Trial Information

Pharmacokinetics of Anidulafungin Given Intravenously as Antifungal Prophylaxis to Recipients of an Allogeneic Haematopoietic Stem Cell Transplant Following Myeloablative Chemotherapy or Patients Receiving Intensive Chemotherapy for AML-MDS

Alternate dosing strategies of echinocandin drugs might provide a better efficacy in the
treatment of fungal infections as compared to the current label dosing strategy. Before
conducting a controlled efficacy trial of echinocandins in haematology patients, the
pharmacokinetics of these alternate dosing strategies need to be tested before bringing this
idea to practice in a large randomised trial.

Therefore we want to conduct a pharmacokinetic study with anidulafungin given every 48 hours
or every 72 hours. This research can be performed best in a group of patients at high risk
for developing invasive fungal infections.

Recipients of an allogeneic haematopoietic stem cell transplant (HSCT) or patients receiving
intensive chemotherapy for acute myeloid leukaemia (AML) or myelodysplastic syndrome (MDS)
are at a relatively high risk of developing invasive fungal infections and are therefore
candidates for primary prophylaxis. However, the options are limited to fluconazole which
affords no protection against mould infections. Amphotericin B is not considered useful
because of its desoxycholate formulation has too many side effects and its lipid
formulations are too expensive nor have the broad-spectrum triazoles itraconazole and
voriconazole proved their value in this setting. Anidulafungin is the first of a new class
of antifungal drugs quite unlike any others attacking specifically the ß 1-3 -D-glucan
synthase of the cell wall. It has relatively few side effects and appears safe and effective
for treating Aspergillus and Candida infections. Since these two genera account for 90% of
fungal infections in HSCT recipients the drug would seem an ideal candidate for prophylaxis.

Importantly, nothing is known about the pharmacokinetics of alternate dosing regimens of
anidulafungin in this patient population. Therefore a pharmacokinetic study of a homogenous
cohort of patients is necessary to test the assumption, that adequate exposure is obtained
with alternate dosing and that it is safe.