The purpose of this study is to evaluate the pharmacokinetics and safety of posaconazole intravenous solution in Chinese participants at high risk for invasive fungal infections. Neutropenic participants undergoing chemotherapy for acute myelogenous leukemia or myelodysplastic syndromes will be enrolled in the study. The primary hypothesis is to evaluate the pharmacokinetic parameters of intravenous (IV) posaconazole (POS) solution in Chinese participants at high risk of invasive fungal infections and determine the percentage of Chinese participants who reach steady-state concentration averages of POS in blood plasma of 500 ng/ml and higher. Two subgroups were evaluated: Subgroup 1 from serial PK blood draw sampling and Subgroup 2 from sparse limited PK blood draw sampling.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
PREVENTION
Masking
NONE
Enrollment
70
Posaconazole 18 mg/mL IV solution; posaconazole 40 mg/mL oral suspension
Guangdong General Hospital, Guangdong Academy of Medical Science ( Site 0002)
Guangzhou, Guangdong, China
The First Affiliated Hospital of Soochow University ( Site 0004)
Suzhou, Jiangsu, China
Peking University People's Hospital ( Site 0008)
Beijing, China
Peking University Third Hospital ( Site 0009)
Beijing, China
Peking Union Medical College Hospital ( Site 0006)
Beijing, China
Shanghai General Hospital ( Site 0007)
Shanghai, China
Institute of Hematology and Blood Diseases Hosp CAMS&PUMC ( Site 0001)
Tianjin, China
Steady State (ss) Average Concentration (Cavg) of Posaconazole of Serial PK (Subgroup 1) on Day 10
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.
Time frame: 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
Percentage of Participants With ssCavg ≥500 ng/mL of Serial PK (Subgroup 1) on Day 10
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.
Time frame: 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
Steady-state Area Under the Concentration-time Curve (ssAUC0-24hr) of POS of Serial PK (Subgroup 1) on Day 10
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.
Time frame: 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
Steady State Maximum Concentration (ssCmax) of POS of Serial PK (Subgroup 1) on Day 10
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.
Time frame: 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
Steady State Minimum Concentration (ssCmin) of POS of Serial PK (Subgroup 1) on Day 10
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.
Time frame: 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
Time to Steady-state Maximum Concentration (ssTmax) of POS of Serial PK (Subgroup 1) on Day 10
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.
Time frame: 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
Total Body Clearance (CL) of POS of Serial PK (Subgroup 1) on Day 10
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.
Time frame: 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
POS Plasma Trough Concentrations in the Serial PK and Sparse PK Subgroups
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
Time frame: Day 3, Day 6, Day 10, Day 15, Day 22, Day 28
Adverse Events (AEs)
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.
Time frame: Up to 58 days
Discontinuations Due to an AE
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.
Time frame: Up to 28 days
Medically Significant Changes in Clinical Laboratory Results - Lab Values
The number of participants with clinical laboratory values outside of normal range
Time frame: Up to 28 days
Medically Significant Changes in Clinical Laboratory Results - Vital Signs
The number of participants with values of vital signs outside of normal range
Time frame: Up to 28 days
Survival Status
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
Time frame: Up to 98 days
Participants With Invasive Fungal Infection (IFI)
Number of participants with possible, probable, or proven IFI observed during the whole study period
Time frame: Up to 28 days
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