Lung transplant recipients with a diagnosis of invasive fungal disease
Conditions
Interventions
Trade Name: CRESEMBA
Product Name: CRESEMBA
Pharmaceutical Form: Capsule
INN or Proposed INN: isavuconazole
CAS Number: 241479-67-4
Current Sponsor code: CRESEMBA
Other descriptive name: ISAVUCONAZOLE
Sponsors
FUNDACIÓN PARA LA INVESTIGACION BIOMEDICA HU PUERTA DE HIERRO MAJADAHONDA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Receptors of a lung transplant older than 18 years who, with indication of treatment with isavuconazole according to the technical sheet. - Will and ability to meet scheduled visits, treatment plan, laboratory analysis and other study procedures. - They must be legally competent and able to understand, sign and date the informed consent form. - Signing of the written informed consent in accordance with ICH / GCP and local legislation, obtained before any study procedure. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 12 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - Allergy or intolerance to isavuconazole. - Contraindication for bronchoscopy and / or BAL. - Any clinical condition, and / or analytical alteration to participate in the study. - Individuals who show inability to follow the instructions or collaborate during the study. - Women with positive results of the pregnancy or breastfeeding test. - Having participated in another clinical trial during the 3 months prior to the start of the study in which a research drug or a commercially available drug was tested. - Lack of will or inability to follow the procedures described in the protocol. - Inability to grant written informed consent.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Describe the pharmacokinetic profile of oral isavuconazole at the bronchopulmonary level through the degree of penetration into the epithelial lining fluid and the alveolar macrophages in patients receiving lung transplants diagnosed with invasive fungal disease.;Secondary Objective: - Establish the relationship between the pulmonary and systemic exposure of Isavuconazole. - To evaluate the potential pharmacokinetic interaction of Isavuconazole with immunosuppressive drugs (tacrolimus and mycophenolate). This interaction will be studied in the steady state of the drugs evaluated. - Evaluate the safety and tolerability of Isavuconazole.;Primary end point(s): Isovuconazole Penetration in Lung The concentrations of isavuconazole in plasma, epithelial lining fluid (ELF) and in alveolar macrophages (CA) will be determined by reverse phase HPLC (RP-HPLC). - Serum isavuconazole levels. Four determinations will be made per patient: 72 hours after the start of treatment, the day of bronchoscopy, simultaneously with the BAL and 7 days after the start of treatment. - Levels of isavuconazole in epithelial lining fluid (ELF) and in alveolar macrophages (CA), will be obtained from bronchoalveolar lavage (BAL). Data from the cell count, percentage of alveolar cells and volume of cell lining fluid will be presented at the different times when bronchoscopy is performed. The volume of cell lining fluid will be estimated using the concentration of urea in plasma and in LBA from the following formula: Estimated ELF volume = Amount of total UREA in LBA (mg) / plasma UREA concentration (mg / mL) The AUC of isavuconazole will be estimated at the ELF level and in CAs. The concentration-time-dependent curves in ELF and CA will be calculated using non-compartmental analyzes. The ratio between ELF / plasma and CA / plasma will be estimated from the average of the values ??of the patients included in each group.;Timepoint(s) of evaluation of this end point: 72 hours after the s | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Interaction Evaluation: Tacrolimus and mycophenolate concentrations will be determined before and after 72 hours, 96 hours and 7 days after the start of treatment with isavuconazole. The percentage of patients who required dose adjustment of the immunosuppressive drug after the start of treatment with isavuconazole will be determined. Systemic Security Assessment: According to the recommendations of the EMA (EMA / CPMP / EWP / 280/96 Corr1), systemic safety will be assessed according to the record of adverse effects, physical examination of patients, and the result of analytical studies;Timepoint(s) of evaluation of this end point: Not applicable | — |
Countries
Spain
Contacts
Public ContactPIEDAD USSETTI GIL
PNEUMOLOGY DEPARTMENT (HOSPITAL UNIVERSITARIO PUERTA DE HIERRO MAJADAHONDA)
Outcome results
None listed