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

Merck Sharp & Dohme (MSD)

Status and phase: Enrolling; Phase 2

Conditions: Invasive Fungal Infection

Treatments: Drug: Posaconazole IV 6 mg/kg; Drug: Posaconazole PFS 6 mg/kg

Study type: Interventional

Funder types: Industry

Identifiers

NCT04665037

MK-5592-127 (Other Identifier)

2019-003842-34 (EudraCT Number)

U1111-1292-1190 (Registry Identifier)

5592-127

PHRR230411-005589 (Registry Identifier)

2023-505613-24-00 (Registry Identifier)

Details and patient eligibility

About

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).

Full 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.

Enrollment: 40 estimated patients

Sex: All

Ages: 1 day to 2 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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40 participants in 3 patient groups

Panel A: POS IV

Experimental group

Description:

Posaconazole 6 mg/kg body weight administered in a single dose by IV infusion on Day 1.

Treatment:

Drug: Posaconazole IV 6 mg/kg

Panel B: POS IV

Experimental group

Description:

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.

Treatment:

Drug: Posaconazole IV 6 mg/kg

Panel B: POS PFS

Experimental group

Description:

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.

Treatment:

Drug: Posaconazole PFS 6 mg/kg