Clinical trial NCT03336502: Pharmacokinetics and Safety of Intravenous Posaconazole (MK-5592) in Chinese Participants at High Risk for Invasive Fungal Infections (MK-5592-120)
Official title: Pharmacokinetics and Safety of Intravenous Posaconazole (MK-5592, POS) in Chinese Subjects at High Risk for Invasive Fungal Infections
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Fungal Infection
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2017-11-08
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* Chinese participant
* Female of reproductive potential with a serum of beta human chorionic gonadotropin (β-hCG) level consistent with a nongravid state and agree and/or have their partner use 2 acceptable methods of birth control throughout the study
* Body Mass Index (BMI) \>=15 and \<=30 kg/m\^2
* Have a central line catheter or peripherally central venous catheter in place
* Anticipated or documented prolonged neutropenia and likely to last for at least 7 days due to: a) standard intensive chemotherapy, anthracycline-based or other accepted regimen (excluding any investigational agent) for a new diagnosis of acute myelogenous leukemia (AML); b)chemotherapy for AML in first relapse; or c) therapy for myelodysplastic syndromes in transformation to AML or other diagnoses of secondary AML (therapy related, antecedent hematological disorders) other than chronic myelogenous leukemia in blast crisis
* Free from any clinically significant disease other than the primary hematologic disease that would interfere with administration of study medication or study evaluations
* Able to tolerate central IV solution

Exclusion Criteria:

* Pregnant, intends to become pregnant during the study, or has been nursing
* Mentally or legally incapacitated, has significant emotional problems, or has clinically significant psychiatric disorder over the last 5 years
* Received systemic antifungal therapy (oral, intravenous, or inhaled) within 30 days of study enrollment for reasons other than antifungal prophylaxis
* Known or suspected invasive or systemic fungal infection
* Taken posaconazole within 10 days prior to study enrollment
* Major surgery, donated or lost 1 unit of blood, or participated in another investigational study within 4 weeks prior to the study
* Type 1 hypersensitivity or idiosyncratic reactions to azole agents
* Significant multiple or severe allergies, or has had an anaphylactic reaction or significant intolerability to drugs or food
* Moderate or severe liver dysfunction
* Chronic active hepatitis, cirrhosis, Hepatocellular Carcinoma (HCC), or other hepatic disease caused by a virus
* Previous electrocardiogram with a prolonged QTc interval
* Prior enrollment in this study or other posaconazole studies within 90 days of study entry
* Eastern Cooperative Oncology Group (ECOG) performance status was \>2 prior to induction chemotherapy for the underlying disease
* Known or suspected Gilbert's disease.

Primary outcomes:
measure: Steady State (ss) Average Concentration (Cavg) of Posaconazole of Serial PK (Subgroup 1) on Day 10
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
measure: Percentage of Participants With ssCavg ≥500 ng/mL of Serial PK (Subgroup 1) on Day 10
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
measure: Steady-state Area Under the Concentration-time Curve (ssAUC0-24hr) of POS of Serial PK (Subgroup 1) on Day 10
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
measure: Steady State Maximum Concentration (ssCmax) of POS of Serial PK (Subgroup 1) on Day 10
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
measure: Steady State Minimum Concentration (ssCmin) of POS of Serial PK (Subgroup 1) on Day 10
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
measure: Time to Steady-state Maximum Concentration (ssTmax) of POS of Serial PK (Subgroup 1) on Day 10
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
measure: Total Body Clearance (CL) of POS of Serial PK (Subgroup 1) on Day 10
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
measure: POS Plasma Trough Concentrations in the Serial PK and Sparse PK Subgroups
timeFrame: Day 3, Day 6, Day 10, Day 15, Day 22, Day 28
Secondary outcomes:
measure: Adverse Events (AEs)
timeFrame: Up to 58 days
measure: Discontinuations Due to an AE
timeFrame: Up to 28 days
measure: Medically Significant Changes in Clinical Laboratory Results - Lab Values
timeFrame: Up to 28 days
measure: Medically Significant Changes in Clinical Laboratory Results - Vital Signs
timeFrame: Up to 28 days
measure: Survival Status
timeFrame: Up to 98 days
measure: Participants With Invasive Fungal Infection (IFI)
timeFrame: Up to 28 days
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Guangdong General Hospital, Guangdong Academy of Medical Science ( Site 0002)
state: Guangdong
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University ( Site 0004)
state: Jiangsu
city: Beijing
country: China
facility: Peking University People's Hospital ( Site 0008)
city: Beijing
country: China
facility: Peking University Third Hospital ( Site 0009)
city: Beijing
country: China
facility: Peking Union Medical College Hospital ( Site 0006)
city: Shanghai
country: China
facility: Shanghai General Hospital ( Site 0007)
city: Tianjin
country: China
facility: Institute of Hematology and Blood Diseases Hosp CAMS&PUMC ( Site 0001)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Wu D, Mi Y, Weng J, Zhuang J, Ke X, Wang C, Liu K, Martinho M, Winchell GA, Zang Y, Xu L. Phase 1b/3 Pharmacokinetics and Safety Study of Intravenous Posaconazole in Adult Asian Participants at High Risk for Invasive Fungal Infections. Adv Ther. 2022 Apr;39(4):1697-1710. doi: 10.1007/s12325-021-02012-1. Epub 2022 Feb 15.