Pharmacokinetic Profile of Inhaled Liposomal Amphotericin B in Lung Transplant Recipients - Ambisome Study - Full Text View

Sponsor:	University of Pittsburgh
Collaborator:	Astellas Pharma US, Inc.
Information provided by:	University of Pittsburgh
ClinicalTrials.gov Identifier:	NCT00177710

Purpose

The purpose of this study is to determine the steady state concentrations of inhaled liposomal amphotericin B (Ambisome®) in lung transplant recipients via aerosolized nebulization.

Condition	Intervention	Phase
Lung Transplantation Fungal Infections	Drug: Amphotericin B	Phase III

Study Type:	Interventional
Study Design:	Prevention, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Pharmacokinetics Study
Official Title:	Pharmacokinetic Profile of Inhaled Liposomal Amphotericin B in Lung Transplant Recipients - Ambisome Study

Resource links provided by NLM:

MedlinePlus related topics: Fungal Infections Lung Transplantation

Drug Information available for: Amphotericin B

U.S. FDA Resources

Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:

To characterize the pharmacokinetic profile of liposomal amphotericin B achieved in the serum and epithelial lining fluid of the lung with four doses of liposomal amphotericin B administered via aerosolized nebulization in lung transplant recipients

Secondary Outcome Measures:

The purpose of this study is to determine the steady state concentrations of inhaled liposomal amphotericin B (Ambisome®) in lung transplant recipients via aerosolized nebulization.

Estimated Enrollment:	48
Study Start Date:	January 2006
Study Completion Date:	December 2007

Detailed Description:

Each subject will receive 1 mg/kg/day of inhaled Ambisome® for four days prior to the BAL (bronchoalveolar lavage) procedure. The dosage of 1 mg/kg was calculated by extrapolating the dosage of 1.6 mg/kg for the surface area of the rat lung to the human lung surface area in a 60 kg individual.

All four doses will be given in the presence of a physician and/or study coordinator. The forty eight subjects will be randomized such that six subjects undergo the BAL at 1, 12, 24, 48, 72, 96, 120, and 168 hours after the last dose of inhaled Liposomal amphotericin B (AmBisome®).

A blood sample (5 ml) will be obtained prior to the fourth dose of study medication and on the day of bronchoscopy (pseudo steady state trough). Concentrations of amphotericin in the serum, and bronchoalveolar lavage will be measured at pre-specified intervals after administration of liposomal amphotericin B (AmBisome®) in lung transplant recipients undergoing routine bronchoscopy as mentioned earlier.

A 5 ml blood sample will be recovered at the time of bronchoscopy for the purpose of determination of serum amphotericin B concentration and for the determination of serum urea concentration.

The bronchoscopy and bronchoalveolar lavage of subjects is done as a part of routine transplant care. Subjects will be followed for the follow-up of results of bronchoscopy at the interval deemed necessary by their transplant pulmonologist. The samples (blood and bronchoalveolar samples) will be under the control of the principal investigator of this research project. To protect confidentiality, all personal identifiers (i.e., name, social security number, and birth date) will be removed (de-identified) and replaced with a specific code number. The information linking these code numbers to the corresponding subjects' identities will be kept in a separate, secure location (ID lab at 8th floor Scaife Hall). The investigators on this study will keep the samples indefinitely. Samples may be given to investigators outside of UPMC or may be utilized in future studies about infectious diseases. If the samples are given to investigators not associated with this study, the samples will be provided without any identifiers. No genetic testing will be done on the samples obtained.

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Male and female lung transplant recipients at University of Pittsburgh Medical Center ≥ 18 years of age will be eligible for the study.
Single or double lung transplant recipients
Willing to be available at the testing center for 4 consecutive days
Able to comprehend and complete informed consent

Exclusion Criteria:

Pregnant women or women capable of bearing children, who will not perform a urine pregnancy test
Nursing mothers
Subjects with hypersensitivity to amphotericin deoxycholate or liposomal amphotericin
Subjects with a past history of bronchospasm associated with aerosol drug use
Subjects with active bacterial or viral infection as defined by the current use of non-prophylactic antibiotic anti-viral medications
Subjects with a forced expiratory volume in 1 second (FEV1) < 30% predicted or forced vital capacity (FVC) < 30% will not receive study medication.
Subjects requiring supplemental oxygen
Receipt of inhalational or intravenous (IV) amphotericin B within last 30 days
Subjects with known fungal infection as per Mycoses Study Group (MSG) criteria on therapy with antifungal drugs or diagnosed on the day of bronchoscopy
Serum creatinine > 1.9 mg/dl on the day of screening
Liver enzymes ALT/AST/alkaline phosphatase greater than two times the normal limit
Concurrent intravenous aminoglycoside use
Subject with fever > 38.2°C
Subjects on mechanical ventilation

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00177710

Locations

United States, Pennsylvania
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States, 15213

Sponsors and Collaborators

University of Pittsburgh

Astellas Pharma US, Inc.

Investigators

Principal Investigator:

Shahid Husain, MD

University of Pittsburgh

More Information

No publications provided

Responsible Party:	UPMC ( Shahid Husain, MD )
Study ID Numbers:	IRB# 0408180
Study First Received:	September 13, 2005
Last Updated:	December 16, 2008
ClinicalTrials.gov Identifier:	NCT00177710 History of Changes
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Abelcet
Amphotericin B
Anti-Infective Agents
Antiprotozoal Agents
Infection
Liposomal amphotericin B
Pharmacologic Actions

Mycoses
Anti-Bacterial Agents
Antiparasitic Agents
Therapeutic Uses
Antifungal Agents
Antibiotics, Antifungal
Amebicides

ClinicalTrials.gov processed this record on November 09, 2009