Trial Outcomes & Findings for Pharmacokinetics and Safety of Intravenous Posaconazole (MK-5592) in Chinese Participants at High Risk for Invasive Fungal Infections (MK-5592-120) (NCT NCT03336502)

NCT ID: NCT03336502

Last Updated: 2019-12-19

Results Overview

Characterization of the pharmacokinetics (PK) parameters of POS determined from plasma samples taken at steady-state after receiving IV administration of 300 mg POS twice a day (BID) on Day 1 and then 300 mg POS QD until at least Day 10. Steady-state Cavg, where Cavg is defined as AUC0-24hr divided by the dosing interval. Subgroup 1 - Serial PK, multiple same-day blood draw, performed specifically for determination of PK parameters of Cavg, AUC, Cmin, Cmax, Tmax and Total Body Clearance in addition to plasma trough determination. Subgroup 2 - Sparse PK, once a day blood draw, performed for plasma trough determination only.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 70 participants
• Primary outcome timeframe: Serial PK (Subgroup 1) on Day 10 at pre-dose, 1 hr. post start of infusion (SOI), end of infusion (EOI), 15 min. after EOI and 4, 8, 12, 24 hours post SOI
• Results posted on: 2019-12-19

Participant Flow

70 participants were randomized and 70 received at least one dose of study drug.

Participant milestones

Measure	Serial PK (Subgroup 1) Posaconazole (POS) 300 mg intravenous (IV) infusion twice on Day 1 followed by 300 mg IV infusion once daily on Days 2 to 10 (±1). At the discretion of the investigator, participants may have received POS 300 mg IV infusion once daily or 200 mg oral suspension 3 times daily for up to 18 additional days. Serial PK requires full intensive blood sampling for PK measurements	Sparse PK (Subgroup 2) POS 300 mg intravenous (IV) infusion twice on Day 1 followed by 300 mg IV infusion once daily on Days 2 to 10 (±1). At the discretion of the investigator, participants may have received POS 300 mg IV infusion once daily or 200 mg oral suspension 3 times daily for up to 18 additional days. Sparse PK requires sparse infrequent blood sampling for PK measurements
Overall Study STARTED	30	40
Overall Study COMPLETED	26	31
Overall Study NOT COMPLETED	4	9

Reasons for withdrawal

Measure	Serial PK (Subgroup 1) Posaconazole (POS) 300 mg intravenous (IV) infusion twice on Day 1 followed by 300 mg IV infusion once daily on Days 2 to 10 (±1). At the discretion of the investigator, participants may have received POS 300 mg IV infusion once daily or 200 mg oral suspension 3 times daily for up to 18 additional days. Serial PK requires full intensive blood sampling for PK measurements	Sparse PK (Subgroup 2) POS 300 mg intravenous (IV) infusion twice on Day 1 followed by 300 mg IV infusion once daily on Days 2 to 10 (±1). At the discretion of the investigator, participants may have received POS 300 mg IV infusion once daily or 200 mg oral suspension 3 times daily for up to 18 additional days. Sparse PK requires sparse infrequent blood sampling for PK measurements
Overall Study Physician Decision	0	1
Overall Study Prohibited Drugs	1	1
Overall Study Death	1	2
Overall Study Adverse Event	2	5

Baseline Characteristics

Pharmacokinetics and Safety of Intravenous Posaconazole (MK-5592) in Chinese Participants at High Risk for Invasive Fungal Infections (MK-5592-120)

Baseline characteristics by cohort

Measure	Serial PK (Subgroup 1) n=30 Participants Posaconazole (POS) 300 mg intravenous (IV) infusion twice on Day 1 followed by 300 mg IV infusion once daily on Days 2 to 10 (±1). At the discretion of the investigator, participants may have received POS 300 mg IV infusion once daily or 200 mg oral suspension 3 times daily for up to 18 additional days. Serial PK requires full intensive blood sampling for PK measurements	Sparse PK (Subgroup 2) n=40 Participants POS 300 mg intravenous (IV) infusion twice on Day 1 followed by 300 mg IV infusion once daily on Days 2 to 10 (±1). At the discretion of the investigator, participants may have received POS 300 mg IV infusion once daily or 200 mg oral suspension 3 times daily for up to 18 additional days. Sparse PK requires sparse infrequent blood sampling for PK measurements	Total n=70 Participants Total of all reporting groups
Age, Continuous 18 to 70 Years of Age	39.8 Years STANDARD_DEVIATION 13.3 • n=93 Participants	45.4 Years STANDARD_DEVIATION 15.1 • n=4 Participants	43 Years STANDARD_DEVIATION 14.5 • n=27 Participants
Sex: Female, Male Female	14 Participants n=93 Participants	20 Participants n=4 Participants	34 Participants n=27 Participants
Sex: Female, Male Male	16 Participants n=93 Participants	20 Participants n=4 Participants	36 Participants n=27 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	30 Participants n=93 Participants	40 Participants n=4 Participants	70 Participants n=27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Asian	30 Participants n=93 Participants	40 Participants n=4 Participants	70 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Black or African American	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) White	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants

PRIMARY outcome

Timeframe: Serial PK (Subgroup 1) on Day 10 at pre-dose, 1 hr. post start of infusion (SOI), end of infusion (EOI), 15 min. after EOI and 4, 8, 12, 24 hours post SOI

Population: Analysis population includes participants who had serial blood draws on Day 10. Sparse PK (subgroup 2) is not included in this analysis because blood was drawn only once on Day 10 for plasma trough determination.

