A Study to Examine the Efficacy and Safety of Posaconazole When Introduced Early in the Treatment of Refractory Fungal Infections (P05090 AM2)

Phase 2

Completed

• Conditions: Mycoses
• Interventions: Drug: Posaconazole

• Registration Number: NCT00550732
• Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of posaconazole in the early treatment of fungal infections in participants who are refractory to, intolerant to, or medically precluded from first-line monotherapy or first-line combination antifungal therapy.

Detailed Description

In the past two decades, invasive fungal infections (IFI) have become increasingly common among immunocompromised people, including solid-organ or hematopoietic stem-cell transplant recipients, those with HIV infection, those with hematological malignancies, and individuals on immunosuppressive drug regimens. There is a high rate of morbidity and mortality associated with IFI. Over the past decade, there has been an increase in resistance to commonly used antifungal agents and an epidemiological shift to more drug-resistant strains. This has demonstrated the need for the development of a new generation of azoles.

Study Timeline

• Study First Submitted: 2007-10-29
• Study First Submitted QC: 2007-10-29
• Study First Posted: 2007-10-30
• Study Start: 2007-12
• Primary Completion: 2012-11
• Study Completion: 2012-11
• Results First Submitted: 2013-09-11
• Results First Submitted QC: 2013-12-03
• Results First Posted: 2013-12-27
• Status Verified: 2017-03
• Last Update Submitted: 2017-03-09
• Last Update Posted: 2017-04-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

• Proven or probable invasive fungal infection (IFI) including breakthrough infection while on antifungal treatment for at least 7 days.
• Refractory or intolerant to prior antifungal therapy, or medically unable to receive standard antifungal therapy.
• Age ≥13 years old.
• Expected to survive >1 month.
• Negative pregnancy test (serum or urine) at baseline for women of childbearing potential.

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Exclusion Criteria

• Serum bilirubin >10 times upper limit of normal (ULN).
• Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >10 times ULN.
• Documented allergy to azoles.
• Unable to take oral suspension medications or enteral feeding.
• Pregnant or breastfeeding.
• Participants who have received an investigational drug are allowed to be enrolled if the investigational drug was given 30 days prior to study registration, unless approved by the Sponsor.
• Requires surgery.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Posaconazole	Posaconazole	Posaconazole oral suspension was administered as 400 mg twice daily (bis in die, BID) with food or 200 mg four times daily (quater in die, QID) without food for a minimum of 1 month.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Complete Response (CR) or Partial Response (PR) by 12 Weeks or End of Treatment	Up to 6 months	Complete Response was defined as resolution of all attributable clinical signs and symptoms and radiologic and mycologic abnormalities, if present at baseline. Partial Response was defined as clinically meaningful improvement in attributable clinical signs and symptoms and radiologic and mycologic abnormalities, if present at baseline.

Secondary Outcome Measures

Name	Time	Method
Overall Survival at 3 Months	3 months	Total number of participant survivors was assessed at 3 months.
Percentage of Participants With a CR or PR by 12 Weeks	Up to 12 Weeks	Complete Response was defined as resolution of all attributable clinical signs and symptoms and radiologic and mycologic abnormalities, if present at baseline. Partial Response was defined as clinically meaningful improvement in attributable clinical signs and symptoms and radiologic and mycologic abnormalities, if present at baseline.
Percentage of Participants With CR or PR by 4 Weeks and by 26 Weeks	Up to 26 weeks	Complete Response was defined as resolution of all attributable clinical signs and symptoms and radiologic and mycologic abnormalities, if present at baseline. Partial Response was defined as clinically meaningful improvement in attributable clinical signs and symptoms and radiologic and mycologic abnormalities, if present at baseline.
Percentage of Participants With Infection-free Survival After the Last Dose of Study Drug	Up to 6 months	Infection-free survival was the proportion of evaluable participants included in the efficacy analysis who are infection-free and alive at 6 months post last dose visit. Infection-free is defined as the resolution of signs and symptoms of infection.
Number of Participants With Response to Posaconazole in Combination Therapy	Up to 6 months	Complete Response was defined as resolution of all attributable clinical signs and symptoms and radiologic and mycologic abnormalities, if present at baseline. Partial Response was defined as clinically meaningful improvement in attributable clinical signs and symptoms and radiologic and mycologic abnormalities, if present at baseline.
Number of Participants Experiencing Adverse Events (AEs)	Up to 12 months	An adverse event (AE) is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration whether or not considered related to the use of the study drug.
Number of Participants With ≥50% Decrease in Lesion Size or Number	Up to 6 months	Reduction in lesion size was analyzed by computed tomography (CT) scan. An imaging response was defined as \>=50% reduction in lesion size for pulmonary and cerebral disease or \>=50% reduction in the number of lesions for liver disease.