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Completed

NCT Number: NCT01075984

Pharmacokinetics, Safety, and Tolerability of Intravenous Posaconazole Solution Followed by Oral Posaconazole Suspension in Subjects at High Risk for Invasive Fungal Infections (P05520)

The purpose of this study is to collect pharmacokinetic (PK) information related to how well intravenous Posaconazole (POS IV), is distributed in the body and to determine the safety and tolerability of this new formulation. In addition, the PK, safety, and tolerability of switching from taking POS IV to taking Posaconazole Oral Suspension (POS Oral) will be evaluated. The data collected in this study will be compared to data collected in previous studies.

Individuals who have been diagnosed by their physicians with a blood disease or cancer that can affect their infection-fighting white blood cells will be asked to participate in the trial. Since these blood diseases and their treatments can weaken the immune system, they may put these individuals at a high risk for getting a serious fungal infection of their internal organs or blood (invasive fungal infection). As these fungal 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 (cohorts). The determination of which cohort an individual will be asked to participate in is based on which cohort is open at the site at the time the individual is approached to consider study participation.

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Key information

Conditions

Fungal Infection Bacterial Infections and Mycoses Infections Mycoses

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Who can participate

Healthy volunteers accepted: No

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

Inclusion criteria

  • Adult subjects greater than or equal to 18 years of age (weighing greater than 34 kg [75 lb]), of either sex and of any race/ethnicity.
  • Disease definition for each subject: Anticipated (likely to develop within 3 days to 5 days) or documented prolonged neutropenia (absolute neutrophil count [ANC] <500/mm^3 [0.5 x 10^9/L]) at Baseline and likely to last for at least 7 days due to:
  • a. Standard intensive chemotherapy, anthracycline-based or other accepted regimen (excluding any investigational agent), for a new diagnosis of acute myelogenous leukemia (AML);
  • b. Chemotherapy for AML in first relapse; or
  • c. Therapy for myelodysplastic syndromes in transformation to AML or other diagnoses of secondary AML (therapy related, antecedent hematological disorders) or chronic myelogenous leukemia in blast crisis
  • Disease definition for each Cohort 3 subject: In addition to subjects defined above, allogeneic hematopoietic stem cell transplant (HSCT) subjects may be randomized in either the pre-engraftment period (i.e., after they have received their conditioning regimen for the transplant, but while they are still neutropenic) or in the post-engraftment period if they are receiving immunosuppressive therapy for prevention or treatment of graft-versus-host disease (e.g., steroids, tacrolimus, cyclosporin, mycophenolate mofetil, and antithymocyte globulin).

Exclusion criteria

  • A female subject must not be pregnant, must not intend to become pregnant during the study, or must not be nursing.
  • Excluded prior treatments. A subject must not have received systemic antifungal therapy (oral, intravenous, or inhaled) for the treatment of proven or probable IFI within 30 days of Enrollment.
  • A subject must not have moderate or severe liver dysfunction at Baseline, 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. For Cohorts 1 and 2, a subject must not have a known or suspected history of Gilbert's disease.
  • A subject must not have an electrocardiogram (ECG) with a prolonged QTc interval by manual reading: QTc greater than 500 msec.
  • A subject must not have prior enrollment in this study, or other POS studies within 90 days of study entry.
  • A subject must not have a known or suspected invasive or systemic fungal infection at Baseline. Those subjects receiving empiric anti-fungal therapy within 7 days prior to Baseline must have had a diagnostic work-up that ruled out a possible invasive fungal infection.
  • A subject must not have creatinine clearance levels (measured or calculated) below 50 mL/min.
  • A subject must not have a history of Type I hypersensitivity or idiosyncratic reactions to azole agents.

Treatment and study plan

Posaconazole

Drug

Other names: SCH 056592

Dextrose 5% in water

Drug

Other names: SCH 056592 (2)

Primary outcomes

  1. Single Dose Trough Concentration of IV Posaconazole (Cmin)

    Time frame: 12 hours after start of infusion on Day 1 (Cohorts 0, 1 and 2)

    Blood samples were collected from participants for the determination of plasma POS concentration.

  2. Steady State Trough Concentration of IV Posaconazole (Cmin)

    Time frame: 24 hours after start of infusion on Day 14 (Cohorts 1 and 2), or Day 10 (Cohort 3)

    Blood samples were collected from participants for the determination of plasma POS concentration.

  3. Single Dose Maximum Concentration of IV Posaconazole (Cmax)

    Time frame: Predose and 1, 1.5, 1.75, 4, 8, and 12 hours after start of infusion on Day 1 (Cohorts 0, 1 and 2)

    Blood samples were collected from participants for the determination of plasma POS concentration.

  4. Steady State Maximum Concentration of IV Posaconazole (Cmax)

    Time frame: Predose and 1, 1.5, 1.75, 4, 8, and 12 hours after start of infusion on Day 14 (Cohorts 1 and 2), or Day 10 (Cohort 3)

    Blood samples were collected from participants for the determination of plasma POS concentration.

  5. Single Dose Time of Observed Maximum Concentration of IV Posaconazole (Tmax)

    Time frame: Predose and 1, 1.5, 1.75, 4, 8, and 12 hours after start of infusion on Day 1 (Cohorts 0 and 1)

    Blood samples were collected from participants for the determination of plasma POS concentration.

  6. Steady State Time of Observed Maximum Concentration of IV Posaconazole (Tmax)

    Time frame: Predose and 1, 1.5, 1.75, 4, 8, and 12 hours after start of infusion on Day 14 (Cohorts 1 and 2), or Day 10 (Cohort 3)

    Blood samples were collected from participants for the determination of plasma POS concentration.

  7. Single Dose Area Under the Concentration Versus Time Curve of IV Posaconazole (AUC)

    Time frame: Predose and 1, 1.5, 1.75, 4, 8, and 12 hours after start of infusion on Day 1 (Cohorts 0, 1 and 2)

    Blood samples were collected from participants for the determination of plasma POS concentration.

  8. Steady State Area Under the Concentration Versus Time Curve of IV Posaconazole (AUC)

    Time frame: Predose and 1, 1.5, 1.75, 4, 8, 12, and 24 hours after start of infusion on Day 14 (Cohorts 1 and 2), or Day 10 (Cohort 3)

    Blood samples were collected from participants for the determination of plasma POS concentration.

  9. Steady State Average Concentration of IV Posaconazole (Cavg)

    Time frame: Predose and 1, 1.5, 1.75, 4, 8, 12, and 24 hours after start of infusion on Day 14 (Cohorts 1 and 2), or Day 10 (Cohort 3)

    Blood samples were collected from participants for the determination of plasma POS concentration. Cavg was calculated as steady state AUC / dosing interval (24 hours).

  10. Steady State Total Body Clearance of IV Posaconazole (CL)

    Time frame: Predose and 1, 1.5, 1.75, 4, 8, and 12 hours after start of infusion on Day 14 (Cohorts 1 and 2), or Day 10 (Cohort 3)

    Blood samples were collected from participants for the determination of plasma POS concentration.

  11. Steady State Trough Concentration of Oral Posaconazole (Cmin)

    Time frame: 12 hours after dosing on Day 7 (Cohort 0), or Day 28 (Cohorts 1 and 2)

    Blood samples were collected from participants for the determination of plasma POS concentration.

  12. Steady State Maximum Concentration of Oral Posaconazole (Cmax)

    Time frame: Predose and 3, 5, 8 and 12 hours after dosing on Day 7 (Cohort 0), or Day 28 (Cohorts 1 and 2)

    Blood samples were collected from participants for the determination of plasma POS concentration.

  13. Steady State Time of Observed Maximum Concentration of Oral Posaconazole (Tmax)

    Time frame: Predose and 3, 5, 8 and 12 hours after dosing on Day 7 (Cohort 0), or Day 28 (Cohorts 1 and 2)

    Blood samples were collected from participants for the determination of plasma POS concentration.

  14. Steady State Area Under the Concentration Versus Time Curve of Oral Posaconazole (AUC)

    Time frame: Predose and 3, 5, 8 and 12 hours after dosing on Day 7 (Cohort 0), or Day 28 (Cohorts 1 and 2)

    Blood samples were collected from participants for the determination of plasma POS concentration.

  15. Steady State Average Concentration of Oral Posaconazole (Cavg)

    Time frame: Predose and 3, 5, 8 and 12 hours after dosing on Day 7 (Cohort 0), or Day 28 (Cohorts 1 and 2)

    Blood samples were collected from participants for the determination of plasma POS concentration. Cavg was calculated as steady state AUC / dosing interval (12 hours).

  16. Steady State Apparent Total Body Clearance of Oral Posaconazole (CL/F)

    Time frame: Predose and 3, 5, 8 and 12 hours after dosing on Day 7 (Cohort 0), or Day 28 (Cohorts 1 and 2)

    Blood samples were collected from participants for the determination of plasma POS concentration.

Sponsors and collaborators

Lead sponsor

Merck Sharp & Dohme LLC

Industry

Registry information

Official study title

Pharmacokinetics, Safety, and Tolerability of Intravenous Posaconazole Solution Followed by Oral Posaconazole Suspension (SCH 56592) in Subjects at High Risk for Invasive Fungal Infections (Phase 1b; Protocol No. P05520)

Important dates

Study start
2010
Primary completion
2012
Study completion
2012
First posted
Feb 25, 2010
Registry last updated
Nov 13, 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.

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