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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Radboud University
ClinicalTrials.gov Identifier:
NCT01249820
First received: August 23, 2010
Last updated: January 31, 2013
Last verified: January 2013
  Purpose

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.


Condition Intervention Phase
Leukemia
Myelodysplastic Syndrome
Leukemia, Myeloid, Acute
Drug: anidulafungin 200 mg q48h
Drug: anidulafungin 300 mg q72h
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Radboud University:

Primary Outcome Measures:
  • pharmacokinetics [ Time Frame: two weeks per subject ] [ Designated as safety issue: No ]
    comparison of pharmacokinetics of anidulafungin given once in every two days or once in every three days


Secondary Outcome Measures:
  • adequate exposure [ Time Frame: 2 weeks for each subject; analysis after 3 months after last subject inclusion ] [ Designated as safety issue: No ]
    To determine whether adequate exposure is attained by patients undergoing an allogeneic haematopoietic stem cell transplant following myeloablative chemotherapy or receiving intensive chemotherapy for AML-MDS when using a q48 hour or a q72 hour dosing regimen

  • safety [ Time Frame: 3 weeks ] [ Designated as safety issue: Yes ]
    To determine the safety of anidulafungin in the patient population


Enrollment: 26
Study Start Date: November 2010
Study Completion Date: January 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: group A
Day 1-15: anidulafungin 200 mg q48h IV maintenance dose (8 dosages)
Drug: anidulafungin 200 mg q48h
Day 1-15: anidulafungin 200 mg q48h IV maintenance dose (8 dosages)
Other Name: Ecalta
Experimental: group B
Day 1-13: anidulafungin 300 mg q72h IV maintenance dose (5 dosages)
Drug: anidulafungin 300 mg q72h
Day 1-13: anidulafungin 300 mg q72h IV maintenance dose (5 dosages)
Other Name: Ecalta

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years to 64 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01249820

Locations
Netherlands
Radboud University Nijmegen Medical Centre
Nijmegen, Netherlands
Sponsors and Collaborators
Radboud University
Investigators
Principal Investigator: R Brüggemann, PharmD Radboud University
  More Information

No publications provided

Responsible Party: Radboud University
ClinicalTrials.gov Identifier: NCT01249820     History of Changes
Other Study ID Numbers: UMCN-AKF 10.01 / SC25
Study First Received: August 23, 2010
Last Updated: January 31, 2013
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Radboud University:
anidulafungin
antifungal prophylaxis
allogeneic haematopoietic stem cell transplant
myeloablative chemotherapy
AML-MDS
pharmacokinetics

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Preleukemia
Bone Marrow Diseases
Hematologic Diseases
Neoplasms
Neoplasms by Histologic Type
Precancerous Conditions
Anidulafungin
Echinocandins
Anti-Infective Agents
Antifungal Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 29, 2014