Safety and Efficacy Study of Posaconazole vs. Fluconazole for Prevention of Invasive Fungal Infection (P05387 AM1)(COMPLETED)

Study Overview
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Brief Summary
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A randomized, open label parallel controlled, multicenter study to evaluate safety and efficacy of Posaconazole oral suspension vs Fluconazole (capsule) in high-risk leukopenic patients for prevention of invasive fungal infection

Official Title
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A Randomized, Open Label Parallel Controlled, Multicenter Study to Evaluate Safety and Efficacy of Posaconazole Oral Suspension Vs. Fluconazole (Capsule) in High-risk Leukopenic Patients for Prevention of Invasive Fungal Infection

Conditions
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Leukopenia

Intervention / Treatment
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* Drug: Posaconazole
* Drug: Fluconazole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must be 18-70 years of age of either sex Persistent neutropenia (Absolute Neutrophil Count [ANC] < 500/mm^3 [0.5x10^9/L]）or probable neutropenia in 3-5 days is anticipated. Neutropenia >= 7 days caused by the following reasons Standard or dose-intense chemotherapy, anthracyclines or other acceptable chemotherapies ( any investigational drug is not permitted) for Acute Myelogenous Leukemia (AML) treatment Retreatment of chemotherapy in case of AML recurrence Myelodysplastic syndrome (MDS) shifts to AML and bone marrow arrest induction chemotherapy is required (not including acute phase of chronic myelogenous leukemia [CML]) Informed consent obtained from participant or legal guardian Exclusion Criteria: Participants previously treated with amphotericin B (AMB), fluconazole (FLZ), or itraconazole (ITZ) within 30 days of enrollment. Participants who have taken the following drugs: terfenadine, cisapride, and ebastine within 24 hours before entry astemizole at entry or within 10 days before entry cimetidine, rifampin, carbamazepine, phenytoin, rifabutin, barbiturates, isoniazid atharanthine and anthracyclines within 24 hours before entry The above drugs are refrained during the investigation Serious organ diseases except hematological disorder such as cardiac or neurologic disorders or impairment expected to be unstable or progressive during the course of this study (eg, seizures or demyelinating syndromes, acute myocardial infarction within 3 months of study entry, myocardial ischemia, congestive heart failure, atrial fibrillation with ventricular rate <60/min, or history of torsades de pointes, symptomatic ventricular or sustained arrhythmias), unstable electrolyte abnormalities. Participants who have used any investigational drugs or biologic agents other than their chemotherapy regimens within 30 days of study entry. Prior enrollment in this study. Participants with known or suspected hypersensitivity or idiosyncratic reaction to azole agents or amphotericin B. Participants with known or suspected invasive fungal infection (IFI) at screen Participants with severe renal insufficiency (estimated creatinine clearance less than 50 mL/minute or likely to require dialysis during the study), Alanine transaminase (ALT), Aspartate transaminase (AST), alkaline phosphatase or total bilirubin are >2× (Upper Limit of Normal) ULN. Participants having an electrocardiogram (ECG) with a prolonged QTc interval: QTc greater than 450 msec for men and greater than 470 msec for women. Participants with AML or CML history. Participants with a history of allogeneic hematopoietic stem cell, bone marrow transplantation, autologous stem cell transplantation history. Female participants who are pregnant or are nursing. Alcohol and/or drug abuse. Participants cannot be compliant in the opinion of the investigator.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Posaconazole<br>Posaconazole oral suspension 200 mg three times a day (TID) | Drug: Posaconazole<br>* 40 mg/mL; 200 mg (5 mL) TID Treatment was continued with each cycle of chemotherapy until: The onset of a proven or probable diagnosis of invasive fungal infection (IFI) 3 chemotherapy cycles or Total treatment duration up to 12 weeks (84 days)<br>* Other names: SCH 056592;|
| Active Comparator: Fluconazole<br>Fluconazole 400 mg once daily (QD) | Drug: Fluconazole<br>* 50 mg/capsule (2 capsules), 150 mg/capsule (2 capsules); 400 mg QD Treatment was continued with each cycle of chemotherapy until: The onset of a proven or probable diagnosis of invasive fungal infection (IFI) 3 chemotherapy cycles or Total treatment duration up to 12 weeks (84 days)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Proven or Probable Diagnosis of Invasive Fungal Infection (IFI) During the Treatment Period | Number of participants developing a proven or probable IFI from randomization to the last dosage date (up to 12 weeks [84 days]) plus 7 days. IFI diagnosis criteria may include: persistent fever, failure of appropriate broad-spectrum antibiotic treatment concomitant with lower respiratory tract infection symptoms, microbiological criteria with corresponding clinical signs and symptoms. | Up to 12 Weeks (84 days) plus 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Proven or Probable Diagnosis of IFI Within 100 Days From Randomization | Number of participants who developed a proven or probable IFI from randomization date to Day 100 of follow-up visit. IFI diagnosis criteria may include: persistent fever, failure of appropriate broad-spectrum antibiotic treatment concomitant with lower respiratory tract infection symptoms, microbiological criteria with corresponding clinical signs and symptoms. | From randomization date to Day 100 | 
| Time From Randomization to the First Onset of Proven or Probable IFI | The time measured in days to the first occurrence of proven/probable IFI diagnosis in the entire FAS population from randomization to Day 100 of follow-up visit. Participants may not have accepted immediate antifungal treatment and later received antifungal treatment based upon further investigator review of the participant's IFI condition. IFI diagnosis criteria may include: persistent fever, failure of appropriate broad-spectrum antibiotic treatment concomitant with lower respiratory tract infection symptoms, positive blood/biopsy cultures with corresponding clinical signs and symptoms. | From randomization date to Day 100 | 
| Time From Randomization to Administration of First Systemic Antifungal Intravenous (IV) Therapy | The time measured in days from randomization to the administration of the first concomitant systemic anti-fungal therapy in the entire FAS population. Not all participants who accepted systemic anti-fungal therapy may have had a IFI clinical diagnosis. IFI diagnosis criteria for antifungal therapy administration may include: persistent fever, failure of appropriate broad-spectrum antibiotic treatment concomitant with lower respiratory tract infection symptoms, microbiological criteria with corresponding clinical signs and symptoms. | Up to 12 weeks (84 days) | 
| Number of Participants With Clinical Failure During Treatment | Clinical failure was defined as follows: Presence of a proven or probable IFI Systemic antifungal treatment (IV) for 4 consecutive days or more than 10 days total Discontinuation due to adverse event (AE) possibly or probably related to study drug Lost-to-follow-up or discontinuation from the study for any reason with loss to follow-up during the Treatment Phase | Up to 12 weeks (84 days) | 
| Number of Participants in Whom All-cause Mortality Occurred Within 100 Days From Randomization | Death from any cause. | Randomization date to Day 100 | 
| Number of Participants in Whom Mortality is Unlikely, Possibly, and Probably Related to Fungal Infection Occurred Within 100 Days From Randomization | Exact Causes of Death and Their Relationship to IFI Episode Were As Follows: Unlikely related: participant completed treatment and cause of death was due to primary disease or complication Possibly related: IFI undergoing treatment without stabilization, or with failure to have a complete remission, where cause of death might have been due to IFI, including progression or relapse of primary disease Probably related: autopsy or clinical signs suggested that progression of IFI was the probable cause of death | From randomization date to Day 100 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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high-risk leukopenic patients