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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01777763
First received: January 25, 2013
Last updated: October 1, 2014
Last verified: October 2014
  Purpose

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).


Condition Intervention Phase
Fungal Infections
Drug: Posaconazole 200 mg
Drug: Posaconazole 300 mg
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Pharmacokinetics and Safety of Solid Oral Posaconazole (SCH 56592) in Subjects at High Risk for Invasive Fungal Infections (Phase 1b; Protocol No. P05615)

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Average Concentration (Cavg) of Posaconazole Tablet [ Time Frame: Predose on Day 1 up to 24 hours postdose on Day 8 ] [ Designated as safety issue: No ]

    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.


  • Minimum Concentration (Cmin) of Posaconazole Tablet [ Time Frame: Predose on Day 1 up to 24 hours postdose on Day 8 ] [ Designated as safety issue: No ]
    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.

  • Maximum Concentration (Cmax) of Posaconazole Tablet [ Time Frame: Predose on Day 1 up to 24 hours postdose on Day 8 ] [ Designated as safety issue: No ]
    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.

  • Time to Maximum Concentration (Tmax) of Posaconazole Tablet [ Time Frame: Predose on Day 1 up to 24 hours postdose on Day 8 ] [ Designated as safety issue: No ]
    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.

  • Apparent Total Body Clearance (CL/F) for Posaconazole Tablet [ Time Frame: Predose on Day 1 up to 24 hours postdose on Day 8 ] [ Designated as safety issue: No ]
    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 Outcome Measures:
  • Number of Participants Surviving at Day 65 [ Time Frame: Day 65 ] [ Designated as safety issue: Yes ]
    Number of Participants Alive at Day 65

  • Number of Participants With Treatment-Emergent Adverse Events (AEs) [ Time Frame: Up to Day 65 ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants With Treatment-Related AEs [ Time Frame: Up to Day 65 ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants Discontinuing Study Treatment Due to an AE [ Time Frame: Up to Day 28 ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 230
Study Start Date: June 2009
Study Completion Date: February 2012
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Posaconazole 200 mg
Posaconazole 200 mg (two 100 mg tablets) twice daily (BID) on Day 1 followed by 200 mg (two 100 mg tablets) once daily (QD) for up to 28 days
Drug: Posaconazole 200 mg
Other Names:
  • SCH 056592
  • MK-5592
  • Noxafil®
Experimental: Posaconazole 300 mg
Posaconazole 300 mg (three 100 mg tablets) BID on Day 1 followed by 300 mg (three 100 mg tablets) QD for up to 28 days
Drug: Posaconazole 300 mg
Other Names:
  • SCH 056592
  • MK-5592
  • Noxafil®

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

Publications:
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01777763     History of Changes
Other Study ID Numbers: P05615, 2008-006684-36, 5592-065
Study First Received: January 25, 2013
Results First Received: February 20, 2013
Last Updated: October 1, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Communicable Diseases
Infection
Mycoses
Posaconazole
14-alpha Demethylase Inhibitors
Anti-Infective Agents
Antifungal Agents
Antiparasitic Agents
Antiprotozoal Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Trypanocidal Agents

ClinicalTrials.gov processed this record on November 24, 2014