Characterization of the pharmacokinetics (PK) parameters of POS determined from plasma samples taken at steady-state after receiving IV administration of 300 mg POS twice a day (BID) on Day 1 and then 300 mg POS QD until at least Day 10. Steady-state Cavg, where Cavg is defined as AUC0-24hr divided by the dosing interval.

Subgroup 1 - Serial PK, multiple same-day blood draw, performed specifically for determination of PK parameters of Cavg, AUC, Cmin, Cmax, Tmax and Total Body Clearance in addition to plasma trough determination.

Subgroup 2 - Sparse PK, once a day blood draw, performed for plasma trough determination only.

Outcome measures

Measure	Serial PK (Subgroup 1) n=27 Participants Posaconazole (POS) 300 mg intravenous (IV) infusion twice on Day 1 followed by 300 mg IV infusion once daily on Days 2 to 10 (±1). At the discretion of the investigator, participants may have received POS 300 mg IV infusion once daily or 200 mg oral suspension 3 times daily for up to 18 additional days. Serial PK requires full intensive blood sampling for PK measurements	Sparse PK (Subgroup 2) POS 300 mg intravenous (IV) infusion twice on Day 1 followed by 300 mg IV infusion once daily on Days 2 to 10 (±1). At the discretion of the investigator, participants may have received POS 300 mg IV infusion once daily or 200 mg oral suspension 3 times daily for up to 18 additional days. Sparse PK requires sparse infrequent blood sampling for PK measurements
Steady State (ss) Average Concentration (Cavg) of Posaconazole of Serial PK (Subgroup 1) on Day 10	2986.28 ng/mL Standard Deviation 1074.5	—

PRIMARY outcome

Timeframe: Serial PK (Subgroup 1) on Day 10 at pre-dose, 1 hr. post start of infusion (SOI), end of infusion (EOI), 15 min. after EOI and 4, 8, 12, 24 hours post SOI

Population: Analysis population includes participants who had serial blood draws on Day 10. Sparse PK (subgroup 2) is not included in this analysis because blood was drawn only once on Day 10 for plasma trough determination.

Characterization of the PK parameters of POS determined from plasma samples taken at steady-state after receiving IV administration of 300 mg POS twice a day (BID) on Day 1 and then 300 mg POS QD until at least Day 10. Steady-state Cavg, where Cavg is defined as AUC0-24hr divided by the dosing interval. The percentage of participants with ssCavg ≥500 ng/mL are presented.

Subgroup 1 - Serial PK, multiple same-day blood draw, performed specifically for determination of PK parameters of Cavg, AUC, Cmin, Cmax, Tmax and Total Body Clearance in addition to plasma trough determination.

Subgroup 2 - Sparse PK, once a day blood draw, performed for plasma trough determination only.

Outcome measures

Measure	Serial PK (Subgroup 1) n=27 Participants Posaconazole (POS) 300 mg intravenous (IV) infusion twice on Day 1 followed by 300 mg IV infusion once daily on Days 2 to 10 (±1). At the discretion of the investigator, participants may have received POS 300 mg IV infusion once daily or 200 mg oral suspension 3 times daily for up to 18 additional days. Serial PK requires full intensive blood sampling for PK measurements	Sparse PK (Subgroup 2) POS 300 mg intravenous (IV) infusion twice on Day 1 followed by 300 mg IV infusion once daily on Days 2 to 10 (±1). At the discretion of the investigator, participants may have received POS 300 mg IV infusion once daily or 200 mg oral suspension 3 times daily for up to 18 additional days. Sparse PK requires sparse infrequent blood sampling for PK measurements
Percentage of Participants With ssCavg ≥500 ng/mL of Serial PK (Subgroup 1) on Day 10 Cavg 3650 ng/mL or higher	25.9 Percentage of Participants	—
Percentage of Participants With ssCavg ≥500 ng/mL of Serial PK (Subgroup 1) on Day 10 Cavg 500 ng/mL to < 2500 ng/mL	40.7 Percentage of Participants	—
Percentage of Participants With ssCavg ≥500 ng/mL of Serial PK (Subgroup 1) on Day 10 Cavg 2500 ng/ML to < 3650 ng/mL	33.3 Percentage of Participants	—

PRIMARY outcome

Timeframe: Serial PK (Subgroup 1) on Day 10 at pre-dose, 1 hr. post start of infusion (SOI), end of infusion (EOI), 15 min. after EOI and 4, 8, 12, 24 hours post SOI

Population: Analysis population includes participants who had serial blood draws on Day 10. Sparse PK (subgroup 2) is not included in this analysis because blood was drawn only once on Day 10 for plasma trough determination.

