Pharmacokinetics, Safety, and Tolerability of Intravenous Posaconazole Solution Followed by Oral Posaconazole Suspension (SCH 56592) in Subjects at High Risk for Invasive Fungal Infections (Phase 1b; Protocol No. P05520)
- 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).
- 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
- A subject must not have creatinine clearance levels (measured or calculated) below 50
- A subject must not have a history of Type I hypersensitivity or idiosyncratic
reactions to azole agents.