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

NCT00811928 | Completed Phase 3 Results

• 1 other identifier: P05387
• Study Type: interventional
• Target: 252
• Locations: 0 countries
• Sites: N/A

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

Conditions

Leukopenia

Keywords

high-risk leukopenic patients

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Number of Participants With Proven or Probable Diagnosis of IFI Within 100 Days From Randomization

  From randomization date to Day 100

• Time From Randomization to the First Onset of Proven or Probable IFI

  From randomization date to Day 100

• Time From Randomization to Administration of First Systemic Antifungal Intravenous (IV) Therapy

  Up to 12 weeks (84 days)

• Number of Participants With Clinical Failure During Treatment

  Up to 12 weeks (84 days)

• Number of Participants in Whom All-cause Mortality Occurred Within 100 Days From Randomization

  Randomization date to Day 100

Study Arms (2)

Posaconazole

ACTIVE COMPARATOR

Posaconazole oral suspension 200 mg three times a day (TID)

Drug: Posaconazole

Fluconazole

ACTIVE COMPARATOR

Fluconazole 400 mg once daily (QD)

Drug: Fluconazole

Interventions

Posaconazole DRUG

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)

Also known as: Noxafil, SCH 056592

Posaconazole

Fluconazole DRUG

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)

Fluconazole

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• Shen Y, Huang XJ, Wang JX, Jin J, Hu JD, Yu K, Wu DP, Wang SJ, Yu L, Chen XQ, Liu T, Liang YM, Chen FP, Li Y, Shen ZX. Posaconazole vs. fluconazole as invasive fungal infection prophylaxis in China: a multicenter, randomized, open-label study. Int J Clin Pharmacol Ther. 2013 Sep;51(9):738-45. doi: 10.5414/CP201880.

  PMID: 23924680 DERIVED

MeSH Terms

Conditions

Leukopenia

Interventions

posaconazole; Fluconazole

Condition Hierarchy (Ancestors)

Cytopenia; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukocyte Disorders

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2008
• First Posted: December 19, 2008
• Study Start: November 1, 2008
• Primary Completion: May 1, 2010
• Study Completion: May 1, 2010
• Last Updated: April 7, 2017
• Results First Posted: September 13, 2011

Record last verified: 2017-03

Data Sharing

• IPD Sharing: Will share