Pharmacokinetics and Safety of Intravenous Posaconazole (MK-5592) in Chinese Participants at High Risk for Invasive Fungal Infections (MK-5592-120)
Condition: Fungal Infection
MeSH terms: Infections; Communicable Diseases; Mycoses; Invasive Fungal Infections
Intervention: Posaconazole
Intervention description: Posaconazole 18 mg/mL IV solution; posaconazole 40 mg/mL oral suspension
Intervention MeSH terms: Posaconazole
Phase: Phase 1
Study type: Interventional
Primary purpose: Prevention
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 70.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No

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.