Clinical trial NCT02387983: Pharmacokinetics and Safety of Oral Posaconazole (MK-5592)Tablets in Chinese Participants at High Risk for Invasive Fungal Infections (MK-5592-117)
Official title: Pharmacokinetics and Safety of Solid Oral 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: 2015-03-13
Enrollment: 65
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 oral posaconazole tablets 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.


Eligibility criteria: Inclusion Criteria:

* Chinese participant
* Female of reproductive potential with a serum hCG level consistent with a nongravid state and agree to use 2 acceptable methods of birth control throughout the study
* Body Mass Index (BMI) \>=15 and \<=30 kg/m\^2
* 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) or 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

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 Average Concentration (ssCavg) of Posaconazole on Day 8
timeFrame: Pre-dose and 2, 4, 6, 8, 12, and 24 hours post-dose on Day 8
measure: Steady-state Area Under the Concentration-time Curve (ssAUC0-24hr) of Posaconazole on Day 8
timeFrame: Pre-dose and 2, 4, 6, 8, 12, and 24 hours post-dose on Day 8
measure: Steady-state Maximum Concentration (ssCmax) of Posaconazole on Day 8
timeFrame: Pre-dose and 2, 4, 6, 8, 12, and 24 hours post-dose on Day 8
measure: Steady-state Minimum Concentration (ssCmin) of Posaconazole on Day 8
timeFrame: Pre-dose and 2, 4, 6, 8, 12, and 24 hours post-dose on Day 8
measure: Time to Steady-state Maximum Concentration (ssTmax) of Posaconazole on Day 8
timeFrame: Pre-dose and 2, 4, 6, 8, 12, and 24 hours post-dose on Day 8
measure: AUC0-24hr of Posaconazole on Day 1
timeFrame: Pre-dose and 2, 4, 6, 8, 12, and 24 hours post-dose on Day 1
measure: Cmax of Posaconazole on Day 1
timeFrame: Pre-dose and 2, 4, 6, 8, 12, and 24 hours post-dose on Day 1
measure: Cmin of Posaconazole on Day 1
timeFrame: Pre-dose and 2, 4, 6, 8, 12, and 24 hours post-dose on Day 1
measure: Tmax of Posaconazole on Day 1
timeFrame: Pre-dose and 2, 4, 6, 8, 12, and 24 hours post-dose on Day 1
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Liu K, Wu D, Li J, Chen H, Ning H, Zhao T, Dai H, Chen L, Mangin E, Winchell GA, Waskin H, Jiang J, Qiu Y, Zhao XM. Pharmacokinetics and Safety of Posaconazole Tablet Formulation in Chinese Participants at High Risk for Invasive Fungal Infection. Adv Ther. 2020 May;37(5):2493-2506. doi: 10.1007/s12325-020-01341-x. Epub 2020 Apr 22.