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

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

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).

Study Overview

• Status: Recruiting
• Conditions: Invasive Fungal Infection
• Intervention / Treatment: Drug: Posaconazole IV 6 mg/kg; Drug: Posaconazole PFS 6 mg/kg

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.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Toll Free Number; Phone Number: 1-888-577-8839; Email: Trialsites@merck.com

Study Locations

• Belgium
  • Bruxelles-Capitale, Region De
    • Brussels, Bruxelles-Capitale, Region De, Belgium, 1200
      • Recruiting
      • UCL Saint Luc ( Site 1050)
      • Contact: Study Coordinator; Phone Number: +3227646086
  • Oost-Vlaanderen
    • Gent, Oost-Vlaanderen, Belgium, 9000
      • Recruiting
      • UZ Gent ( Site 1052)
      • Contact: Study Coordinator; Phone Number: +3293324986
  • Vlaams-Brabant
    • Leuven, Vlaams-Brabant, Belgium, 3000
      • Recruiting
      • UZ Leuven ( Site 1051)
      • Contact: Study Coordinator; Phone Number: +3216343972
• Greece
  • Thessaloniki, Greece, 546 42
    • Recruiting
    • General Hospital of Thessaloniki "Ippokrateio" ( Site 1100)
    • Contact: Study Coordinator; Phone Number: 306937442644
  • Attiki
    • Athens, Attiki, Greece, 115 27
      • Recruiting
      • Athens Childrens Hospital Aglaia Kyriakou ( Site 1102)
      • Contact: Study Coordinator; Phone Number: +306973973179
• Israel
  • Haifa, Israel, 3109601
    • Recruiting
    • Rambam Medical Center ( Site 1402)
    • Contact: Study Coordinator; Phone Number: +97247774512
  • Jerusalem, Israel, 9112001
    • Recruiting
    • Hadassah Ein Karem Hebrew University Medical Center ( Site 1401)
    • Contact: Study Coordinator; Phone Number: +97226777111
  • Tel Aviv, Israel, 6423906
    • Recruiting
    • Sourasky Medical Center ( Site 1403)
    • Contact: Study Coordinator; Phone Number: +97236974521
• Mexico
  • Distrito Federal
    • Mexico City, Distrito Federal, Mexico, 04530
      • Recruiting
      • Instituto Nacional de Pediatria-Unidad de Apoyo a la Investigación Clínica ( Site 2200)
      • Contact: Study Coordinator; Phone Number: 5525600809
    • Mexico City, Distrito Federal, Mexico, 06720
      • Recruiting
      • Hospital Infantil de Mexico Federico Gomez-Infectious Diseases ( Site 2202)
      • Contact: Study Coordinator; Phone Number: 525539391946
• Peru
  • Lima, Peru, 15038
    • Recruiting
    • Instituto Nacional de Enfermedades Neoplasicas ( Site 1601)
    • Contact: Study Coordinator; Phone Number: +5112016500
• Poland
  • Dolnoslaskie
    • Wrocław, Dolnoslaskie, Poland, 50-556
      • Recruiting
      • Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckieg-Klinika Transplantacji Szpiku, Onkolog
      • Contact: Study Coordinator; Phone Number: 48717332840
  • Warminsko-mazurskie
    • Olsztyn, Warminsko-mazurskie, Poland, 10-561
      • Recruiting
      • Wojewodzki Specjalistyczny Szpital Dzieciecy ( Site 1705)
      • Contact: Study Coordinator; Phone Number: 0048895393370
• Russian Federation
  • Sankt-Peterburg
    • Saint Petersburg, Sankt-Peterburg, Russian Federation, 194291
      • Completed
      • Mechnikov State Medical University ( Site 1803)
    • Saint Petersburg, Sankt-Peterburg, Russian Federation, 197022
      • Completed
      • Pavlov State Medical University ( Site 1801)
  • Sverdlovskaya Oblast
    • Ekaterinburg, Sverdlovskaya Oblast, Russian Federation, 620149
      • Completed
      • Regional Children Clinical Hospital 1 ( Site 1802)
• United States
  • California
    • San Diego, California, United States, 92123
      • Completed
      • Rady Children's Hospital-San Diego ( Site 2101)
  • Florida
    • Miami, Florida, United States, 33155
      • Completed
      • Nicklaus Children's Hospital ( Site 2109)
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Recruiting
      • Ann & Robert H. Lurie Children's Hospital of Chicago ( Site 2104)
      • Contact: Study Coordinator; Phone Number: 312-227-6280
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Completed
      • Duke University Medical Center ( Site 2106)
  • Texas
    • Corpus Christi, Texas, United States, 78411
      • Completed
      • Driscoll Children's Hospital ( Site 2113)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 day to 2 years (Child)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Panel A: POS IV; Posaconazole 6 mg/kg body weight administered in a single dose by IV infusion on Day 1.	Drug: Posaconazole IV 6 mg/kg; POS 6 mg/kg body weight by IV infusion; Other Names: NOXAFIL®; MK-5592; SCH56592
Experimental: Panel B: POS IV; 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.	Drug: Posaconazole IV 6 mg/kg; POS 6 mg/kg body weight by IV infusion; Other Names: NOXAFIL®; MK-5592; SCH56592
Experimental: Panel B: POS PFS; 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.	Drug: Posaconazole PFS 6 mg/kg; POS nominal 6 mg/kg body weight based on weight bands taken orally; Other Names: NOXAFIL®; MK-5592; SCH56592

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
Area under the plasma concentration-time curve from dosing to infinity (AUC0-∞) of single-dose IV POS (Panel A)	The AUC0-∞ of IV POS is based on population PK analysis.	Predose, 0.25 and 24 hours post-infusion on Day 1
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
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
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
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
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
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
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
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Percentage of participants with all-cause mortality (ACM) [Panel B]	The percentage of participants with ACM will be reported.	Up to 28 days
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
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
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
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

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

Helpful Links

• Merck Clinical Trials Information
• Plain Language Summary

Study record dates

Study Major Dates

• Study Start (Actual): February 22, 2022
• Primary Completion (Estimated): December 16, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: December 9, 2020
• First Submitted That Met QC Criteria: December 9, 2020
• First Posted (Actual): December 11, 2020

Study Record Updates

• Last Update Posted (Actual): March 15, 2024
• Last Update Submitted That Met QC Criteria: March 12, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Bacterial Infections and Mycoses; Infections; Communicable Diseases; Mycoses; Invasive Fungal Infections; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; 14-alpha Demethylase Inhibitors; Trypanocidal Agents; Posaconazole
• Other Study ID Numbers: 5592-127; MK-5592-127 (Other Identifier: Merck); 2019-003842-34 (EudraCT Number); PHRR230411-005589 (Registry Identifier: PHRR); 2023-505613-24 (Registry Identifier: EU CT)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No