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

NCT ID: NCT03336502

Last Updated: 2019-12-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-12-20
• Study Completion Date: 2018-11-26

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.

Conditions

Fungal Infection

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Posaconazole

All participants will receive posaconazole 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 will received posaconazole 300 mg IV infusion once daily or 200 mg oral suspension three times daily for up to 18 additional days.

Group Type: EXPERIMENTAL

Posaconazole

Intervention Type: DRUG

Posaconazole 18 mg/mL IV solution; posaconazole 40 mg/mL oral suspension

Interventions

Posaconazole

Posaconazole 18 mg/mL IV solution; posaconazole 40 mg/mL oral suspension

Intervention Type: DRUG

Other Intervention Names

MK-5592; Noxafil

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

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

Countries

China

References

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.

Reference Type: DERIVED

PMID: 35167031 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

MK-5992-120

Identifier Type: OTHER

Identifier Source: secondary_id

5592-120

Identifier Type: -

Identifier Source: org_study_id