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

Merck Sharp & Dohme (MSD)

Status and phase

Completed

Phase 1

Conditions

Fungal Infections

Treatments

Drug: Posaconazole 200 mg

Drug: Posaconazole 300 mg

Study type

Interventional

Funder types

Industry

Identifiers

NCT01777763

5592-065 (Other Identifier)

2008-006684-36 (EudraCT Number)

P05615

Details and patient eligibility

About

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).

Full 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.

Enrollment

230 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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