens will be compared

Trial Locations

Locations (2)

Radboudumc; 🇳🇱 Nijmegen, Netherlands

UZ Leuven; 🇧🇪 Leuven, Belgium