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

Sponsor:	Schering-Plough
Information provided by:	Schering-Plough
ClinicalTrials.gov Identifier:	NCT00811928

Purpose

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

Condition	Intervention	Phase
Leukopenia	Drug: Posaconazole Drug: Fluconazole	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Prevention
Official Title:	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

Resource links provided by NLM:

MedlinePlus related topics: Fungal Infections Molds

Drug Information available for: Fluconazole Posaconazole

U.S. FDA Resources

Further study details as provided by Schering-Plough:

Primary Outcome Measures:

Number of Participants With Proven or Probable Diagnosis of Invasive Fungal Infection (IFI) During the Treatment Period [ Time Frame: Up to 12 Weeks (84 days) plus 7 days ] [ Designated as safety issue: No ]
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:

Number of Participants With Proven or Probable Diagnosis of IFI Within 100 Days From Randomization [ Time Frame: From randomization date to Day 100 ] [ Designated as safety issue: No ]
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 [ Time Frame: From randomization date to Day 100 ] [ Designated as safety issue: No ]
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.
Time From Randomization to Administration of First Systemic Antifungal Intravenous (IV) Therapy [ Time Frame: Up to 12 weeks (84 days) ] [ Designated as safety issue: No ]
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 [ Time Frame: Up to 12 weeks (84 days) ] [ Designated as safety issue: No ]
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 [ Time Frame: Randomization date to Day 100 ] [ Designated as safety issue: Yes ]
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 [ Time Frame: From randomization date to Day 100 ] [ Designated as safety issue: Yes ]
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

Enrollment:	252
Study Start Date:	November 2008
Study Completion Date:	May 2010
Primary Completion Date:	May 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Posaconazole Posaconazole oral suspension 200 mg three times a day (TID)	Drug: Posaconazole 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) Other Names: Noxafil SCH 056592
Active Comparator: Fluconazole Fluconazole 400 mg once daily (QD)	Drug: Fluconazole 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)

Eligibility

Ages Eligible for Study:	18 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

No Contacts or Locations Provided

More Information

No publications provided

Responsible Party:	Vice President, Late Stage Development Group Leader, Merck Sharp & Dohme Corp
ClinicalTrials.gov Identifier:	NCT00811928 History of Changes
Other Study ID Numbers:	P05387
Study First Received:	December 18, 2008
Results First Received:	May 26, 2011
Last Updated:	September 16, 2011
Health Authority:	China: State Food and Drug Administration

Keywords provided by Schering-Plough:

high-risk leukopenic patients

Additional relevant MeSH terms:

Leukopenia
Mycoses
Leukocyte Disorders
Hematologic Diseases
Fluconazole
Posaconazole
Antifungal Agents
Anti-Infective Agents

Therapeutic Uses
Pharmacologic Actions
14-alpha Demethylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Trypanocidal Agents
Antiprotozoal Agents
Antiparasitic Agents

ClinicalTrials.gov processed this record on February 09, 2012