Characterization of the PK parameters of POS determined from plasma samples taken at steady-state after receiving IV administration of 300 mg POS twice a day (BID) on Day 1 and then 300 mg POS QD until at least Day 10. AUC0-24 is defined as area under the plasma concentration-time curve from time 0 extrapolated to 24 hours.

Subgroup 1 - Serial PK, multiple same-day blood draw, performed specifically for determination of PK parameters of Cavg, AUC, Cmin, Cmax, Tmax and Total Body Clearance in addition to plasma trough determination.

Subgroup 2 - Sparse PK, once a day blood draw, performed for plasma trough determination only.

Outcome measures

Measure	Serial PK (Subgroup 1) n=27 Participants Posaconazole (POS) 300 mg intravenous (IV) infusion twice on Day 1 followed by 300 mg IV infusion once daily on Days 2 to 10 (±1). At the discretion of the investigator, participants may have received POS 300 mg IV infusion once daily or 200 mg oral suspension 3 times daily for up to 18 additional days. Serial PK requires full intensive blood sampling for PK measurements	Sparse PK (Subgroup 2) POS 300 mg intravenous (IV) infusion twice on Day 1 followed by 300 mg IV infusion once daily on Days 2 to 10 (±1). At the discretion of the investigator, participants may have received POS 300 mg IV infusion once daily or 200 mg oral suspension 3 times daily for up to 18 additional days. Sparse PK requires sparse infrequent blood sampling for PK measurements
Steady-state Area Under the Concentration-time Curve (ssAUC0-24hr) of POS of Serial PK (Subgroup 1) on Day 10	71670.8 hr*ng/mL Standard Deviation 25788.11	—

PRIMARY outcome

Timeframe: Serial PK (Subgroup 1) on Day 10 at pre-dose, 1 hr. post start of infusion (SOI), end of infusion (EOI), 15 min. after EOI and 4, 8, 12, 24 hours post SOI

Population: Analysis population includes participants who had serial blood draws on Day 10. Sparse PK (subgroup 2) is not included in this analysis because blood was drawn only once on Day 10 for plasma trough determination.

Characterization of the PK parameters of POS determined from plasma samples taken at steady-state after receiving IV administration of 300 mg POS twice a day (BID) on Day 1 and then 300 mg POS QD until at least Day 10. Cmax is defined as the maximum concentration of POS in plasma.

Subgroup 1 - Serial PK, multiple same-day blood draw, performed specifically for determination of PK parameters of Cavg, AUC, Cmin, Cmax, Tmax and Total Body Clearance in addition to plasma trough determination.

Subgroup 2 - Sparse PK, once a day blood draw, performed for plasma trough determination only.

Outcome measures

Measure	Serial PK (Subgroup 1) n=27 Participants Posaconazole (POS) 300 mg intravenous (IV) infusion twice on Day 1 followed by 300 mg IV infusion once daily on Days 2 to 10 (±1). At the discretion of the investigator, participants may have received POS 300 mg IV infusion once daily or 200 mg oral suspension 3 times daily for up to 18 additional days. Serial PK requires full intensive blood sampling for PK measurements	Sparse PK (Subgroup 2) POS 300 mg intravenous (IV) infusion twice on Day 1 followed by 300 mg IV infusion once daily on Days 2 to 10 (±1). At the discretion of the investigator, participants may have received POS 300 mg IV infusion once daily or 200 mg oral suspension 3 times daily for up to 18 additional days. Sparse PK requires sparse infrequent blood sampling for PK measurements
Steady State Maximum Concentration (ssCmax) of POS of Serial PK (Subgroup 1) on Day 10	4612.22 ng/mL Standard Deviation 1221.68	—

PRIMARY outcome

Timeframe: Serial PK (Subgroup 1) on Day 10 at pre-dose, 1 hr. post start of infusion (SOI), end of infusion (EOI), 15 min. after EOI and 4, 8, 12, 24 hours post SOI

Population: Analysis population includes participants who had serial blood draws on Day 10. Sparse PK (subgroup 2) is not included in this analysis because blood was drawn only once on Day 10 for plasma trough determination.

Characterization of the PK parameters of POS determined from plasma samples taken at steady-state after receiving IV administration of 300 mg POS twice a day (BID) on Day 1 and then 300 mg POS QD until at least Day 10. Cmin is defined as the minimum concentration of POS in plasma.

Subgroup 1 - Serial PK, multiple same-day blood draw, performed specifically for determination of PK parameters of Cavg, AUC, Cmin, Cmax, Tmax and Total Body Clearance in addition to plasma trough determination.

