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

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

Overview

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

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

Primary outcome measures

• Average concentration (Cavg) of single-dose IV POS (Panel A) [Time frame: Predose, 0.25 and 24 hours post-infusion on Day 1]
• Maximum concentration (Cmax) of single-dose IV POS (Panel A) [Time frame: Predose, 0.25 and 24 hours post-infusion on Day 1]
• Time to maximum concentration (Tmax) of single-dose IV POS (Panel A) [Time frame: Predose, 0.25 and 24 hours post-infusion on Day 1]
• Area under the plasma concentration-time curve from dosing to 24 hours postdose (AUC0-24) of single-dose IV POS (Panel A) [Time frame: Predose, 0.25 and 24 hours post-infusion on Day 1]
• Clearance (CL) of single-dose IV POS (Panel A) [Time frame: Predose, 0.25 and 24 hours post-infusion on Day 1]
• Area under the plasma concentration-time curve from dosing to infinity (AUC0-∞) of single-dose IV POS (Panel A) [Time frame: Predose, 0.25 and 24 hours post-infusion on Day 1]
• Cavg of multiple-dose IV POS (Panel B) [Time frame: Predose and 0.25 post-infusion on Day 1; Weeks 1, 2, 4, 6, 9, and 12]
• Cmax of multiple-dose IV POS (Panel B) [Time frame: Predose and 0.25 post-infusion on Day 1; Weeks 1, 2, 4, 6, 9, and 12]
• Tmax of multiple-dose IV POS (Panel B) [Time frame: Predose and 0.25 post-infusion on Day 1; Weeks 1, 2, 4, 6, 9, and 12]
• AUC0-24 of multiple-dose IV POS (Panel B) [Time frame: Predose and 0.25 post-infusion on Day 1; Weeks 1, 2, 4, 6, 9, and 12]

Secondary outcome measures (6)

• Cavg of IV POS in neonates and infants <2 years of age compared to adults and older pediatric populations (Panel B) [Time frame: Predose and 0.25 post-infusion on Day 1; Weeks 1, 2, 4, 6, 9, and 12]
• Percentage of participants with an ≥ 1 adverse event (AE) [Panels A and B] [Time frame: Up to 98 days]
• Percentage of participants who discontinued study therapy due to an AE (Panels A and B) [Time frame: Up to 84 days]
• Percentage of participants with a drug-related AE (Panels A and B) [Time frame: Up to 98 days]
• Percentage of participants with all-cause mortality (ACM) [Panel B] [Time frame: Up to 28 days]
• Percentage of participants with need for systemic antifungal therapy (other than POS) during the study period (Panel B) [Time frame: Up to 84 days]

Eligibility 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 5 centers

• Rady Children's Hospital-San Diego ( Site 2101) — San Diego
• Nicklaus Children's Hospital ( Site 2109) — Miami
• Ann & Robert H. Lurie Children's Hospital of Chicago ( Site 2104) — Chicago
• Duke University Medical Center ( Site 2106) — Durham
• Driscoll Children's Hospital ( Site 2113) — Corpus Christi

Israel · 4 centers

• Rambam Medical Center ( Site 1402) — Haifa
• Hadassah Ein Karem Hebrew University Medical Center ( Site 1401) — Jerusalem
• Sheba Medical Center ( Site 1404) — Ramat Gan
• Sourasky Medical Center ( Site 1403) — Tel Aviv

Belgium · 3 centers

• UCL Saint Luc ( Site 1050) — Brussels
• UZ Gent ( Site 1052) — Ghent
• UZ Leuven ( Site 1051) — Leuven

Mexico · 3 centers

• Instituto Nacional de Pediatria-Unidad de Apoyo a la Investigación Clínica ( Site 2200) — Mexico City
• Hospital Infantil de Mexico Federico Gomez-Infectious Diseases ( Site 2202) — Mexico City
• Hospital Universitario "Dr. Jose Eleuterio Gonzalez"-Infectologia ( Site 2203) — Monterrey

Russia · 3 centers

• Mechnikov State Medical University ( Site 1803) — Saint Petersburg
• Pavlov State Medical University ( Site 1801) — Saint Petersburg
• Regional Children Clinical Hospital 1 ( Site 1802) — Yekaterinburg

Greece · 2 centers

• Athens Childrens Hospital Aglaia Kyriakou ( Site 1102) — Athens
• General Hospital of Thessaloniki "Ippokrateio" ( Site 1100) — Thessaloniki

Poland · 2 centers

• Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckieg-Klinika Transplantacji Szpiku — Wroclaw
• Wojewodzki Specjalistyczny Szpital Dzieciecy ( Site 1705) — Olsztyn

Ukraine · 2 centers

• Ivano-Frankivsk Regional Pediatric Clinical Hospital ( Site 1911) — Ivano-Frankivsk
• NATIONAL CHILDREN'S SPECIALIZED HOSPITAL "OKHMATDYT" OF THE -Intensive Care Unit ( Site 19 — Kiev

Peru · 1 center

• Instituto Nacional de Enfermedades Neoplasicas ( Site 1601) — Lima

South Korea · 1 center

• Seoul National University Hospital-Pediatrics ( Site 2600) — Seoul

Identifiers

NCT: NCT04665037 · 5592-127 · MK-5592-127 · PHRR230411-005589 · 2023-505613-24-00 · U1111-1292-1190 · 2019-003842-34

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