Invasive Fungal Infection MedDRA version: 20.0 Level: PT Classification code 10017533 Term: Fungal infection System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Trade Name: Noxafil® (posaconazole)
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: POSACONAZOLE
Other descriptive name: POSACONAZOLE
Concentration unit: mg/ml milligra
Sponsors
Merck Sharp & Dohme LLC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Panel A Participants Only 1. Is undergoing treatment for possible, probable, or proven IFI known or suspected to be caused by fungal pathogens against which POS has demonstrated activity (which can include candidiasis) per the modified 2008 EORTC/MSG consensus criteria Panel B Participants Only 2. Has an investigator-assessed diagnosis of possible, probable, or proven IFI known or suspected to be caused by fungal pathogens against which POS has demonstrated activity (see Appendix 8 of the protocol for diagnostic guidance per the modified 2020 EORTC/MSG consensus criteria) Panel A and Panel B Participants 3. Has a central line (eg, central venous catheter, peripherally inserted central catheter) in place or planned to be in place before beginning IV study intervention 4. Is male or female, from birth to =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Panel A and B Participants 1. Has cystic fibrosis, pulmonary sarcoidosis, aspergilloma, or allergic bronchopulmonary aspergillosis 2. Has known or suspected active COVID-19 infection. 3. Has a known hypersensitivity or other serious adverse reaction to any azole antifungal therapy, or to any other ingredient of the study intervention used 4. Has any known history of torsade de pointes, unstable cardiac arrhythmia or proarrhythmic conditions, a history of recent myocardial infarction, congenital or acquired QT prolongation, or cardiomyopathy in the context of cardiac failure within 90 days of first dose of study intervention 5. Has any condition that, in the opinion of the investigator, may interfere with optimal participation in the study Panel B Participants Only 6. Has a known hereditary problem of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption. 7. Has suspected/proven invasive candidiasis. Panel A Participants Only 8. Has received any treatment specifically listed in the protocol within the specified time period before the start of study intervention Panel B Participants Only 9. Has received any treatment specifically listed in the protocol within the specified time period before the start of study intervention. Panel A and Panel B Participants 10. Has enrolled previously in the current study and been discontinued 11. Has QTc prolongation (based on either Fridericia or Bazett's correction) at screening >500 msec 12. Has significant liver dysfunction at screening, defined as: - Total bilirubin >1.5 × ULN and AST or ALT >3 × ULN with normal alkaline phosphatase 13. Has calculated creatinine clearance <20 mL/min/1.73 m2 (modified Schwartz formula) at screening 14. Is hemodynamically unstable, exhibits hemodynamic compromise, or is not expected to survive at least 5 days 15. Has an immediate family member (eg, parent/legal guardian, sibling) who is investigational site or Sponsor staff directly involved with this study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To estimate the pharmacokinetics (PK) of posaconazole (POS) intravenous (IV) and powder for oral suspension (PFS) in participants <2 years of age (Panels A and B).;Secondary Objective: 1. To compare the exposures to POS in neonates and infants <2 years of age to those from adult and older pediatric population (Panel B only). 2. To evaluate the safety and tolerability of POS in participants <2 years of age (Panels A and B separately). 3. To evaluate all-cause mortality at Day 28 in participants treated with POS (Panel B only). 4. To evaluate the need for additional antifungal therapy (Panel B only). ;Primary end point(s): 1. Average concentration (Cavg) of single-dose IV POS (Panel A) 2. Maximum concentration (Cmax) of single-dose IV POS (Panel A) 3. Time to maximum concentration (Tmax) of single-dose IV POS (Panel A) 4. Area under the plasma concentration-time curve from dosing to 24 hours postdose (AUC0-24) of single-dose IV POS (Panel A) 5. Clearance (CL) of single-dose IV POS (Panel A) 6. Area under the plasma concentration-time curve from dosing to infinity (AUC0-8) of single-dose IV POS (Panel A) 7. Cavg of multiple-dose IV POS (Panel B) 8. Cmax of multiple-dose IV POS (Panel B) 9. Tmax of multiple-dose IV POS (Panel B) 10. AUC0-24 of multiple-dose IV POS (Panel B) 11. CL of multiple-dose IV POS (Panel B) 12. AUC0-8 of multiple-dose IV POS (Panel B) 13. Cavg of multiple-dose PFS (Panel B) 14. Cmax of multiple-dose PFS (Panel B) 15. Tmax of multiple-dose PFS (Panel B) 16. AUC0-24 of multiple-dose PFS (Panel B) 17. CL of multiple-dose PFS (Panel B) 18. AUC0-8 of multiple-dose PFS (Panel B);Timepoint(s) of evaluation of this end point: 1. Day 1 and Day 2 2. Day 1 and Day 2 3. Day 1 and Day 2 4. Day 1 and Day 2 5. Day 1 and Day 2 6. Day 1 and Day 2 7. Weeks 1, 2, 4, 6, 9, and 12 8. Weeks 1, 2, 4, 6, 9, and 12 9. Weeks 1, 2, 4, 6, 9, and 12 10. Weeks 1, 2, 4, 6, 9, and 12 11. Weeks 1, 2, 4, 6, 9, and 12 12. Weeks 1, 2, 4, 6, 9, and 12 13. Weeks 1 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Cavg of IV POS in neonates and infants <2 years of age compared to adults and older pediatric populations (Panel B only) 2. Percentage of participants with =1 adverse events (AEs) (Panels A and B) 3. Percentage of participants with =1 drug-related AEs (Panels A and B) 4. Percentage of participants discontinuing from study treatment due to AE(s) (Panels A and B) 5. Percentage of participants with all-cause mortality through 28 days (Panel B) 6. Percentage of participants with need for systemic antifungal therapy (other than POS) during the study period [Panel B] ;Timepoint(s) of evaluation of this end point: 1. Day 1 and Day 2 2. Up to 98 days 3. Up to 98 days 4. Up to 84 days 5. Up to Day 28 6. Up to 84 days | — |
Countries
Belgium, Greece, Israel, Peru, Poland, Russian Federation, United Kingdom, United States
Outcome results
None listed