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

Allogeneic Stem Cell Transplant Clinical Trial

— MATADOR  

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02172768
• Other study ID #: MATADOR
• Status: Completed
• Phase: Phase 2
• Start date: October 2014
• Est. completion date: July 2016

Study information

• Verified date: December 2020
• Source: Radboud University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: July 2016
• Est. primary completion date: June 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Graft Versus Host Disease Grade II-IV
• Acute Myeloid Leucaemia
• Allogeneic Stem Cell Transplant
• Graft vs Host Disease
• Invasive Fungal Infections
• Mycoses
• Myelo Dysplastic Syndrome
• Myelodysplastic Syndromes
• Preleukemia

Intervention

Other:
• alternate dosing
treatment for 8 days with intravenous micafungin twice weekly
• daily dosing
micafungin daily for 8 days

Drug:
• micafungin

Locations

Country	Name	City	State
Belgium	UZ Leuven	Leuven
Netherlands	Radboudumc	Nijmegen

Sponsors (1)

Lead Sponsor	Collaborator
Radboud University

Countries where clinical trial is conducted

Belgium,  Netherlands, 

References & Publications (1)

Muilwijk EW, Maertens JA, van der Velden WJFM, Ter Heine R, Colbers A, Burger DM, Andes D, Theunissen K, Blijlevens NMA, Brüggemann RJM. Pharmacokinetics of extended dose intervals of micafungin in haematology patients: optimizing antifungal prophylaxis. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	area under the curve	Full pharmacokinetic curves will be taken op Day 4 or 5 and Day 8 (micafungin). AUC of two dosing regimens will be compared.	day 4 and day 8
Secondary	population PK model	to perform Monte Carlo simulations to provide the scientific background for alternate dosing strategies in the prophylactic setting	Day 4 and Day 8
Secondary	adverse events	number and severity of adverse events will be recorded during the study and both treatment regimens will be compared	day 1- 11