Safety and Pharmacokinetics of Intravenous and Oral Posaconazole in Immunocompromised Children (MK-5592-097)

Phase 1CompletedNCT02452034

Merck Sharp & Dohme LLC118 enrolled

Overview

This study aims to evaluate the pharmacokinetics of posaconazole (POS) administered intravenously (IV) or orally to immunocompromised pediatric participants.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

PREVENTION

Masking

NONE

Enrollment

118

Conditions

Neutropenia

Interventions

Posaconazole IV solutionDRUG

Posaconazole by IV solution twice on Day 1, then once daily on Days 2-10.

Posaconazole powder for oral suspensionDRUG

Posaconazole once daily by PFS for a minimum of 10 days

Eligibility

Sex: ALLMin age: 2 YearsMax age: 17 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Have documented or anticipated neutropenia expected to last for at least 7 days, following treatment in at least one of the following clinical situations: acute leukemia, myelodysplasia, severe aplastic anemia, recipients of Autologous Hematopoietic Stem Cell Transplant (HSCT), high risk neuroblastoma, advanced stage non-Hodgkin's lymphoma, hemophagocytic lymphohistiocytosis * Have a central line in place prior to IV study therapy * Participants of reproductive potential agree to remain abstinent, or use a medically accepted method of birth control Exclusion Criteria: * Has a proven or probable invasive fungal infection * Has received any formulation of POS within prior 10 days * Is receiving any prohibited drugs * Has laboratory results that are outside of normal limits at screening, as follows: a) Moderate or severe liver dysfunction, as defined as: Aspartate Aminotransferase (AST) \> 5 times the upper limit of normal (ULN), OR Alanine Aminotransferase (ALT) \> 5 times the ULN, OR Serum total bilirubin \>2.5 times the ULN, OR AST or ALT \> 3 times ULN with total bilirubin \> 2 times ULN; b) Calculated creatinine clearance \<30 mL/min. * Has QTc (QT interval corrected for rate) prolongation defined as: a) Symptomatic QTc prolongation \>450 msec (males) or \>470 msec (females) OR b) Any QTc prolongation of \>500 msec * Is pregnant, intends to become pregnant during study, or is breastfeeding * Has a history of anaphylaxis attributed to the azole class of antifungal agents * Is not expected to receive a minimum of 10 days of POS IV solution * Has participated in any Phase 1 Investigational New Drug (IND) study within prior 30 days or expects to do so within the following 60 days * Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling or child) who is investigational site or sponsor staff directly involved with this trial

Outcomes

Primary Outcomes

Area Under the Plasma Concentration Versus Time Curve (AUC) From Time 0 to 24 Hours Post-dose for POS

Blood was collected from pre-dose up to 24 hours post-dose in order to determine the plasma AUC from time 0-24 hours post-dose (AUC0-24hr) of posaconazole. A non compartmental analysis of posaconazole plasma concentrations was performed. Results are reported for each treatment arm according to the formulation that participants received (IV or PFS). Participants receiving both formulations were counted once for each formulation.

Time frame: Any day from Day 7 to Day 10 of therapy for each formulation (up to 28 days) at pre-dose, within 15 minutes after end of infusion (up to 2 hours), and 4, 6, 8, 12, 24 hours post-infusion

Maximum Plasma Concentration (Cmax) for POS

Blood was collected from pre-dose up to 24 hours post-dose in order to determine the plasma Cmax of posaconazole. A non-compartmental analysis of posaconazole plasma concentrations was performed. Results are reported for each treatment arm according to the formulation that participants received (IV or PFS). Participants receiving both formulations were counted once for each formulation.

Time frame: Any day from Day 7 to Day 10 of therapy for each formulation (up to 28 days) at pre-dose, within 15 minutes after end of infusion (up to 2 hours), and 4, 6, 8, 12, 24 hours post-infusion

Minimum Plasma Concentration (Cmin) for POS

Blood was collected from pre-dose up to 24 hours post-dose in order to determine the plasma Cmin of posaconazole. A non-compartmental analysis of posaconazole plasma concentrations was performed. Results are reported for each treatment arm according to the formulation that participants received (IV or PFS). Participants receiving both formulations were counted once for each formulation.

Time frame: Any day from Day 7 to Day 10 of therapy for each formulation (up to 28 days) at pre-dose, within 15 minutes after end of infusion (up to 2 hours), and 4, 6, 8, 12, 24 hours post-infusion

Average Steady-state Plasma Concentration (Cavg) for POS

Blood was collected from pre-dose up to 24 hours post-dose in order to determine the plasma Cavg of posaconazole. A non-compartmental analysis of posaconazole plasma concentrations was performed. Results are reported for each treatment arm according to the formulation that participants received (IV or PFS). Participants receiving both formulations were counted once for each formulation.

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Secondary Outcomes

Number of Participants With an Adverse Event (AE)

An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol - specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.

Time frame: 14 days after end of treatment (Up to 42 days)

Number of Participants Who Discontinued Treatment of Study Drug Due to an Adverse Event (AE)

Time frame: Up to 28 days