Clinical trial NCT02452034: Safety and Pharmacokinetics of Intravenous and Oral Posaconazole in Immunocompromised Children (MK-5592-097)
Official title: A Study of the Safety, Tolerability, and Pharmacokinetics of Intravenous (IV) and Powder for Oral Suspension Formulations of Posaconazole (POS) in Immunocompromised Pediatric Subjects With Neutropenia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neutropenia
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2015-05-22
Enrollment: 118
Sex: ALL
Minimum age (years): 2
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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


Eligibility criteria: 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

Primary outcomes:
measure: Area Under the Plasma Concentration Versus Time Curve (AUC) From Time 0 to 24 Hours Post-dose for POS
timeFrame: 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
measure: Maximum Plasma Concentration (Cmax) for POS
timeFrame: 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
measure: Minimum Plasma Concentration (Cmin) for POS
timeFrame: 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
measure: Average Steady-state Plasma Concentration (Cavg) for POS
timeFrame: 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
measure: Time of Maximum Plasma Concentration (Tmax) for POS
timeFrame: 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
measure: Total Body Clearance (CL) for POS Administered by IV
timeFrame: Any day from Day 7 to Day 10 of therapy (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
measure: Apparent Total Body Clearance (CL/F) for POS Administered by PFS
timeFrame: Any day from Day 7 to Day 10 of therapy (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
Secondary outcomes:
measure: Number of Participants With an Adverse Event (AE)
timeFrame: 14 days after end of treatment (Up to 42 days)
measure: Number of Participants Who Discontinued Treatment of Study Drug Due to an Adverse Event (AE)
timeFrame: Up to 28 days
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Groll AH, Abdel-Azim H, Lehrnbecher T, Steinbach WJ, Paschke A, Mangin E, Winchell GA, Waskin H, Bruno CJ. Pharmacokinetics and safety of posaconazole intravenous solution and powder for oral suspension in children with neutropenia: an open-label, sequential dose-escalation trial. Int J Antimicrob Agents. 2020 Sep;56(3):106084. doi: 10.1016/j.ijantimicag.2020.106084. Epub 2020 Jul 17.