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

Phase 3

Completed

• Conditions: Leukopenia
• Interventions: Drug: Posaconazole; Drug: Fluconazole

• Registration Number: NCT00811928
• Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study Start: 2008-11
• Study First Submitted: 2008-12-18
• Study First Submitted QC: 2008-12-18
• Study First Posted: 2008-12-19
• Primary Completion: 2010-05
• Study Completion: 2010-05
• Disposition First Submitted: 2011-04-27
• Disposition First Submitted QC: 2011-04-27
• Disposition First Posted: 2011-05-04
• Results First Submitted: 2011-05-26
• Results First Submitted QC: 2011-08-09
• Results First Posted: 2011-09-13
• Status Verified: 2017-03
• Last Update Submitted: 2017-03-09
• Last Update Posted: 2017-04-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 252

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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Posaconazole	Posaconazole	Posaconazole oral suspension 200 mg three times a day (TID)
Fluconazole	Fluconazole	Fluconazole 400 mg once daily (QD)

Primary Outcome Measures

Name	Time	Method
Number of Participants With Proven or Probable Diagnosis of Invasive Fungal Infection (IFI) During the Treatment Period	Up to 12 Weeks (84 days) plus 7 days	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.

Secondary Outcome Measures

Name	Time	Method
Time From Randomization to Administration of First Systemic Antifungal Intravenous (IV) Therapy	Up to 12 weeks (84 days)	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.
Number of Participants With Clinical Failure During Treatment	Up to 12 weeks (84 days)	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
Number of Participants in Whom All-cause Mortality Occurred Within 100 Days From Randomization	Randomization date to Day 100	Death from any cause.
Number of Participants in Whom Mortality is Unlikely, Possibly, and Probably Related to Fungal Infection Occurred Within 100 Days From Randomization	From randomization date to Day 100	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
Number of Participants With Proven or Probable Diagnosis of IFI Within 100 Days From Randomization	From randomization date to Day 100	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.
Time From Randomization to the First Onset of Proven or Probable IFI	From randomization date to Day 100	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.