Invasive Fungal Infection
Conditions
Brief summary
This study aims to estimate the pharmacokinetics (PK) of posaconazole (POS, MK-5592) intravenous (IV) and powder for oral suspension (PFS) formulations in pediatric participants \<2 years of age with invasive fungal infection (IFI).
Detailed description
There are 2 panels in this study. In Panel A, POS IV will be evaluated in ≥8 participants. In Panel B, both POS IV and POS PFS will be evaluated in ≥14 participants, including ≥6 who are \<3 months of age and ≥5 who transition to the PFS formulation of POS.
Interventions
DRUGPosaconazole IV 6 mg/kg
POS 6 mg/kg body weight by IV infusion
DRUGPosaconazole PFS 6 mg/kg
POS nominal 6 mg/kg body weight based on weight bands taken orally
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Days to 2 Years
Healthy volunteers
No
Inclusion criteria
* Panel A: is undergoing treatment for possible, probable, or proven IFI known or suspected to be cause by fungal pathogens against which POS has demonstrated activity (which can include candidiasis) * Panel B: has an investigator-assessed diagnosis of possible, probable, or proven IFI known or suspected to be cause by fungal pathogens against which POS has demonstrated activity (and cannot include candidiasis) * 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. * Has a body weight of ≥500 g * The participant (or legally acceptable representative) has provided documented informed consent for the study.
Exclusion criteria
* Has received POS within 30 days before Day 1 * Has cystic fibrosis, pulmonary sarcoidosis, aspergilloma, or allergic bronchopulmonary aspergillosis * Has a known hereditary problem of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption * Has known or suspected active COVID-19 infection * Has a known hypersensitivity or other serious adverse reaction to any azole antifungal therapy, or to any other ingredient of the study intervention used * Has any known history of torsade de pointes, unstable cardiac arrhythmia or proarrhythmic conditions, a history of recent myocardial infarction, congenital or acquired QT interval (QT) prolongation, or cardiomyopathy in the context of cardiac failure within 90 days of first dose of study intervention * Has received any listed prohibited medications within the specified timeframes before the start of study intervention * Has a known hereditary problem of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption (Part B) * Has suspected/proven invasive candidiasis (Part B) * Has enrolled previously in the current study and been discontinued * Has QTc prolongation at screening \>500 msec * Has significant liver dysfunction * Is hemodynamically unstable, exhibits hemodynamic compromise, or is not expected to survive at least 5 days
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Average concentration (Cavg) of single-dose IV POS (Panel A) | Predose, 0.25 and 24 hours post-infusion on Day 1 | The Cavg of IV POS is based on population PK analysis. |
| Maximum concentration (Cmax) of single-dose IV POS (Panel A) | Predose, 0.25 and 24 hours post-infusion on Day 1 | The Cmax of IV POS is based on population PK analysis. |
| Time to maximum concentration (Tmax) of single-dose IV POS (Panel A) | Predose, 0.25 and 24 hours post-infusion on Day 1 | The Tmax of IV POS is based on population PK analysis. |
| Area under the plasma concentration-time curve from dosing to 24 hours postdose (AUC0-24) of single-dose IV POS (Panel A) | Predose, 0.25 and 24 hours post-infusion on Day 1 | The AUC 0-24 of IV POS is based on population PK analysis. |
| Clearance (CL) of single-dose IV POS (Panel A) | Predose, 0.25 and 24 hours post-infusion on Day 1 | The clearance (CL) of IV POS is based on population PK analysis. |
| Area under the plasma concentration-time curve from dosing to infinity (AUC0-∞) of single-dose IV POS (Panel A) | Predose, 0.25 and 24 hours post-infusion on Day 1 | The AUC0-∞ of IV POS is based on population PK analysis. |
| Cavg of multiple-dose IV POS (Panel B) | Predose and 0.25 post-infusion on Day 1; Weeks 1, 2, 4, 6, 9, and 12 | The Cavg of IV POS is based on population PK analysis. |
| Cmax of multiple-dose IV POS (Panel B) | Predose and 0.25 post-infusion on Day 1; Weeks 1, 2, 4, 6, 9, and 12 | The Cmax of IV POS is based on population PK analysis. |
| Tmax of multiple-dose IV POS (Panel B) | Predose and 0.25 post-infusion on Day 1; Weeks 1, 2, 4, 6, 9, and 12 | The Tmax of IV POS is based on population PK analysis. |
| AUC0-24 of multiple-dose IV POS (Panel B) | Predose and 0.25 post-infusion on Day 1; Weeks 1, 2, 4, 6, 9, and 12 | The AUC0-24 of IV POS is based on population PK analysis. |
| CL of multiple-dose IV POS (Panel B) | Predose and 0.25 post-infusion on Day 1; Weeks 1, 2, 4, 6, 9, and 12 | The CL of IV POS is based on population PK analysis. |
| Cavg of multiple-dose PFS POS (Panel B) | Predose and 0.25 post-infusion on Day 1; Weeks 1, 2, 4, 6, 9, and 12 | The Cavg of PFS POS is based on population PK analysis. |
| Cmax of multiple-dose PFS POS (Panel B) | Predose and 0.25 post-infusion on Day 1; Weeks 1, 2, 4, 6, 9, and 12 | The Cmax of PFS POS is based on population PK analysis. |
| AUC0-24 of multiple-dose PFSPOS (Panel B) | Predose and 0.25 post-infusion on Day 1; Weeks 1, 2, 4, 6, 9, and 12 | The AUC0-24 of PFS POS is based on population PK analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cavg of IV POS in neonates and infants <2 years of age compared to adults and older pediatric populations (Panel B) | Predose and 0.25 post-infusion on Day 1; Weeks 1, 2, 4, 6, 9, and 12 | The Cavg of IV POS is based on population PK analysis. Comparisons between participants in Panel B will be made to data that was previously collected in older participants. |
| Percentage of participants with an ≥ 1 adverse event (AE) [Panels A and B] | Up to 98 days | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. |
| Percentage of participants who discontinued study therapy due to an AE (Panels A and B) | Up to 84 days | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. |
| Percentage of participants with a drug-related AE (Panels A and B) | Up to 98 days | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. |
| Percentage of participants with all-cause mortality (ACM) [Panel B] | Up to 28 days | The percentage of participants with ACM will be reported. |
| Percentage of participants with need for systemic antifungal therapy (other than POS) during the study period (Panel B) | Up to 84 days | Percentage of participants who received additional antifungal therapy in Panel B will be reported. |
Countries
Belgium, Greece, Israel, Mexico, Peru, Poland, Russia, South Korea, Ukraine, United States
Contacts
CONTACTToll Free Number
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Outcome results
None listed