A Study of the Safety, Tolerance, and Pharmacokinetics of Oral Posaconazole in Immunocompromised Children (P03579)

Phase 1B Study of the Safety, Tolerance, and Pharmacokinetics of Oral Posaconazole in Immunocompromised Children With Neutropenia (P03579)

The purpose of this dose-escalation study is to evaluate the pharmacokinetics, safety, and tolerability of oral posaconazole in immunocompromised children with neutropenia or expected neutropenia.

Study Overview

• Status: Terminated
• Conditions: Fungal Infections
• Intervention / Treatment: Drug: Posaconazole 12 mg/kg/day BID; Drug: Posaconazole 18 mg/kg/day BID; Drug: Posaconazole 18 mg/kg/day TID; Drug: Posaconazole 12 mg/kg/day TID

• Study Type: Interventional
• Enrollment (Actual): 142
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 months to 17 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Documented or anticipated neutropenia expected to last at least 7 days and only in the following clinical situations: acute leukemia; myelodysplasia; severe aplastic anemia; autologous hematopoietic stem cell transplantation (HSCT) recipients; high risk neuroblastoma; advanced stage non-Hodgkin's lymphoma; recipients of allogeneic HSCT during the pre-engraftment (neutropenia) period
• Participants of child-bearing potential must use a medically accepted method of

contraception throughout the study and for at least 30 days after stopping study medication, unless they are surgically or medically sterile or agree to remain abstinent.

Exclusion Criteria:

• Proven invasive fungal infection (IFI) before study entry
• Severe nausea and/or vomiting at screening
• Received posaconazole within 10 days before screening
• Unable to receive study drug by mouth or via an intestinal (enteral) tube
• Females who are pregnant, intend to become pregnant during the study, or are breastfeeding
• History of anaphylaxis attributed to the azole class of antifungal agents

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: POS 12 BID 2 to <7 Years; Participants aged 2 to <7 years received posaconazole oral suspension 12 mg/kg/day divided into 2 doses (BID) until recovery from neutropenia or up to 28 days.	Drug: Posaconazole 12 mg/kg/day BID; Posaconazole oral suspension 12 mg/kg/day divided into 2 doses (BID) (maximum 800 mg/day); Other Names: SCH 056592; MK-5592; Noxafil®
EXPERIMENTAL: POS 12 BID 7 to <18 Years; Participants aged 7 to <18 years received posaconazole oral suspension 12 mg/kg/day divided into 2 doses (BID) until recovery from neutropenia or up to 28 days.	Drug: Posaconazole 12 mg/kg/day BID; Posaconazole oral suspension 12 mg/kg/day divided into 2 doses (BID) (maximum 800 mg/day); Other Names: SCH 056592; MK-5592; Noxafil®
EXPERIMENTAL: POS 18 BID 2 to <7 Years; Participants aged 2 to <7 years received posaconazole oral suspension 18 mg/kg/day divided into 2 doses (BID) until recovery from neutropenia or up to 28 days.	Drug: Posaconazole 18 mg/kg/day BID; Posaconazole oral suspension 18 mg/kg/day divided into 2 doses (BID) (maximum 1200 mg/day); Other Names: SCH 056592; MK-5592; Noxafil®
EXPERIMENTAL: POS 18 BID 7 to <18 Years; Participants aged 7 to <18 years received posaconazole oral suspension 18 mg/kg/day divided into 2 doses (BID) until recovery from neutropenia or up to 28 days.	Drug: Posaconazole 18 mg/kg/day BID; Posaconazole oral suspension 18 mg/kg/day divided into 2 doses (BID) (maximum 1200 mg/day); Other Names: SCH 056592; MK-5592; Noxafil®
EXPERIMENTAL: POS 18 TID 2 to <7 Years; Participants aged 2 to <7 years received posaconazole oral suspension 18 mg/kg/day divided into 3 doses (TID) until recovery from neutropenia or up to 28 days.	Drug: Posaconazole 18 mg/kg/day TID; Posaconazole oral suspension 18 mg/kg/day divided into 3 doses (TID) (maximum 1200 mg/day); Other Names: SCH 056592; MK-5592; Noxafil®
EXPERIMENTAL: POS 18 TID 7 to <18 Years; Participants aged 7 to <18 years received posaconazole oral suspension 18 mg/kg/day divided into 3 doses (TID) until recovery from neutropenia or up to 28 days.	Drug: Posaconazole 18 mg/kg/day TID; Posaconazole oral suspension 18 mg/kg/day divided into 3 doses (TID) (maximum 1200 mg/day); Other Names: SCH 056592; MK-5592; Noxafil®
EXPERIMENTAL: POS 12 TID 3 months to <2 Years; Participants aged 3 months to <2 years received posaconazole oral suspension 12 mg/kg/day divided into 3 doses (TID) until recovery from neutropenia or up to 28 days.	Drug: Posaconazole 12 mg/kg/day TID; Posaconazole oral suspension 12 mg/kg/day divided into 3 doses (TID) (maximum 800 mg/day); Other Names: SCH 056592; MK-5592; Noxafil®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average Concentration of Posaconazole (Cavg) on Day 1 (Single Dose)	Blood samples for determination of plasma posaconazole concentration were collected predose and approximately 3, 5, 8, and 12 hours after the first dose on Day 1. The 12-hour sample was not obtained for the TID dose groups. Day 1 pharmacokinetic samples were not collected for participants 3 months to <2 years of age weighing <6.5 kg.	Up to 12 hours after the first dose (BID dose groups) or up to 8 hours after the first dose (TID dose (TID dose groups)
Average Concentration of Posaconazole (Cavg) on Day 7 (Steady State)	Blood samples for determination of plasma posaconazole concentration were collected predose and approximately 3, 5, 8, and 12 hours after the first dose on Day 7 (steady state). The 12-hour sample was not obtained for the TID dose groups. The target Cavg range was 500 to <2500 ng/mL.	Up to 12 hours after the first dose on Day 7 (BID dose groups) or up to 8 hours after the first dose on Day 7 (TID dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With an Adverse Event	An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product, biologic (at any dose), or medical device, which does not necessarily have a causal relationship with the treatment. Adverse events may include the onset of new illness and the exacerbation of preexisting conditions.	Up to Day 58
Number of Participants With an Adverse Event Leading to Study Drug Discontinuation	An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product, biologic (at any dose), or medical device, which does not necessarily have a causal relationship with the treatment. Adverse events may include the onset of new illness and the exacerbation of preexisting conditions.	Up to Day 28

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Arrieta AC, Sung L, Bradley JS, Zwaan CM, Gates D, Waskin H, Carmelitano P, Groll AH, Lehrnbecher T, Mangin E, Joshi A, Kartsonis NA, Walsh TJ, Paschke A. A non-randomized trial to assess the safety, tolerability, and pharmacokinetics of posaconazole oral suspension in immunocompromised children with neutropenia. PLoS One. 2019 Mar 26;14(3):e0212837. doi: 10.1371/journal.pone.0212837. eCollection 2019.

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 17, 2008
• Primary Completion (ACTUAL): April 1, 2015
• Study Completion (ACTUAL): April 1, 2015

Study Registration Dates

• First Submitted: October 25, 2012
• First Submitted That Met QC Criteria: October 25, 2012
• First Posted (ESTIMATE): October 29, 2012

Study Record Updates

• Last Update Posted (ACTUAL): August 27, 2018
• Last Update Submitted That Met QC Criteria: July 27, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections and Mycoses; Mycoses; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; 14-alpha Demethylase Inhibitors; Trypanocidal Agents; Posaconazole
• Other Study ID Numbers: P03579; 2007-004645-15 (EUDRACT_NUMBER); MK-5592-032 (OTHER: Merck)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf