Posaconazole Treatment of Invasive Fungal Infection (IFI) (P05551)

A Multicenter, Open Label Study to Evaluate Safety and Efficacy of Posaconazole Oral Suspension in Treatment of Invasive Fungal Infection

The purpose of this multicenter, open label study, is to evaluate the safety and efficacy of a 12-week treatment with Posaconazole Oral Suspension in participants with IFI

Study Overview

• Status: Completed
• Conditions: Fungal Infection
• Intervention / Treatment: Drug: Posaconazole

• Study Type: Interventional
• Enrollment (Actual): 63
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Participants must be 18-70 years male or female
• Identified or clinically diagnosed IFI participants or high risk population who are resistant to, or recurrent from, or intolerable to, or may suffer toxic reaction from standard antifungal treatment.
• Sign informed consent form

Exclusion Criteria:

• Female participants who are pregnant or are nursing.
• Participants with known or suspected hypersensitivity or idiosyncratic reaction to azole agents or amphotericin B
• Participants with progressive nervous system diseases( excluding those IFI caused)

• Participants who take the following drugs known with interference with azole antifungal preparations

  • 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 drugs listed above are prohibited 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 having an ECG with a prolonged QTc interval: QTc greater than 450 msec for men and greater than 470 msec for women.
• Expected to take during investigation or is taking systemic antifungal treatment
• Participants with severe renal insufficiency (estimated creatinine clearance less than 50 mL/minute or likely to require dialysis during the study), ALT,AST AKP or total bilirubin are >2×ULN.
• Participants expected to survive no more than 72hrs
• Participants receiving artificial aeration and will not withdraw within 24hrs
• Participants who have used any investigational drugs or biologic agents or anticipated other clinical trials within 30 days of study entry.
• Prior enrollment in this study.
• History of alcohol and/or drug abuse.
• Participants cannot be compliant in investigator's opinion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Posaconazole; Posaconazole 400 mg twice a day (BID) oral suspension for 12 weeks	Drug: Posaconazole; 400mg BID oral suspension for 12 weeks; Other Names: Noxafil

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Had Clinical Response at 12 Weeks With Posaconazole Treatment	EVALUATION OF PARTICIPANTS' CLINICAL RESPONSE BASED ON CRITERIA: Complete Response: resolution of Invasive Fungal Infection (IFI) attributable symptoms, signs and laboratory or etiological abnormalities, if present at enrollment. Partial Response: clinically significant improvement in IFI attributable symptoms, signs and laboratory or etiological abnormalities, if present at enrollment, of which, one still had not achieved complete recession. Stable disease: no progress in IFI attributable symptoms, if present at enrollment. Failure: deterioration in IFI attributable clinical symptoms.	Treatment week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Had Clinical Response at 4 Weeks With Posaconazole Treatment	EVALUATION OF PARTICIPANTS' CLINICAL RESPONSE BASED ON CRITERIA: Complete Response: resolution of IFI attributable symptoms, signs and laboratory or etiological abnormalities, if present at enrollment. Partial Response: clinically significant improvement in IFI attributable symptoms, signs and laboratory or etiological abnormalities, if present at enrollment, of which, one still had not achieved complete recession. Stable disease: no progress in IFI attributable symptoms, if present at enrollment. Failure: deterioration in IFI attributable clinical symptoms.	Treatment week 4
Number of Participants Who Had Clinical Response at 8 Weeks With Posaconazole Treatment	EVALUATION OF PARTICIPANTS' CLINICAL RESPONSE BASED ON CRITERIA: Complete Response: resolution of IFI attributable symptoms, signs and laboratory or etiological abnormalities, if present at enrollment. Partial Response: clinically significant improvement in IFI attributable symptoms, signs and laboratory or etiological abnormalities, if present at enrollment, of which, one still had not achieved complete recession. Stable disease: no progress in IFI attributable symptoms, if present at enrollment. Failure: deterioration in IFI attributable clinical symptoms.	Treatment week 8
Number of Participants With Pathogenic Fungal Eradication at 4 Weeks With Posaconazole Treatment	EVALUATION OF FUNGAL ERADICATION: Participants' mycological response to therapy was assessed by the following: Eradication: Negative culture or histologically documented absence of infecting fungal pathogen from a primary site previously positive. Presumed Eradication: Resolution of all IFI attributable symptoms, signs and laboratory or radiological abnormalities in which a repeat culture/biopsy was contraindicated. Persistence: Continued isolation of fungal pathogen from a primary site previously positive or cytological documentation of presence of fungal pathogen.	Treatment week 4
Number of Participants With Pathogenic Fungal Eradication at 8 Weeks With Posaconazole Treatment	EVALUATION OF FUNGAL ERADICATION: Participants' mycological response to therapy was assessed by the following: Eradication: Negative culture or histologically documented absence of infecting fungal pathogen from a primary site previously positive. Presumed Eradication: Resolution of all IFI attributable symptoms, signs and laboratory or radiological abnormalities in which a repeat culture/biopsy was contraindicated. Persistence: Continued isolation of fungal pathogen from a primary site previously positive or cytological documentation of presence of fungal pathogen.	Treatment week 8
Number of Participants With Pathogenic Fungal Eradication at 12 Weeks With Posaconazole Treatment	EVALUATION OF FUNGAL ERADICATION: Participants' mycological response to therapy was assessed by the following: Eradication: Negative culture or histologically documented absence of infecting fungal pathogen from a primary site previously positive. Presumed Eradication: Resolution of all IFI attributable symptoms, signs and laboratory or radiological abnormalities in which a repeat culture/biopsy was contraindicated. Persistence: Continued isolation of fungal pathogen from a primary site previously positive or cytological documentation of presence of fungal pathogen.	Treatment week 12
Number of Participant Survivors at Week 14 of Post-Posaconazole Treatment Follow-up	Total number of participant deaths was assessed at the end of 2 week post-treatment follow-up (14 weeks). The total number of deaths was compared to the number of survivors at baseline.	Follow-up week 14

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Huang X, Wang F, Chen Y, Liu T, Wang J, Hu J, Jie J, Chen F, Wang S, Shen Z, Yu L, Yu K, Liang Y. A multicenter, open-label study of posaconazole oral suspension in the treatment of invasive fungal infections in patients refractory to or intolerant of first-line therapy. Future Microbiol. 2012 Feb;7(2):201-9. doi: 10.2217/fmb.11.158.

Study record dates

Study Major Dates

• Study Start: November 1, 2008
• Primary Completion (Actual): March 1, 2010
• Study Completion (Actual): March 1, 2010

Study Registration Dates

• First Submitted: December 18, 2008
• First Submitted That Met QC Criteria: December 18, 2008
• First Posted (Estimate): December 19, 2008

Study Record Updates

• Last Update Posted (Actual): April 7, 2017
• Last Update Submitted That Met QC Criteria: March 9, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: refractory or first line medication intolerable invasive fungal infection
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Bacterial Infections and Mycoses; Infections; Communicable Diseases; Mycoses; Invasive Fungal Infections; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; 14-alpha Demethylase Inhibitors; Trypanocidal Agents; Posaconazole
• Other Study ID Numbers: P05551

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf

http://engagezone.msd.com/ds_documentation.php