Pharmacokinetics Clinical Trial
Official title:
Pharmacokinetics of Isavuconazole (Cresemba®) Given as Treatment of Invasive Fungal Infections in Patients in the Intensive Care Unit
20 patients admitted to the ICU department and receiving isavuconazole as part of standard care for the treatment of fungal infections will be included in the study. Between day 3 and 7, 8 samples will be collected at t = 0 (pre-dose), and t = 0.5, 1, 2, 4, 6, 8 and 12 hours after end of infusion to obtain a PK curve. An optional, additional sample can be collected after discontinuation of isavuconazole therapy if possible. Total and free isavuconazole concentrations will be determined. A pharmacokinetic model will be fitted to the data from all individuals simultaneously. Data will be analysed using non-linear mixed effects modelling (NONMEM).
Fungal infections are a serious threat to immunocompromised patients and represent a major burden in the critical care setting. The azole antifungal drugs are the most important drugs for managing infections caused by Aspergillus moulds and the prevention of invasive fungal infections in general. Azoles are currently used as first line prophylaxis and treatment of invasive aspergillosis and their use has substantially improved the survival of the overall population. Recently, there has been increased awareness for invasive aspergillosis cases in critically ill patients, including patients with severe influenza (influenza associated pulmonary aspergillosis, IAPA), and recently COVID-19 associated pulmonary aspergillosis (CAPA). These patients require azole-based therapy, for which voriconazole and isavuconazole are recommended first choice drugs. Isavuconazole is a relatively novel azole drug with promising efficacy, a broad antifungal spectrum, favourable side effect profile and limited drug-drug interactions compared to other azole agents. Isavuconazole is registered for the primary treatment of adults with invasive aspergillosis, and patients with mucormycosis where amphotericin B is not suitable. Efficacy and safety information in the isavuconazole label is mostly derived from clinical studies in healthy volunteers. However, the pharmacokinetics in some specific patient populations may differ greatly from those in the healthy population. Changes in pharmacokinetics of isavuconazole in ICU patients are to be expected due to a wide variety of factors, e.g. changes in protein binding and changes in fluid distribution. Therefore, it is likely that the present standard dosing regimens of isavuconazole lead to suboptimal outcomes for ICU patients, similar to observations made for fluconazole and echinocandins. Optimizing dosing regimens in ICU patients for existing antifungal agents such as isavuconazole is important to improve clinical outcome rates. To date, limited information on the pharmacokinetics of isavuconazole in critically ill patients is available and optimal dosing regimens remain uncertain. With this study we aim to describe isavuconazole pharmacokinetics in ICU admitted patients. 20 patients admitted to the ICU department and receiving isavuconazole as part of standard care for the treatment of fungal infections will be included in the study. Between day 3 and 7, 8 samples will be collected at t = 0 (pre-dose), and t = 0.5, 1, 2, 4, 6, 8 and 12 hours after end of infusion to obtain a PK curve. An optional, additional sample can be collected after discontinuation of isavuconazole therapy if possible. Total and free isavuconazole concentrations will be determined. A pharmacokinetic model will be fitted to the data from all individuals simultaneously. Data will be analysed using non-linear mixed effects modelling (NONMEM). NONMEM is a one-stage analysis that simultaneously estimates mean parameters, fixed effect parameters, interindividual variability, and residual random effects. Since allowance can be made for individual differences, this method can be used with both intensive sampling and sparse data (and in the occasion of missing values: an unbalanced number of data points per patients). Primary objective: • To determine the pharmacokinetics of isavuconazole given as treatment of invasive fungal infections in ICU patients as part of standard care. Secondary objectives: - To investigate the protein binding of isavuconazole in ICU patients and the variability in protein binding between patients in the ICU population. - To explore if unbound isavuconazole concentrations can be predicted from total isavuconazole concentrations. - To assess pharmacokinetic/pharmacodynamic target attainment in the ICU patient population. ;
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT04092725 -
Study to Evaluate the Effect of SCY-078 on the PK of Dabigatran in Healthy Subjects
|
Phase 1 | |
| Completed |
NCT04181008 -
Pharmacokinetics of Amiloride Nasal Spray in Healthy Volunteers
|
Early Phase 1 | |
| Active, not recruiting |
NCT03258151 -
Association of Genetic Polymorphisms With Docetaxel-based Chemotherapy Toxicities in Chinese Solid Tumor Patients
|
||
| Completed |
NCT04406415 -
Oral Nafamostat in Healthy Volunteers
|
Phase 1 | |
| Not yet recruiting |
NCT05421312 -
Periarticular Penetration of Cefazolin and Clindamycin in Second Stage Revision Arthroplasty of the Hip
|
Phase 4 | |
| Completed |
NCT02534753 -
A Pharmacokinetics Study of Intravenous Ascorbic Acid
|
Phase 1 | |
| Completed |
NCT01976078 -
Development of Voriconazole Pharmacokinetics and Metabolism in Children and Adolescents
|
N/A | |
| Completed |
NCT01682408 -
Assess Pharmacokinetics of Fostamatinib in Fed and Fasted State in Combination With Ranitidine to Assess Bioavailability
|
Phase 1 | |
| Completed |
NCT01636024 -
To Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Ascending Doses of Inhaled AZD7594
|
Phase 1 | |
| Completed |
NCT01415102 -
A First In Human Study In Healthy People To Evaluate Safety, Toleration And Time Course Of Plasma Concentration Of Single Inhaled Doses Of PF-05212372.
|
Phase 1 | |
| Completed |
NCT01214941 -
Effect of Itraconazole and Ticlopidine on the Pharmacokinetics and Pharmacodynamics of Oral Tramadol
|
Phase 4 | |
| Completed |
NCT01208155 -
Study in Healthy Males to Assess Bioavailability of 4 Different Fostamatinib Tablets
|
Phase 1 | |
| Completed |
NCT01260025 -
Tolerability and Pharmacokinetics of M2ES in the Treatment of Advanced Solid Tumor
|
Phase 1 | |
| Completed |
NCT00983242 -
Drug-Drug Interaction Between Colchicine and Verapamil ER
|
Phase 1 | |
| Completed |
NCT00746499 -
Pharmacokinetic Study of Raltegravir in Healthy Premenopausal Women.
|
Phase 1 | |
| Completed |
NCT01055964 -
a Comparative Pharmacokinetic Study of Two Oral Formulations of Tacrolimus in Renal Allograft Recipients
|
Phase 3 | |
| Completed |
NCT00730145 -
A Single Dose Study Investigating The Elimination Of PD-0332334 In Patients Receiving Regular Hemodialysis
|
Phase 1 | |
| Completed |
NCT00747721 -
Pharmacokinetics of Dexmedetomidine During Prolonged Infusion in ICU
|
Phase 1 | |
| Completed |
NCT00856570 -
A Clinical Study to Determine the Effect of YM178 on the Pharmacokinetics of Warfarin in Healthy Subjects
|
Phase 1 | |
| Completed |
NCT00984009 -
A Drug-Food Interaction Study Between Colchicine and Grapefruit Juice
|
Phase 1 |