Posaconazole (MK-5592) Intravenous and Oral in Children (<2 Years) With Invasive Fungal Infection (MK-5592-127)

Invasive Fungal Infection Clinical Trial

Official title:

A Phase 2, Open-Label, Single-Arm, Sequential-Panel Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Posaconazole (POS, MK-5592) Intravenous and Powder for Oral Suspension Formulations in Pediatric Participants From Birth to Less Than 2 Years of Age With Possible, Probable, or Proven Invasive Fungal Infection

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04665037
• Other study ID #: 5592-127
• Secondary ID: MK-5592-127PHRR2
• Status: Recruiting
• Phase: Phase 2
• Start date: February 22, 2022
• Est. completion date: December 31, 2025

Study information

• Verified date: March 2024
• Source: Merck Sharp & Dohme LLC
• Contact: Toll Free Number
• Phone: 1-888-577-8839
• Email: Trialsites[@]merck.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: December 31, 2025
• Est. primary completion date: December 16, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Day to 2 Years

Eligibility

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

Related Conditions & MeSH terms

• Communicable Diseases
• Infections
• Invasive Fungal Infection
• Invasive Fungal Infections
• Mycoses

Intervention

Drug:
• Posaconazole IV 6 mg/kg
POS 6 mg/kg body weight by IV infusion
• Posaconazole PFS 6 mg/kg
POS nominal 6 mg/kg body weight based on weight bands taken orally

Locations

Country	Name	City	State
Belgium	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
Greece	Athens Childrens Hospital Aglaia Kyriakou ( Site 1102)	Athens	Attiki
Greece	General Hospital of Thessaloniki "Ippokrateio" ( Site 1100)	Thessaloniki
Israel	Rambam Medical Center ( Site 1402)	Haifa
Israel	Hadassah Ein Karem Hebrew University Medical Center ( Site 1401)	Jerusalem
Israel	Sourasky Medical Center ( Site 1403)	Tel Aviv
Mexico	Hospital Infantil de Mexico Federico Gomez-Infectious Diseases ( Site 2202)	Mexico City	Distrito Federal
Mexico	Instituto Nacional de Pediatria-Unidad de Apoyo a la Investigación Clínica ( Site 2200)	Mexico City	Distrito Federal
Peru	Instituto Nacional de Enfermedades Neoplasicas ( Site 1601)	Lima
Poland	Wojewodzki Specjalistyczny Szpital Dzieciecy ( Site 1705)	Olsztyn	Warminsko-mazurskie
Poland	Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckieg-Klinika Transplantacji Szpiku, Onkolog	Wroclaw	Dolnoslaskie
Russian Federation	Regional Children Clinical Hospital 1 ( Site 1802)	Ekaterinburg	Sverdlovskaya Oblast
Russian Federation	Mechnikov State Medical University ( Site 1803)	Saint Petersburg	Sankt-Peterburg
Russian Federation	Pavlov State Medical University ( Site 1801)	Saint Petersburg	Sankt-Peterburg
United States	Ann & Robert H. Lurie Children's Hospital of Chicago ( Site 2104)	Chicago	Illinois
United States	Driscoll Children's Hospital ( Site 2113)	Corpus Christi	Texas
United States	Duke University Medical Center ( Site 2106)	Durham	North Carolina
United States	Nicklaus Children's Hospital ( Site 2109)	Miami	Florida
United States	Rady Children's Hospital-San Diego ( Site 2101)	San Diego	California

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Belgium,  Greece,  Israel,  Mexico,  Peru,  Poland,  Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Average concentration (Cavg) of single-dose IV POS (Panel A)	The Cavg of IV POS is based on population PK analysis.	Predose, 0.25 and 24 hours post-infusion on Day 1
Primary	Maximum concentration (Cmax) of single-dose IV POS (Panel A)	The Cmax of IV POS is based on population PK analysis.	Predose, 0.25 and 24 hours post-infusion on Day 1
Primary	Time to maximum concentration (Tmax) of single-dose IV POS (Panel A)	The Tmax of IV POS is based on population PK analysis.	Predose, 0.25 and 24 hours post-infusion on Day 1
Primary	Area under the plasma concentration-time curve from dosing to 24 hours postdose (AUC0-24) of single-dose IV POS (Panel A)	The AUC 0-24 of IV POS is based on population PK analysis.	Predose, 0.25 and 24 hours post-infusion on Day 1
Primary	Clearance (CL) of single-dose IV POS (Panel A)	The clearance (CL) of IV POS is based on population PK analysis.	Predose, 0.25 and 24 hours post-infusion on Day 1
Primary	Area under the plasma concentration-time curve from dosing to infinity (AUC0-8) of single-dose IV POS (Panel A)	The AUC0-8 of IV POS is based on population PK analysis.	Predose, 0.25 and 24 hours post-infusion on Day 1
Primary	Cavg of multiple-dose IV POS (Panel B)	The Cavg of IV POS is based on population PK analysis.	Predose and 0.25 post-infusion on Day 1; Weeks 1, 2, 4, 6, 9, and 12
Primary	Cmax of multiple-dose IV POS (Panel B)	The Cmax of IV POS is based on population PK analysis.	Predose and 0.25 post-infusion on Day 1; Weeks 1, 2, 4, 6, 9, and 12
Primary	Tmax of multiple-dose IV POS (Panel B)	The Tmax of IV POS is based on population PK analysis.	Predose and 0.25 post-infusion on Day 1; Weeks 1, 2, 4, 6, 9, and 12
Primary	AUC0-24 of multiple-dose IV POS (Panel B)	The AUC0-24 of IV POS is based on population PK analysis.	Predose and 0.25 post-infusion on Day 1; Weeks 1, 2, 4, 6, 9, and 12
Primary	CL of multiple-dose IV POS (Panel B)	The CL of IV POS is based on population PK analysis.	Predose and 0.25 post-infusion on Day 1; Weeks 1, 2, 4, 6, 9, and 12
Primary	Cavg of multiple-dose PFS POS (Panel B)	The Cavg of PFS POS is based on population PK analysis.	Predose and 0.25 post-infusion on Day 1; Weeks 1, 2, 4, 6, 9, and 12
Primary	Cmax of multiple-dose PFS POS (Panel B)	The Cmax of PFS POS is based on population PK analysis.	Predose and 0.25 post-infusion on Day 1; Weeks 1, 2, 4, 6, 9, and 12
Primary	AUC0-24 of multiple-dose PFSPOS (Panel B)	The AUC0-24 of PFS POS is based on population PK analysis.	Predose and 0.25 post-infusion on Day 1; Weeks 1, 2, 4, 6, 9, and 12
Secondary	Cavg of IV POS in neonates and infants <2 years of age compared to adults and older pediatric populations (Panel B)	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.	Predose and 0.25 post-infusion on Day 1; Weeks 1, 2, 4, 6, 9, and 12
Secondary	Percentage of participants with an = 1 adverse event (AE) [Panels A and B]	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.	Up to 98 days
Secondary	Percentage of participants who discontinued study therapy due to an AE (Panels A and B)	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.	Up to 84 days
Secondary	Percentage of participants with a drug-related AE (Panels A and B)	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.	Up to 98 days
Secondary	Percentage of participants with all-cause mortality (ACM) [Panel B]	The percentage of participants with ACM will be reported.	Up to 28 days
Secondary	Percentage of participants with need for systemic antifungal therapy (other than POS) during the study period (Panel B)	Percentage of participants who received additional antifungal therapy in Panel B will be reported.	Up to 84 days

External Links

•   Merck Clinical Trials Information
•   Plain Language Summary