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

NCT01716234 | Terminated Phase 1 Results DMC

• 3 other identifiers: P035792007-004645-15MK-5592-032
• Study Type: interventional
• Target: 142
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Fungal Infections

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (2)

• Number of Participants With an Adverse Event

  Up to Day 58

• Number of Participants With an Adverse Event Leading to Study Drug Discontinuation

  Up to Day 28

Study Arms (7)

POS 12 BID 2 to <7 Years

EXPERIMENTAL

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

POS 12 BID 7 to <18 Years

EXPERIMENTAL

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

POS 18 BID 2 to <7 Years

EXPERIMENTAL

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

POS 18 BID 7 to <18 Years

EXPERIMENTAL

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

POS 18 TID 2 to <7 Years

EXPERIMENTAL

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

POS 18 TID 7 to <18 Years

EXPERIMENTAL

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

POS 12 TID 3 months to <2 Years

EXPERIMENTAL

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

Interventions

Posaconazole 12 mg/kg/day BID DRUG

Posaconazole oral suspension 12 mg/kg/day divided into 2 doses (BID) (maximum 800 mg/day)

Also known as: SCH 056592, MK-5592, Noxafil®

POS 12 BID 2 to <7 Years; POS 12 BID 7 to <18 Years

Posaconazole 18 mg/kg/day BID DRUG

Posaconazole oral suspension 18 mg/kg/day divided into 2 doses (BID) (maximum 1200 mg/day)

Also known as: SCH 056592, MK-5592, Noxafil®

POS 18 BID 2 to <7 Years; POS 18 BID 7 to <18 Years

Posaconazole 18 mg/kg/day TID DRUG

Posaconazole oral suspension 18 mg/kg/day divided into 3 doses (TID) (maximum 1200 mg/day)

Also known as: SCH 056592, MK-5592, Noxafil®

POS 18 TID 2 to <7 Years; POS 18 TID 7 to <18 Years

Posaconazole 12 mg/kg/day TID DRUG

Posaconazole oral suspension 12 mg/kg/day divided into 3 doses (TID) (maximum 800 mg/day)

Also known as: SCH 056592, MK-5592, Noxafil®

POS 12 TID 3 months to <2 Years

Eligibility Criteria

• Age: 3 Months - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• 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.

  PMID: 30913226 DERIVED

MeSH Terms

Conditions

Mycoses

Interventions

posaconazole; BID protein, human

Condition Hierarchy (Ancestors)

Bacterial Infections and Mycoses; Infections

Limitations and Caveats

Only 1 participant was enrolled in the POS 12 TID 3 months to \<2 years group, limiting conclusions that may be drawn for pharmacokinetics or safety.

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 25, 2012
• First Posted: October 29, 2012
• Study Start: April 17, 2008
• Primary Completion: April 1, 2015
• Study Completion: April 1, 2015
• Last Updated: August 27, 2018
• Results First Posted: April 15, 2016

Record last verified: 2018-07

Data Sharing

• IPD Sharing: Will share