Subgroup 2 - Sparse PK, once a day blood draw, performed for plasma trough determination only.

Outcome measures

Measure	Serial PK (Subgroup 1) n=27 Participants Posaconazole (POS) 300 mg intravenous (IV) infusion twice on Day 1 followed by 300 mg IV infusion once daily on Days 2 to 10 (±1). At the discretion of the investigator, participants may have received POS 300 mg IV infusion once daily or 200 mg oral suspension 3 times daily for up to 18 additional days. Serial PK requires full intensive blood sampling for PK measurements	Sparse PK (Subgroup 2) POS 300 mg intravenous (IV) infusion twice on Day 1 followed by 300 mg IV infusion once daily on Days 2 to 10 (±1). At the discretion of the investigator, participants may have received POS 300 mg IV infusion once daily or 200 mg oral suspension 3 times daily for up to 18 additional days. Sparse PK requires sparse infrequent blood sampling for PK measurements
Steady State Minimum Concentration (ssCmin) of POS of Serial PK (Subgroup 1) on Day 10	2311.33 ng/mL Standard Deviation 1119.28	—

PRIMARY outcome

Timeframe: Serial PK (Subgroup 1) on Day 10 at pre-dose, 1 hr. post start of infusion (SOI), end of infusion (EOI), 15 min. after EOI and 4, 8, 12, 24 hours post SOI

Population: Analysis population includes participants who had serial blood draws on Day 10. Sparse PK (subgroup 2) is not included in this analysis because blood was drawn only once on Day 10 for plasma trough determination.

Characterization of the PK parameters of POS determined from plasma samples taken at steady-state after receiving IV administration of 300 mg POS twice a day (BID) on Day 1 and then 300 mg POS QD until at least Day 10. Tmax is defined as the time it takes to achieve maximum concentration of POS in plasma.

Subgroup 1 - Serial PK, multiple same-day blood draw, performed specifically for determination of PK parameters of Cavg, AUC, Cmin, Cmax, Tmax and Total Body Clearance in addition to plasma trough determination.

Subgroup 2 - Sparse PK, once a day blood draw, performed for plasma trough determination only.

Outcome measures

Measure	Serial PK (Subgroup 1) n=27 Participants Posaconazole (POS) 300 mg intravenous (IV) infusion twice on Day 1 followed by 300 mg IV infusion once daily on Days 2 to 10 (±1). At the discretion of the investigator, participants may have received POS 300 mg IV infusion once daily or 200 mg oral suspension 3 times daily for up to 18 additional days. Serial PK requires full intensive blood sampling for PK measurements	Sparse PK (Subgroup 2) POS 300 mg intravenous (IV) infusion twice on Day 1 followed by 300 mg IV infusion once daily on Days 2 to 10 (±1). At the discretion of the investigator, participants may have received POS 300 mg IV infusion once daily or 200 mg oral suspension 3 times daily for up to 18 additional days. Sparse PK requires sparse infrequent blood sampling for PK measurements
Time to Steady-state Maximum Concentration (ssTmax) of POS of Serial PK (Subgroup 1) on Day 10	1.63 hr Standard Deviation 0.23	—

PRIMARY outcome

Timeframe: Serial PK (Subgroup 1) on Day 10 at pre-dose, 1 hr. post start of infusion (SOI), end of infusion (EOI), 15 min. after EOI and 4, 8, 12, 24 hours post SOI

Population: Analysis population includes participants who had serial blood draws on Day 10. Sparse PK (subgroup 2) is not included in this analysis because blood was drawn only once on Day 10 for plasma trough determination.

Characterization of the PK parameters of POS determined from plasma samples taken at steady-state after receiving IV administration of 300 mg POS twice a day (BID) on Day 1 and then 300 mg POS QD until at least Day 10. CL is defined as the time it takes for POS to be completely removed from the body's blood stream.

Subgroup 1 - Serial PK, multiple same-day blood draw, performed specifically for determination of PK parameters of Cavg, AUC, Cmin, Cmax, Tmax and Total Body Clearance in addition to plasma trough determination.

Subgroup 2 - Sparse PK, once a day blood draw, performed for plasma trough determination only.

Outcome measures

Measure	Serial PK (Subgroup 1) n=27 Participants Posaconazole (POS) 300 mg intravenous (IV) infusion twice on Day 1 followed by 300 mg IV infusion once daily on Days 2 to 10 (±1). At the discretion of the investigator, participants may have received POS 300 mg IV infusion once daily or 200 mg oral suspension 3 times daily for up to 18 additional days. Serial PK requires full intensive blood sampling for PK measurements	Sparse PK (Subgroup 2) POS 300 mg intravenous (IV) infusion twice on Day 1 followed by 300 mg IV infusion once daily on Days 2 to 10 (±1). At the discretion of the investigator, participants may have received POS 300 mg IV infusion once daily or 200 mg oral suspension 3 times daily for up to 18 additional days. Sparse PK requires sparse infrequent blood sampling for PK measurements
Total Body Clearance (CL) of POS of Serial PK (Subgroup 1) on Day 10	4767.90 mL/hr Standard Deviation 1805.24	—

PRIMARY outcome

Timeframe: Day 3, Day 6, Day 10, Day 15, Day 22, Day 28

Population: All evaluable participants in Subgroup 1 (Serial PK) and Subgroup 2 (Sparse PK) not yet switched to oral suspension. Both groups received the same dose and drug administration and reflect only different blood sampling schedules.

