Posaconazole (MK-5592) Intravenous and Oral in Children (<2 Years) With Invasive Fungal Infection (MK-5592-127)
- Conditions
- Invasive Fungal Infection
- Interventions
- Registration Number
- NCT04665037
- Lead Sponsor
- Merck Sharp & Dohme LLC
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 40
- 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
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Panel B: POS PFS Posaconazole PFS 6 mg/kg Following a minimum of 7 days IV dosing, participants as clinically able will be transitioned from POS IV to POS PFS nominal 6 mg/kg body weight based on weight bands administered on Day 8, once daily to a maximum 84 days. Panel A: POS IV Posaconazole IV 6 mg/kg Posaconazole 6 mg/kg body weight administered in a single dose by IV infusion on Day 1. Panel B: POS IV Posaconazole IV 6 mg/kg Posaconazole 6 mg/kg body weight administered twice daily by IV infusion on Day 1, and then once daily from Day 2 to a maximum 84 days.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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.
Trial Locations
- Locations (25)
Rady Children's Hospital-San Diego ( Site 2101)
🇺🇸San Diego, California, United States
Nicklaus Children's Hospital ( Site 2109)
🇺🇸Miami, Florida, United States
Ann & Robert H. Lurie Children's Hospital of Chicago ( Site 2104)
🇺🇸Chicago, Illinois, United States
Duke University Medical Center ( Site 2106)
🇺🇸Durham, North Carolina, United States
Driscoll Children's Hospital ( Site 2113)
🇺🇸Corpus Christi, Texas, United States
UCL Saint Luc ( Site 1050)
🇧🇪Brussels, Bruxelles-Capitale, Region De, Belgium
UZ Gent ( Site 1052)
🇧🇪Gent, Oost-Vlaanderen, Belgium
UZ Leuven ( Site 1051)
🇧🇪Leuven, Vlaams-Brabant, Belgium
Athens Childrens Hospital Aglaia Kyriakou ( Site 1102)
🇬🇷Athens, Attiki, Greece
General Hospital of Thessaloniki "Ippokrateio" ( Site 1100)
🇬🇷Thessaloniki, Greece
Rambam Medical Center ( Site 1402)
🇮🇱Haifa, Israel
Hadassah Ein Karem Hebrew University Medical Center ( Site 1401)
🇮🇱Jerusalem, Israel
Sheba Medical Center ( Site 1404)
🇮🇱Ramat Gan, Israel
Sourasky Medical Center ( Site 1403)
🇮🇱Tel Aviv, Israel
Seoul National University Hospital-Pediatrics ( Site 2600)
🇰🇷Seoul, Korea, Republic of
Instituto Nacional de Pediatria-Unidad de Apoyo a la Investigación Clínica ( Site 2200)
🇲🇽Mexico City, Distrito Federal, Mexico
Hospital Infantil de Mexico Federico Gomez-Infectious Diseases ( Site 2202)
🇲🇽Mexico City, Distrito Federal, Mexico
Instituto Nacional de Enfermedades Neoplasicas ( Site 1601)
🇵🇪Lima, Peru
Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckieg-Klinika Transplantacji Szpiku, Onkolog ( Site 1708)
🇵🇱Wrocław, Dolnoslaskie, Poland
Wojewodzki Specjalistyczny Szpital Dzieciecy ( Site 1705)
🇵🇱Olsztyn, Warminsko-mazurskie, Poland
Mechnikov State Medical University ( Site 1803)
🇷🇺Saint Petersburg, Sankt-Peterburg, Russian Federation
Pavlov State Medical University ( Site 1801)
🇷🇺Saint Petersburg, Sankt-Peterburg, Russian Federation
Regional Children Clinical Hospital 1 ( Site 1802)
🇷🇺Ekaterinburg, Sverdlovskaya Oblast, Russian Federation
Ivano-Frankivsk Regional Pediatric Clinical Hospital ( Site 1911)
🇺🇦Ivano-Frankivsk, Ivano-Frankivska Oblast, Ukraine
NATIONAL CHILDREN'S SPECIALIZED HOSPITAL "OKHMATDYT" OF THE -Intensive Care Unit ( Site 1912)
🇺🇦Kiev, Kyiv, Ukraine