POSACONAZOLE for Invasive fungal infection

Inclusion criteria

• {"criterion_text":"- Panel A: Is undergoing treatment for possible, probable, or proven invasive fungal infection (IFI) known or suspected to be cause by fungal pathogens against which POS has demonstrated activity (which can include candidiasis)\n- 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)\n- 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\n- Has a body weight of ≥500 g\n- The participant (or legally acceptable representative) has provided documented informed consent for the study."}

Exclusion criteria

• {"criterion_text":"- Has received POS within 30 days before Day 1\n- Has enrolled previously in the current study and been discontinued\n- Has QTc prolongation at screening >500 msec\n- Has significant liver dysfunction\n- Is hemodynamically unstable, exhibits hemodynamic compromise, or is not expected to survive at least 5 days\n- Has cystic fibrosis, pulmonary sarcoidosis, aspergilloma, or allergic bronchopulmonary aspergillosis.\n- Has a known hereditary problem of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption\n- Has known or suspected active COVID-19 infection\n- Has a known hypersensitivity or other serious adverse reaction to any azole antifungal therapy, or to any other ingredient of the study intervention used\n- 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\n- Has received any listed prohibited medications within the specified timeframes before the start of study intervention\n- Has a known hereditary problem of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption (Panel B)\n- Has suspected/proven invasive candidiasis (Panel B)"}

Primary endpoints

• {"endpoint_text":"- Average concentration (Cavg) of single-dose IV POS (Panel A)","definition_or_measurement_approach":"Pharmacokinetic parameter Cavg measured following single intravenous dose of posaconazole in Panel A (plasma concentration-time)."}
• {"endpoint_text":"- Maximum concentration (Cmax) of single-dose IV POS (Panel A)","definition_or_measurement_approach":"Pharmacokinetic parameter Cmax measured following single intravenous dose of posaconazole in Panel A (plasma concentration-time)."}
• {"endpoint_text":"- Time to maximum concentration (Tmax) of single-dose IV POS (Panel A)","definition_or_measurement_approach":"Pharmacokinetic parameter Tmax measured following single intravenous dose of posaconazole in Panel A."}
• {"endpoint_text":"- Area under the plasma concentration-time curve from dosing to 24 hours postdose (AUC0-24) of single-dose IV POS (Panel A)","definition_or_measurement_approach":"AUC0-24 calculated from plasma concentration-time profile from dosing to 24 hours after a single IV dose in Panel A."}
• {"endpoint_text":"- Clearance (CL) of single-dose IV POS (Panel A)","definition_or_measurement_approach":"Apparent plasma clearance (CL) derived from single-dose IV posaconazole pharmacokinetic data in Panel A."}
• {"endpoint_text":"- Area under the plasma concentration-time curve from dosing to infinity (AUC0-∞) of single-dose IV POS (Panel A)","definition_or_measurement_approach":"AUC0-∞ calculated from plasma concentration-time profile from dosing to infinity for single IV dose in Panel A."}
• {"endpoint_text":"- Cavg of multiple-dose IV POS (Panel B)","definition_or_measurement_approach":"Average concentration (Cavg) derived from multiple IV dosing pharmacokinetic profile in Panel B."}
• {"endpoint_text":"- Cmax of multiple-dose IV POS (Panel B)","definition_or_measurement_approach":"Maximum concentration (Cmax) measured during multiple IV dosing in Panel B."}
• {"endpoint_text":"- Tmax of multiple-dose IV POS (Panel B)","definition_or_measurement_approach":"Time to maximum concentration (Tmax) measured during multiple IV dosing in Panel B."}
• {"endpoint_text":"- AUC0-24 of multiple-dose IV POS (Panel B)","definition_or_measurement_approach":"Area under the plasma concentration-time curve from dosing to 24 hours postdose (AUC0-24) after multiple IV dosing in Panel B."}
• {"endpoint_text":"- CL of multiple-dose IV POS (Panel B)","definition_or_measurement_approach":"Clearance (CL) determined from multiple IV dosing pharmacokinetic data in Panel B."}
• {"endpoint_text":"- Cavg of multiple-dose PFS (Panel B)","definition_or_measurement_approach":"Average concentration (Cavg) derived from multiple dosing of powder for oral suspension (PFS) pharmacokinetic profile in Panel B."}
• {"endpoint_text":"- Cmax of multiple-dose PFS (Panel B)","definition_or_measurement_approach":"Maximum concentration (Cmax) measured during multiple dosing of PFS in Panel B."}
• {"endpoint_text":"- AUC0-24 of multiple-dose PFS (Panel B)","definition_or_measurement_approach":"Area under the plasma concentration-time curve from dosing to 24 hours postdose (AUC0-24) after multiple dosing of PFS in Panel B."}

Secondary endpoints

• {"endpoint_text":"- Cavg of IV POS in neonates and infants <2 years of age compared to adults and older pediatric populations (Panel B only)","definition_or_measurement_approach":"Comparison of average concentration (Cavg) of IV posaconazole in neonates/infants <2 years versus adult and older pediatric populations (Panel B)."}
• {"endpoint_text":"- Percentage of participants with ≥1 adverse events (AEs) [Panels A and B]","definition_or_measurement_approach":"Proportion of participants experiencing one or more adverse events during the study treatment period (Panels A and B)."}
• {"endpoint_text":"- Percentage of participants with ≥1 drug-related AEs (Panels A and B)","definition_or_measurement_approach":"Proportion of participants with one or more adverse events assessed as drug-related (Panels A and B)."}
• {"endpoint_text":"- Percentage of participants discontinuing from study treatment due to AE(s) (Panels A and B)","definition_or_measurement_approach":"Proportion of participants who discontinue study treatment because of adverse event(s) (Panels A and B)."}
• {"endpoint_text":"- Percentage of participants with all-cause mortality through 28 days (Panel B)","definition_or_measurement_approach":"All-cause mortality assessed through Day 28 in participants in Panel B."}
• {"endpoint_text":"- Percentage of participants with need for systemic antifungal therapy (other than POS) during the study period [Panel B]","definition_or_measurement_approach":"Proportion of participants in Panel B who require systemic antifungal therapy other than posaconazole during the study period."}

Methods

• Physician referral materials (Physician Referral Poster/Flyer/Letter) — target: physicians; documents present for Greece and Belgium (e.g. K2_Recruitment Doc Physician Referral Poster_GRC_EL_for pub, K2_Recruitment Doc Physician Referral Flyer_GRC_EN_for pub);
• Patient brochures and patient letters (Patient Brochure, Patient Letter) — target: patients/parents; country versions for Belgium and Greece (e.g. K2_Recruitment Doc Patient Brochure_BEL_EN_for pub, K2_Recruitment Doc Patient Brochure_GRC_EL_for pub, K2_Recruitment Doc Patient Letter_GRC_EL_for pub);
• Study fact sheets and appointment cards (Study Fact Sheet, Appointment Card) — informational materials for potential participants/parents; available for Greece and Belgium (e.g. K2_Recruitment Doc Study Fact Sheet_GRC_EN_for pub, K2_Recruitment Doc Appointment Card_GRC_EL_for pub);
• Patient visit guides and site visit guides (Patient Visit Guide, Site Visit Guide) — operational guidance for visits; country-specific versions for Belgium and Greece (e.g. K2_Recruitment Doc Patient Visit Guide_BEL_EN_for pub, K2_Recruitment Doc Site Visit Guide_GRC_EL_for pub);
• Recruitment arrangements and informed consent procedure documents (K1_Recruitment Arrangements and IC Procedure) — country-specific versions for Belgium, Poland and Greece (e.g. K1_Recruitment Arrangements_EN_K1..., K1_Recruitment Arrangements_POL_PL_for pub, K1_Recruitment Arrangements_GRC_EN_for pub).

Belgium

Earliest CTIS Part Ii Submission Date

18-03-2024

Latest Decision Or Authorization Date

08-08-2024

Processing Time Days

143

Number Of Sites

3

Number Of Participants

6

Poland

Earliest CTIS Part Ii Submission Date

18-03-2024

Latest Decision Or Authorization Date

09-08-2024

Processing Time Days

144

Number Of Sites

1

Number Of Participants

3

Greece

Earliest CTIS Part Ii Submission Date

18-03-2024

Latest Decision Or Authorization Date

16-05-2025

Processing Time Days

424

Number Of Sites

2

Number Of Participants

4

Primary sponsor

Full Name

Merck Sharp & Dohme LLC

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Syneos Health Clinique Inc.

Responsibilities

sponsorDuties code 4

Name

Covance Central Laboratory Services Inc.

Responsibilities

sponsorDuties code 4

Name

Parexel International Corp.

Responsibilities

Investigational Product Information

Third parties

• {"country":"Canada","full_name":"Syneos Health Clinique Inc.","duties_or_roles":"code 4","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United States","full_name":"Covance Central Laboratory Services Inc.","duties_or_roles":"code 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Parexel International Corp.","duties_or_roles":"Investigational Product Information","organisation_type":"Pharmaceutical company"}