Pre-dose plasma trough concentrations by study day between serial PK and Sparse PK - where serial PK is defined as multiple serial blood sampling of more than 6 timepoints; and sparse PK is defined as few blood samples taken and single or limited timepoints

Outcome measures

Measure	Serial PK (Subgroup 1) n=30 Participants Posaconazole (POS) 300 mg intravenous (IV) infusion twice on Day 1 followed by 300 mg IV infusion once daily on Days 2 to 10 (±1). At the discretion of the investigator, participants may have received POS 300 mg IV infusion once daily or 200 mg oral suspension 3 times daily for up to 18 additional days. Serial PK requires full intensive blood sampling for PK measurements	Sparse PK (Subgroup 2) n=40 Participants POS 300 mg intravenous (IV) infusion twice on Day 1 followed by 300 mg IV infusion once daily on Days 2 to 10 (±1). At the discretion of the investigator, participants may have received POS 300 mg IV infusion once daily or 200 mg oral suspension 3 times daily for up to 18 additional days. Sparse PK requires sparse infrequent blood sampling for PK measurements
POS Plasma Trough Concentrations in the Serial PK and Sparse PK Subgroups Day 15	2471.63 ng/mL Standard Deviation 1495.20	2680 ng/mL Standard Deviation 1269
POS Plasma Trough Concentrations in the Serial PK and Sparse PK Subgroups Day 22	—	2603 ng/mL Standard Deviation 1325
POS Plasma Trough Concentrations in the Serial PK and Sparse PK Subgroups Day 28	—	3180 ng/mL Standard Deviation 1527
POS Plasma Trough Concentrations in the Serial PK and Sparse PK Subgroups Day 3	1800.93 ng/mL Standard Deviation 525.20	2033 ng/mL Standard Deviation 650.9
POS Plasma Trough Concentrations in the Serial PK and Sparse PK Subgroups Day 6	2106.07 ng/mL Standard Deviation 764.16	2514 ng/mL Standard Deviation 927.5
POS Plasma Trough Concentrations in the Serial PK and Sparse PK Subgroups Day 10	2473.78 ng/mL Standard Deviation 1247.86	2466 ng/mL Standard Deviation 1045

SECONDARY outcome

Timeframe: Up to 58 days

Population: All participants who received at least one dose of study drug.

Number of participants with one or more AEs where AEs are defined as 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.

Outcome measures

Measure	Serial PK (Subgroup 1) n=70 Participants Posaconazole (POS) 300 mg intravenous (IV) infusion twice on Day 1 followed by 300 mg IV infusion once daily on Days 2 to 10 (±1). At the discretion of the investigator, participants may have received POS 300 mg IV infusion once daily or 200 mg oral suspension 3 times daily for up to 18 additional days. Serial PK requires full intensive blood sampling for PK measurements	Sparse PK (Subgroup 2) POS 300 mg intravenous (IV) infusion twice on Day 1 followed by 300 mg IV infusion once daily on Days 2 to 10 (±1). At the discretion of the investigator, participants may have received POS 300 mg IV infusion once daily or 200 mg oral suspension 3 times daily for up to 18 additional days. Sparse PK requires sparse infrequent blood sampling for PK measurements
Adverse Events (AEs)	70 Number of Participants	—

SECONDARY outcome

Timeframe: Up to 28 days

Population: All participants who received at least one dose of study drug.

Number of participants discontinued from study medication due to an AE where AEs are defined as 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.

Outcome measures

Measure	Serial PK (Subgroup 1) n=70 Participants Posaconazole (POS) 300 mg intravenous (IV) infusion twice on Day 1 followed by 300 mg IV infusion once daily on Days 2 to 10 (±1). At the discretion of the investigator, participants may have received POS 300 mg IV infusion once daily or 200 mg oral suspension 3 times daily for up to 18 additional days. Serial PK requires full intensive blood sampling for PK measurements	Sparse PK (Subgroup 2) POS 300 mg intravenous (IV) infusion twice on Day 1 followed by 300 mg IV infusion once daily on Days 2 to 10 (±1). At the discretion of the investigator, participants may have received POS 300 mg IV infusion once daily or 200 mg oral suspension 3 times daily for up to 18 additional days. Sparse PK requires sparse infrequent blood sampling for PK measurements
Discontinuations Due to an AE	9 Participants	—

SECONDARY outcome

Timeframe: Up to 28 days

Population: All evaluable participants in Subgroup 1 (Serial PK) and Subgroup 2 (Sparse PK) not yet switched to oral suspension. Both groups received the same dose and drug administration and reflect only different blood sampling schedules.

