Pharmacokinetics, Safety, and Tolerability of Intravenous Posaconazole Solution Followed by Oral Posaconazole Suspension in Subjects at High Risk for Invasive Fungal Infections (P05520)
Condition: Fungal Infection
MeSH terms: Infections; Communicable Diseases; Mycoses; Invasive Fungal Infections
Intervention: Posaconazole; Dextrose 5% in water
Intervention MeSH terms: Posaconazole
Phase: Phase 1
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 279.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Antifungal Agents pharmacokinetics; Mycoses prevention and control

Summary:

      The purpose of this study is to collect pharmacokinetic (PK) information related to how well
      intravenous Posaconazole (POS IV), is distributed in the body and to determine the safety and
      tolerability of this new formulation. In addition, the PK, safety, and tolerability of
      switching from taking POS IV to taking Posaconazole Oral Suspension (POS Oral) will be
      evaluated. The data collected in this study will be compared to data collected in previous
      studies.

      Individuals who have been diagnosed by their physicians with a blood disease or cancer that
      can affect their infection-fighting white blood cells will be asked to participate in the
      trial. Since these blood diseases and their treatments can weaken the immune system, they may
      put these individuals at a high risk for getting a serious fungal infection of their internal
      organs or blood (invasive fungal infection). As these fungal infections can be hard to detect
      early and can be life-threatening, many physicians believe that individuals diagnosed with
      these diseases should receive antifungal therapy to try to lower their risk of getting this
      type of infection.

      Enrollment into this study will take place in several stages (cohorts). The determination of
      which cohort an individual will be asked to participate in is based on which cohort is open
      at the site at the time the individual is approached to consider study participation.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Adult subjects greater than or equal to 18 years of age (weighing greater than 34 kg
             [75 lb]), of either sex and of any race/ethnicity.

          -  Disease definition for each subject: Anticipated (likely to develop within 3 days to 5
             days) or documented prolonged neutropenia (absolute neutrophil count [ANC] <500/mm^3
             [0.5 x 10^9/L]) at Baseline 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

          -  Disease definition for each Cohort 3 subject: In addition to subjects defined above,
             allogeneic hematopoietic stem cell transplant (HSCT) subjects may be randomized in
             either the pre-engraftment period (i.e., after they have received their conditioning
             regimen for the transplant, but while they are still neutropenic) or in the
             post-engraftment period if they are receiving immunosuppressive therapy for prevention
             or treatment of graft-versus-host disease (e.g., steroids, tacrolimus, cyclosporin,
             mycophenolate mofetil, and antithymocyte globulin).

        Exclusion Criteria:

          -  A female subject must not be pregnant, must not intend to become pregnant during the
             study, or must not be nursing.

          -  Excluded prior treatments. A subject must not have received systemic antifungal
             therapy (oral, intravenous, or inhaled) for the treatment of proven or probable IFI
             within 30 days of Enrollment.

          -  A subject must not have moderate or severe liver dysfunction at Baseline, defined as
             aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels greater than
             three times the upper limit of normal (ULN), AND a total bilirubin level greater than
             two times the ULN. For Cohorts 1 and 2, a subject must not have a known or suspected
             history of Gilbert's disease.

          -  A subject must not have an electrocardiogram (ECG) with a prolonged QTc interval by
             manual reading: QTc greater than 500 msec.

          -  A subject must not have prior enrollment in this study, or other POS studies within 90
             days of study entry.

          -  A subject must not have a known or suspected invasive or systemic fungal infection at
             Baseline. Those subjects receiving empiric anti-fungal therapy within 7 days prior to
             Baseline must have had a diagnostic work-up that ruled out a possible invasive fungal
             infection.

          -  A subject must not have creatinine clearance levels (measured or calculated) below 50
             mL/min.

          -  A subject must not have a history of Type I hypersensitivity or idiosyncratic
             reactions to azole agents.