Skip to main content
OpenTrials
Completed

NCT Number: NCT01777763

Pharmacokinetics and Safety of Posaconazole Tablet in Participants at High Risk for Invasive Fungal Infections (MK-5592-065/P05615)

The purpose of this study is to collect pharmacokinetic (PK) information related to how well posaconazole tablet is distributed in the body and to determine the safety of this new formulation. The study consists of a Phase 1B study that includes participants with neutropenia undergoing chemotherapy for acute myelogenous leukemia (AML) or myelodysplasia (MDS) and a Phase 3 study that includes participants who are undergoing chemotherapy for AML or MDS and participants who are recipients of allogeneic hematopoietic stem cell transplant (HSCT).

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Fungal Infections Bacterial Infections and Mycoses Infections Mycoses

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

About this study

Participants with a blood disease or cancer that can affect their infection-fighting white blood cells and those who have undergone a hematopoietic stem cell transplant (HSCT) and are receiving immunosuppressive therapy and have or are at risk of graft-vs-host disease (GVHD) are eligible for the study. These blood diseases and their treatments can weaken the immune system and may put individuals at high risk for a serious fungal infection of their internal organs or blood (invasive fungal infection). As these infections can be hard to detect early and can be life-threatening, many physicians believe that individuals diagnosed with these diseases should receive antifungal therapy to try to lower their risk of getting this type of infection.

Enrollment into this study will take place in several stages (parts). The determination of which part a participant will be in is based on which part is open at the site at the time of enrollment.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Body weight >34 kg (75 lb) and of any race/ethnicity
  • Able to swallow oral tablets whole
  • Anticipated (likely to develop within 3-5 days) or documented neutropenia due to chemotherapy, chemotherapy for a new diagnosis of acute myelogenous leukemia (AML), or AML in first relapse; myelodysplastic syndromes (MDS) in transformation to AML; allogeneic hematopoietic stem cell transplant (HSCT) participants in the pre-engraftment period or in the post-engraftment period if they are receiving immunosuppressive therapy for graft versus host disease

Exclusion criteria

  • Female must not be pregnant, must not intend to become pregnant

during the study, and must not be nursing

  • History of hypersensitivity to azoles
  • Moderate or severe liver dysfunction defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels greater than three times the upper limit of normal (ULN), AND a total bilirubin level greater than two times the ULN
  • Electrocardiogram (ECG) with corrected QTc interval greater than 500 msec
  • Posaconazole within 10 days before study enrollment
  • Receipt of systemic antifungal therapy within 30 days of study enrollment for reasons other than antifungal prophylaxis
  • Evidence of known or suspected invasive or systemic fungal infection at baseline
  • Known or suspected history of Gilbert's disease
  • Creatinine clearance levels below 30 mL/min

Treatment and study plan

Posaconazole 200 mg

Drug

Other names: SCH 056592, MK-5592, Noxafil®

Posaconazole 300 mg

Drug

Other names: SCH 056592, MK-5592, Noxafil®

Primary outcomes

  1. Average Concentration (Cavg) of Posaconazole Tablet

    Time frame: Predose on Day 1 up to 24 hours postdose on Day 8

    Posaconazole steady-state concentrations of posaconazole in the plasma reached after regular and repeated dosing were used to estimate pharmacokinetic (PK) parameters for each participant where Cavg was defined as area under the plasma concentration versus time curve divided by the dosing interval.

    Blood samples for the assessment of Cavg were collected on Day 1 and Day 8 predose and then at specified time points up to 24 hours postdose.

  2. Minimum Concentration (Cmin) of Posaconazole Tablet

    Time frame: Predose on Day 1 up to 24 hours postdose on Day 8

    Cmin was defined as posaconazole trough level immediately before a participant received the dose of posaconazole tablets on the specified day. Trough (Cmin) level blood samples for determination of posaconazole in plasma were collected for all participants on Day 1, Day 2, Day 3, and Day 8. On Day 1, the trough level sample was collected the before the first dose of study drug. On Day 2, trough samples were collected approximately 12 hours after the second dose of study drug was administered on Day 1. On all subsequent days, trough samples were collected approximately 24 hours following the previous day's dose of study drug.

  3. Maximum Concentration (Cmax) of Posaconazole Tablet

    Time frame: Predose on Day 1 up to 24 hours postdose on Day 8

    Blood samples for the assessment of Cmax were collected on Day 1 and Day 8 predose and then at specified time points up to 24 hours postdose.

  4. Time to Maximum Concentration (Tmax) of Posaconazole Tablet

    Time frame: Predose on Day 1 up to 24 hours postdose on Day 8

    Blood samples for the assessment of Tmax were collected on Day 1 and Day 8 predose and then at specified time points up to 24 hours postdose.

  5. Apparent Total Body Clearance (CL/F) for Posaconazole Tablet

    Time frame: Predose on Day 1 up to 24 hours postdose on Day 8

    Blood samples for the assessment of CL/F, the rate at which posaconazole was removed from the body, were collected on Day 1 and Day 8 predose and then at specified time points up to 24 hours postdose.

Other outcomes

  1. Number of Participants Surviving at Day 65

    Time frame: Day 65

    Number of Participants Alive at Day 65

  2. Number of Participants With Treatment-Emergent Adverse Events (AEs)

    Time frame: Up to Day 65

    AEs are any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a study drug, whether or not considered related to this study drug. Treatment-emergent AEs are any events not present before starting study drug treatment or any events that were present before treatment that worsened in either intensity or frequency after exposure to study drug.

  3. Number of Participants With Treatment-Related AEs

    Time frame: Up to Day 65

    AEs are any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a study drug, whether or not considered related to this study drug. Treatment-related AEs were considered by the investigator to be related to the study drug.

  4. Number of Participants Discontinuing Study Treatment Due to an AE

    Time frame: Up to Day 28

    AEs are any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a study drug, whether or not considered related to this study drug. These AEs resulted in participants stopping study drug treatment. This measure includes participants who discontinued due to AEs and also includes treatment failures that were attributed to AEs.

Sponsors and collaborators

Lead sponsor

Merck Sharp & Dohme LLC

Industry

Registry information

Official study title

Pharmacokinetics and Safety of Solid Oral Posaconazole (SCH 56592) in Subjects at High Risk for Invasive Fungal Infections (Phase 1b; Protocol No. P05615)

Important dates

Study start
2009
Primary completion
2012
Study completion
2012
First posted
Jan 29, 2013
Registry last updated
Apr 7, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.