The number of participants with clinical laboratory values outside of normal range

Outcome measures

Measure	Serial PK (Subgroup 1) n=30 Participants Posaconazole (POS) 300 mg intravenous (IV) infusion twice on Day 1 followed by 300 mg IV infusion once daily on Days 2 to 10 (±1). At the discretion of the investigator, participants may have received POS 300 mg IV infusion once daily or 200 mg oral suspension 3 times daily for up to 18 additional days. Serial PK requires full intensive blood sampling for PK measurements	Sparse PK (Subgroup 2) n=40 Participants POS 300 mg intravenous (IV) infusion twice on Day 1 followed by 300 mg IV infusion once daily on Days 2 to 10 (±1). At the discretion of the investigator, participants may have received POS 300 mg IV infusion once daily or 200 mg oral suspension 3 times daily for up to 18 additional days. Sparse PK requires sparse infrequent blood sampling for PK measurements
Medically Significant Changes in Clinical Laboratory Results - Lab Values	30 Participants	35 Participants

SECONDARY outcome

Timeframe: Up to 28 days

Population: All evaluable participants in Subgroup 1 (Serial PK) and Subgroup 2 (Sparse PK) not yet switched to oral suspension. Both groups received the same dose and drug administration and reflect only different blood sampling schedules.

The number of participants with values of vital signs outside of normal range

Outcome measures

Measure	Serial PK (Subgroup 1) n=30 Participants Posaconazole (POS) 300 mg intravenous (IV) infusion twice on Day 1 followed by 300 mg IV infusion once daily on Days 2 to 10 (±1). At the discretion of the investigator, participants may have received POS 300 mg IV infusion once daily or 200 mg oral suspension 3 times daily for up to 18 additional days. Serial PK requires full intensive blood sampling for PK measurements	Sparse PK (Subgroup 2) n=40 Participants POS 300 mg intravenous (IV) infusion twice on Day 1 followed by 300 mg IV infusion once daily on Days 2 to 10 (±1). At the discretion of the investigator, participants may have received POS 300 mg IV infusion once daily or 200 mg oral suspension 3 times daily for up to 18 additional days. Sparse PK requires sparse infrequent blood sampling for PK measurements
Medically Significant Changes in Clinical Laboratory Results - Vital Signs	27 Participants	31 Participants

SECONDARY outcome

Timeframe: Up to 98 days

Population: All participants who received at least one dose of study drug.

Survival assessment as to whether a participant is alive or dead, included all participants who died - 2 during study treatment, 1 during safety follow-up, 2 during survival follow-up (Day 60 to 70 post dose), and 1 participant who died during serious AE (SAE) follow-up at 97 days after first dose but was beyond the safety and the survival follow-up period

Outcome measures

Measure	Serial PK (Subgroup 1) n=70 Participants Posaconazole (POS) 300 mg intravenous (IV) infusion twice on Day 1 followed by 300 mg IV infusion once daily on Days 2 to 10 (±1). At the discretion of the investigator, participants may have received POS 300 mg IV infusion once daily or 200 mg oral suspension 3 times daily for up to 18 additional days. Serial PK requires full intensive blood sampling for PK measurements	Sparse PK (Subgroup 2) POS 300 mg intravenous (IV) infusion twice on Day 1 followed by 300 mg IV infusion once daily on Days 2 to 10 (±1). At the discretion of the investigator, participants may have received POS 300 mg IV infusion once daily or 200 mg oral suspension 3 times daily for up to 18 additional days. Sparse PK requires sparse infrequent blood sampling for PK measurements
Survival Status Alive	64 Participants	—
Survival Status Dead	6 Participants	—

SECONDARY outcome

Timeframe: Up to 28 days

Population: All participants who received at least one dose of study drug.

Number of participants with possible, probable, or proven IFI observed during the whole study period

Outcome measures

Measure	Serial PK (Subgroup 1) n=70 Participants Posaconazole (POS) 300 mg intravenous (IV) infusion twice on Day 1 followed by 300 mg IV infusion once daily on Days 2 to 10 (±1). At the discretion of the investigator, participants may have received POS 300 mg IV infusion once daily or 200 mg oral suspension 3 times daily for up to 18 additional days. Serial PK requires full intensive blood sampling for PK measurements	Sparse PK (Subgroup 2) POS 300 mg intravenous (IV) infusion twice on Day 1 followed by 300 mg IV infusion once daily on Days 2 to 10 (±1). At the discretion of the investigator, participants may have received POS 300 mg IV infusion once daily or 200 mg oral suspension 3 times daily for up to 18 additional days. Sparse PK requires sparse infrequent blood sampling for PK measurements
Participants With Invasive Fungal Infection (IFI)	2 Participants	—

