Clinical trial NCT04665037: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Invasive Fungal Infection
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2020-12-11
Enrollment: 40
Sex: ALL
Minimum age (years): 1
Maximum age (years): 2
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Average concentration (Cavg) of single-dose IV POS (Panel A)
timeFrame: Predose, 0.25 and 24 hours post-infusion on Day 1
measure: Maximum concentration (Cmax) of single-dose IV POS (Panel A)
timeFrame: Predose, 0.25 and 24 hours post-infusion on Day 1
measure: Time to maximum concentration (Tmax) of single-dose IV POS (Panel A)
timeFrame: Predose, 0.25 and 24 hours post-infusion on Day 1
measure: Area under the plasma concentration-time curve from dosing to 24 hours postdose (AUC0-24) of single-dose IV POS (Panel A)
timeFrame: Predose, 0.25 and 24 hours post-infusion on Day 1
measure: Clearance (CL) of single-dose IV POS (Panel A)
timeFrame: Predose, 0.25 and 24 hours post-infusion on Day 1
measure: Area under the plasma concentration-time curve from dosing to infinity (AUC0-∞) of single-dose IV POS (Panel A)
timeFrame: Predose, 0.25 and 24 hours post-infusion on Day 1
measure: Cavg of multiple-dose IV POS (Panel B)
timeFrame: Predose and 0.25 post-infusion on Day 1; Weeks 1, 2, 4, 6, 9, and 12
measure: Cmax of multiple-dose IV POS (Panel B)
timeFrame: Predose and 0.25 post-infusion on Day 1; Weeks 1, 2, 4, 6, 9, and 12
measure: Tmax of multiple-dose IV POS (Panel B)
timeFrame: Predose and 0.25 post-infusion on Day 1; Weeks 1, 2, 4, 6, 9, and 12
measure: AUC0-24 of multiple-dose IV POS (Panel B)
timeFrame: Predose and 0.25 post-infusion on Day 1; Weeks 1, 2, 4, 6, 9, and 12
measure: CL of multiple-dose IV POS (Panel B)
timeFrame: Predose and 0.25 post-infusion on Day 1; Weeks 1, 2, 4, 6, 9, and 12
measure: Cavg of multiple-dose PFS POS (Panel B)
timeFrame: Predose and 0.25 post-infusion on Day 1; Weeks 1, 2, 4, 6, 9, and 12
measure: Cmax of multiple-dose PFS POS (Panel B)
timeFrame: Predose and 0.25 post-infusion on Day 1; Weeks 1, 2, 4, 6, 9, and 12
measure: AUC0-24 of multiple-dose PFSPOS (Panel B)
timeFrame: Predose and 0.25 post-infusion on Day 1; Weeks 1, 2, 4, 6, 9, and 12
Secondary outcomes:
measure: Cavg of IV POS in neonates and infants <2 years of age compared to adults and older pediatric populations (Panel B)
timeFrame: Predose and 0.25 post-infusion on Day 1; Weeks 1, 2, 4, 6, 9, and 12
measure: Percentage of participants with an ≥ 1 adverse event (AE) [Panels A and B]
timeFrame: Up to 98 days
measure: Percentage of participants who discontinued study therapy due to an AE (Panels A and B)
timeFrame: Up to 84 days
measure: Percentage of participants with a drug-related AE (Panels A and B)
timeFrame: Up to 98 days
measure: Percentage of participants with all-cause mortality (ACM) [Panel B]
timeFrame: Up to 28 days
measure: Percentage of participants with need for systemic antifungal therapy (other than POS) during the study period (Panel B)
timeFrame: Up to 84 days
Other outcomes:
Locations:
city: San Diego
country: United States
facility: Rady Children's Hospital-San Diego ( Site 2101)
state: California
city: Miami
country: United States
facility: Nicklaus Children's Hospital ( Site 2109)
state: Florida
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago ( Site 2104)
state: Illinois
city: Durham
country: United States
facility: Duke University Medical Center ( Site 2106)
state: North Carolina
city: Corpus Christi
country: United States
facility: Driscoll Children's Hospital ( Site 2113)
state: Texas
city: Brussels
country: Belgium
facility: UCL Saint Luc ( Site 1050)
state: Bruxelles-Capitale, Region De
city: Gent
country: Belgium
facility: UZ Gent ( Site 1052)
state: Oost-Vlaanderen
city: Leuven
country: Belgium
facility: UZ Leuven ( Site 1051)
state: Vlaams-Brabant
city: Athens
country: Greece
facility: Athens Childrens Hospital Aglaia Kyriakou ( Site 1102)
state: Attiki
city: Thessaloniki
country: Greece
facility: General Hospital of Thessaloniki "Ippokrateio" ( Site 1100)
city: Haifa
country: Israel
facility: Rambam Medical Center ( Site 1402)
city: Jerusalem
country: Israel
facility: Hadassah Ein Karem Hebrew University Medical Center ( Site 1401)
city: Ramat Gan
country: Israel
facility: Sheba Medical Center ( Site 1404)
city: Tel Aviv
country: Israel
facility: Sourasky Medical Center ( Site 1403)
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital-Pediatrics ( Site 2600)
city: Mexico City
country: Mexico
facility: Instituto Nacional de Pediatria-Unidad de Apoyo a la Investigación Clínica ( Site 2200)
state: Distrito Federal
city: Mexico City
country: Mexico
facility: Hospital Infantil de Mexico Federico Gomez-Infectious Diseases ( Site 2202)
state: Distrito Federal
city: Lima
country: Peru
facility: Instituto Nacional de Enfermedades Neoplasicas ( Site 1601)
city: Wrocław
country: Poland
facility: Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckieg-Klinika Transplantacji Szpiku, Onkolog ( Site 1708)
state: Dolnoslaskie
city: Olsztyn
country: Poland
facility: Wojewodzki Specjalistyczny Szpital Dzieciecy ( Site 1705)
state: Warminsko-mazurskie
city: Saint Petersburg
country: Russian Federation
facility: Mechnikov State Medical University ( Site 1803)
state: Sankt-Peterburg
city: Saint Petersburg
country: Russian Federation
facility: Pavlov State Medical University ( Site 1801)
state: Sankt-Peterburg
city: Ekaterinburg
country: Russian Federation
facility: Regional Children Clinical Hospital 1 ( Site 1802)
state: Sverdlovskaya Oblast
city: Ivano-Frankivsk
country: Ukraine
facility: Ivano-Frankivsk Regional Pediatric Clinical Hospital ( Site 1911)
state: Ivano-Frankivska Oblast
city: Kiev
country: Ukraine
facility: NATIONAL CHILDREN'S SPECIALIZED HOSPITAL "OKHMATDYT" OF THE -Intensive Care Unit ( Site 1912)
state: Kyiv
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: