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

Primary Purpose

Fungal Infections

Status
Terminated
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Posaconazole 12 mg/kg/day BID
Posaconazole 18 mg/kg/day BID
Posaconazole 18 mg/kg/day TID
Posaconazole 12 mg/kg/day TID
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Fungal Infections

Eligibility Criteria

3 Months - 17 Years (Child)All SexesDoes not accept healthy volunteers

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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm 4

    Arm 5

    Arm 6

    Arm 7

    Arm Type

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Arm Label

    POS 12 BID 2 to <7 Years

    POS 12 BID 7 to <18 Years

    POS 18 BID 2 to <7 Years

    POS 18 BID 7 to <18 Years

    POS 18 TID 2 to <7 Years

    POS 18 TID 7 to <18 Years

    POS 12 TID 3 months to <2 Years

    Arm Description

    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.

    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.

    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.

    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.

    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.

    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.

    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.

    Outcomes

    Primary Outcome Measures

    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.
    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.

    Secondary Outcome Measures

    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.
    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.

    Full Information

    First Posted
    October 25, 2012
    Last Updated
    July 27, 2018
    Sponsor
    Merck Sharp & Dohme LLC
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    1. Study Identification

    Unique Protocol Identification Number
    NCT01716234
    Brief Title
    A Study of the Safety, Tolerance, and Pharmacokinetics of Oral Posaconazole in Immunocompromised Children (P03579)
    Official Title
    Phase 1B Study of the Safety, Tolerance, and Pharmacokinetics of Oral Posaconazole in Immunocompromised Children With Neutropenia (P03579)
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    July 2018
    Overall Recruitment Status
    Terminated
    Why Stopped
    Study was terminated early (10 July 2015) based on preliminary analysis of pharmacokinetic data.
    Study Start Date
    April 17, 2008 (Actual)
    Primary Completion Date
    April 1, 2015 (Actual)
    Study Completion Date
    April 1, 2015 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Merck Sharp & Dohme LLC

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Fungal Infections

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Non-Randomized
    Enrollment
    142 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    POS 12 BID 2 to <7 Years
    Arm Type
    Experimental
    Arm Description
    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.
    Arm Title
    POS 12 BID 7 to <18 Years
    Arm Type
    Experimental
    Arm Description
    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.
    Arm Title
    POS 18 BID 2 to <7 Years
    Arm Type
    Experimental
    Arm Description
    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.
    Arm Title
    POS 18 BID 7 to <18 Years
    Arm Type
    Experimental
    Arm Description
    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.
    Arm Title
    POS 18 TID 2 to <7 Years
    Arm Type
    Experimental
    Arm Description
    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.
    Arm Title
    POS 18 TID 7 to <18 Years
    Arm Type
    Experimental
    Arm Description
    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.
    Arm Title
    POS 12 TID 3 months to <2 Years
    Arm Type
    Experimental
    Arm Description
    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.
    Intervention Type
    Drug
    Intervention Name(s)
    Posaconazole 12 mg/kg/day BID
    Other Intervention Name(s)
    SCH 056592, MK-5592, Noxafil®
    Intervention Description
    Posaconazole oral suspension 12 mg/kg/day divided into 2 doses (BID) (maximum 800 mg/day)
    Intervention Type
    Drug
    Intervention Name(s)
    Posaconazole 18 mg/kg/day BID
    Other Intervention Name(s)
    SCH 056592, MK-5592, Noxafil®
    Intervention Description
    Posaconazole oral suspension 18 mg/kg/day divided into 2 doses (BID) (maximum 1200 mg/day)
    Intervention Type
    Drug
    Intervention Name(s)
    Posaconazole 18 mg/kg/day TID
    Other Intervention Name(s)
    SCH 056592, MK-5592, Noxafil®
    Intervention Description
    Posaconazole oral suspension 18 mg/kg/day divided into 3 doses (TID) (maximum 1200 mg/day)
    Intervention Type
    Drug
    Intervention Name(s)
    Posaconazole 12 mg/kg/day TID
    Other Intervention Name(s)
    SCH 056592, MK-5592, Noxafil®
    Intervention Description
    Posaconazole oral suspension 12 mg/kg/day divided into 3 doses (TID) (maximum 800 mg/day)
    Primary Outcome Measure Information:
    Title
    Average Concentration of Posaconazole (Cavg) on Day 1 (Single Dose)
    Description
    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.
    Time Frame
    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)
    Title
    Average Concentration of Posaconazole (Cavg) on Day 7 (Steady State)
    Description
    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.
    Time Frame
    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 Measure Information:
    Title
    Number of Participants With an Adverse Event
    Description
    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.
    Time Frame
    Up to Day 58
    Title
    Number of Participants With an Adverse Event Leading to Study Drug Discontinuation
    Description
    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.
    Time Frame
    Up to Day 28

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    3 Months
    Maximum Age & Unit of Time
    17 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    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
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Medical Director
    Organizational Affiliation
    Merck Sharp & Dohme LLC
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
    IPD Sharing URL
    http://engagezone.msd.com/ds_documentation.php
    Citations:
    PubMed Identifier
    30913226
    Citation
    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.
    Results Reference
    derived

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

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