Adverse Events

POS IV (MK-5592)

Serious events: 15 serious events

Other events: 70 other events

Deaths: 6 deaths

Serious adverse events

Measure	POS IV (MK-5592) n=70 participants at risk POS 300 mg intravenous (IV) infusion twice on Day 1 followed by 300 mg IV infusion once daily on Days 2 to 10 (±1). At the discretion of the investigator, participants may have received POS 300 mg IV infusion once daily or 200 mg oral suspension 3 times daily for up to 18 additional days
Blood and lymphatic system disorders Agranulocytosis	1.4% 1/70 • Number of events 1 • Up to 98 days post first study dose All participants who received at least one dose of study drug.
Blood and lymphatic system disorders Thrombocytopenia	5.7% 4/70 • Number of events 4 • Up to 98 days post first study dose All participants who received at least one dose of study drug.
Cardiac disorders Cardiac failure	2.9% 2/70 • Number of events 2 • Up to 98 days post first study dose All participants who received at least one dose of study drug.
Infections and infestations Lung infection	1.4% 1/70 • Number of events 1 • Up to 98 days post first study dose All participants who received at least one dose of study drug.
Infections and infestations Tuberculosis	1.4% 1/70 • Number of events 1 • Up to 98 days post first study dose All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypokalaemia	1.4% 1/70 • Number of events 1 • Up to 98 days post first study dose All participants who received at least one dose of study drug.
Nervous system disorders Cerebral haemorrhage	1.4% 1/70 • Number of events 1 • Up to 98 days post first study dose All participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Cough	1.4% 1/70 • Number of events 1 • Up to 98 days post first study dose All participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Pulmonary hypertension	1.4% 1/70 • Number of events 1 • Up to 98 days post first study dose All participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Respiratory failure	2.9% 2/70 • Number of events 2 • Up to 98 days post first study dose All participants who received at least one dose of study drug.
Vascular disorders Distributive shock	1.4% 1/70 • Number of events 1 • Up to 98 days post first study dose All participants who received at least one dose of study drug.

