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.

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. - MATADOR

Status

Active, not recruiting

Phases

Phase 2

Study type

Interventional

Source

NL-OMON

Registry ID

NL-OMON57754

Enrollment

Registered

2013-11-04

Start date

2014-11-11

Completion date

Unknown

Last updated

2025-09-08

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

fungal prophylaxis pharmacokinetics

Interventions

• 15 subjects (group A) will start with twice weekly 300 mg micafungin at 8.00 AM on Mondays and Thursdays. They can start on either Monday or Thursday with the first dose. Micafungin will be infuse

4 in case of start on Monday, 5 in case of start on Thursday) and 8 (after 3 dosages). • Day 9-11: washout period to determine elimination of micafungin.

Eligibility

Age

18 Years to 99 Years

Inclusion criteria

Inclusion criteria: 1. Patient receives immunosuppressive therapy for acuteGvHD grade II-IV or reduced in-tensity conditioning regimens for allogeneic stem cell transplant, or patients receiving first remission induction chemotherapy for AML/MDS. ;2. Subject is at least 18 of age on the day of providing informed consent.;3. Has no signs or symptoms of invasive fungal disease;4. If a woman, is neither pregnant nor able to become pregnant and is not nursing an infant;5. Less than 1 week of immunosuppressive therapy for grade II-IV acute GvHD;6. Is managed with a central venous catheter (preferably a quadruple Ar-row-Howes* Quad-Lumen 8.5,5 French; Arrow International);7. Subject is able and willing to sign the Informed Consent before screening evaluations.

Exclusion criteria

Exclusion criteria: 1. Documented history of sensitivity to medicinal products or excipients similar to those found in the micafungin preparation;2. History of or current abuse of drugs, alcohol or solvents. ;3. Inability to understand the nature of the trial and the procedures re-quired.;4. Has not previously participated in this trial.

Design outcomes

Primary

Measure	Time frame
An initial non-compartmental pharmacokinetic analysis will be performed using Phoenix 64 (Pharsight Corporation, CA, USA). Results from the noncompartmental analysis will be used as initial input in for the compartmental analysis. A pharmacokinetic model will be fitted to the data from all individuals simultaneously. Data will be analyzed using non-linear mixed effects modelling (NONMEM). NONMEM is a one-stage analysis that simultaneously estimates mean parameters, fixed effect parameters, interindividual variability, and residual random effects. Since allowance can be made for individual differ-ences, this method can be used with both intensive sampling and sparse data (and in the occasion of missing values: an unbalanced number of data points per patients. Multiple compartment models with first-order or saturable elimination will be tested. Between subject variability (BSV) and, when applicable, between occasion variability (BOV) will be included on all pharmacokinetic parameters. Residual unexplained variability (RUV) will be estimated with additive or proportional error models. The first-order conditional estimation method with interaction will be used, other estimation methods like SAEM of non-parametric methods may be investigated. The effect of concomitant use of co-medication will be included as dichotomous covariate on the appropriate parameters (i.e. clearance). The log-likelihood ratio test will be used to assess significance of this effect, with a p-value of 0.05 as significance cut-off. Other co-variates will be tested in this analysis. Finally, simulations may be performed to justify the appropriateness of this dosing scheme for antifungal prophylaxis.	—

Measure

Time frame

An initial non-compartmental pharmacokinetic analysis will be performed using Phoenix 64 (Pharsight Corporation, CA, USA). Results from the noncompartmental analysis will be used as initial input in for the compartmental analysis. A pharmacokinetic model will be fitted to the data from all individuals simultaneously. Data will be analyzed using non-linear mixed effects modelling (NONMEM). NONMEM is a one-stage analysis that simultaneously estimates mean parameters, fixed effect parameters, interindividual variability, and residual random effects. Since allowance can be made for individual differ-ences, this method can be used with both intensive sampling and sparse data (and in the occasion of missing values: an unbalanced number of data points per patients. Multiple compartment models with first-order or saturable elimination will be tested. Between subject variability (BSV) and, when applicable, between occasion variability (BOV) will be included on all pharmacokinetic parameters. Residual unexplained variability (RUV) will be estimated with additive or proportional error models. The first-order conditional estimation method with interaction will be used, other estimation methods like SAEM of non-parametric methods may be investigated. The effect of concomitant use of co-medication will be included as dichotomous covariate on the appropriate parameters (i.e. clearance). The log-likelihood ratio test will be used to assess significance of this effect, with a p-value of 0.05 as significance cut-off. Other co-variates will be tested in this analysis. Finally, simulations may be performed to justify the appropriateness of this dosing scheme for antifungal prophylaxis.

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Secondary

Measure	Time frame
Safety of micafungin at alternate dosing strategies.	—

Countries

Netherlands

Outcome results

None listed

Source: NL-OMON (via WHO ICTRP)