Pharmacokinetics of Anidulafungin (Ecalta ®) Intravenous Given to Patients at High Risk for Developing Invasive Fungal Disease (ANIDULAPK)

Radboud University Medical Center

Status and phase

Completed

Phase 2

Conditions

Leukemia, Myeloid, Acute

Myelodysplastic Syndrome

Leukemia

Treatments

Drug: anidulafungin 300 mg q72h

Drug: anidulafungin 200 mg q48h

Study type

Interventional

Funder types

Other

Identifiers

NCT01249820

UMCN-AKF 10.01 / SC25

Details and patient eligibility

About

The purpose of this study is to study the pharmacokinetics of anidulafungin (Ecalta ®) 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 who are at high risk for developing invasive fungal disease.

Full description

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.

Enrollment

26 patients

Sex

All

Ages

18 to 64 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Patient receives an allogeneic haematopoietic stem cell transplant following myeloablative chemotherapy or receives intensive chemotherapy for AML-MDS
Subject is at least 18 and not older than 65 years of age on the day of the first dosing
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
Has an ALAT, ALAT, alkaline phosphatase < 5 times the upper limit of normal and a bilirubin level < 3 times the upper limit of normal
Is not known to be hypersensitive to echinocandin antifungal agents
Is managed with a quadruple central venous catheter (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 anidulafungin preparation
Known of Positive HIV test or hepatitis B or C test in history
History of QT time prolongation
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