Other adverse events

Measure	POS IV (MK-5592) n=70 participants at risk POS 300 mg intravenous (IV) infusion twice on Day 1 followed by 300 mg IV infusion once daily on Days 2 to 10 (±1). At the discretion of the investigator, participants may have received POS 300 mg IV infusion once daily or 200 mg oral suspension 3 times daily for up to 18 additional days
Blood and lymphatic system disorders Anaemia	47.1% 33/70 • Number of events 64 • Up to 98 days post first study dose All participants who received at least one dose of study drug.
Blood and lymphatic system disorders Febrile neutropenia	5.7% 4/70 • Number of events 5 • Up to 98 days post first study dose All participants who received at least one dose of study drug.
Blood and lymphatic system disorders Leukocytosis	5.7% 4/70 • Number of events 4 • Up to 98 days post first study dose All participants who received at least one dose of study drug.
Blood and lymphatic system disorders Leukopenia	18.6% 13/70 • Number of events 25 • Up to 98 days post first study dose All participants who received at least one dose of study drug.
Blood and lymphatic system disorders Thrombocytopenia	14.3% 10/70 • Number of events 17 • Up to 98 days post first study dose All participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal distension	8.6% 6/70 • Number of events 6 • Up to 98 days post first study dose All participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal pain	5.7% 4/70 • Number of events 4 • Up to 98 days post first study dose All participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal pain upper	8.6% 6/70 • Number of events 9 • Up to 98 days post first study dose All participants who received at least one dose of study drug.
Gastrointestinal disorders Constipation	25.7% 18/70 • Number of events 21 • Up to 98 days post first study dose All participants who received at least one dose of study drug.
Gastrointestinal disorders Diarrhoea	34.3% 24/70 • Number of events 28 • Up to 98 days post first study dose All participants who received at least one dose of study drug.
Gastrointestinal disorders Gingival ulceration	8.6% 6/70 • Number of events 6 • Up to 98 days post first study dose All participants who received at least one dose of study drug.
Gastrointestinal disorders Nausea	41.4% 29/70 • Number of events 44 • Up to 98 days post first study dose All participants who received at least one dose of study drug.
Gastrointestinal disorders Proctalgia	5.7% 4/70 • Number of events 4 • Up to 98 days post first study dose All participants who received at least one dose of study drug.
Gastrointestinal disorders Vomiting	31.4% 22/70 • Number of events 33 • Up to 98 days post first study dose All participants who received at least one dose of study drug.
General disorders Asthenia	20.0% 14/70 • Number of events 22 • Up to 98 days post first study dose All participants who received at least one dose of study drug.
General disorders Chest discomfort	14.3% 10/70 • Number of events 13 • Up to 98 days post first study dose All participants who received at least one dose of study drug.
General disorders Chest pain	5.7% 4/70 • Number of events 4 • Up to 98 days post first study dose All participants who received at least one dose of study drug.
General disorders Oedema peripheral	8.6% 6/70 • Number of events 7 • Up to 98 days post first study dose All participants who received at least one dose of study drug.
General disorders Pyrexia	57.1% 40/70 • Number of events 81 • Up to 98 days post first study dose All participants who received at least one dose of study drug.
Infections and infestations Gastrointestinal infection	5.7% 4/70 • Number of events 4 • Up to 98 days post first study dose All participants who received at least one dose of study drug.
Infections and infestations Lung infection	17.1% 12/70 • Number of events 12 • Up to 98 days post first study dose All participants who received at least one dose of study drug.
Infections and infestations Oral infection	8.6% 6/70 • Number of events 6 • Up to 98 days post first study dose All participants who received at least one dose of study drug.
Infections and infestations Upper respiratory tract infection	11.4% 8/70 • Number of events 8 • Up to 98 days post first study dose All participants who received at least one dose of study drug.
Investigations Alanine aminotransferase increased	22.9% 16/70 • Number of events 22 • Up to 98 days post first study dose All participants who received at least one dose of study drug.
Investigations Aspartate aminotransferase increased	11.4% 8/70 • Number of events 10 • Up to 98 days post first study dose All participants who received at least one dose of study drug.
Investigations Blood bilirubin increased	40.0% 28/70 • Number of events 39 • Up to 98 days post first study dose All participants who received at least one dose of study drug.
Investigations Brain natriuretic peptide increased	8.6% 6/70 • Number of events 6 • Up to 98 days post first study dose All participants who received at least one dose of study drug.
Investigations Gamma-glutamyltransferase increased	5.7% 4/70 • Number of events 4 • Up to 98 days post first study dose All participants who received at least one dose of study drug.
Investigations Lymphocyte count decreased	54.3% 38/70 • Number of events 112 • Up to 98 days post first study dose All participants who received at least one dose of study drug.
Investigations Neutrophil count decreased	57.1% 40/70 • Number of events 81 • Up to 98 days post first study dose All participants who received at least one dose of study drug.
Investigations Platelet count decreased	45.7% 32/70 • Number of events 88 • Up to 98 days post first study dose All participants who received at least one dose of study drug.
Investigations Weight increased	12.9% 9/70 • Number of events 10 • Up to 98 days post first study dose All participants who received at least one dose of study drug.
Investigations White blood cell count decreased	71.4% 50/70 • Number of events 108 • Up to 98 days post first study dose All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Decreased appetite	12.9% 9/70 • Number of events 10 • Up to 98 days post first study dose All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hyperglycaemia	25.7% 18/70 • Number of events 28 • Up to 98 days post first study dose All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hyperuricaemia	7.1% 5/70 • Number of events 5 • Up to 98 days post first study dose All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypoalbuminaemia	31.4% 22/70 • Number of events 35 • Up to 98 days post first study dose All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypocalcaemia	24.3% 17/70 • Number of events 32 • Up to 98 days post first study dose All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypokalaemia	65.7% 46/70 • Number of events 75 • Up to 98 days post first study dose All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hyponatraemia	22.9% 16/70 • Number of events 23 • Up to 98 days post first study dose All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypophosphataemia	8.6% 6/70 • Number of events 7 • Up to 98 days post first study dose All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypoproteinaemia	11.4% 8/70 • Number of events 13 • Up to 98 days post first study dose All participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Back pain	5.7% 4/70 • Number of events 4 • Up to 98 days post first study dose All participants who received at least one dose of study drug.
Nervous system disorders Dizziness	14.3% 10/70 • Number of events 18 • Up to 98 days post first study dose All participants who received at least one dose of study drug.
Nervous system disorders Headache	7.1% 5/70 • Number of events 6 • Up to 98 days post first study dose All participants who received at least one dose of study drug.
Nervous system disorders Poor quality sleep	5.7% 4/70 • Number of events 8 • Up to 98 days post first study dose All participants who received at least one dose of study drug.
Psychiatric disorders Insomnia	5.7% 4/70 • Number of events 5 • Up to 98 days post first study dose All participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Cough	20.0% 14/70 • Number of events 18 • Up to 98 days post first study dose All participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	10.0% 7/70 • Number of events 9 • Up to 98 days post first study dose All participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Productive cough	11.4% 8/70 • Number of events 10 • Up to 98 days post first study dose All participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Rash	17.1% 12/70 • Number of events 14 • Up to 98 days post first study dose All participants who received at least one dose of study drug.
Vascular disorders Hypertension	7.1% 5/70 • Number of events 6 • Up to 98 days post first study dose All participants who received at least one dose of study drug.

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: ClinicalTrialsDisclosure@merck.com

Results disclosure agreements

• Principal investigator is a sponsor employee The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results. Sponsor review can be expedited to meet publication timelines.
• Publication restrictions are in place

Restriction type: OTHER